Jennifer Meddings, MD, MSC

A 73-year-old man presented to the emergency department in late winter with fevers, myalgias, fatigue, low back pain, and poor oral intake. Four days earlier, he had fallen and hit his head. His partner also noticed a few episodes of confusion in the days leading up to presentation.

The patient’s symptoms are nonspecific. Fevers prompt the consideration of systemic infection, though fevers can also be seen in a broad range of noninfectious processes, including malignancy, vasculitis, autoimmune conditions, endocrinopathies, and drug reaction. The clinical picture warrants prompt and comprehensive evaluation, beginning with further detailed history (current illnesses, exposures, travel, vaccinations, medications, cancer screenings, weight change) and a careful physical examination, which will help guide laboratory testing and imaging.

His past medical history was notable for coronary artery disease for which he underwent coronary artery bypass grafting five years prior, hypertension, hyperlipidemia, diet-controlled type 2 diabetes mellitus, gastroesophageal reflux disease, osteoarthritis leading to chronic knee and hand pain, and a history of mildly low testosterone levels. His medications included hydrocodone and acetaminophen, metoprolol tartrate, omeprazole, topical testosterone gel (prescribed for daily use, used intermittently), and aspirin. He was retired and lived in rural Michigan with his female partner. He previously worked as a truck driver and used to train racehorses. He had quit smoking five years earlier. He denied alcohol or injection drug use.

The patient has significant underlying medical conditions. Considering infectious causes of his symptoms, it is notable that he has no reported immunodeficiency. It would be relevant to know if he has been tested for HIV. His rural residence and work with horses raise the possibility of zoonotic infections, including plague (Yersinia pestis), brucellosis (Brucella species), Q fever (Coxiella burnetti), Rhodococcus equi, or group C or G Streptococci. Information about tuberculosis risk factors, other geographic exposures, recent dental work, and ill contacts might be helpful to elucidate the causes of this nonspecific febrile illness with a possible CNS component. With regard to malignancy, it would be helpful to ask about recent weight loss, lymphadenopathy, and prior cancer screenings. Considering other etiologies, he does not report a history of autoimmune or endocrine conditions. However, it is important to consider a vasculitis, such as giant cell arteritis or polyarteritis nodosa, autoimmune conditions, and endocrinopathies such as thyrotoxicosis. The differential diagnosis for his clinical syndrome remains broad.

Vital signs were temperature 37.3°C, heart rate 88 beats per minute, respiratory rate 18 breaths per minute, blood pressure 105/64 mmHg, and oxygen saturation 93% on room air. Oral examination revealed poor dentition. The heart had a normal rate and regular rhythm with no murmurs, rubs, or gallops, and lungs were clear to auscultation bilaterally. The abdomen was unremarkable. Examination of the back was notable for mild tenderness to palpation over the sacrum. He was oriented to person, place, and time, with intact cranial nerves and a nonfocal neurologic examination. The remainder of his examination was normal. The white blood cell (WBC) count was 11.1 × 10³/μL, with 84% neutrophils and 9% bands, hemoglobin 13.6 g/dL, platelet count 54 × 10³/μL, sodium 122 mmol/L, potassium 3.3 mmol/L, chloride 89 mmol/L, bicarbonate 21 mmol/L, creatinine 1.64 mg/dL, albumin 2.7 g/dL, alkaline phosphatase 136 U/L, AST 60 U/L, ALT 37 U/L, and total bilirubin 2.1 mg/dL.

He had presented to the emergency department five days earlier with fever, flank pain, nausea, vomiting, and weakness. At that time, he had a temperature of 38.2°C, but vital signs otherwise had been normal. Laboratory studies had revealed WBC count 14.0 × 10³/μL, hemoglobin 13.7 g/dL, platelet count 175 × 10³/μL, sodium 129 mmol/L, chloride 97 mmol/dL, bicarbonate 23 mmol/L, creatinine 1.1 mg/dL, and total bilirubin 1.6 mg/dL. Urinalysis had been negative. He had received one liter of intravenous normal saline and ketorolac for pain and had been discharged with the diagnosis of a viral illness.

A picture of a progressive, subacute illness with multisystem involvement appears to be emerging, and there are several abnormalities consistent with infection, including fever, leukocytosis with bandemia, thrombocytopenia, renal dysfunction, and elevated bilirubin. His borderline hypotension may be due to uninterrupted use of his antihypertensive medication in the setting of poor oral intake or may indicate incipient sepsis. Focal sacral tenderness raises the possibility of vertebral osteomyelitis or epidural abscess, either from a contiguous focus of infection from the surrounding structures, or as a site of seeding from bacteremia. His prior confusion episodes might have been secondary to a systemic process; however, CNS imaging should be done, given the history of confusion and recent fall. Further diagnostic studies are warranted, including: blood cultures; peripheral blood smear; imaging of the spine, chest, abdomen, and pelvis; electrocardiogram; and possibly echocardiogram. Although noninfectious etiologies should not be discounted, the constellation of findings is more compatible with infection.

Two sets of blood cultures and a viral respiratory swab were obtained. Computed tomography (CT) of the head without contrast was negative for acute bleeding or other intracranial pathology. Lumbosacral radiography revealed degenerative changes with intact alignment of the sacrum. The patient was admitted with plans to pursue lumbar puncture if altered mental status recurred. The viral swab was negative. Within 24 hours, one set of blood cultures (both bottles) grew lactose-negative, oxidase-negative, gram-negative rods.

Gram-negative rods (GNRs) rarely are contaminants in blood cultures and should be considered significant until proven otherwise. Prompt empiric therapy and investigation to identify the primary source of bacteremia must be initiated. Although the most common GNRs isolated from blood cultures are enteric coliform organisms such as E. coli, Klebsiella, and Enterobacter, these typically are lactose-positive. Additional possibilities should be considered, including Salmonella species or other organisms comprising the “HACEK” group. This latter group is commonly associated with endocarditis, but the majority are oxidase-positive and have more fastidious growth requirements. Although there are other gram-negative organisms to consider, they have other distinguishing characteristics that have not been indicated in the microbiology results. Broad-spectrum antibiotic therapy is appropriate while awaiting the final identification of the GNR. A thorough search for a primary source and secondary sites of hematogenous seeding should be conducted. His only localizing symptom was tenderness over the sacrum, and this should be further assessed by sensitive imaging such as magnetic resonance imaging (MRI). The identity of the GNR would guide further diagnostic evaluation. For example, a respiratory organism such as Haemophilus influenzae would prompt a CT scan of the chest. Isolation of an enteric or a coliform GNR such as E. coli would prompt abdominal and pelvic imaging to assess for occult abscess. An “HACEK” group organism would prompt echocardiography to evaluate for endocarditis.

He was started on piperacillin–tazobactam. GNR bacteremia without a clear source prompted a CT of the chest, abdomen, and pelvis with and without contrast. The images were unremarkable, with the exception of a signal abnormality in the left psoas muscle concerning for abscess (Figure 1). MRI of the same region revealed L2-4 osteomyelitis and discitis with bilateral psoas abscesses but without epidural abscess (Figure 2).

Because of increasing reports of antibiotic resistance in GNRs, even in community-acquired infections, it is appropriate to initially treat with a broad-spectrum antibiotic such as a fourth-generation cephalosporin or carbapenem while awaiting identification and susceptibility results to guide definitive therapy. In addition to antimicrobial therapy, treatment of psoas abscess usually requires drainage. Vertebral osteomyelitis from a hematogenous source can often be treated with antibiotics alone, as long as there are no associated complications such as epidural abscess and spine instability. Imaging should be reviewed for pathology of the surrounding structures, and surgical consultation should be obtained.

Neurosurgery, Interventional Radiology, and Infectious Disease services were consulted. Antibiotic coverage was expanded to vancomycin, cefepime, and metronidazole due to the possibility of polymicrobial infection. No surgical intervention was recommended since the abscesses were too small to drain.

The next day, the GNR was identified as Serratia marcescens.

S. marcescens is a widely distributed organism in the environment, but not a common component of endogenous human flora. Serratia is generally considered as an opportunistic nosocomial pathogen. Community-acquired infection with this organism is unusual and implies exogenous acquisition. A careful re-evaluation of exposures, including injection drug use or other parenteral exposures is important to identify the likely source of infection, as these have been previously linked to outbreaks of environmental organisms. Based on the presumed pathogenesis of infection and the initial microbiology suggesting monomicrobial Serratia infection, antibiotics should be narrowed based on the susceptibility results. There is concern that antibiotics might not adequately penetrate the abscesses and result in a lack of clinical improvement and/or lead to the emergence of antibiotic resistance during therapy. This is an important concern with Serratia, which typically harbors an AmpC beta-lactamase that can mediate resistance to broad-spectrum cephalosporins. If medical therapy alone without drainage is planned, short-interval re-imaging is warranted.

Blood cultures from days two and three of hospitalization also grew S. marcescens. No other organisms grew. Based on culture sensitivity data, antibiotics were narrowed to ceftriaxone.

This surprising culture result prompted the medical team to obtain screening laboratory tests for immunocompromising conditions and to revisit the patient’s history. His type 2 diabetes mellitus was well controlled with a hemoglobin A1c of 6.5%. HIV testing was negative. Further questioning of the patient revealed that he had fallen from a truck onto rocks four months prior, injuring his back and hip, but without puncture of the skin or loss of consciousness; he denied recent falls or other injuries but reported significant chronic knee pain. He had not been hospitalized recently. He had never taken corticosteroids or immunomodulatory medications. He continued to deny injection drug use. He did, however, clarify that his work with racehorses, which was originally understood to be a prior hobby, was ongoing, including recent work of cleaning the stables.

The following morning, he experienced confusion, rigors, and hypoxia, which prompted transfer to the intensive care unit (ICU).

Acute worsening during treatment is worrisome, and could be a potential complication of his infection or treatment – or even a separate process altogether. Knee pain in the setting of bacteremia raises the possibility of septic or crystal-induced arthritis and warrants imaging. Confusion and hypoxia might represent secondary sites of seeding from bacteremia (CNS infection and pneumonia, respectively) or manifestations of endocarditis, the latter being unusual for Serratia. An echocardiogram should be obtained. Other neurologic causes, including seizure, should also be considered. Further evaluation by chest imaging and repeat neurologic examination and imaging should be performed. Emergence of resistance during therapy is a theoretical concern with Serratia as an AmpC beta-lactamase-containing organism. While awaiting additional microbiology data, an empiric change to an AmpC beta-lactamase stable antibiotic such as a carbapenem should be made, especially since he has clinically deteriorated on therapy with a β-lactamase susceptible antibiotic, raising concerns of the emergence of resistance on initial therapy.

Antibiotics were changed to meropenem, vancomycin, and metronidazole given the clinical worsening and concerns that this represented infection unresponsive to prior antibiotics. The acute episode resolved spontaneously after one hour. His neurologic examination remained nonfocal. Chest radiography, urinalysis, urine culture, and right upper quadrant ultrasound were unremarkable. Transesophageal echocardiogram revealed no heart valve vegetations. MRI and bone scan of the lower extremities did not show any evidence of septic arthritis or other infection. He remained stable and was transferred out of the ICU the following day. Antibiotic coverage was switched to cefepime. On discussion with his significant other, this event was found to be similar to the intermittent confusion that occurred in the days prior to admission.

The acute onset and other features of these intermittent periods of deterioration are compatible with infection; intermittent seeding of the blood with microbes or their products (eg, lipopolysaccharides) from an abscess or vascular infection could explain these episodes. Some of the previous hypotheses to explain the episodes, such as a secondary infectious process, have not been supported by diagnostic testing or the clinical course. He needs close clinical monitoring and interval assessment of the known sites of infection.

Ten days after osteomyelitis and discitis were diagnosed, the patient developed worsening low back pain, prompting repeat spine MRI. This was significant for bilateral psoas abscess enlargement and extension of osteomyelitis and discitis (Figure 3). He was re-evaluated by Neurosurgery and Interventional Radiology and underwent psoas abscess drainage; abscess cultures grew S. marcescens.

He slowly improved over several weeks and was discharged to a subacute rehabilitation facility. He completed a 3.5-week course of intravenous antibiotics before leaving against medical advice. He completed eight weeks of oral trimethoprim-sulfamethoxazole and remains without long-term sequelae from the infection.

S. marcescens is a gram-negative rod in the Enterobacteriaceae family known for its red pigment. Primarily, S. marcescens causes nosocomial infections, most commonly of the respiratory and urinary tracts. However, a wide range of manifestations has been documented, including meningitis, ocular infections (conjunctivitis, keratitis, endophthalmitis), endocarditis, skin infections (cellulitis, necrotizing fasciitis), and osteomyelitis.^{1, 2} S. marcescens is often reported as the cause of outbreaks in ICUs;^3-6 infection is thought to occur via contamination of water pipes, hospital equipment, and disinfectants.^{3, 7} Its natural environment includes soil, water, and GI tracts of animals,⁴ and there are published reports of S. marcescens infection in horses.^{8, 9} This patient was most likely exposed to S. marcescens through his work with horses and their environment.

S. marcescens has wide-ranging target organs, and successful treatment can be difficult. S. marcescens can infect the renal, respiratory, gastrointestinal, ocular, cardiovascular, and musculoskeletal systems. S. marcescens, like other “SPACE” organisms (Serratia, Pseudomonas, Acinetobacter, Citrobacter, Enterobacter), expresses inducible AmpC beta-lactamase.¹⁰ At baseline, AmpC beta-lactamase expression is repressed.¹¹ Mutants with stably de-repressed (constitutively expressed) AmpC can be selected during therapy and lead to clinical failure, as has been best described during therapy for Enterobacter infections.¹² Infectious Disease consultation may be helpful when caring for patients with S. marcescens bacteremia given these complexities.

This was an unusual case of S. marcescens infection. It most commonly infects immunocompromised hosts. Reported risk factors include solid organ or hematopoietic stem cell transplant, malignancy, HIV/AIDS, and receipt of immunosuppressive agents. The patient did not have these risk factors, but did have well-controlled type 2 diabetes mellitus. Although diabetes is associated with an increased risk of infection and more severe infections,^{13, 14} there is no evidence in the literature that well-controlled type 2 diabetes mellitus compromises the immune system. A few case reports document cutaneous S. marcescens infection in immunocompetent adults.^15,16 A case report of S. marcescens septic arthritis and adjacent osteomyelitis has also been published, but the patient had poorly controlled diabetes.¹⁷ This case provides a report of systemic S. marcescens infection in an individual without clear risk factors.

S. marcescens osteomyelitis is rare, and there have been only a few prior case reports.^2,18 The presentation of osteomyelitis, regardless of the causative organism, is subtle, often insidious, and can easily be missed. Hospitalists should have a high index of suspicion for the diagnosis as it requires prompt evaluation and treatment for complications, including epidural abscess. Risk factors include diabetes mellitus, rheumatoid arthritis, injection drug use, and other immunocompromising illnesses.¹⁹ Degenerative changes in the spine such as osteoarthritis may be risk factors as well,²⁰ though not well studied or quantified. A hypothesized mechanism involves local inflammation and joint damage, leaving the area susceptible to bacterial seeding. Osteoarthritis and degenerative disc disease, along with exposure to racehorses, likely put this patient at risk for bacterial seeding in the vertebrae, ultimately leading to a “dark horse” diagnosis.

• Serratia marcescens is a gram-negative rod bacterium that most commonly infects immunocompromised individuals in hospital settings. This report demonstrates that S. marcescens can cause serious infection in immunocompetent, nonhospitalized adults.
• S. marcescens bacteremia or infection of organs outside of the urinary or respiratory systems is uncommon, and therapy can be complicated by emergence of resistance.
• The clinical presentation of vertebral osteomyelitis and discitis and psoas abscess can be subtle and may present without typical signs and symptoms of infection.

ACKNOWLEDGEMENTS

The authors thank the patient and his partner for their willingness to have his story published, Laura Petersen, MHSA, for providing assistance with references and manuscript editing, and Shadi Azar, MBBS, for assistance in selecting the cross-sectional images.

Disclosures

The authors have no conflicts of interest to disclose.

A 73-year-old man presented to the emergency department in late winter with fevers, myalgias, fatigue, low back pain, and poor oral intake. Four days earlier, he had fallen and hit his head. His partner also noticed a few episodes of confusion in the days leading up to presentation.

The patient’s symptoms are nonspecific. Fevers prompt the consideration of systemic infection, though fevers can also be seen in a broad range of noninfectious processes, including malignancy, vasculitis, autoimmune conditions, endocrinopathies, and drug reaction. The clinical picture warrants prompt and comprehensive evaluation, beginning with further detailed history (current illnesses, exposures, travel, vaccinations, medications, cancer screenings, weight change) and a careful physical examination, which will help guide laboratory testing and imaging.

His past medical history was notable for coronary artery disease for which he underwent coronary artery bypass grafting five years prior, hypertension, hyperlipidemia, diet-controlled type 2 diabetes mellitus, gastroesophageal reflux disease, osteoarthritis leading to chronic knee and hand pain, and a history of mildly low testosterone levels. His medications included hydrocodone and acetaminophen, metoprolol tartrate, omeprazole, topical testosterone gel (prescribed for daily use, used intermittently), and aspirin. He was retired and lived in rural Michigan with his female partner. He previously worked as a truck driver and used to train racehorses. He had quit smoking five years earlier. He denied alcohol or injection drug use.

The patient has significant underlying medical conditions. Considering infectious causes of his symptoms, it is notable that he has no reported immunodeficiency. It would be relevant to know if he has been tested for HIV. His rural residence and work with horses raise the possibility of zoonotic infections, including plague (Yersinia pestis), brucellosis (Brucella species), Q fever (Coxiella burnetti), Rhodococcus equi, or group C or G Streptococci. Information about tuberculosis risk factors, other geographic exposures, recent dental work, and ill contacts might be helpful to elucidate the causes of this nonspecific febrile illness with a possible CNS component. With regard to malignancy, it would be helpful to ask about recent weight loss, lymphadenopathy, and prior cancer screenings. Considering other etiologies, he does not report a history of autoimmune or endocrine conditions. However, it is important to consider a vasculitis, such as giant cell arteritis or polyarteritis nodosa, autoimmune conditions, and endocrinopathies such as thyrotoxicosis. The differential diagnosis for his clinical syndrome remains broad.

