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Decreasing Hospital Observation Time for Febrile Infants
Febrile infants aged 0 to 60 days often undergo diagnostic testing to evaluate for invasive bacterial infections (IBI; ie, bacteremia and meningitis) and are subsequently hospitalized pending culture results. Only 1% to 2% of infants 0 to 60 days old have an IBI,1-3 and most hospitalized infants are discharged once physicians feel confident that pathogens are unlikely to be isolated from blood and cerebrospinal fluid (CSF) cultures. Practice regarding duration of hospitalization while awaiting blood and CSF culture results is not standardized in this population. Longer hospitalizations can lead to increased costs and familial stress, including difficulty with breastfeeding and anxiety in newly postpartum mothers.4,5
In 2010, an institutional evidence-based guideline for the management of febrile infants aged 0 to 60 days recommended discharge after 36 hours of observation if all cultures were negative.6 However, recent studies demonstrate that 85% to 93% of pathogens in blood and CSF cultures grow within 24 hours of incubation.7-9 Assuming a 2% prevalence of IBI, if 15% of pathogens were identified after 24 hours of incubation, only one out of 333 infants would have an IBI identified after 24 hours of hospital observation.7
Furthermore, a review of our institution’s electronic health records (EHR) over the past 5 years revealed that an observation period of 24 hours would have resulted in the discharge of three infants with an IBI. Two infants had bacteremia; both were discharged from the emergency department (ED) without antibiotics, returned to care after cultures were reported positive at 27 hours, and had no adverse outcomes. The third infant had meningitis, but also had an abnormal CSF Gram stain, which led to a longer hospitalization.
In 2019, our institution appraised the emerging literature and institutional data supporting the low absolute risk of missed IBI, and also leveraged local consensus among key stakeholders to update its evidence-based guideline for the evaluation and management of febrile infants aged 60 days and younger. The updated guideline recommends that clinicians consider discharging well-appearing neonates and infants if blood and CSF cultures remain negative at 24 hours.10 The objective of this study was to decrease the average hospital culture observation time (COT; culture incubation to hospital discharge) from 38 to 30 hours over a 12-month period in febrile infants aged 0 to 60 days.
METHODS
Context
Improvement efforts were conducted at Cincinnati Children’s Hospital Medical Center (CCHMC), a large, urban, academic hospital that admitted more than 8,000 noncritically ill patients to the hospital medicine (HM) service from July 1, 2018, through June 30, 2019. Hospital medicine teams, located at both the main and satellite campuses, are staffed by attending physicians, fellows, residents, medical students, and nurse practitioners. The two campuses, which are about 20 miles apart, share clinician providers but have distinct nursing pools.
Microbiology services for all CCHMC patients are provided at the main campus. Blood and CSF cultures at the satellite campus are transported to the main campus for incubation and monitoring via an urgent courier service. The microbiology laboratory at CCHMC uses a continuous monitoring system for blood cultures (BACT/ALERT Virtuo, BioMérieux). The system automatically alerts laboratory technicians of positive cultures; these results are reported to clinical providers within 30 minutes of detection. Laboratory technicians manually evaluate CSF cultures once daily for 5 days.
Improvement Team
Our improvement team included three HM attending physicians; two HM fellows; a pediatric chief resident; two nurses, who represented nursing pools at the main and satellite campuses; and a clinical pharmacist, who is a co-leader of the antimicrobial stewardship program at CCHMC. Supporting members for the improvement team included the CCHMC laboratory director; the microbiology laboratory director; an infectious disease physician, who is a co-leader of the antimicrobial stewardship program; and nursing directors of the HM units at both campuses.
Evidence-Based Guideline
Our improvement initiative was based on recommendations from the updated CCHMC Evidence-Based Care Guideline for Management of Infants 0 to 60 days with Fever of Unknown Source.10 This guideline, published in May 2019, was developed by a multidisciplinary working group composed of key stakeholders from HM, community pediatrics, emergency medicine, the pediatric residency program, infectious disease, and laboratory medicine. Several improvement team members were participants on the committee that published the evidence-based guideline. The committee first performed a systematic literature review and critical appraisal of the literature. Care recommendations were formulated via a consensus process directed by best evidence, patient and family preferences, and clinical expertise; the recommendations were subsequently reviewed and approved by clinical experts who were not involved in the development process.
Based on evidence review and multistakeholder consensus, the updated guideline recommends clinicians consider discharging neonates and infants aged 60 days and younger if there is no culture growth after an observation period of 24 hours (as documented in the EHR) and patients are otherwise medically ready for discharge (ie, well appearing with adequate oral intake).10,11 In addition, prior to discharge, there must be a documented working phone number on file for the patient’s parents/guardians, an established outpatient follow-up plan within 24 hours, and communication with the primary pediatrician who is in agreement with discharge at 24 hours.
Study Population
Infants 0 to 60 days old who had a documented or reported fever without an apparent source based on history and physical exam upon presentation to the ED, and who were subsequently admitted to the HM service at CCHMC between October 30, 2018, and July 10, 2020, were eligible for inclusion. We excluded infants who were admitted to other clinical services (eg, intensive care unit); had organisms identified on blood, urine, or CSF culture within 24 hours of incubation; had positive herpes simplex virus testing; had skin/soft tissue infections or another clearly documented source of bacterial infection; or had an alternative indication for hospitalization (eg, need for intravenous fluid or deep suctioning) after cultures had incubated for 24 hours. Infants who had a positive blood, urine, or CSF culture result after 24 hours of incubation were included in the study population. Organisms were classified as pathogen or contaminant based on treatment decisions made by the care team.