Vital signs were temperature 37.3°C, heart rate 88 beats per minute, respiratory rate 18 breaths per minute, blood pressure 105/64 mmHg, and oxygen saturation 93% on room air. Oral examination revealed poor dentition. The heart had a normal rate and regular rhythm with no murmurs, rubs, or gallops, and lungs were clear to auscultation bilaterally. The abdomen was unremarkable. Examination of the back was notable for mild tenderness to palpation over the sacrum. He was oriented to person, place, and time, with intact cranial nerves and a nonfocal neurologic examination. The remainder of his examination was normal. The white blood cell (WBC) count was 11.1 × 10³/μL, with 84% neutrophils and 9% bands, hemoglobin 13.6 g/dL, platelet count 54 × 10³/μL, sodium 122 mmol/L, potassium 3.3 mmol/L, chloride 89 mmol/L, bicarbonate 21 mmol/L, creatinine 1.64 mg/dL, albumin 2.7 g/dL, alkaline phosphatase 136 U/L, AST 60 U/L, ALT 37 U/L, and total bilirubin 2.1 mg/dL.

He had presented to the emergency department five days earlier with fever, flank pain, nausea, vomiting, and weakness. At that time, he had a temperature of 38.2°C, but vital signs otherwise had been normal. Laboratory studies had revealed WBC count 14.0 × 10³/μL, hemoglobin 13.7 g/dL, platelet count 175 × 10³/μL, sodium 129 mmol/L, chloride 97 mmol/dL, bicarbonate 23 mmol/L, creatinine 1.1 mg/dL, and total bilirubin 1.6 mg/dL. Urinalysis had been negative. He had received one liter of intravenous normal saline and ketorolac for pain and had been discharged with the diagnosis of a viral illness.

A picture of a progressive, subacute illness with multisystem involvement appears to be emerging, and there are several abnormalities consistent with infection, including fever, leukocytosis with bandemia, thrombocytopenia, renal dysfunction, and elevated bilirubin. His borderline hypotension may be due to uninterrupted use of his antihypertensive medication in the setting of poor oral intake or may indicate incipient sepsis. Focal sacral tenderness raises the possibility of vertebral osteomyelitis or epidural abscess, either from a contiguous focus of infection from the surrounding structures, or as a site of seeding from bacteremia. His prior confusion episodes might have been secondary to a systemic process; however, CNS imaging should be done, given the history of confusion and recent fall. Further diagnostic studies are warranted, including: blood cultures; peripheral blood smear; imaging of the spine, chest, abdomen, and pelvis; electrocardiogram; and possibly echocardiogram. Although noninfectious etiologies should not be discounted, the constellation of findings is more compatible with infection.

Two sets of blood cultures and a viral respiratory swab were obtained. Computed tomography (CT) of the head without contrast was negative for acute bleeding or other intracranial pathology. Lumbosacral radiography revealed degenerative changes with intact alignment of the sacrum. The patient was admitted with plans to pursue lumbar puncture if altered mental status recurred. The viral swab was negative. Within 24 hours, one set of blood cultures (both bottles) grew lactose-negative, oxidase-negative, gram-negative rods.

Gram-negative rods (GNRs) rarely are contaminants in blood cultures and should be considered significant until proven otherwise. Prompt empiric therapy and investigation to identify the primary source of bacteremia must be initiated. Although the most common GNRs isolated from blood cultures are enteric coliform organisms such as E. coli, Klebsiella, and Enterobacter, these typically are lactose-positive. Additional possibilities should be considered, including Salmonella species or other organisms comprising the “HACEK” group. This latter group is commonly associated with endocarditis, but the majority are oxidase-positive and have more fastidious growth requirements. Although there are other gram-negative organisms to consider, they have other distinguishing characteristics that have not been indicated in the microbiology results. Broad-spectrum antibiotic therapy is appropriate while awaiting the final identification of the GNR. A thorough search for a primary source and secondary sites of hematogenous seeding should be conducted. His only localizing symptom was tenderness over the sacrum, and this should be further assessed by sensitive imaging such as magnetic resonance imaging (MRI). The identity of the GNR would guide further diagnostic evaluation. For example, a respiratory organism such as Haemophilus influenzae would prompt a CT scan of the chest. Isolation of an enteric or a coliform GNR such as E. coli would prompt abdominal and pelvic imaging to assess for occult abscess. An “HACEK” group organism would prompt echocardiography to evaluate for endocarditis.

He was started on piperacillin–tazobactam. GNR bacteremia without a clear source prompted a CT of the chest, abdomen, and pelvis with and without contrast. The images were unremarkable, with the exception of a signal abnormality in the left psoas muscle concerning for abscess (Figure 1). MRI of the same region revealed L2-4 osteomyelitis and discitis with bilateral psoas abscesses but without epidural abscess (Figure 2).

Because of increasing reports of antibiotic resistance in GNRs, even in community-acquired infections, it is appropriate to initially treat with a broad-spectrum antibiotic such as a fourth-generation cephalosporin or carbapenem while awaiting identification and susceptibility results to guide definitive therapy. In addition to antimicrobial therapy, treatment of psoas abscess usually requires drainage. Vertebral osteomyelitis from a hematogenous source can often be treated with antibiotics alone, as long as there are no associated complications such as epidural abscess and spine instability. Imaging should be reviewed for pathology of the surrounding structures, and surgical consultation should be obtained.

Neurosurgery, Interventional Radiology, and Infectious Disease services were consulted. Antibiotic coverage was expanded to vancomycin, cefepime, and metronidazole due to the possibility of polymicrobial infection. No surgical intervention was recommended since the abscesses were too small to drain.

The next day, the GNR was identified as Serratia marcescens.

S. marcescens is a widely distributed organism in the environment, but not a common component of endogenous human flora. Serratia is generally considered as an opportunistic nosocomial pathogen. Community-acquired infection with this organism is unusual and implies exogenous acquisition. A careful re-evaluation of exposures, including injection drug use or other parenteral exposures is important to identify the likely source of infection, as these have been previously linked to outbreaks of environmental organisms. Based on the presumed pathogenesis of infection and the initial microbiology suggesting monomicrobial Serratia infection, antibiotics should be narrowed based on the susceptibility results. There is concern that antibiotics might not adequately penetrate the abscesses and result in a lack of clinical improvement and/or lead to the emergence of antibiotic resistance during therapy. This is an important concern with Serratia, which typically harbors an AmpC beta-lactamase that can mediate resistance to broad-spectrum cephalosporins. If medical therapy alone without drainage is planned, short-interval re-imaging is warranted.

Blood cultures from days two and three of hospitalization also grew S. marcescens. No other organisms grew. Based on culture sensitivity data, antibiotics were narrowed to ceftriaxone.

This surprising culture result prompted the medical team to obtain screening laboratory tests for immunocompromising conditions and to revisit the patient’s history. His type 2 diabetes mellitus was well controlled with a hemoglobin A1c of 6.5%. HIV testing was negative. Further questioning of the patient revealed that he had fallen from a truck onto rocks four months prior, injuring his back and hip, but without puncture of the skin or loss of consciousness; he denied recent falls or other injuries but reported significant chronic knee pain. He had not been hospitalized recently. He had never taken corticosteroids or immunomodulatory medications. He continued to deny injection drug use. He did, however, clarify that his work with racehorses, which was originally understood to be a prior hobby, was ongoing, including recent work of cleaning the stables.

The following morning, he experienced confusion, rigors, and hypoxia, which prompted transfer to the intensive care unit (ICU).

Acute worsening during treatment is worrisome, and could be a potential complication of his infection or treatment – or even a separate process altogether. Knee pain in the setting of bacteremia raises the possibility of septic or crystal-induced arthritis and warrants imaging. Confusion and hypoxia might represent secondary sites of seeding from bacteremia (CNS infection and pneumonia, respectively) or manifestations of endocarditis, the latter being unusual for Serratia. An echocardiogram should be obtained. Other neurologic causes, including seizure, should also be considered. Further evaluation by chest imaging and repeat neurologic examination and imaging should be performed. Emergence of resistance during therapy is a theoretical concern with Serratia as an AmpC beta-lactamase-containing organism. While awaiting additional microbiology data, an empiric change to an AmpC beta-lactamase stable antibiotic such as a carbapenem should be made, especially since he has clinically deteriorated on therapy with a β-lactamase susceptible antibiotic, raising concerns of the emergence of resistance on initial therapy.

Antibiotics were changed to meropenem, vancomycin, and metronidazole given the clinical worsening and concerns that this represented infection unresponsive to prior antibiotics. The acute episode resolved spontaneously after one hour. His neurologic examination remained nonfocal. Chest radiography, urinalysis, urine culture, and right upper quadrant ultrasound were unremarkable. Transesophageal echocardiogram revealed no heart valve vegetations. MRI and bone scan of the lower extremities did not show any evidence of septic arthritis or other infection. He remained stable and was transferred out of the ICU the following day. Antibiotic coverage was switched to cefepime. On discussion with his significant other, this event was found to be similar to the intermittent confusion that occurred in the days prior to admission.

The acute onset and other features of these intermittent periods of deterioration are compatible with infection; intermittent seeding of the blood with microbes or their products (eg, lipopolysaccharides) from an abscess or vascular infection could explain these episodes. Some of the previous hypotheses to explain the episodes, such as a secondary infectious process, have not been supported by diagnostic testing or the clinical course. He needs close clinical monitoring and interval assessment of the known sites of infection.

Ten days after osteomyelitis and discitis were diagnosed, the patient developed worsening low back pain, prompting repeat spine MRI. This was significant for bilateral psoas abscess enlargement and extension of osteomyelitis and discitis (Figure 3). He was re-evaluated by Neurosurgery and Interventional Radiology and underwent psoas abscess drainage; abscess cultures grew S. marcescens.

He slowly improved over several weeks and was discharged to a subacute rehabilitation facility. He completed a 3.5-week course of intravenous antibiotics before leaving against medical advice. He completed eight weeks of oral trimethoprim-sulfamethoxazole and remains without long-term sequelae from the infection.

S. marcescens is a gram-negative rod in the Enterobacteriaceae family known for its red pigment. Primarily, S. marcescens causes nosocomial infections, most commonly of the respiratory and urinary tracts. However, a wide range of manifestations has been documented, including meningitis, ocular infections (conjunctivitis, keratitis, endophthalmitis), endocarditis, skin infections (cellulitis, necrotizing fasciitis), and osteomyelitis.^{1, 2} S. marcescens is often reported as the cause of outbreaks in ICUs;^3-6 infection is thought to occur via contamination of water pipes, hospital equipment, and disinfectants.^{3, 7} Its natural environment includes soil, water, and GI tracts of animals,⁴ and there are published reports of S. marcescens infection in horses.^{8, 9} This patient was most likely exposed to S. marcescens through his work with horses and their environment.

S. marcescens has wide-ranging target organs, and successful treatment can be difficult. S. marcescens can infect the renal, respiratory, gastrointestinal, ocular, cardiovascular, and musculoskeletal systems. S. marcescens, like other “SPACE” organisms (Serratia, Pseudomonas, Acinetobacter, Citrobacter, Enterobacter), expresses inducible AmpC beta-lactamase.¹⁰ At baseline, AmpC beta-lactamase expression is repressed.¹¹ Mutants with stably de-repressed (constitutively expressed) AmpC can be selected during therapy and lead to clinical failure, as has been best described during therapy for Enterobacter infections.¹² Infectious Disease consultation may be helpful when caring for patients with S. marcescens bacteremia given these complexities.

This was an unusual case of S. marcescens infection. It most commonly infects immunocompromised hosts. Reported risk factors include solid organ or hematopoietic stem cell transplant, malignancy, HIV/AIDS, and receipt of immunosuppressive agents. The patient did not have these risk factors, but did have well-controlled type 2 diabetes mellitus. Although diabetes is associated with an increased risk of infection and more severe infections,^{13, 14} there is no evidence in the literature that well-controlled type 2 diabetes mellitus compromises the immune system. A few case reports document cutaneous S. marcescens infection in immunocompetent adults.^15,16 A case report of S. marcescens septic arthritis and adjacent osteomyelitis has also been published, but the patient had poorly controlled diabetes.¹⁷ This case provides a report of systemic S. marcescens infection in an individual without clear risk factors.

S. marcescens osteomyelitis is rare, and there have been only a few prior case reports.^2,18 The presentation of osteomyelitis, regardless of the causative organism, is subtle, often insidious, and can easily be missed. Hospitalists should have a high index of suspicion for the diagnosis as it requires prompt evaluation and treatment for complications, including epidural abscess. Risk factors include diabetes mellitus, rheumatoid arthritis, injection drug use, and other immunocompromising illnesses.¹⁹ Degenerative changes in the spine such as osteoarthritis may be risk factors as well,²⁰ though not well studied or quantified. A hypothesized mechanism involves local inflammation and joint damage, leaving the area susceptible to bacterial seeding. Osteoarthritis and degenerative disc disease, along with exposure to racehorses, likely put this patient at risk for bacterial seeding in the vertebrae, ultimately leading to a “dark horse” diagnosis.

• Serratia marcescens is a gram-negative rod bacterium that most commonly infects immunocompromised individuals in hospital settings. This report demonstrates that S. marcescens can cause serious infection in immunocompetent, nonhospitalized adults.
• S. marcescens bacteremia or infection of organs outside of the urinary or respiratory systems is uncommon, and therapy can be complicated by emergence of resistance.
• The clinical presentation of vertebral osteomyelitis and discitis and psoas abscess can be subtle and may present without typical signs and symptoms of infection.

ACKNOWLEDGEMENTS

The authors thank the patient and his partner for their willingness to have his story published, Laura Petersen, MHSA, for providing assistance with references and manuscript editing, and Shadi Azar, MBBS, for assistance in selecting the cross-sectional images.

Disclosures

The authors have no conflicts of interest to disclose.

A 73-year-old man presented to the emergency department in late winter with fevers, myalgias, fatigue, low back pain, and poor oral intake. Four days earlier, he had fallen and hit his head. His partner also noticed a few episodes of confusion in the days leading up to presentation.

The patient’s symptoms are nonspecific. Fevers prompt the consideration of systemic infection, though fevers can also be seen in a broad range of noninfectious processes, including malignancy, vasculitis, autoimmune conditions, endocrinopathies, and drug reaction. The clinical picture warrants prompt and comprehensive evaluation, beginning with further detailed history (current illnesses, exposures, travel, vaccinations, medications, cancer screenings, weight change) and a careful physical examination, which will help guide laboratory testing and imaging.

His past medical history was notable for coronary artery disease for which he underwent coronary artery bypass grafting five years prior, hypertension, hyperlipidemia, diet-controlled type 2 diabetes mellitus, gastroesophageal reflux disease, osteoarthritis leading to chronic knee and hand pain, and a history of mildly low testosterone levels. His medications included hydrocodone and acetaminophen, metoprolol tartrate, omeprazole, topical testosterone gel (prescribed for daily use, used intermittently), and aspirin. He was retired and lived in rural Michigan with his female partner. He previously worked as a truck driver and used to train racehorses. He had quit smoking five years earlier. He denied alcohol or injection drug use.

The patient has significant underlying medical conditions. Considering infectious causes of his symptoms, it is notable that he has no reported immunodeficiency. It would be relevant to know if he has been tested for HIV. His rural residence and work with horses raise the possibility of zoonotic infections, including plague (Yersinia pestis), brucellosis (Brucella species), Q fever (Coxiella burnetti), Rhodococcus equi, or group C or G Streptococci. Information about tuberculosis risk factors, other geographic exposures, recent dental work, and ill contacts might be helpful to elucidate the causes of this nonspecific febrile illness with a possible CNS component. With regard to malignancy, it would be helpful to ask about recent weight loss, lymphadenopathy, and prior cancer screenings. Considering other etiologies, he does not report a history of autoimmune or endocrine conditions. However, it is important to consider a vasculitis, such as giant cell arteritis or polyarteritis nodosa, autoimmune conditions, and endocrinopathies such as thyrotoxicosis. The differential diagnosis for his clinical syndrome remains broad.

Vital signs were temperature 37.3°C, heart rate 88 beats per minute, respiratory rate 18 breaths per minute, blood pressure 105/64 mmHg, and oxygen saturation 93% on room air. Oral examination revealed poor dentition. The heart had a normal rate and regular rhythm with no murmurs, rubs, or gallops, and lungs were clear to auscultation bilaterally. The abdomen was unremarkable. Examination of the back was notable for mild tenderness to palpation over the sacrum. He was oriented to person, place, and time, with intact cranial nerves and a nonfocal neurologic examination. The remainder of his examination was normal. The white blood cell (WBC) count was 11.1 × 10³/μL, with 84% neutrophils and 9% bands, hemoglobin 13.6 g/dL, platelet count 54 × 10³/μL, sodium 122 mmol/L, potassium 3.3 mmol/L, chloride 89 mmol/L, bicarbonate 21 mmol/L, creatinine 1.64 mg/dL, albumin 2.7 g/dL, alkaline phosphatase 136 U/L, AST 60 U/L, ALT 37 U/L, and total bilirubin 2.1 mg/dL.

He had presented to the emergency department five days earlier with fever, flank pain, nausea, vomiting, and weakness. At that time, he had a temperature of 38.2°C, but vital signs otherwise had been normal. Laboratory studies had revealed WBC count 14.0 × 10³/μL, hemoglobin 13.7 g/dL, platelet count 175 × 10³/μL, sodium 129 mmol/L, chloride 97 mmol/dL, bicarbonate 23 mmol/L, creatinine 1.1 mg/dL, and total bilirubin 1.6 mg/dL. Urinalysis had been negative. He had received one liter of intravenous normal saline and ketorolac for pain and had been discharged with the diagnosis of a viral illness.

A picture of a progressive, subacute illness with multisystem involvement appears to be emerging, and there are several abnormalities consistent with infection, including fever, leukocytosis with bandemia, thrombocytopenia, renal dysfunction, and elevated bilirubin. His borderline hypotension may be due to uninterrupted use of his antihypertensive medication in the setting of poor oral intake or may indicate incipient sepsis. Focal sacral tenderness raises the possibility of vertebral osteomyelitis or epidural abscess, either from a contiguous focus of infection from the surrounding structures, or as a site of seeding from bacteremia. His prior confusion episodes might have been secondary to a systemic process; however, CNS imaging should be done, given the history of confusion and recent fall. Further diagnostic studies are warranted, including: blood cultures; peripheral blood smear; imaging of the spine, chest, abdomen, and pelvis; electrocardiogram; and possibly echocardiogram. Although noninfectious etiologies should not be discounted, the constellation of findings is more compatible with infection.

Two sets of blood cultures and a viral respiratory swab were obtained. Computed tomography (CT) of the head without contrast was negative for acute bleeding or other intracranial pathology. Lumbosacral radiography revealed degenerative changes with intact alignment of the sacrum. The patient was admitted with plans to pursue lumbar puncture if altered mental status recurred. The viral swab was negative. Within 24 hours, one set of blood cultures (both bottles) grew lactose-negative, oxidase-negative, gram-negative rods.

Gram-negative rods (GNRs) rarely are contaminants in blood cultures and should be considered significant until proven otherwise. Prompt empiric therapy and investigation to identify the primary source of bacteremia must be initiated. Although the most common GNRs isolated from blood cultures are enteric coliform organisms such as E. coli, Klebsiella, and Enterobacter, these typically are lactose-positive. Additional possibilities should be considered, including Salmonella species or other organisms comprising the “HACEK” group. This latter group is commonly associated with endocarditis, but the majority are oxidase-positive and have more fastidious growth requirements. Although there are other gram-negative organisms to consider, they have other distinguishing characteristics that have not been indicated in the microbiology results. Broad-spectrum antibiotic therapy is appropriate while awaiting the final identification of the GNR. A thorough search for a primary source and secondary sites of hematogenous seeding should be conducted. His only localizing symptom was tenderness over the sacrum, and this should be further assessed by sensitive imaging such as magnetic resonance imaging (MRI). The identity of the GNR would guide further diagnostic evaluation. For example, a respiratory organism such as Haemophilus influenzae would prompt a CT scan of the chest. Isolation of an enteric or a coliform GNR such as E. coli would prompt abdominal and pelvic imaging to assess for occult abscess. An “HACEK” group organism would prompt echocardiography to evaluate for endocarditis.

He was started on piperacillin–tazobactam. GNR bacteremia without a clear source prompted a CT of the chest, abdomen, and pelvis with and without contrast. The images were unremarkable, with the exception of a signal abnormality in the left psoas muscle concerning for abscess (Figure 1). MRI of the same region revealed L2-4 osteomyelitis and discitis with bilateral psoas abscesses but without epidural abscess (Figure 2).

Because of increasing reports of antibiotic resistance in GNRs, even in community-acquired infections, it is appropriate to initially treat with a broad-spectrum antibiotic such as a fourth-generation cephalosporin or carbapenem while awaiting identification and susceptibility results to guide definitive therapy. In addition to antimicrobial therapy, treatment of psoas abscess usually requires drainage. Vertebral osteomyelitis from a hematogenous source can often be treated with antibiotics alone, as long as there are no associated complications such as epidural abscess and spine instability. Imaging should be reviewed for pathology of the surrounding structures, and surgical consultation should be obtained.

Neurosurgery, Interventional Radiology, and Infectious Disease services were consulted. Antibiotic coverage was expanded to vancomycin, cefepime, and metronidazole due to the possibility of polymicrobial infection. No surgical intervention was recommended since the abscesses were too small to drain.

The next day, the GNR was identified as Serratia marcescens.

S. marcescens is a widely distributed organism in the environment, but not a common component of endogenous human flora. Serratia is generally considered as an opportunistic nosocomial pathogen. Community-acquired infection with this organism is unusual and implies exogenous acquisition. A careful re-evaluation of exposures, including injection drug use or other parenteral exposures is important to identify the likely source of infection, as these have been previously linked to outbreaks of environmental organisms. Based on the presumed pathogenesis of infection and the initial microbiology suggesting monomicrobial Serratia infection, antibiotics should be narrowed based on the susceptibility results. There is concern that antibiotics might not adequately penetrate the abscesses and result in a lack of clinical improvement and/or lead to the emergence of antibiotic resistance during therapy. This is an important concern with Serratia, which typically harbors an AmpC beta-lactamase that can mediate resistance to broad-spectrum cephalosporins. If medical therapy alone without drainage is planned, short-interval re-imaging is warranted.

Blood cultures from days two and three of hospitalization also grew S. marcescens. No other organisms grew. Based on culture sensitivity data, antibiotics were narrowed to ceftriaxone.

This surprising culture result prompted the medical team to obtain screening laboratory tests for immunocompromising conditions and to revisit the patient’s history. His type 2 diabetes mellitus was well controlled with a hemoglobin A1c of 6.5%. HIV testing was negative. Further questioning of the patient revealed that he had fallen from a truck onto rocks four months prior, injuring his back and hip, but without puncture of the skin or loss of consciousness; he denied recent falls or other injuries but reported significant chronic knee pain. He had not been hospitalized recently. He had never taken corticosteroids or immunomodulatory medications. He continued to deny injection drug use. He did, however, clarify that his work with racehorses, which was originally understood to be a prior hobby, was ongoing, including recent work of cleaning the stables.

The following morning, he experienced confusion, rigors, and hypoxia, which prompted transfer to the intensive care unit (ICU).

Acute worsening during treatment is worrisome, and could be a potential complication of his infection or treatment – or even a separate process altogether. Knee pain in the setting of bacteremia raises the possibility of septic or crystal-induced arthritis and warrants imaging. Confusion and hypoxia might represent secondary sites of seeding from bacteremia (CNS infection and pneumonia, respectively) or manifestations of endocarditis, the latter being unusual for Serratia. An echocardiogram should be obtained. Other neurologic causes, including seizure, should also be considered. Further evaluation by chest imaging and repeat neurologic examination and imaging should be performed. Emergence of resistance during therapy is a theoretical concern with Serratia as an AmpC beta-lactamase-containing organism. While awaiting additional microbiology data, an empiric change to an AmpC beta-lactamase stable antibiotic such as a carbapenem should be made, especially since he has clinically deteriorated on therapy with a β-lactamase susceptible antibiotic, raising concerns of the emergence of resistance on initial therapy.

Antibiotics were changed to meropenem, vancomycin, and metronidazole given the clinical worsening and concerns that this represented infection unresponsive to prior antibiotics. The acute episode resolved spontaneously after one hour. His neurologic examination remained nonfocal. Chest radiography, urinalysis, urine culture, and right upper quadrant ultrasound were unremarkable. Transesophageal echocardiogram revealed no heart valve vegetations. MRI and bone scan of the lower extremities did not show any evidence of septic arthritis or other infection. He remained stable and was transferred out of the ICU the following day. Antibiotic coverage was switched to cefepime. On discussion with his significant other, this event was found to be similar to the intermittent confusion that occurred in the days prior to admission.

The acute onset and other features of these intermittent periods of deterioration are compatible with infection; intermittent seeding of the blood with microbes or their products (eg, lipopolysaccharides) from an abscess or vascular infection could explain these episodes. Some of the previous hypotheses to explain the episodes, such as a secondary infectious process, have not been supported by diagnostic testing or the clinical course. He needs close clinical monitoring and interval assessment of the known sites of infection.

Ten days after osteomyelitis and discitis were diagnosed, the patient developed worsening low back pain, prompting repeat spine MRI. This was significant for bilateral psoas abscess enlargement and extension of osteomyelitis and discitis (Figure 3). He was re-evaluated by Neurosurgery and Interventional Radiology and underwent psoas abscess drainage; abscess cultures grew S. marcescens.

He slowly improved over several weeks and was discharged to a subacute rehabilitation facility. He completed a 3.5-week course of intravenous antibiotics before leaving against medical advice. He completed eight weeks of oral trimethoprim-sulfamethoxazole and remains without long-term sequelae from the infection.

S. marcescens is a gram-negative rod in the Enterobacteriaceae family known for its red pigment. Primarily, S. marcescens causes nosocomial infections, most commonly of the respiratory and urinary tracts. However, a wide range of manifestations has been documented, including meningitis, ocular infections (conjunctivitis, keratitis, endophthalmitis), endocarditis, skin infections (cellulitis, necrotizing fasciitis), and osteomyelitis.^{1, 2} S. marcescens is often reported as the cause of outbreaks in ICUs;^3-6 infection is thought to occur via contamination of water pipes, hospital equipment, and disinfectants.^{3, 7} Its natural environment includes soil, water, and GI tracts of animals,⁴ and there are published reports of S. marcescens infection in horses.^{8, 9} This patient was most likely exposed to S. marcescens through his work with horses and their environment.

S. marcescens has wide-ranging target organs, and successful treatment can be difficult. S. marcescens can infect the renal, respiratory, gastrointestinal, ocular, cardiovascular, and musculoskeletal systems. S. marcescens, like other “SPACE” organisms (Serratia, Pseudomonas, Acinetobacter, Citrobacter, Enterobacter), expresses inducible AmpC beta-lactamase.¹⁰ At baseline, AmpC beta-lactamase expression is repressed.¹¹ Mutants with stably de-repressed (constitutively expressed) AmpC can be selected during therapy and lead to clinical failure, as has been best described during therapy for Enterobacter infections.¹² Infectious Disease consultation may be helpful when caring for patients with S. marcescens bacteremia given these complexities.

This was an unusual case of S. marcescens infection. It most commonly infects immunocompromised hosts. Reported risk factors include solid organ or hematopoietic stem cell transplant, malignancy, HIV/AIDS, and receipt of immunosuppressive agents. The patient did not have these risk factors, but did have well-controlled type 2 diabetes mellitus. Although diabetes is associated with an increased risk of infection and more severe infections,^{13, 14} there is no evidence in the literature that well-controlled type 2 diabetes mellitus compromises the immune system. A few case reports document cutaneous S. marcescens infection in immunocompetent adults.^15,16 A case report of S. marcescens septic arthritis and adjacent osteomyelitis has also been published, but the patient had poorly controlled diabetes.¹⁷ This case provides a report of systemic S. marcescens infection in an individual without clear risk factors.

S. marcescens osteomyelitis is rare, and there have been only a few prior case reports.^2,18 The presentation of osteomyelitis, regardless of the causative organism, is subtle, often insidious, and can easily be missed. Hospitalists should have a high index of suspicion for the diagnosis as it requires prompt evaluation and treatment for complications, including epidural abscess. Risk factors include diabetes mellitus, rheumatoid arthritis, injection drug use, and other immunocompromising illnesses.¹⁹ Degenerative changes in the spine such as osteoarthritis may be risk factors as well,²⁰ though not well studied or quantified. A hypothesized mechanism involves local inflammation and joint damage, leaving the area susceptible to bacterial seeding. Osteoarthritis and degenerative disc disease, along with exposure to racehorses, likely put this patient at risk for bacterial seeding in the vertebrae, ultimately leading to a “dark horse” diagnosis.

• Serratia marcescens is a gram-negative rod bacterium that most commonly infects immunocompromised individuals in hospital settings. This report demonstrates that S. marcescens can cause serious infection in immunocompetent, nonhospitalized adults.
• S. marcescens bacteremia or infection of organs outside of the urinary or respiratory systems is uncommon, and therapy can be complicated by emergence of resistance.
• The clinical presentation of vertebral osteomyelitis and discitis and psoas abscess can be subtle and may present without typical signs and symptoms of infection.

ACKNOWLEDGEMENTS

The authors thank the patient and his partner for their willingness to have his story published, Laura Petersen, MHSA, for providing assistance with references and manuscript editing, and Shadi Azar, MBBS, for assistance in selecting the cross-sectional images.

Disclosures

The authors have no conflicts of interest to disclose.

Central line–associated bloodstream infection (CLABSI) and catheter-associated urinary tract infection (CAUTI) are morbid and expensive healthcare-associated infections (HAIs).^1-8 While these HAIs are prevalent in intensive care units (ICUs) and general wards, most of the research, prevention efforts, and financial penalties have been focused in the ICU.^9,10 For hospitalists, who are taking a larger role in caring for the critically ill,^11,12 it is optimal to understand best preventive practices.

There has been a national puTash to standardize procedures and products to prevent CLABSI and CAUTI.^2,13-16 CLABSI has transitioned from a common ICU complication to a “never event.” Success has been reflected in the prevention of 25,000 CLABSIs over the last decade, translating to a 58% reduction in infections, with 6000 deaths prevented and $414 million saved.² CLABSI prevention principles have been applied to CAUTI prevention (ie, aseptic insertion, maintenance care, prompting removal) but with slower adoption¹⁷ and fewer dramatic CAUTI reductions,¹⁸ due in part to weaker recognition¹⁹ of CAUTI as a serious clinical event, despite its morbidity²⁰ and cost.²¹

Despite recent improvements in preventing HAIs, there is a marked variability in how hospitals perform in preventing these infections.²² To inform infection prevention strategies for a large-scale implementation project funded by the Agency for Healthcare Research and Quality and focused on ICUs with persistently elevated CLABSI and/or CAUTI rates,²³ we performed a systematic search of interventions to prevent CLABSI and CAUTI in the ICU setting. This evidence was synthesized to help units select and prioritize interventions to prevent these HAIs.

Literature Search Strategy

We performed a systematic search to identify CLABSI and CAUTI prevention studies and synthesized findings using a narrative review process. Using criteria developed and refined from seminal articles on the topic,^10,14,24-34 we searched the PubMed and Cochrane databases from their inception to October of 2015 using Medical Subject Headings (MeSHs) for “central venous catheters,” “CLABSI,” “central line associated bloodstream infection,” “catheter related bloodstream infection,” “intravascular devices,” “urinary catheterization,” “urinary catheters,” “urinary tract infections,” “CAUTI,” and “catheter associated urinary tract infections” and filtered for articles containing the MeSHs “intensive care unit” and “ICU.” Supplemental Figure 1 details the search, yielding 102 studies for CLABSI and 28 studies for CAUTI, including 7 studies with CLABSI and CAUTI interventions.

Eligibility Criteria Review

Study Design

We included randomized and nonrandomized studies that implemented at least 1 intervention to prevent CLABSI or CAUTI in an adult ICU setting and reported the preintervention or control group data to compare with the postintervention data. We excluded general ward, outpatient/ambulatory, and neonatal/pediatric settings. Interventions to prevent CLABSI or CAUTI were included. We excluded interventions focused on diagnosis or treatment or those that lacked adequate description of the intervention for replication. Studies with interventions that are no longer standard of care in the United States (US) were excluded, as were studies not available in English.

Outcomes

Primary Outcomes for Central Vascular Catheter Infection

• CLABSI: A lab-confirmed bloodstream infection in a patient who has had a central line for at least 48 hours on the date of the development of the bloodstream infection and without another known source of infection. We included studies that reported CLABSIs per 1000 central line days or those that provided data to permit calculation of this ratio. This measure is similar to current National Healthcare Safety Network (NHSN) surveillance definitions.²²
• Catheter-related bloodstream infection (CRBSI): A lab-confirmed bloodstream infection attributed to an intravascular catheter by a quantitative culture of the catheter tip or by differences in growth between catheter and peripheral venipuncture blood culture specimens.³⁵ This microbiologic definition of a central line bloodstream infection was often used prior to NHSN reporting, with rates provided as the number of CRBSIs per 1000 central line days.

Primary Outcome for Urinary Catheter Infection

• CAUTI: Urinary tract infection occurring in patients during or after the recent use of an indwelling urinary catheter. We included studies that reported CAUTIs per 1000 urinary catheter days or those that provided data to permit calculation of this ratio (similar to the current NHSN surveillance definitions).²² We excluded studies where CAUTI was defined as bacteriuria alone, without symptoms.

Secondary Outcomes

• Central line utilization ratio: The device utilization ratio (DUR) measure of central line use is calculated as central line days divided by patient days.
• Urinary catheter utilization ratio: The DUR measure of urinary catheter use is calculated as indwelling urinary catheter days divided by patient days, as used in NHSN surveillance, excluding other catheter types.²² We excluded other measures of urinary catheter use because of a large variation in definitions, which limits the ability to compare measures across studies.

Data Synthesis and Analysis

Information on the ICU and intervention type, intervention components, outcomes, and whether interventions were in use prior to the study was abstracted by CAUTI and CLABSI experts (JM and PKP) and confirmed by a second author.

We compared interventions found in the literature to components of the previously published urinary catheter “life cycle,” a conceptual model used to organize and prioritize interventions for a reduction in CAUTI (Figure 1).³⁶

Conceptual Model for Disrupting the Life Cycle of a Catheter

Our data analysis demonstrated that components of the urinary catheter life cycle (Figure 1) were useful and could be applied to vascular catheters, but changes were needed to make the model more valuable to hospitalists implementing CLABSI and CAUTI prevention interventions. We found that the previously named stage 1 (catheter placement) is better described in 2 stages: stage 0, avoid catheter if possible, and stage 1, ensure aseptic placement. Additionally, we tailored the model to include actionable language, describing ways to disrupt the life cycle. Finally, we added a component to represent interventions to improve implementation and sustainability, such as auditing compliance and timely feedback to clinicians. Thus, we introduce a new conceptual model, “Disrupting the Life Cycle of a Catheter” (Figure 2)

Central Vascular Catheter Interventional Study Results

Characteristics of Included Central Vascular Catheter Infection Studies

Of the 102 central vascular catheter (CVC) studies that met the inclusion criteria (reporting outcomes for 105 intervention cohorts), 59 studies^{10,14,16,24-27,38-89} reporting outcomes for 61 intervention cohorts were performed in the US. Study designs included 14 randomized controlled trials (RCTs)^{48,64,68,74,79,90-98} and 88 before–after studies (Appendix Table 1). ^{10,14,16,24-27,33,38-47,49-63,69-73,75-78,80-89,99-131} Many RCTs evaluated antimicrobial products (CVCs, hubs, bathing) as interventions,^{48,68,74,90-95,97,98} but a few RCTs studied interventions^64,79,93 impacting catheter care or use (Appendix Table 1). Fifty-one studies took place in tertiary care hospitals and 55 in academic hospitals. Thirty-one studies were multicenter; the largest included 792 hospitals and 1071 ICUs.²⁴ ICU bed size ranged from 5 to 59.

CVC Study Outcomes

Sixty-three studies reported CLABSI outcomes, and 39 reported CRBSI outcomes (Table 2). Many studies had preintervention or control rates above the 2013 NHSN 75th percentiles,²² which varied by ICU type. Preintervention or control infection rates per 1000 catheter days varied widely (means: CLABSI 7.5, CRBSI 6.3); US studies reported ranges of 1.1 to 12.1 CLABSI and 1.2 to 11.0 CRBSI per 1000 catheter days; non-US studies reported ranges of 1.4 to 45.9 CLABSI and 1.6 to 22.7 CRBSI per 1000 catheter days. Postintervention rates varied widely, with overall means of 2.8 CLABSI and 2.5 CRBSI per 1000 catheter days, including US study ranges of 0 to 8.9 CLABSI and 0 to 5.4 CRBSI, and non-US study ranges of 0 to 17.1 CLABSI and 0 to 15.9 CRBSI.

CVC Interventions

CVC study interventions are summarized in Table 1, categorized by catheter life cycle component (Figure 2). Thirty-two included studies used a single intervention to prevent CVC infection. Interventions to avoid placement when possible were infrequent. Insertion-stage interventions were common and included avoiding the femoral site during placement, ensuring maximal sterile barriers, and chlorhexidine skin preparation. Standardizing basic products for central line insertion was often done by providing ICUs with a CLABSI insertion kit or stocked cart. In some studies, this was implemented prior to the intervention, and in others, the kit or cart itself was the intervention. Maintenance-stage interventions included scrubbing the hub prior to use, replacing wet or soiled dressings, accessing the catheter with sterile devices, and performing aseptic dressing changes. A recent systematic review and meta-analysis of CVC infection prevention studies indicated that implementing care bundles and/or checklists appears to yield stronger risk reductions than interventions without these components.¹³² The most common catheter removal interventions were daily audits of line removal and CLABSI rounds focused on ongoing catheter necessity.

Common implementation and sustainability interventions included outcome surveillance, such as feedback on CLABSI, and socio-adaptive interventions to prompt improvements in patient safety culture. Process and outcome surveillance as interventions were implemented in about one-quarter of the studies reviewed (AppendixTable 1).

CAUTI Interventional Study Results

Characteristics of Included CAUTI Studies

Of the 28 CAUTI studies that met the inclusion criteria (reporting outcomes for 30 intervention cohorts), 14 studies (reporting outcomes for 16 intervention cohorts) were performed in the US.^{28,34,53,66,68,133-141} Study designs included 2 RCTs (focused on urinary catheter avoidance or removal¹⁴² and chlorhexidine bathing⁶⁸) and 26 nonrandomized, before–after studies^{28,30,33,34,53,66,109,114-116,133-141,143-149} (Appendix Table 1). The number of hospitals per study varied from 1 to 53, with the majority being single-hospital interventions.

CAUTI Study Outcomes

All 28 studies reported CAUTIs per 1000 catheter days for both intervention and comparison groups (Table 2). Preintervention or control CAUTI rates varied widely, with an overall mean of 12.5 CAUTIs per 1000 catheter days; US studies reported a range from 1.4 to 15.8 CAUTIs per 1000 catheter days; non-US studies reported a range from 0.8 to 90.1 CAUTIs per 1000 catheter days. Many studies had preintervention or control rates above the 2013 NHSN 75th percentiles.²² Postintervention CAUTI rates varied widely, with an overall mean of 7.0 CAUTIs per 1000 catheter days, including a US study range from 0 to 11.2 and a non-US study range from 1.9 to 65.7.

Overall (Table 2), 27 of the 30 intervention cohorts described in the 28 studies reported fewer CAUTIs, including all ICU types. Lower postintervention CAUTI rates were reported in 25 studies, with a mean 49.4% reduction, including 11 statistically significant reductions; many studies did not report the level of statistical significance or described inadequate power to detect a significant change (Table 2).

Urinary catheter utilization rates were reported for 11 studies (Table 2). A decreased urinary catheter utilization rate was reported in 7 studies (4 with statistically signficiant reductions), with a mean 16% reduction (Table 2). Other outcomes included cost savings, the potential for unintended negative outcomes, and clinician compliance with intervention components. Positive cost savings were reported in 5 studies.^{30,34,133,141,149}

CAUTI Interventions

Of the 28 included CAUTI prevention studies, only 5 studied single interventions. Interventions were categorized in Table 1 by “life cycle” stages or as interventions to improve implementation and sustainability (Figure 2). Interventions to restrict indwelling urinary catheter use were common, including creating lists of approved indications selected by unit or hospital policy and requiring catheter orders with approved indications. Eight studies published approved indication lists.^{28,34,133-135,138,142,146} Although several studies describe the encouragement and use of bladder scanners and urinary catheter alternatives, none described purchasing these catheter alternatives.

Interventions to avoid indwelling urinary catheters included education about external catheters,^{28,34,109,133,140,144-146} urinary retention protocols,^{34,144,135,141} and bladder scanner simulation training.¹³³ Interventions to improve aseptic insertion^{28,34,66,109,116,139-141-143-146,150} and maintenance care^{28,34,66,109,116,133,135,136,139-141,143-146,150} of urinary catheters were common. Four studies used a standardized urinary catheter kit or cart,^{28,34,139,142} and 2 studies used a commercial urinary catheter securement device.^34,140 A CAUTI bundle checklist in daily patient care rounds was tested in 3 studies (Table 1).^66,136,150 Reminder and stop order strategies, with the potential to reduce CAUTI rates by >50%,¹⁵¹ were included in 15 studies, with inteventions such as nurse-empowered stop orders. Several implementation and sustainability interventions were described, including socio-adaptive strategies such as holding multidisciplinary meetings to obtain unit or clinician feedback to inform design and improve buy-in and providing frequent feedback to ICU clinicians, including audits of catheter use appropriateness and catheter-associated infections.

This extensive literature review yielded a large body of literature demonstrating success in preventing CLABSI and CAUTI in all types of adult ICUs, including in general medical and surgical ICUs and in specialized units with historically higher rates, such as trauma, burn, and neurosurgical. Reported reductions in catheter infections were impressive (>65% for CLABSI or CRBSI and nearly 50% for CAUTI), though several studies had limited power to detect statistical significance. DURs were reported more rarely (particularly for vascular catheters) and often without power to detect statistical significance. Nevertheless, 7 studies reported reduced urinary catheter use (16% mean reduction), which would be anticipated to be clinically significant.

The conceptual model introduced for “Disrupting the Life Cycle of a Catheter” (Figure 2) can be a helpful tool for hospitalists and intensivists to assess and prioritize potential strategies for reducing catheter-associated infections. This study’s results indicate that CLABSI prevention studies often used interventions that optimize best practices during aseptic insertion and maintenance, but few studies emphasized reducing inappropriate central line use. Conversely, CAUTI prevention often targeted avoiding placement and prompting the removal of urinary catheters, with fewer studies evaluating innovative products or technical skill advancement for aseptic insertion or maintenance, though educational interventions to standardize aseptic catheter use were common. Recently, recommendations for reducing the inappropriate use of urinary catheters and intravenous catheters, including scenarios common in ICUs, were developed by using the rigorous RAND/UCLA Appropriateness Method^152,153; these resources may be helpful to hospitalists designing and implementing interventions to reduce catheter use.

In reviewing the US studies of 5 units demonstrating the greatest success in preventing CLABSI^{56,62,65,78,83} and CAUTI,^28,34,66,134 several shared features emerged. Interventions that addressed multiple steps within the life cycle of a catheter (avoidance, insertion, maintenance, and removal) were common. Previous work has shown that assuring compliance in infection prevention efforts is a key to success,¹⁵⁴ and in both CLABSI and CAUTI studies, auditing was included in these successful interventions. Specifically for CLABSI, the checklist, a central quality improvement tool, was frequently associated with success. Unique to CAUTI, engaging a multidisciplinary team including nurse leadership seemed critical to optimize implementation and sustainability efforts. In addition, a focus on stage 3 (removal), including protocols to remove by default, was associated with success in CAUTI studies.

Our review was limited by a frequent lack of reporting of statistical significance or by inadequate power to detect a significant change and great variety. The ability to compare the impact of specific interventions is limited because studies varied greatly with respect to the type of intervention, duration of data collection, and outcomes assessed. We also anticipate that successful interventions are more likely to be published than are trials without success. Strengths include the use of a rigorous search process and the inclusion and review of several types of interventions implemented in ICUs.

In conclusion, despite high catheter use in ICUs, the literature includes many successful interventions for the prevention of vascular and urinary catheter infections in multiple ICU types. This review indicates that targeting multiple steps within the life cycle of a catheter, particularly when combined with interventions to optimize implementation and sustainability, can improve success in reducing CLABSI and CAUTI in the ICU.

Acknowledgments

The authors thank all members of the National Project Team for the AHRQ Safety Program for Intensive Care Units: Preventing CLABSI and CAUTI.

Disclosure

Agency for Healthcare Research and Quality (AHRQ) contract #HHSP233201500016I/HHSP23337002T provided funding for this study. J.M.’s other research is funded by AHRQ (2R01HS018334-04), the NIH-LRP program, the VA National Center for Patient Safety, VA Ann Arbor Patient Safety Center of Inquiry, the Health Research and Educational Trust, American Hospital Association and the Centers for Disease Control and Prevention. The findings and conclusions in this report are those of the authors and do not necessarily represent those of the sponsor, the Agency for Healthcare Research and Quality, or the US Department of Veterans Affairs. All authors report no conflicts of interest relevant to this article.

Central line–associated bloodstream infection (CLABSI) and catheter-associated urinary tract infection (CAUTI) are morbid and expensive healthcare-associated infections (HAIs).^1-8 While these HAIs are prevalent in intensive care units (ICUs) and general wards, most of the research, prevention efforts, and financial penalties have been focused in the ICU.^9,10 For hospitalists, who are taking a larger role in caring for the critically ill,^11,12 it is optimal to understand best preventive practices.

There has been a national puTash to standardize procedures and products to prevent CLABSI and CAUTI.^2,13-16 CLABSI has transitioned from a common ICU complication to a “never event.” Success has been reflected in the prevention of 25,000 CLABSIs over the last decade, translating to a 58% reduction in infections, with 6000 deaths prevented and $414 million saved.² CLABSI prevention principles have been applied to CAUTI prevention (ie, aseptic insertion, maintenance care, prompting removal) but with slower adoption¹⁷ and fewer dramatic CAUTI reductions,¹⁸ due in part to weaker recognition¹⁹ of CAUTI as a serious clinical event, despite its morbidity²⁰ and cost.²¹

Despite recent improvements in preventing HAIs, there is a marked variability in how hospitals perform in preventing these infections.²² To inform infection prevention strategies for a large-scale implementation project funded by the Agency for Healthcare Research and Quality and focused on ICUs with persistently elevated CLABSI and/or CAUTI rates,²³ we performed a systematic search of interventions to prevent CLABSI and CAUTI in the ICU setting. This evidence was synthesized to help units select and prioritize interventions to prevent these HAIs.

Literature Search Strategy

We performed a systematic search to identify CLABSI and CAUTI prevention studies and synthesized findings using a narrative review process. Using criteria developed and refined from seminal articles on the topic,^10,14,24-34 we searched the PubMed and Cochrane databases from their inception to October of 2015 using Medical Subject Headings (MeSHs) for “central venous catheters,” “CLABSI,” “central line associated bloodstream infection,” “catheter related bloodstream infection,” “intravascular devices,” “urinary catheterization,” “urinary catheters,” “urinary tract infections,” “CAUTI,” and “catheter associated urinary tract infections” and filtered for articles containing the MeSHs “intensive care unit” and “ICU.” Supplemental Figure 1 details the search, yielding 102 studies for CLABSI and 28 studies for CAUTI, including 7 studies with CLABSI and CAUTI interventions.

Eligibility Criteria Review

Study Design

We included randomized and nonrandomized studies that implemented at least 1 intervention to prevent CLABSI or CAUTI in an adult ICU setting and reported the preintervention or control group data to compare with the postintervention data. We excluded general ward, outpatient/ambulatory, and neonatal/pediatric settings. Interventions to prevent CLABSI or CAUTI were included. We excluded interventions focused on diagnosis or treatment or those that lacked adequate description of the intervention for replication. Studies with interventions that are no longer standard of care in the United States (US) were excluded, as were studies not available in English.

Outcomes

Primary Outcomes for Central Vascular Catheter Infection

• CLABSI: A lab-confirmed bloodstream infection in a patient who has had a central line for at least 48 hours on the date of the development of the bloodstream infection and without another known source of infection. We included studies that reported CLABSIs per 1000 central line days or those that provided data to permit calculation of this ratio. This measure is similar to current National Healthcare Safety Network (NHSN) surveillance definitions.²²
• Catheter-related bloodstream infection (CRBSI): A lab-confirmed bloodstream infection attributed to an intravascular catheter by a quantitative culture of the catheter tip or by differences in growth between catheter and peripheral venipuncture blood culture specimens.³⁵ This microbiologic definition of a central line bloodstream infection was often used prior to NHSN reporting, with rates provided as the number of CRBSIs per 1000 central line days.

Primary Outcome for Urinary Catheter Infection

• CAUTI: Urinary tract infection occurring in patients during or after the recent use of an indwelling urinary catheter. We included studies that reported CAUTIs per 1000 urinary catheter days or those that provided data to permit calculation of this ratio (similar to the current NHSN surveillance definitions).²² We excluded studies where CAUTI was defined as bacteriuria alone, without symptoms.

Secondary Outcomes

• Central line utilization ratio: The device utilization ratio (DUR) measure of central line use is calculated as central line days divided by patient days.
• Urinary catheter utilization ratio: The DUR measure of urinary catheter use is calculated as indwelling urinary catheter days divided by patient days, as used in NHSN surveillance, excluding other catheter types.²² We excluded other measures of urinary catheter use because of a large variation in definitions, which limits the ability to compare measures across studies.

Data Synthesis and Analysis

Information on the ICU and intervention type, intervention components, outcomes, and whether interventions were in use prior to the study was abstracted by CAUTI and CLABSI experts (JM and PKP) and confirmed by a second author.

We compared interventions found in the literature to components of the previously published urinary catheter “life cycle,” a conceptual model used to organize and prioritize interventions for a reduction in CAUTI (Figure 1).³⁶

Conceptual Model for Disrupting the Life Cycle of a Catheter

Our data analysis demonstrated that components of the urinary catheter life cycle (Figure 1) were useful and could be applied to vascular catheters, but changes were needed to make the model more valuable to hospitalists implementing CLABSI and CAUTI prevention interventions. We found that the previously named stage 1 (catheter placement) is better described in 2 stages: stage 0, avoid catheter if possible, and stage 1, ensure aseptic placement. Additionally, we tailored the model to include actionable language, describing ways to disrupt the life cycle. Finally, we added a component to represent interventions to improve implementation and sustainability, such as auditing compliance and timely feedback to clinicians. Thus, we introduce a new conceptual model, “Disrupting the Life Cycle of a Catheter” (Figure 2)

Central Vascular Catheter Interventional Study Results

Characteristics of Included Central Vascular Catheter Infection Studies

Of the 102 central vascular catheter (CVC) studies that met the inclusion criteria (reporting outcomes for 105 intervention cohorts), 59 studies^{10,14,16,24-27,38-89} reporting outcomes for 61 intervention cohorts were performed in the US. Study designs included 14 randomized controlled trials (RCTs)^{48,64,68,74,79,90-98} and 88 before–after studies (Appendix Table 1). ^{10,14,16,24-27,33,38-47,49-63,69-73,75-78,80-89,99-131} Many RCTs evaluated antimicrobial products (CVCs, hubs, bathing) as interventions,^{48,68,74,90-95,97,98} but a few RCTs studied interventions^64,79,93 impacting catheter care or use (Appendix Table 1). Fifty-one studies took place in tertiary care hospitals and 55 in academic hospitals. Thirty-one studies were multicenter; the largest included 792 hospitals and 1071 ICUs.²⁴ ICU bed size ranged from 5 to 59.

CVC Study Outcomes

Sixty-three studies reported CLABSI outcomes, and 39 reported CRBSI outcomes (Table 2). Many studies had preintervention or control rates above the 2013 NHSN 75th percentiles,²² which varied by ICU type. Preintervention or control infection rates per 1000 catheter days varied widely (means: CLABSI 7.5, CRBSI 6.3); US studies reported ranges of 1.1 to 12.1 CLABSI and 1.2 to 11.0 CRBSI per 1000 catheter days; non-US studies reported ranges of 1.4 to 45.9 CLABSI and 1.6 to 22.7 CRBSI per 1000 catheter days. Postintervention rates varied widely, with overall means of 2.8 CLABSI and 2.5 CRBSI per 1000 catheter days, including US study ranges of 0 to 8.9 CLABSI and 0 to 5.4 CRBSI, and non-US study ranges of 0 to 17.1 CLABSI and 0 to 15.9 CRBSI.

CVC Interventions

CVC study interventions are summarized in Table 1, categorized by catheter life cycle component (Figure 2). Thirty-two included studies used a single intervention to prevent CVC infection. Interventions to avoid placement when possible were infrequent. Insertion-stage interventions were common and included avoiding the femoral site during placement, ensuring maximal sterile barriers, and chlorhexidine skin preparation. Standardizing basic products for central line insertion was often done by providing ICUs with a CLABSI insertion kit or stocked cart. In some studies, this was implemented prior to the intervention, and in others, the kit or cart itself was the intervention. Maintenance-stage interventions included scrubbing the hub prior to use, replacing wet or soiled dressings, accessing the catheter with sterile devices, and performing aseptic dressing changes. A recent systematic review and meta-analysis of CVC infection prevention studies indicated that implementing care bundles and/or checklists appears to yield stronger risk reductions than interventions without these components.¹³² The most common catheter removal interventions were daily audits of line removal and CLABSI rounds focused on ongoing catheter necessity.

Common implementation and sustainability interventions included outcome surveillance, such as feedback on CLABSI, and socio-adaptive interventions to prompt improvements in patient safety culture. Process and outcome surveillance as interventions were implemented in about one-quarter of the studies reviewed (AppendixTable 1).

CAUTI Interventional Study Results

Characteristics of Included CAUTI Studies

Of the 28 CAUTI studies that met the inclusion criteria (reporting outcomes for 30 intervention cohorts), 14 studies (reporting outcomes for 16 intervention cohorts) were performed in the US.^{28,34,53,66,68,133-141} Study designs included 2 RCTs (focused on urinary catheter avoidance or removal¹⁴² and chlorhexidine bathing⁶⁸) and 26 nonrandomized, before–after studies^{28,30,33,34,53,66,109,114-116,133-141,143-149} (Appendix Table 1). The number of hospitals per study varied from 1 to 53, with the majority being single-hospital interventions.

CAUTI Study Outcomes

All 28 studies reported CAUTIs per 1000 catheter days for both intervention and comparison groups (Table 2). Preintervention or control CAUTI rates varied widely, with an overall mean of 12.5 CAUTIs per 1000 catheter days; US studies reported a range from 1.4 to 15.8 CAUTIs per 1000 catheter days; non-US studies reported a range from 0.8 to 90.1 CAUTIs per 1000 catheter days. Many studies had preintervention or control rates above the 2013 NHSN 75th percentiles.²² Postintervention CAUTI rates varied widely, with an overall mean of 7.0 CAUTIs per 1000 catheter days, including a US study range from 0 to 11.2 and a non-US study range from 1.9 to 65.7.

Overall (Table 2), 27 of the 30 intervention cohorts described in the 28 studies reported fewer CAUTIs, including all ICU types. Lower postintervention CAUTI rates were reported in 25 studies, with a mean 49.4% reduction, including 11 statistically significant reductions; many studies did not report the level of statistical significance or described inadequate power to detect a significant change (Table 2).

Urinary catheter utilization rates were reported for 11 studies (Table 2). A decreased urinary catheter utilization rate was reported in 7 studies (4 with statistically signficiant reductions), with a mean 16% reduction (Table 2). Other outcomes included cost savings, the potential for unintended negative outcomes, and clinician compliance with intervention components. Positive cost savings were reported in 5 studies.^{30,34,133,141,149}

CAUTI Interventions

Of the 28 included CAUTI prevention studies, only 5 studied single interventions. Interventions were categorized in Table 1 by “life cycle” stages or as interventions to improve implementation and sustainability (Figure 2). Interventions to restrict indwelling urinary catheter use were common, including creating lists of approved indications selected by unit or hospital policy and requiring catheter orders with approved indications. Eight studies published approved indication lists.^{28,34,133-135,138,142,146} Although several studies describe the encouragement and use of bladder scanners and urinary catheter alternatives, none described purchasing these catheter alternatives.

Interventions to avoid indwelling urinary catheters included education about external catheters,^{28,34,109,133,140,144-146} urinary retention protocols,^{34,144,135,141} and bladder scanner simulation training.¹³³ Interventions to improve aseptic insertion^{28,34,66,109,116,139-141-143-146,150} and maintenance care^{28,34,66,109,116,133,135,136,139-141,143-146,150} of urinary catheters were common. Four studies used a standardized urinary catheter kit or cart,^{28,34,139,142} and 2 studies used a commercial urinary catheter securement device.^34,140 A CAUTI bundle checklist in daily patient care rounds was tested in 3 studies (Table 1).^66,136,150 Reminder and stop order strategies, with the potential to reduce CAUTI rates by >50%,¹⁵¹ were included in 15 studies, with inteventions such as nurse-empowered stop orders. Several implementation and sustainability interventions were described, including socio-adaptive strategies such as holding multidisciplinary meetings to obtain unit or clinician feedback to inform design and improve buy-in and providing frequent feedback to ICU clinicians, including audits of catheter use appropriateness and catheter-associated infections.

This extensive literature review yielded a large body of literature demonstrating success in preventing CLABSI and CAUTI in all types of adult ICUs, including in general medical and surgical ICUs and in specialized units with historically higher rates, such as trauma, burn, and neurosurgical. Reported reductions in catheter infections were impressive (>65% for CLABSI or CRBSI and nearly 50% for CAUTI), though several studies had limited power to detect statistical significance. DURs were reported more rarely (particularly for vascular catheters) and often without power to detect statistical significance. Nevertheless, 7 studies reported reduced urinary catheter use (16% mean reduction), which would be anticipated to be clinically significant.

The conceptual model introduced for “Disrupting the Life Cycle of a Catheter” (Figure 2) can be a helpful tool for hospitalists and intensivists to assess and prioritize potential strategies for reducing catheter-associated infections. This study’s results indicate that CLABSI prevention studies often used interventions that optimize best practices during aseptic insertion and maintenance, but few studies emphasized reducing inappropriate central line use. Conversely, CAUTI prevention often targeted avoiding placement and prompting the removal of urinary catheters, with fewer studies evaluating innovative products or technical skill advancement for aseptic insertion or maintenance, though educational interventions to standardize aseptic catheter use were common. Recently, recommendations for reducing the inappropriate use of urinary catheters and intravenous catheters, including scenarios common in ICUs, were developed by using the rigorous RAND/UCLA Appropriateness Method^152,153; these resources may be helpful to hospitalists designing and implementing interventions to reduce catheter use.

In reviewing the US studies of 5 units demonstrating the greatest success in preventing CLABSI^{56,62,65,78,83} and CAUTI,^28,34,66,134 several shared features emerged. Interventions that addressed multiple steps within the life cycle of a catheter (avoidance, insertion, maintenance, and removal) were common. Previous work has shown that assuring compliance in infection prevention efforts is a key to success,¹⁵⁴ and in both CLABSI and CAUTI studies, auditing was included in these successful interventions. Specifically for CLABSI, the checklist, a central quality improvement tool, was frequently associated with success. Unique to CAUTI, engaging a multidisciplinary team including nurse leadership seemed critical to optimize implementation and sustainability efforts. In addition, a focus on stage 3 (removal), including protocols to remove by default, was associated with success in CAUTI studies.

Our review was limited by a frequent lack of reporting of statistical significance or by inadequate power to detect a significant change and great variety. The ability to compare the impact of specific interventions is limited because studies varied greatly with respect to the type of intervention, duration of data collection, and outcomes assessed. We also anticipate that successful interventions are more likely to be published than are trials without success. Strengths include the use of a rigorous search process and the inclusion and review of several types of interventions implemented in ICUs.

In conclusion, despite high catheter use in ICUs, the literature includes many successful interventions for the prevention of vascular and urinary catheter infections in multiple ICU types. This review indicates that targeting multiple steps within the life cycle of a catheter, particularly when combined with interventions to optimize implementation and sustainability, can improve success in reducing CLABSI and CAUTI in the ICU.

Acknowledgments

The authors thank all members of the National Project Team for the AHRQ Safety Program for Intensive Care Units: Preventing CLABSI and CAUTI.

Disclosure

Agency for Healthcare Research and Quality (AHRQ) contract #HHSP233201500016I/HHSP23337002T provided funding for this study. J.M.’s other research is funded by AHRQ (2R01HS018334-04), the NIH-LRP program, the VA National Center for Patient Safety, VA Ann Arbor Patient Safety Center of Inquiry, the Health Research and Educational Trust, American Hospital Association and the Centers for Disease Control and Prevention. The findings and conclusions in this report are those of the authors and do not necessarily represent those of the sponsor, the Agency for Healthcare Research and Quality, or the US Department of Veterans Affairs. All authors report no conflicts of interest relevant to this article.

Central line–associated bloodstream infection (CLABSI) and catheter-associated urinary tract infection (CAUTI) are morbid and expensive healthcare-associated infections (HAIs).^1-8 While these HAIs are prevalent in intensive care units (ICUs) and general wards, most of the research, prevention efforts, and financial penalties have been focused in the ICU.^9,10 For hospitalists, who are taking a larger role in caring for the critically ill,^11,12 it is optimal to understand best preventive practices.

There has been a national puTash to standardize procedures and products to prevent CLABSI and CAUTI.^2,13-16 CLABSI has transitioned from a common ICU complication to a “never event.” Success has been reflected in the prevention of 25,000 CLABSIs over the last decade, translating to a 58% reduction in infections, with 6000 deaths prevented and $414 million saved.² CLABSI prevention principles have been applied to CAUTI prevention (ie, aseptic insertion, maintenance care, prompting removal) but with slower adoption¹⁷ and fewer dramatic CAUTI reductions,¹⁸ due in part to weaker recognition¹⁹ of CAUTI as a serious clinical event, despite its morbidity²⁰ and cost.²¹

Despite recent improvements in preventing HAIs, there is a marked variability in how hospitals perform in preventing these infections.²² To inform infection prevention strategies for a large-scale implementation project funded by the Agency for Healthcare Research and Quality and focused on ICUs with persistently elevated CLABSI and/or CAUTI rates,²³ we performed a systematic search of interventions to prevent CLABSI and CAUTI in the ICU setting. This evidence was synthesized to help units select and prioritize interventions to prevent these HAIs.

Literature Search Strategy

We performed a systematic search to identify CLABSI and CAUTI prevention studies and synthesized findings using a narrative review process. Using criteria developed and refined from seminal articles on the topic,^10,14,24-34 we searched the PubMed and Cochrane databases from their inception to October of 2015 using Medical Subject Headings (MeSHs) for “central venous catheters,” “CLABSI,” “central line associated bloodstream infection,” “catheter related bloodstream infection,” “intravascular devices,” “urinary catheterization,” “urinary catheters,” “urinary tract infections,” “CAUTI,” and “catheter associated urinary tract infections” and filtered for articles containing the MeSHs “intensive care unit” and “ICU.” Supplemental Figure 1 details the search, yielding 102 studies for CLABSI and 28 studies for CAUTI, including 7 studies with CLABSI and CAUTI interventions.

Eligibility Criteria Review

Study Design

We included randomized and nonrandomized studies that implemented at least 1 intervention to prevent CLABSI or CAUTI in an adult ICU setting and reported the preintervention or control group data to compare with the postintervention data. We excluded general ward, outpatient/ambulatory, and neonatal/pediatric settings. Interventions to prevent CLABSI or CAUTI were included. We excluded interventions focused on diagnosis or treatment or those that lacked adequate description of the intervention for replication. Studies with interventions that are no longer standard of care in the United States (US) were excluded, as were studies not available in English.

Outcomes

Primary Outcomes for Central Vascular Catheter Infection

• CLABSI: A lab-confirmed bloodstream infection in a patient who has had a central line for at least 48 hours on the date of the development of the bloodstream infection and without another known source of infection. We included studies that reported CLABSIs per 1000 central line days or those that provided data to permit calculation of this ratio. This measure is similar to current National Healthcare Safety Network (NHSN) surveillance definitions.²²
• Catheter-related bloodstream infection (CRBSI): A lab-confirmed bloodstream infection attributed to an intravascular catheter by a quantitative culture of the catheter tip or by differences in growth between catheter and peripheral venipuncture blood culture specimens.³⁵ This microbiologic definition of a central line bloodstream infection was often used prior to NHSN reporting, with rates provided as the number of CRBSIs per 1000 central line days.

Primary Outcome for Urinary Catheter Infection

• CAUTI: Urinary tract infection occurring in patients during or after the recent use of an indwelling urinary catheter. We included studies that reported CAUTIs per 1000 urinary catheter days or those that provided data to permit calculation of this ratio (similar to the current NHSN surveillance definitions).²² We excluded studies where CAUTI was defined as bacteriuria alone, without symptoms.

Secondary Outcomes

• Central line utilization ratio: The device utilization ratio (DUR) measure of central line use is calculated as central line days divided by patient days.
• Urinary catheter utilization ratio: The DUR measure of urinary catheter use is calculated as indwelling urinary catheter days divided by patient days, as used in NHSN surveillance, excluding other catheter types.²² We excluded other measures of urinary catheter use because of a large variation in definitions, which limits the ability to compare measures across studies.

Data Synthesis and Analysis

Information on the ICU and intervention type, intervention components, outcomes, and whether interventions were in use prior to the study was abstracted by CAUTI and CLABSI experts (JM and PKP) and confirmed by a second author.

We compared interventions found in the literature to components of the previously published urinary catheter “life cycle,” a conceptual model used to organize and prioritize interventions for a reduction in CAUTI (Figure 1).³⁶

Conceptual Model for Disrupting the Life Cycle of a Catheter

Our data analysis demonstrated that components of the urinary catheter life cycle (Figure 1) were useful and could be applied to vascular catheters, but changes were needed to make the model more valuable to hospitalists implementing CLABSI and CAUTI prevention interventions. We found that the previously named stage 1 (catheter placement) is better described in 2 stages: stage 0, avoid catheter if possible, and stage 1, ensure aseptic placement. Additionally, we tailored the model to include actionable language, describing ways to disrupt the life cycle. Finally, we added a component to represent interventions to improve implementation and sustainability, such as auditing compliance and timely feedback to clinicians. Thus, we introduce a new conceptual model, “Disrupting the Life Cycle of a Catheter” (Figure 2)

Central Vascular Catheter Interventional Study Results

Characteristics of Included Central Vascular Catheter Infection Studies

Of the 102 central vascular catheter (CVC) studies that met the inclusion criteria (reporting outcomes for 105 intervention cohorts), 59 studies^{10,14,16,24-27,38-89} reporting outcomes for 61 intervention cohorts were performed in the US. Study designs included 14 randomized controlled trials (RCTs)^{48,64,68,74,79,90-98} and 88 before–after studies (Appendix Table 1). ^{10,14,16,24-27,33,38-47,49-63,69-73,75-78,80-89,99-131} Many RCTs evaluated antimicrobial products (CVCs, hubs, bathing) as interventions,^{48,68,74,90-95,97,98} but a few RCTs studied interventions^64,79,93 impacting catheter care or use (Appendix Table 1). Fifty-one studies took place in tertiary care hospitals and 55 in academic hospitals. Thirty-one studies were multicenter; the largest included 792 hospitals and 1071 ICUs.²⁴ ICU bed size ranged from 5 to 59.

CVC Study Outcomes

Sixty-three studies reported CLABSI outcomes, and 39 reported CRBSI outcomes (Table 2). Many studies had preintervention or control rates above the 2013 NHSN 75th percentiles,²² which varied by ICU type. Preintervention or control infection rates per 1000 catheter days varied widely (means: CLABSI 7.5, CRBSI 6.3); US studies reported ranges of 1.1 to 12.1 CLABSI and 1.2 to 11.0 CRBSI per 1000 catheter days; non-US studies reported ranges of 1.4 to 45.9 CLABSI and 1.6 to 22.7 CRBSI per 1000 catheter days. Postintervention rates varied widely, with overall means of 2.8 CLABSI and 2.5 CRBSI per 1000 catheter days, including US study ranges of 0 to 8.9 CLABSI and 0 to 5.4 CRBSI, and non-US study ranges of 0 to 17.1 CLABSI and 0 to 15.9 CRBSI.

CVC Interventions

CVC study interventions are summarized in Table 1, categorized by catheter life cycle component (Figure 2). Thirty-two included studies used a single intervention to prevent CVC infection. Interventions to avoid placement when possible were infrequent. Insertion-stage interventions were common and included avoiding the femoral site during placement, ensuring maximal sterile barriers, and chlorhexidine skin preparation. Standardizing basic products for central line insertion was often done by providing ICUs with a CLABSI insertion kit or stocked cart. In some studies, this was implemented prior to the intervention, and in others, the kit or cart itself was the intervention. Maintenance-stage interventions included scrubbing the hub prior to use, replacing wet or soiled dressings, accessing the catheter with sterile devices, and performing aseptic dressing changes. A recent systematic review and meta-analysis of CVC infection prevention studies indicated that implementing care bundles and/or checklists appears to yield stronger risk reductions than interventions without these components.¹³² The most common catheter removal interventions were daily audits of line removal and CLABSI rounds focused on ongoing catheter necessity.

Common implementation and sustainability interventions included outcome surveillance, such as feedback on CLABSI, and socio-adaptive interventions to prompt improvements in patient safety culture. Process and outcome surveillance as interventions were implemented in about one-quarter of the studies reviewed (AppendixTable 1).

CAUTI Interventional Study Results

Characteristics of Included CAUTI Studies

Of the 28 CAUTI studies that met the inclusion criteria (reporting outcomes for 30 intervention cohorts), 14 studies (reporting outcomes for 16 intervention cohorts) were performed in the US.^{28,34,53,66,68,133-141} Study designs included 2 RCTs (focused on urinary catheter avoidance or removal¹⁴² and chlorhexidine bathing⁶⁸) and 26 nonrandomized, before–after studies^{28,30,33,34,53,66,109,114-116,133-141,143-149} (Appendix Table 1). The number of hospitals per study varied from 1 to 53, with the majority being single-hospital interventions.

CAUTI Study Outcomes

All 28 studies reported CAUTIs per 1000 catheter days for both intervention and comparison groups (Table 2). Preintervention or control CAUTI rates varied widely, with an overall mean of 12.5 CAUTIs per 1000 catheter days; US studies reported a range from 1.4 to 15.8 CAUTIs per 1000 catheter days; non-US studies reported a range from 0.8 to 90.1 CAUTIs per 1000 catheter days. Many studies had preintervention or control rates above the 2013 NHSN 75th percentiles.²² Postintervention CAUTI rates varied widely, with an overall mean of 7.0 CAUTIs per 1000 catheter days, including a US study range from 0 to 11.2 and a non-US study range from 1.9 to 65.7.

Overall (Table 2), 27 of the 30 intervention cohorts described in the 28 studies reported fewer CAUTIs, including all ICU types. Lower postintervention CAUTI rates were reported in 25 studies, with a mean 49.4% reduction, including 11 statistically significant reductions; many studies did not report the level of statistical significance or described inadequate power to detect a significant change (Table 2).

Urinary catheter utilization rates were reported for 11 studies (Table 2). A decreased urinary catheter utilization rate was reported in 7 studies (4 with statistically signficiant reductions), with a mean 16% reduction (Table 2). Other outcomes included cost savings, the potential for unintended negative outcomes, and clinician compliance with intervention components. Positive cost savings were reported in 5 studies.^{30,34,133,141,149}

CAUTI Interventions

Of the 28 included CAUTI prevention studies, only 5 studied single interventions. Interventions were categorized in Table 1 by “life cycle” stages or as interventions to improve implementation and sustainability (Figure 2). Interventions to restrict indwelling urinary catheter use were common, including creating lists of approved indications selected by unit or hospital policy and requiring catheter orders with approved indications. Eight studies published approved indication lists.^{28,34,133-135,138,142,146} Although several studies describe the encouragement and use of bladder scanners and urinary catheter alternatives, none described purchasing these catheter alternatives.

Interventions to avoid indwelling urinary catheters included education about external catheters,^{28,34,109,133,140,144-146} urinary retention protocols,^{34,144,135,141} and bladder scanner simulation training.¹³³ Interventions to improve aseptic insertion^{28,34,66,109,116,139-141-143-146,150} and maintenance care^{28,34,66,109,116,133,135,136,139-141,143-146,150} of urinary catheters were common. Four studies used a standardized urinary catheter kit or cart,^{28,34,139,142} and 2 studies used a commercial urinary catheter securement device.^34,140 A CAUTI bundle checklist in daily patient care rounds was tested in 3 studies (Table 1).^66,136,150 Reminder and stop order strategies, with the potential to reduce CAUTI rates by >50%,¹⁵¹ were included in 15 studies, with inteventions such as nurse-empowered stop orders. Several implementation and sustainability interventions were described, including socio-adaptive strategies such as holding multidisciplinary meetings to obtain unit or clinician feedback to inform design and improve buy-in and providing frequent feedback to ICU clinicians, including audits of catheter use appropriateness and catheter-associated infections.

This extensive literature review yielded a large body of literature demonstrating success in preventing CLABSI and CAUTI in all types of adult ICUs, including in general medical and surgical ICUs and in specialized units with historically higher rates, such as trauma, burn, and neurosurgical. Reported reductions in catheter infections were impressive (>65% for CLABSI or CRBSI and nearly 50% for CAUTI), though several studies had limited power to detect statistical significance. DURs were reported more rarely (particularly for vascular catheters) and often without power to detect statistical significance. Nevertheless, 7 studies reported reduced urinary catheter use (16% mean reduction), which would be anticipated to be clinically significant.

The conceptual model introduced for “Disrupting the Life Cycle of a Catheter” (Figure 2) can be a helpful tool for hospitalists and intensivists to assess and prioritize potential strategies for reducing catheter-associated infections. This study’s results indicate that CLABSI prevention studies often used interventions that optimize best practices during aseptic insertion and maintenance, but few studies emphasized reducing inappropriate central line use. Conversely, CAUTI prevention often targeted avoiding placement and prompting the removal of urinary catheters, with fewer studies evaluating innovative products or technical skill advancement for aseptic insertion or maintenance, though educational interventions to standardize aseptic catheter use were common. Recently, recommendations for reducing the inappropriate use of urinary catheters and intravenous catheters, including scenarios common in ICUs, were developed by using the rigorous RAND/UCLA Appropriateness Method^152,153; these resources may be helpful to hospitalists designing and implementing interventions to reduce catheter use.

In reviewing the US studies of 5 units demonstrating the greatest success in preventing CLABSI^{56,62,65,78,83} and CAUTI,^28,34,66,134 several shared features emerged. Interventions that addressed multiple steps within the life cycle of a catheter (avoidance, insertion, maintenance, and removal) were common. Previous work has shown that assuring compliance in infection prevention efforts is a key to success,¹⁵⁴ and in both CLABSI and CAUTI studies, auditing was included in these successful interventions. Specifically for CLABSI, the checklist, a central quality improvement tool, was frequently associated with success. Unique to CAUTI, engaging a multidisciplinary team including nurse leadership seemed critical to optimize implementation and sustainability efforts. In addition, a focus on stage 3 (removal), including protocols to remove by default, was associated with success in CAUTI studies.

Our review was limited by a frequent lack of reporting of statistical significance or by inadequate power to detect a significant change and great variety. The ability to compare the impact of specific interventions is limited because studies varied greatly with respect to the type of intervention, duration of data collection, and outcomes assessed. We also anticipate that successful interventions are more likely to be published than are trials without success. Strengths include the use of a rigorous search process and the inclusion and review of several types of interventions implemented in ICUs.

In conclusion, despite high catheter use in ICUs, the literature includes many successful interventions for the prevention of vascular and urinary catheter infections in multiple ICU types. This review indicates that targeting multiple steps within the life cycle of a catheter, particularly when combined with interventions to optimize implementation and sustainability, can improve success in reducing CLABSI and CAUTI in the ICU.

Acknowledgments

The authors thank all members of the National Project Team for the AHRQ Safety Program for Intensive Care Units: Preventing CLABSI and CAUTI.

Disclosure

Agency for Healthcare Research and Quality (AHRQ) contract #HHSP233201500016I/HHSP23337002T provided funding for this study. J.M.’s other research is funded by AHRQ (2R01HS018334-04), the NIH-LRP program, the VA National Center for Patient Safety, VA Ann Arbor Patient Safety Center of Inquiry, the Health Research and Educational Trust, American Hospital Association and the Centers for Disease Control and Prevention. The findings and conclusions in this report are those of the authors and do not necessarily represent those of the sponsor, the Agency for Healthcare Research and Quality, or the US Department of Veterans Affairs. All authors report no conflicts of interest relevant to this article.

Given the limited number of geriatricians in the U.S., hospitalists commonly manage nursing home residents admitted for post-acute care.^1-4 Urinary tract infection (UTI) is one of the most common infections in nursing homes, often leading to sepsis and readmission to acute care.⁵ Inappropriate use of antibiotics to treat asymptomatic bacteriuria is both common and hazardous to nursing home residents.⁶ Up to 10% of nursing home residents will have an indwelling urinary catheter at some point during their stay.^7-9 Residents with indwelling urinary catheters are at increased risk for catheter-associated urinary tract infection (CAUTI) and bacteriuria, with an estimated 50% of catheterized residents developing symptomatic CAUTI.⁵ While urinary catheter prevalence is lower in nursing homes than in the acute care setting, duration of use is often prolonged.^7,10 In a setting where utilization is low, but use is prolonged, interventions designed to reduce UTI in acutely ill patients¹¹ may not be as helpful for preventing infection in nursing home residents.

Our objective was to review the available evidence to prevent UTIs in nursing home residents to inform both bedside care and research efforts. Two types of literature review and summary were performed. First, we conducted a systematic review of individual studies reporting outcomes of UTI, CAUTI, bacteriuria, or urinary catheter use after interventions for reducing catheter use, improving insertion and maintenance of catheters, and/or general infection prevention strategies (eg, improving hand hygiene, infection surveillance, contact precautions, standardizing UTI diagnosis, and antibiotic use). Second, we performed a narrative review to generate an overview of evidence and published recommendations in both acute care and nursing home settings to prevent UTI in catheterized and non-catheterized older adults, which is provided as a comprehensive reference table for clinicians and researchers choosing and refining interventions to reduce UTIs.

The systematic review was performed according to the criteria of the Preferred Reporting Items for Systematic Reviews and Meta-Analysis recommendations. The protocol was registered at the PROSPERO International Prospective Register of Systematic Reviews, (CRD42013005787). The narrative review was performed using the articles obtained from the systematic search and a targeted literature review by topic for a comprehensive list of interventions, including other interventions summarized in published reviews and guidelines.

Eligibility Criteria Review

Study Design. To address the breadth and depth of literature available to inform interventions to prevent UTI in nursing homes, broad eligibility criteria were applied with the expectation of varied designs and outcomes. All included studies for the systematic review were published manuscripts reporting a comparison group. We included randomized controlled trials as well as nonrandomized trials (pretest/posttest, with or without concurrent or nonconcurrent controls), with any duration of postintervention follow-up. Observational and retrospective studies were excluded.

Participants. We were interested in interventions and outcomes reported for nursing homes, defined as facilities providing short-stay skilled nursing care and/or rehabilitation, as well as long-term care. We also included evidence derived from rehabilitation facilities and spinal cord injury programs focused on reducing CAUTI risk for chronically catheterized residents. We excluded long-term acute care hospitals, hospice, psychiatric/mental health facilities, pediatric, and community dwelling/outpatient settings.

Interventions. We included interventions involving urinary catheter use such as improving appropriate use, aseptic placement, maintenance care, and prompting removal of unnecessary catheters. We included infection prevention strategies with a particular interest in hand hygiene, barrier precautions, infection control strategies, infection surveillance, use of standardized infection definitions, and interventions to improve antibiotic use. We included single and multiple interventions.

Outcomes
1. Healthcare-associated urinary tract infection: UTI occurring after admission to a healthcare facility, not identified specifically as catheter-associated. We categorized UTI outcomes with as much detail as provided, such as whether the reported outcome included only noncatheter-associated UTIs, the time required after admission (eg, more than 2 days), and whether the UTIs were defined by only laboratory criteria, clinically diagnosed infections, symptomatic, or long-term care specific surveillance definitions.

2. Catheter-associated urinary tract infection: UTI occurring in patients during or immediately after use of a urinary catheter. We noted whether CAUTI was defined by laboratory criteria, clinical symptoms, provider diagnosis, or antimicrobial treatment for case identification. We were primarily interested in CAUTI developing after placing an indwelling urinary catheter, commonly known as a Foley, but also in CAUTI occurring with other catheter types such as intermittent straight catheters, external or “condom” catheters, and suprapubic catheters.

3. Bacteriuria: We included the laboratory-based definition of bacteriuria as an outcome to include studies that reduced asymptomatic bacteriuria.

4. Urinary catheter use measures: This includes measures such as urinary catheter utilization ratios (catheter-days/patient-days), prevalence of urinary catheter use, or percentage of catheters with an appropriate indication.

Study Characteristics for Inclusion. Our systematic search included published papers in the English language. We did not exclude studies based on the number of facilities included or eligible, residents/patients included (based on age, gender, catheter use or type, or antibiotic use), intervention details, study withdrawal, loss to follow-up, death, or duration of pre-intervention and postintervention phases.

Data Sources and Searches

The following data sources were searched: Ovid MEDLINE (1950 to June 22, 2015), Cochrane Library via Wiley (1960 to June 22, 2015), CINAHL (1981 to June 22, 2015), Web of Science (1926 to June 22, 2015), and Embase.com (1946 to June 22, 2015). Two major systematic search strategies were performed for this review (Figure). Systematic search 1 was designed broadly using all data sources described above to identify interventions aimed at reducing all UTI events (defined under “Outcomes” above) or urinary catheter use (all types), focusing on interventions evaluated in nursing homes. Systematic search 2 was conducted in Ovid MEDLINE to identify studies to reduce UTI events or urinary catheter use measures for patients with a history of long-term or chronic catheter use, including nursing homes and other post-acute care settings such as rehabilitation units or hospitals and spinal cord injury programs, which have large populations of patients with chronic catheter needs. To inform the completeness of the broader systematic searches, supplemental systematic search strategies were performed for specific topics including hydration (supplemental search 1), published work by nursing home researchers known to the authors (supplemental search 2), and contact precautions (supplemental search 3). Search 1 is available at http://www.crd.york.ac.uk/PROSPERO/display_record.asp?ID=CRD42013005787. Full search strategies for search 2 and supplemental searches are available upon request.

Study Selection

One author performed an initial screen of all records retrieved by the systematic searches by title and abstract and applied the initial exclusions (eg, non-human, no outcomes of interest), identified duplicate records, and assigned potentially relevant studies into groups such as review articles, epidemiology, interventions, and articles requiring further text review before categorization (Figure). After initial screening, Dr. Meddings reviewed the records by title/abstract. Reference lists were reviewed for potential articles for inclusion. Full-text article review informed the selection of those for dual abstraction and quality scoring performed by 2 authors, with discrepancies resolved by a third author. We requested additional information from authors from whom our search had generated only an abstract or brief report, or when additional information such as pre-intervention data was needed.^12-18

Data Extraction and Quality Assessment

Relevant data regarding study design, participants, inclusion/exclusion criteria, outcomes, and quality criteria were abstracted independently by 2 authors. Methodological quality scores were assigned using a modification of the Quality index checklist developed by Downs and Black appropriate for assessing both randomized and nonrandomized studies of healthcare interventions.¹⁹ We also reviewed study funding sources and other potential quality concerns.

Data Analysis

Due to large trial heterogeneity among these studies about interventions and outcomes reported, outcome data could not be combined into summary measures for meta-analysis to give overall estimates of treatment effects.

Systematic Search Results and Study Selection

As detailed in the study flow diagram (Figure), 5794 total records were retrieved by systematic search 1 (4697 studies), search 2 (909 studies), and supplemental searches (188 studies). Hand searching of reference lists of 41 reviews (including narrative and systematic reviews) yielded 77 additional studies for consideration. Twenty-nine records on interventions that were the focus of systematic reviews, including topics of cranberry use, catheter coatings, antimicrobial prophylaxis, washout/irrigation strategies, and sterile versus clean intermittent straight catheterization, were excluded from dual abstraction. Two records were excluded after team discussion of the dual-abstraction results, because 1 study did not meet criteria as an intervention study and 1 study’s setting was not applicable in nursing homes. A total of 20 records^15,20-38 (in which 19 studies were described) were selected for final inclusion for detailed assessment and reporting for the systematic review.

Characteristics of Included Studies

Table 1 describes the 19 intervention studies in terms of design, participants, setting, and whether the study included specific categories of interventions expected to decrease UTI or catheter use. These studies included 8 randomized controlled trials (4 with cluster-randomization at the facility or unit level), 10 pre-post nonrandomized interventions, and 1 nonrandomized intervention with concurrent controls. Twelve studies included participants with or without catheters (ie, not limited to catheterized patients only) in nursing homes.^15,20-31 Seven^32-38 studies included catheterized patients only or settings with high expected catheterization rates; settings for these studies included spinal cord units (n=3), nursing homes (n=2), rehabilitation ward (n=1) and VA hospital (n=1), including acute care, nursing home, and rehabilitation units. Total quality scores for the studies ranged from 8 to 25 (median, 15), detailed in Supplemental Table 1.

As detailed in Table 1 and Supplemental Table 2, 7 studies^{22,24,26,31,32,35,36} involved single interventions and 12 studies^{15,20,21,23,25,27-30,33,34,37,38} included multiple interventions. Interventions to impact catheter use and care were evaluated in 13 studies, including appropriateness of use,^21,25,29,30 improving catheter maintenance care,^15,20,29,30 securement,^15,29,30,32 prompting removal of unnecessary catheters,^21,25,29,30 improving incontinence care,^15,21,23,25 bladder scanners,^37,38 catheter changes,³⁵and comparing alternatives (condom catheter or intermittent straight catheter) to use of an indwelling catheter.^36,38 None focused on improving aseptic insertion. General infection control practices studied included improving hand hygiene,^{20-22,29-31,33,34} improving antibiotic use,^{15,20,21,28,34} initiation of infection control programs,^20,21,28 interventions to improve identification of UTIs/CAUTIs using infection symptom/sign criteria,^15,20,21,34 infection surveillance as an intervention,^28-30,33,34 and barrier precautions,^33,34 including preemptive precautions for catheterized patients.³⁴ Hydration was assessed in 3 studies.^24-26

Outcomes of Included Studies

Table 2 describes the studies’ outcomes reported for UTI, CAUTI, or bacteriuria.^15,20-38 The outcome definitions of UTI and CAUTI varied widely. Only 2 studies^22,39 reported UTI outcomes using definitions specific for nursing home settings such as McGeer’s criteria⁴⁰ a detailed review and comparison of published CAUTI definitions used clinically and for surveillance in nursing homes is provided in Supplemental Table 3. Two studies reported symptomatic CAUTIs per 1000 catheter-days.^32,34 Another study²² reported symptomatic CAUTIs per 1000 resident-days. Three reported symptomatic CAUTIs as counts.^35,38 Saint et al³⁶ reported CAUTIs as part of a combined outcome (ie, bacteriuria, CAUTI, or death).

The 19 studies (Table 2) reported 12 UTI outcomes,^{15,20,21,23,25-31,33} 9 CAUTI outcomes,^{15,22,32,34,35,38} 4 bacteriuria outcomes,^24,36,38 and 5 catheter use outcomes.^{21,29,30,37,38} Five studies showed CAUTI reduction^{15,22,32,34,35} (1 significantly³⁴); 9 studies showed UTI reduction^{13,18,19,21,23-25,27,28,31} (none significantly); 2 studies showed bacteriuria reduction (none significantly). One study³⁶ reported 2 composite outcomes including bacteriuria or CAUTI or death, with statistically significant improvement reported for 1 composite measure. Four studies reported catheter use, with all showing reduced catheter use in the intervention group; however, only 1 achieved statistically significant reduction.³⁷

Synthesis of Systematic Review Results

Overall, many studies reported decreases in UTI, CAUTI, and urinary catheter use measures but without statistical significance, with many studies likely underpowered for our outcomes of interest. Often, the outcomes of interest in this systematic review were not the main outcome for which the study was designed and originally powered. The interventions studied included several currently implemented as part of CAUTI bundles in the acute care setting, such as improving catheter use, and care and infection control strategies. Other included interventions target common challenges specific to the nursing home setting such as removing indwelling catheters upon admission to the nursing home from an acute-care facility^21,25 and applying interventions to address incontinence by either general strategies^{21,23,25,30,38} or the use of an incontinence specialist²³ to provide individual treatment plans. The only intervention that demonstrated a statistically significant reduction in CAUTI in chronically catheterized patients employed a comprehensive program to improve antimicrobial use, hand hygiene (including hand hygiene and gloves for catheter care), and preemptive precautions for patients with devices, along with promotion of standardized CAUTI definitions and active multidrug resistant organism surveillance.³⁴

Narrative Review Results

Table 3 includes a comprehensive list of potential interventions that have been considered for prevention of UTI or CAUTI (including those in acute care and nursing home settings), as summarized from this systematic review and prior narrative or systematic reviews.^43-115

We performed a broad systematic review of strategies to decrease UTI, CAUTI, and urinary catheter use that may be helpful in nursing homes. While many studies reported decreased UTI, CAUTI, or urinary catheter use measures, few demonstrated statistically significant reductions perhaps because many were underpowered to assess statistical significance. Pooled analyses were not feasible to provide the expected impact of these interventions in the nursing home setting.

This review confirms that bundles of interventions for prevention of CAUTI have been implemented with some evidence of success in nursing home settings, with several components in common with those implemented in the acute care setting, such as hand hygiene and strategies to reduce and improve catheter use.⁴¹ Some studies focused on issues more common in nursing homes such as chronic catheterization and incontinence. A nursing home CAUTI bundle should be designed with the resources and challenges present in the nursing home environment in mind, and with recognition that, although the number of patients with catheters is less than in acute care, there will be more patients with chronic catheterization needs and incontinence.

Although catheter utilization in nursing homes is low, further reductions in catheter days and CAUTIs can be achieved. Catheter removal reminders and stop orders have demonstrated a greater than 50% reduction in CAUTIs in acute care settings;¹¹ an example of a stop-order intervention in nursing homes is trial removal of indwelling catheters present at facility admission without clear urologic need present at the time of admission.²⁵ Nursing home interventions to avoid catheter placement should include incontinence programs, discussion of alternatives to indwelling urinary catheters with patients, families, and frontline personnel, and urinary retention protocols. Programs to reduce CAUTI should include education to improve aseptic insertion, and to maintain awareness and proper care of catheters in place by regular assessment of catheter necessity, securement, hand hygiene, and preemptive barrier precautions for catheterized patients. Interventions that focus on improving appropriate use of urine tests and antibiotics to treat UTIs can also significantly affect the rates of reported symptomatic CAUTIs, with the potential to decrease unnecessary antibiotic use.^20,21

The main limitation of this review is that many studies provided little information about their intervention and definition of outcomes. The strength of this review is the detailed and broad search strategy applied with generous inclusion of interventions and outcomes to highlight the available evidence and details of interventions that have been studied and implemented.

This review synthesizes the current state of evidence and proposes strategies to reduce UTIs in nursing homes. Interventions that motivate catheter avoidance and catheter removal to prevent CAUTI in acute care¹¹ and nursing home settings are supported by the strongest available evidence, although the strength of that evidence is less in the nursing home setting. Limitations notwithstanding, interventions such as incontinence care planning and hydration programs can reduce UTI in this population and is important for overall wellbeing.

Acknowledgments

The authors appreciate the guidance that Vineet Chopra MD, MSc, provided regarding options for methodological quality assessment tools, and the assistance of Mary Rogers PhD, MS, in interpreting the published Downs and Black Quality Index items, which informed our modification of this tool for application in this study. The authors appreciate, also, the feedback provided by the Agency for Healthcare Research and Quality (AHRQ) Content and Materials Development Committee for the AHRQ Safety Program for Long-Term Care: Preventing CAUTI and other Healthcare-associated Infections.

Disclosures

Agency for Healthcare Research and Quality (AHRQ) contract #HHSA290201000025I provided funding for this study, which was developed in response to AHRQ Task Order #8 for ACTION II RFTO 26 CUSP for CAUTI in LTC. AHRQ developed the details of the task and provided comments on a draft report, which informed the report submitted to AHRQ in December 2013, used to inform the interventions for a national collaborative (http://www.hret.org/quality/projects/long-term-care-cauti.shtml). Dr. Meddings’s effort on this project was funded by concurrent effort from her AHRQ (K08 HS19767). Dr. Saint’s and Dr. Krein’s effort on this project was funded by concurrent effort from the Veterans Affairs National Center for Patient Safety, Ann Arbor Patient Safety Center of Inquiry. Dr. Meddings’s other research is funded by AHRQ (2R01HS018334-04), the NIH-LRP program, the VA National Center for Patient Safety, and the VA Ann Arbor Patient Safety Center of Inquiry. Dr. Krein’s other research is funded by a VA Health Services Research and Development Award (RCS 11-222). Dr. Mody’s other research is funded by VA Healthcare System Geriatric Research Clinical Care Center (GRECC), NIA-Pepper Center, NIA (R01AG032298, R01AG041780, K24AG050685-01). Dr. Saint has received fees for serving on advisory boards for Doximity and Jvion. All other authors report no financial conflicts of interest. The findings and conclusions in this report are those of the authors and do not necessarily represent those of the sponsor, the Agency for Healthcare Research and Quality, or the U.S. Department of Veterans Affairs. These analyses were presented in part as a poster presentation at the ID Week Annual Meeting on October 10, 2014 in Philadelphia, PA.

Given the limited number of geriatricians in the U.S., hospitalists commonly manage nursing home residents admitted for post-acute care.^1-4 Urinary tract infection (UTI) is one of the most common infections in nursing homes, often leading to sepsis and readmission to acute care.⁵ Inappropriate use of antibiotics to treat asymptomatic bacteriuria is both common and hazardous to nursing home residents.⁶ Up to 10% of nursing home residents will have an indwelling urinary catheter at some point during their stay.^7-9 Residents with indwelling urinary catheters are at increased risk for catheter-associated urinary tract infection (CAUTI) and bacteriuria, with an estimated 50% of catheterized residents developing symptomatic CAUTI.⁵ While urinary catheter prevalence is lower in nursing homes than in the acute care setting, duration of use is often prolonged.^7,10 In a setting where utilization is low, but use is prolonged, interventions designed to reduce UTI in acutely ill patients¹¹ may not be as helpful for preventing infection in nursing home residents.

Our objective was to review the available evidence to prevent UTIs in nursing home residents to inform both bedside care and research efforts. Two types of literature review and summary were performed. First, we conducted a systematic review of individual studies reporting outcomes of UTI, CAUTI, bacteriuria, or urinary catheter use after interventions for reducing catheter use, improving insertion and maintenance of catheters, and/or general infection prevention strategies (eg, improving hand hygiene, infection surveillance, contact precautions, standardizing UTI diagnosis, and antibiotic use). Second, we performed a narrative review to generate an overview of evidence and published recommendations in both acute care and nursing home settings to prevent UTI in catheterized and non-catheterized older adults, which is provided as a comprehensive reference table for clinicians and researchers choosing and refining interventions to reduce UTIs.

The systematic review was performed according to the criteria of the Preferred Reporting Items for Systematic Reviews and Meta-Analysis recommendations. The protocol was registered at the PROSPERO International Prospective Register of Systematic Reviews, (CRD42013005787). The narrative review was performed using the articles obtained from the systematic search and a targeted literature review by topic for a comprehensive list of interventions, including other interventions summarized in published reviews and guidelines.

Eligibility Criteria Review

Study Design. To address the breadth and depth of literature available to inform interventions to prevent UTI in nursing homes, broad eligibility criteria were applied with the expectation of varied designs and outcomes. All included studies for the systematic review were published manuscripts reporting a comparison group. We included randomized controlled trials as well as nonrandomized trials (pretest/posttest, with or without concurrent or nonconcurrent controls), with any duration of postintervention follow-up. Observational and retrospective studies were excluded.

Participants. We were interested in interventions and outcomes reported for nursing homes, defined as facilities providing short-stay skilled nursing care and/or rehabilitation, as well as long-term care. We also included evidence derived from rehabilitation facilities and spinal cord injury programs focused on reducing CAUTI risk for chronically catheterized residents. We excluded long-term acute care hospitals, hospice, psychiatric/mental health facilities, pediatric, and community dwelling/outpatient settings.

Interventions. We included interventions involving urinary catheter use such as improving appropriate use, aseptic placement, maintenance care, and prompting removal of unnecessary catheters. We included infection prevention strategies with a particular interest in hand hygiene, barrier precautions, infection control strategies, infection surveillance, use of standardized infection definitions, and interventions to improve antibiotic use. We included single and multiple interventions.

Outcomes
1. Healthcare-associated urinary tract infection: UTI occurring after admission to a healthcare facility, not identified specifically as catheter-associated. We categorized UTI outcomes with as much detail as provided, such as whether the reported outcome included only noncatheter-associated UTIs, the time required after admission (eg, more than 2 days), and whether the UTIs were defined by only laboratory criteria, clinically diagnosed infections, symptomatic, or long-term care specific surveillance definitions.

2. Catheter-associated urinary tract infection: UTI occurring in patients during or immediately after use of a urinary catheter. We noted whether CAUTI was defined by laboratory criteria, clinical symptoms, provider diagnosis, or antimicrobial treatment for case identification. We were primarily interested in CAUTI developing after placing an indwelling urinary catheter, commonly known as a Foley, but also in CAUTI occurring with other catheter types such as intermittent straight catheters, external or “condom” catheters, and suprapubic catheters.

3. Bacteriuria: We included the laboratory-based definition of bacteriuria as an outcome to include studies that reduced asymptomatic bacteriuria.

4. Urinary catheter use measures: This includes measures such as urinary catheter utilization ratios (catheter-days/patient-days), prevalence of urinary catheter use, or percentage of catheters with an appropriate indication.

Study Characteristics for Inclusion. Our systematic search included published papers in the English language. We did not exclude studies based on the number of facilities included or eligible, residents/patients included (based on age, gender, catheter use or type, or antibiotic use), intervention details, study withdrawal, loss to follow-up, death, or duration of pre-intervention and postintervention phases.

Data Sources and Searches

The following data sources were searched: Ovid MEDLINE (1950 to June 22, 2015), Cochrane Library via Wiley (1960 to June 22, 2015), CINAHL (1981 to June 22, 2015), Web of Science (1926 to June 22, 2015), and Embase.com (1946 to June 22, 2015). Two major systematic search strategies were performed for this review (Figure). Systematic search 1 was designed broadly using all data sources described above to identify interventions aimed at reducing all UTI events (defined under “Outcomes” above) or urinary catheter use (all types), focusing on interventions evaluated in nursing homes. Systematic search 2 was conducted in Ovid MEDLINE to identify studies to reduce UTI events or urinary catheter use measures for patients with a history of long-term or chronic catheter use, including nursing homes and other post-acute care settings such as rehabilitation units or hospitals and spinal cord injury programs, which have large populations of patients with chronic catheter needs. To inform the completeness of the broader systematic searches, supplemental systematic search strategies were performed for specific topics including hydration (supplemental search 1), published work by nursing home researchers known to the authors (supplemental search 2), and contact precautions (supplemental search 3). Search 1 is available at http://www.crd.york.ac.uk/PROSPERO/display_record.asp?ID=CRD42013005787. Full search strategies for search 2 and supplemental searches are available upon request.

Study Selection

One author performed an initial screen of all records retrieved by the systematic searches by title and abstract and applied the initial exclusions (eg, non-human, no outcomes of interest), identified duplicate records, and assigned potentially relevant studies into groups such as review articles, epidemiology, interventions, and articles requiring further text review before categorization (Figure). After initial screening, Dr. Meddings reviewed the records by title/abstract. Reference lists were reviewed for potential articles for inclusion. Full-text article review informed the selection of those for dual abstraction and quality scoring performed by 2 authors, with discrepancies resolved by a third author. We requested additional information from authors from whom our search had generated only an abstract or brief report, or when additional information such as pre-intervention data was needed.^12-18

Data Extraction and Quality Assessment

Relevant data regarding study design, participants, inclusion/exclusion criteria, outcomes, and quality criteria were abstracted independently by 2 authors. Methodological quality scores were assigned using a modification of the Quality index checklist developed by Downs and Black appropriate for assessing both randomized and nonrandomized studies of healthcare interventions.¹⁹ We also reviewed study funding sources and other potential quality concerns.

Data Analysis

Due to large trial heterogeneity among these studies about interventions and outcomes reported, outcome data could not be combined into summary measures for meta-analysis to give overall estimates of treatment effects.

Systematic Search Results and Study Selection

As detailed in the study flow diagram (Figure), 5794 total records were retrieved by systematic search 1 (4697 studies), search 2 (909 studies), and supplemental searches (188 studies). Hand searching of reference lists of 41 reviews (including narrative and systematic reviews) yielded 77 additional studies for consideration. Twenty-nine records on interventions that were the focus of systematic reviews, including topics of cranberry use, catheter coatings, antimicrobial prophylaxis, washout/irrigation strategies, and sterile versus clean intermittent straight catheterization, were excluded from dual abstraction. Two records were excluded after team discussion of the dual-abstraction results, because 1 study did not meet criteria as an intervention study and 1 study’s setting was not applicable in nursing homes. A total of 20 records^15,20-38 (in which 19 studies were described) were selected for final inclusion for detailed assessment and reporting for the systematic review.

Characteristics of Included Studies

Table 1 describes the 19 intervention studies in terms of design, participants, setting, and whether the study included specific categories of interventions expected to decrease UTI or catheter use. These studies included 8 randomized controlled trials (4 with cluster-randomization at the facility or unit level), 10 pre-post nonrandomized interventions, and 1 nonrandomized intervention with concurrent controls. Twelve studies included participants with or without catheters (ie, not limited to catheterized patients only) in nursing homes.^15,20-31 Seven^32-38 studies included catheterized patients only or settings with high expected catheterization rates; settings for these studies included spinal cord units (n=3), nursing homes (n=2), rehabilitation ward (n=1) and VA hospital (n=1), including acute care, nursing home, and rehabilitation units. Total quality scores for the studies ranged from 8 to 25 (median, 15), detailed in Supplemental Table 1.

As detailed in Table 1 and Supplemental Table 2, 7 studies^{22,24,26,31,32,35,36} involved single interventions and 12 studies^{15,20,21,23,25,27-30,33,34,37,38} included multiple interventions. Interventions to impact catheter use and care were evaluated in 13 studies, including appropriateness of use,^21,25,29,30 improving catheter maintenance care,^15,20,29,30 securement,^15,29,30,32 prompting removal of unnecessary catheters,^21,25,29,30 improving incontinence care,^15,21,23,25 bladder scanners,^37,38 catheter changes,³⁵and comparing alternatives (condom catheter or intermittent straight catheter) to use of an indwelling catheter.^36,38 None focused on improving aseptic insertion. General infection control practices studied included improving hand hygiene,^{20-22,29-31,33,34} improving antibiotic use,^{15,20,21,28,34} initiation of infection control programs,^20,21,28 interventions to improve identification of UTIs/CAUTIs using infection symptom/sign criteria,^15,20,21,34 infection surveillance as an intervention,^28-30,33,34 and barrier precautions,^33,34 including preemptive precautions for catheterized patients.³⁴ Hydration was assessed in 3 studies.^24-26

Outcomes of Included Studies

Table 2 describes the studies’ outcomes reported for UTI, CAUTI, or bacteriuria.^15,20-38 The outcome definitions of UTI and CAUTI varied widely. Only 2 studies^22,39 reported UTI outcomes using definitions specific for nursing home settings such as McGeer’s criteria⁴⁰ a detailed review and comparison of published CAUTI definitions used clinically and for surveillance in nursing homes is provided in Supplemental Table 3. Two studies reported symptomatic CAUTIs per 1000 catheter-days.^32,34 Another study²² reported symptomatic CAUTIs per 1000 resident-days. Three reported symptomatic CAUTIs as counts.^35,38 Saint et al³⁶ reported CAUTIs as part of a combined outcome (ie, bacteriuria, CAUTI, or death).

The 19 studies (Table 2) reported 12 UTI outcomes,^{15,20,21,23,25-31,33} 9 CAUTI outcomes,^{15,22,32,34,35,38} 4 bacteriuria outcomes,^24,36,38 and 5 catheter use outcomes.^{21,29,30,37,38} Five studies showed CAUTI reduction^{15,22,32,34,35} (1 significantly³⁴); 9 studies showed UTI reduction^{13,18,19,21,23-25,27,28,31} (none significantly); 2 studies showed bacteriuria reduction (none significantly). One study³⁶ reported 2 composite outcomes including bacteriuria or CAUTI or death, with statistically significant improvement reported for 1 composite measure. Four studies reported catheter use, with all showing reduced catheter use in the intervention group; however, only 1 achieved statistically significant reduction.³⁷

Synthesis of Systematic Review Results

Overall, many studies reported decreases in UTI, CAUTI, and urinary catheter use measures but without statistical significance, with many studies likely underpowered for our outcomes of interest. Often, the outcomes of interest in this systematic review were not the main outcome for which the study was designed and originally powered. The interventions studied included several currently implemented as part of CAUTI bundles in the acute care setting, such as improving catheter use, and care and infection control strategies. Other included interventions target common challenges specific to the nursing home setting such as removing indwelling catheters upon admission to the nursing home from an acute-care facility^21,25 and applying interventions to address incontinence by either general strategies^{21,23,25,30,38} or the use of an incontinence specialist²³ to provide individual treatment plans. The only intervention that demonstrated a statistically significant reduction in CAUTI in chronically catheterized patients employed a comprehensive program to improve antimicrobial use, hand hygiene (including hand hygiene and gloves for catheter care), and preemptive precautions for patients with devices, along with promotion of standardized CAUTI definitions and active multidrug resistant organism surveillance.³⁴

Narrative Review Results

Table 3 includes a comprehensive list of potential interventions that have been considered for prevention of UTI or CAUTI (including those in acute care and nursing home settings), as summarized from this systematic review and prior narrative or systematic reviews.^43-115

We performed a broad systematic review of strategies to decrease UTI, CAUTI, and urinary catheter use that may be helpful in nursing homes. While many studies reported decreased UTI, CAUTI, or urinary catheter use measures, few demonstrated statistically significant reductions perhaps because many were underpowered to assess statistical significance. Pooled analyses were not feasible to provide the expected impact of these interventions in the nursing home setting.

This review confirms that bundles of interventions for prevention of CAUTI have been implemented with some evidence of success in nursing home settings, with several components in common with those implemented in the acute care setting, such as hand hygiene and strategies to reduce and improve catheter use.⁴¹ Some studies focused on issues more common in nursing homes such as chronic catheterization and incontinence. A nursing home CAUTI bundle should be designed with the resources and challenges present in the nursing home environment in mind, and with recognition that, although the number of patients with catheters is less than in acute care, there will be more patients with chronic catheterization needs and incontinence.

Although catheter utilization in nursing homes is low, further reductions in catheter days and CAUTIs can be achieved. Catheter removal reminders and stop orders have demonstrated a greater than 50% reduction in CAUTIs in acute care settings;¹¹ an example of a stop-order intervention in nursing homes is trial removal of indwelling catheters present at facility admission without clear urologic need present at the time of admission.²⁵ Nursing home interventions to avoid catheter placement should include incontinence programs, discussion of alternatives to indwelling urinary catheters with patients, families, and frontline personnel, and urinary retention protocols. Programs to reduce CAUTI should include education to improve aseptic insertion, and to maintain awareness and proper care of catheters in place by regular assessment of catheter necessity, securement, hand hygiene, and preemptive barrier precautions for catheterized patients. Interventions that focus on improving appropriate use of urine tests and antibiotics to treat UTIs can also significantly affect the rates of reported symptomatic CAUTIs, with the potential to decrease unnecessary antibiotic use.^20,21

The main limitation of this review is that many studies provided little information about their intervention and definition of outcomes. The strength of this review is the detailed and broad search strategy applied with generous inclusion of interventions and outcomes to highlight the available evidence and details of interventions that have been studied and implemented.

This review synthesizes the current state of evidence and proposes strategies to reduce UTIs in nursing homes. Interventions that motivate catheter avoidance and catheter removal to prevent CAUTI in acute care¹¹ and nursing home settings are supported by the strongest available evidence, although the strength of that evidence is less in the nursing home setting. Limitations notwithstanding, interventions such as incontinence care planning and hydration programs can reduce UTI in this population and is important for overall wellbeing.

Acknowledgments

The authors appreciate the guidance that Vineet Chopra MD, MSc, provided regarding options for methodological quality assessment tools, and the assistance of Mary Rogers PhD, MS, in interpreting the published Downs and Black Quality Index items, which informed our modification of this tool for application in this study. The authors appreciate, also, the feedback provided by the Agency for Healthcare Research and Quality (AHRQ) Content and Materials Development Committee for the AHRQ Safety Program for Long-Term Care: Preventing CAUTI and other Healthcare-associated Infections.

Disclosures

Agency for Healthcare Research and Quality (AHRQ) contract #HHSA290201000025I provided funding for this study, which was developed in response to AHRQ Task Order #8 for ACTION II RFTO 26 CUSP for CAUTI in LTC. AHRQ developed the details of the task and provided comments on a draft report, which informed the report submitted to AHRQ in December 2013, used to inform the interventions for a national collaborative (http://www.hret.org/quality/projects/long-term-care-cauti.shtml). Dr. Meddings’s effort on this project was funded by concurrent effort from her AHRQ (K08 HS19767). Dr. Saint’s and Dr. Krein’s effort on this project was funded by concurrent effort from the Veterans Affairs National Center for Patient Safety, Ann Arbor Patient Safety Center of Inquiry. Dr. Meddings’s other research is funded by AHRQ (2R01HS018334-04), the NIH-LRP program, the VA National Center for Patient Safety, and the VA Ann Arbor Patient Safety Center of Inquiry. Dr. Krein’s other research is funded by a VA Health Services Research and Development Award (RCS 11-222). Dr. Mody’s other research is funded by VA Healthcare System Geriatric Research Clinical Care Center (GRECC), NIA-Pepper Center, NIA (R01AG032298, R01AG041780, K24AG050685-01). Dr. Saint has received fees for serving on advisory boards for Doximity and Jvion. All other authors report no financial conflicts of interest. The findings and conclusions in this report are those of the authors and do not necessarily represent those of the sponsor, the Agency for Healthcare Research and Quality, or the U.S. Department of Veterans Affairs. These analyses were presented in part as a poster presentation at the ID Week Annual Meeting on October 10, 2014 in Philadelphia, PA.

Given the limited number of geriatricians in the U.S., hospitalists commonly manage nursing home residents admitted for post-acute care.^1-4 Urinary tract infection (UTI) is one of the most common infections in nursing homes, often leading to sepsis and readmission to acute care.⁵ Inappropriate use of antibiotics to treat asymptomatic bacteriuria is both common and hazardous to nursing home residents.⁶ Up to 10% of nursing home residents will have an indwelling urinary catheter at some point during their stay.^7-9 Residents with indwelling urinary catheters are at increased risk for catheter-associated urinary tract infection (CAUTI) and bacteriuria, with an estimated 50% of catheterized residents developing symptomatic CAUTI.⁵ While urinary catheter prevalence is lower in nursing homes than in the acute care setting, duration of use is often prolonged.^7,10 In a setting where utilization is low, but use is prolonged, interventions designed to reduce UTI in acutely ill patients¹¹ may not be as helpful for preventing infection in nursing home residents.

Our objective was to review the available evidence to prevent UTIs in nursing home residents to inform both bedside care and research efforts. Two types of literature review and summary were performed. First, we conducted a systematic review of individual studies reporting outcomes of UTI, CAUTI, bacteriuria, or urinary catheter use after interventions for reducing catheter use, improving insertion and maintenance of catheters, and/or general infection prevention strategies (eg, improving hand hygiene, infection surveillance, contact precautions, standardizing UTI diagnosis, and antibiotic use). Second, we performed a narrative review to generate an overview of evidence and published recommendations in both acute care and nursing home settings to prevent UTI in catheterized and non-catheterized older adults, which is provided as a comprehensive reference table for clinicians and researchers choosing and refining interventions to reduce UTIs.

The systematic review was performed according to the criteria of the Preferred Reporting Items for Systematic Reviews and Meta-Analysis recommendations. The protocol was registered at the PROSPERO International Prospective Register of Systematic Reviews, (CRD42013005787). The narrative review was performed using the articles obtained from the systematic search and a targeted literature review by topic for a comprehensive list of interventions, including other interventions summarized in published reviews and guidelines.

Eligibility Criteria Review

Study Design. To address the breadth and depth of literature available to inform interventions to prevent UTI in nursing homes, broad eligibility criteria were applied with the expectation of varied designs and outcomes. All included studies for the systematic review were published manuscripts reporting a comparison group. We included randomized controlled trials as well as nonrandomized trials (pretest/posttest, with or without concurrent or nonconcurrent controls), with any duration of postintervention follow-up. Observational and retrospective studies were excluded.

Participants. We were interested in interventions and outcomes reported for nursing homes, defined as facilities providing short-stay skilled nursing care and/or rehabilitation, as well as long-term care. We also included evidence derived from rehabilitation facilities and spinal cord injury programs focused on reducing CAUTI risk for chronically catheterized residents. We excluded long-term acute care hospitals, hospice, psychiatric/mental health facilities, pediatric, and community dwelling/outpatient settings.

Interventions. We included interventions involving urinary catheter use such as improving appropriate use, aseptic placement, maintenance care, and prompting removal of unnecessary catheters. We included infection prevention strategies with a particular interest in hand hygiene, barrier precautions, infection control strategies, infection surveillance, use of standardized infection definitions, and interventions to improve antibiotic use. We included single and multiple interventions.

Outcomes
1. Healthcare-associated urinary tract infection: UTI occurring after admission to a healthcare facility, not identified specifically as catheter-associated. We categorized UTI outcomes with as much detail as provided, such as whether the reported outcome included only noncatheter-associated UTIs, the time required after admission (eg, more than 2 days), and whether the UTIs were defined by only laboratory criteria, clinically diagnosed infections, symptomatic, or long-term care specific surveillance definitions.

2. Catheter-associated urinary tract infection: UTI occurring in patients during or immediately after use of a urinary catheter. We noted whether CAUTI was defined by laboratory criteria, clinical symptoms, provider diagnosis, or antimicrobial treatment for case identification. We were primarily interested in CAUTI developing after placing an indwelling urinary catheter, commonly known as a Foley, but also in CAUTI occurring with other catheter types such as intermittent straight catheters, external or “condom” catheters, and suprapubic catheters.

3. Bacteriuria: We included the laboratory-based definition of bacteriuria as an outcome to include studies that reduced asymptomatic bacteriuria.

4. Urinary catheter use measures: This includes measures such as urinary catheter utilization ratios (catheter-days/patient-days), prevalence of urinary catheter use, or percentage of catheters with an appropriate indication.

Study Characteristics for Inclusion. Our systematic search included published papers in the English language. We did not exclude studies based on the number of facilities included or eligible, residents/patients included (based on age, gender, catheter use or type, or antibiotic use), intervention details, study withdrawal, loss to follow-up, death, or duration of pre-intervention and postintervention phases.

Data Sources and Searches

The following data sources were searched: Ovid MEDLINE (1950 to June 22, 2015), Cochrane Library via Wiley (1960 to June 22, 2015), CINAHL (1981 to June 22, 2015), Web of Science (1926 to June 22, 2015), and Embase.com (1946 to June 22, 2015). Two major systematic search strategies were performed for this review (Figure). Systematic search 1 was designed broadly using all data sources described above to identify interventions aimed at reducing all UTI events (defined under “Outcomes” above) or urinary catheter use (all types), focusing on interventions evaluated in nursing homes. Systematic search 2 was conducted in Ovid MEDLINE to identify studies to reduce UTI events or urinary catheter use measures for patients with a history of long-term or chronic catheter use, including nursing homes and other post-acute care settings such as rehabilitation units or hospitals and spinal cord injury programs, which have large populations of patients with chronic catheter needs. To inform the completeness of the broader systematic searches, supplemental systematic search strategies were performed for specific topics including hydration (supplemental search 1), published work by nursing home researchers known to the authors (supplemental search 2), and contact precautions (supplemental search 3). Search 1 is available at http://www.crd.york.ac.uk/PROSPERO/display_record.asp?ID=CRD42013005787. Full search strategies for search 2 and supplemental searches are available upon request.

Study Selection

One author performed an initial screen of all records retrieved by the systematic searches by title and abstract and applied the initial exclusions (eg, non-human, no outcomes of interest), identified duplicate records, and assigned potentially relevant studies into groups such as review articles, epidemiology, interventions, and articles requiring further text review before categorization (Figure). After initial screening, Dr. Meddings reviewed the records by title/abstract. Reference lists were reviewed for potential articles for inclusion. Full-text article review informed the selection of those for dual abstraction and quality scoring performed by 2 authors, with discrepancies resolved by a third author. We requested additional information from authors from whom our search had generated only an abstract or brief report, or when additional information such as pre-intervention data was needed.^12-18

Data Extraction and Quality Assessment

Relevant data regarding study design, participants, inclusion/exclusion criteria, outcomes, and quality criteria were abstracted independently by 2 authors. Methodological quality scores were assigned using a modification of the Quality index checklist developed by Downs and Black appropriate for assessing both randomized and nonrandomized studies of healthcare interventions.¹⁹ We also reviewed study funding sources and other potential quality concerns.

Data Analysis

Due to large trial heterogeneity among these studies about interventions and outcomes reported, outcome data could not be combined into summary measures for meta-analysis to give overall estimates of treatment effects.

Systematic Search Results and Study Selection

As detailed in the study flow diagram (Figure), 5794 total records were retrieved by systematic search 1 (4697 studies), search 2 (909 studies), and supplemental searches (188 studies). Hand searching of reference lists of 41 reviews (including narrative and systematic reviews) yielded 77 additional studies for consideration. Twenty-nine records on interventions that were the focus of systematic reviews, including topics of cranberry use, catheter coatings, antimicrobial prophylaxis, washout/irrigation strategies, and sterile versus clean intermittent straight catheterization, were excluded from dual abstraction. Two records were excluded after team discussion of the dual-abstraction results, because 1 study did not meet criteria as an intervention study and 1 study’s setting was not applicable in nursing homes. A total of 20 records^15,20-38 (in which 19 studies were described) were selected for final inclusion for detailed assessment and reporting for the systematic review.

Characteristics of Included Studies

Table 1 describes the 19 intervention studies in terms of design, participants, setting, and whether the study included specific categories of interventions expected to decrease UTI or catheter use. These studies included 8 randomized controlled trials (4 with cluster-randomization at the facility or unit level), 10 pre-post nonrandomized interventions, and 1 nonrandomized intervention with concurrent controls. Twelve studies included participants with or without catheters (ie, not limited to catheterized patients only) in nursing homes.^15,20-31 Seven^32-38 studies included catheterized patients only or settings with high expected catheterization rates; settings for these studies included spinal cord units (n=3), nursing homes (n=2), rehabilitation ward (n=1) and VA hospital (n=1), including acute care, nursing home, and rehabilitation units. Total quality scores for the studies ranged from 8 to 25 (median, 15), detailed in Supplemental Table 1.

As detailed in Table 1 and Supplemental Table 2, 7 studies^{22,24,26,31,32,35,36} involved single interventions and 12 studies^{15,20,21,23,25,27-30,33,34,37,38} included multiple interventions. Interventions to impact catheter use and care were evaluated in 13 studies, including appropriateness of use,^21,25,29,30 improving catheter maintenance care,^15,20,29,30 securement,^15,29,30,32 prompting removal of unnecessary catheters,^21,25,29,30 improving incontinence care,^15,21,23,25 bladder scanners,^37,38 catheter changes,³⁵and comparing alternatives (condom catheter or intermittent straight catheter) to use of an indwelling catheter.^36,38 None focused on improving aseptic insertion. General infection control practices studied included improving hand hygiene,^{20-22,29-31,33,34} improving antibiotic use,^{15,20,21,28,34} initiation of infection control programs,^20,21,28 interventions to improve identification of UTIs/CAUTIs using infection symptom/sign criteria,^15,20,21,34 infection surveillance as an intervention,^28-30,33,34 and barrier precautions,^33,34 including preemptive precautions for catheterized patients.³⁴ Hydration was assessed in 3 studies.^24-26

Outcomes of Included Studies

Table 2 describes the studies’ outcomes reported for UTI, CAUTI, or bacteriuria.^15,20-38 The outcome definitions of UTI and CAUTI varied widely. Only 2 studies^22,39 reported UTI outcomes using definitions specific for nursing home settings such as McGeer’s criteria⁴⁰ a detailed review and comparison of published CAUTI definitions used clinically and for surveillance in nursing homes is provided in Supplemental Table 3. Two studies reported symptomatic CAUTIs per 1000 catheter-days.^32,34 Another study²² reported symptomatic CAUTIs per 1000 resident-days. Three reported symptomatic CAUTIs as counts.^35,38 Saint et al³⁶ reported CAUTIs as part of a combined outcome (ie, bacteriuria, CAUTI, or death).

The 19 studies (Table 2) reported 12 UTI outcomes,^{15,20,21,23,25-31,33} 9 CAUTI outcomes,^{15,22,32,34,35,38} 4 bacteriuria outcomes,^24,36,38 and 5 catheter use outcomes.^{21,29,30,37,38} Five studies showed CAUTI reduction^{15,22,32,34,35} (1 significantly³⁴); 9 studies showed UTI reduction^{13,18,19,21,23-25,27,28,31} (none significantly); 2 studies showed bacteriuria reduction (none significantly). One study³⁶ reported 2 composite outcomes including bacteriuria or CAUTI or death, with statistically significant improvement reported for 1 composite measure. Four studies reported catheter use, with all showing reduced catheter use in the intervention group; however, only 1 achieved statistically significant reduction.³⁷

Synthesis of Systematic Review Results

Overall, many studies reported decreases in UTI, CAUTI, and urinary catheter use measures but without statistical significance, with many studies likely underpowered for our outcomes of interest. Often, the outcomes of interest in this systematic review were not the main outcome for which the study was designed and originally powered. The interventions studied included several currently implemented as part of CAUTI bundles in the acute care setting, such as improving catheter use, and care and infection control strategies. Other included interventions target common challenges specific to the nursing home setting such as removing indwelling catheters upon admission to the nursing home from an acute-care facility^21,25 and applying interventions to address incontinence by either general strategies^{21,23,25,30,38} or the use of an incontinence specialist²³ to provide individual treatment plans. The only intervention that demonstrated a statistically significant reduction in CAUTI in chronically catheterized patients employed a comprehensive program to improve antimicrobial use, hand hygiene (including hand hygiene and gloves for catheter care), and preemptive precautions for patients with devices, along with promotion of standardized CAUTI definitions and active multidrug resistant organism surveillance.³⁴

Narrative Review Results

Table 3 includes a comprehensive list of potential interventions that have been considered for prevention of UTI or CAUTI (including those in acute care and nursing home settings), as summarized from this systematic review and prior narrative or systematic reviews.^43-115

We performed a broad systematic review of strategies to decrease UTI, CAUTI, and urinary catheter use that may be helpful in nursing homes. While many studies reported decreased UTI, CAUTI, or urinary catheter use measures, few demonstrated statistically significant reductions perhaps because many were underpowered to assess statistical significance. Pooled analyses were not feasible to provide the expected impact of these interventions in the nursing home setting.

This review confirms that bundles of interventions for prevention of CAUTI have been implemented with some evidence of success in nursing home settings, with several components in common with those implemented in the acute care setting, such as hand hygiene and strategies to reduce and improve catheter use.⁴¹ Some studies focused on issues more common in nursing homes such as chronic catheterization and incontinence. A nursing home CAUTI bundle should be designed with the resources and challenges present in the nursing home environment in mind, and with recognition that, although the number of patients with catheters is less than in acute care, there will be more patients with chronic catheterization needs and incontinence.

Although catheter utilization in nursing homes is low, further reductions in catheter days and CAUTIs can be achieved. Catheter removal reminders and stop orders have demonstrated a greater than 50% reduction in CAUTIs in acute care settings;¹¹ an example of a stop-order intervention in nursing homes is trial removal of indwelling catheters present at facility admission without clear urologic need present at the time of admission.²⁵ Nursing home interventions to avoid catheter placement should include incontinence programs, discussion of alternatives to indwelling urinary catheters with patients, families, and frontline personnel, and urinary retention protocols. Programs to reduce CAUTI should include education to improve aseptic insertion, and to maintain awareness and proper care of catheters in place by regular assessment of catheter necessity, securement, hand hygiene, and preemptive barrier precautions for catheterized patients. Interventions that focus on improving appropriate use of urine tests and antibiotics to treat UTIs can also significantly affect the rates of reported symptomatic CAUTIs, with the potential to decrease unnecessary antibiotic use.^20,21

The main limitation of this review is that many studies provided little information about their intervention and definition of outcomes. The strength of this review is the detailed and broad search strategy applied with generous inclusion of interventions and outcomes to highlight the available evidence and details of interventions that have been studied and implemented.

This review synthesizes the current state of evidence and proposes strategies to reduce UTIs in nursing homes. Interventions that motivate catheter avoidance and catheter removal to prevent CAUTI in acute care¹¹ and nursing home settings are supported by the strongest available evidence, although the strength of that evidence is less in the nursing home setting. Limitations notwithstanding, interventions such as incontinence care planning and hydration programs can reduce UTI in this population and is important for overall wellbeing.

Acknowledgments

The authors appreciate the guidance that Vineet Chopra MD, MSc, provided regarding options for methodological quality assessment tools, and the assistance of Mary Rogers PhD, MS, in interpreting the published Downs and Black Quality Index items, which informed our modification of this tool for application in this study. The authors appreciate, also, the feedback provided by the Agency for Healthcare Research and Quality (AHRQ) Content and Materials Development Committee for the AHRQ Safety Program for Long-Term Care: Preventing CAUTI and other Healthcare-associated Infections.

Disclosures

Agency for Healthcare Research and Quality (AHRQ) contract #HHSA290201000025I provided funding for this study, which was developed in response to AHRQ Task Order #8 for ACTION II RFTO 26 CUSP for CAUTI in LTC. AHRQ developed the details of the task and provided comments on a draft report, which informed the report submitted to AHRQ in December 2013, used to inform the interventions for a national collaborative (http://www.hret.org/quality/projects/long-term-care-cauti.shtml). Dr. Meddings’s effort on this project was funded by concurrent effort from her AHRQ (K08 HS19767). Dr. Saint’s and Dr. Krein’s effort on this project was funded by concurrent effort from the Veterans Affairs National Center for Patient Safety, Ann Arbor Patient Safety Center of Inquiry. Dr. Meddings’s other research is funded by AHRQ (2R01HS018334-04), the NIH-LRP program, the VA National Center for Patient Safety, and the VA Ann Arbor Patient Safety Center of Inquiry. Dr. Krein’s other research is funded by a VA Health Services Research and Development Award (RCS 11-222). Dr. Mody’s other research is funded by VA Healthcare System Geriatric Research Clinical Care Center (GRECC), NIA-Pepper Center, NIA (R01AG032298, R01AG041780, K24AG050685-01). Dr. Saint has received fees for serving on advisory boards for Doximity and Jvion. All other authors report no financial conflicts of interest. The findings and conclusions in this report are those of the authors and do not necessarily represent those of the sponsor, the Agency for Healthcare Research and Quality, or the U.S. Department of Veterans Affairs. These analyses were presented in part as a poster presentation at the ID Week Annual Meeting on October 10, 2014 in Philadelphia, PA.