Improvement Activities
Key drivers critical to success of the improvement efforts were: (1) clearly defined standard of care for duration of observation in febrile infants 0 to 60 days old; (2) improved understanding of microbiology lab procedures; (3) effective communication of discharge criteria between providers and nurses; and (4) transparency of data with feedback (Figure 1).
Education and Structured Dissemination of Evidence-Based Guideline
The CCHMC febrile infant guideline10 was disseminated to HM physicians, residents, and nurses via the following means: (1) in-person announcements at staff meetings and educational conferences, (2) published highlights from the guideline in weekly newsletters, and (3) email announcements. Additionally, members of the study team educated HM attending physicians, nursing staff from the medical units at both campuses, and resident physicians about recent studies demonstrating safety of shorter length of stay (LOS) in febrile infants aged 0 to 60 days. The study team also provided residents, physicians, and nurses with data on the number of positive blood and CSF cultures and outcomes of patients at CCHMC within the past 5 years. In addition, team members led a journal club for residents discussing an article7 describing time-to-positivity of blood and CSF cultures in febrile infants. For ongoing engagement, the evidence-based guideline and a detailed explanation of microbiology procedures were published in the resident handbook, an internal resource that includes vital clinical pearls and practice guidelines across specialties. (Each resident receives an updated hard copy each year, and there is also an online link to the resource in the EHR.) Information about the guideline and COT was also included in the monthly chief resident’s orientation script, which is relayed to all residents on the first day of their HM rotation.
Clear Communication of Microbiology Procedures
Team members created a detailed process map describing the processing protocols for blood and CSF cultures collected at both CCHMC campuses. This information was shared with HM attending physicians and nurses via in-person announcements at staff meetings, flyers in team workrooms, and email communications. Residents received information on microbiology protocols via in-person announcements at educational conferences and dissemination in the weekly residency newsletter.Important information communicated included:
1. Definition of culture start time. We conveyed that there may be a delay of up to 4 hours between culture collection at the satellite campus and culture incubation at the main campus laboratory. As a result, the time of blood or CSF sample arrival to the main campus laboratory was a more accurate reflection of the culture incubation start time than the culture collection time.
2. Explanation of CSF culture processing. We discussed the process by which these cultures are plated upon arrival at the microbiology laboratory and read once per day in the morning. Therefore, a culture incubated at midnight would be evaluated once at 9 hours and not again until 33 hours.
Modification of Febrile Infant Order Set
Enhancements to the febrile infant order set improved communication and cultivated a shared mental model regarding discharge goals among all members of the care team. The EHR order set for febrile infants was updated as follows: (1) mandatory free-text fields that established the culture start time for blood and CSF cultures were added, (2) culture start time was clearly defined (ie, the time culture arrives at the main campus laboratory), and (3) a change was made in the default discharge criteria11 to “culture observation for 24 hours,” with the ability to modify COT (Appendix Figure 1). We embedded hyperlinks to the guideline and microbiology process map within the updated order set, which allowed providers to easily access this information and refresh their knowledge of the recommendations (Appendix Figure 1).
Identification of Failures and Follow-up With Near-Time Feedback
All cases of febrile infants were tracked weekly. For infants hospitalized longer than 24 hours, the study team contacted the discharging clinicians to discuss reasons for prolonged hospitalization, with an emphasis on identifying system-level barriers to earlier discharge.
Study of the Interventions
The institutional microbiology database was queried weekly to identify all infants 0 to 60 days old who had a blood culture obtained and were hospitalized on the HM service. Study team members conducted targeted EHR review to determine whether patients met exclusion criteria and to identify reasons for prolonged COT. Baseline data were collected retrospectively for a 3-month period prior to initiation of improvement activities. During the study period, queries were conducted weekly and reviewed by study team members to evaluate the impact of improvement activities and to inform new interventions.
Measures
Our primary outcome measure was COT, defined as the hours between final culture incubation and hospital discharge. The operational definition for “final culture incubation” was the documented time of arrival of the last collected culture to the microbiology laboratory. Our goal COT was 30 hours to account for a subset of patients whose blood and/or CSF culture were obtained overnight (ie, after 9
Analysis
Measures were evaluated using statistical process control charts and run charts, and Western Electric rules were employed to determine special cause variation.12 Annotated X-bar S control charts tracked the impact of improvement activities on average COT and LOS for all infants. Given that a relatively small number of patients (ie, two to four) met inclusion criteria each week, average COT was calculated per five patients.
This study was considered exempt from review by the CCHMC Institutional Review Board.
RESULTS
Of the 184 infants in this study, 46 were included as part of baseline data collection, and 138 were included during the intervention period. The median age was 26.6 days (range, 3-59 days); 52% of patients were female; two-thirds were non-Hispanic White; 22% were Black, and 5% were Hispanic (Appendix Table).
Average COT decreased from 38 hours to 32 hours with improvement activities (Figure 2) and was sustained for a total of 17 months. There were small decreases in COT after initial education was provided to attendings, nurses, and residents.
After the launch of the updated order set, median usage of the EHR order set increased from 50% to 80%. Medical discharge criteria were entered for 80 (96%) of the 83 patients for whom the updated order set was applied; culture incubation start times were entered for 78 (94%) of these patients.
No infants in our cohort were found to have IBI after hospital discharge. There were no ED revisits within 48 hours of discharge, and there were no hospital readmissions within 7 days of index discharge. Furthermore, none of the patients included in the study had growth of a pathogenic organism after 24 hours.
Of the 138 infants hospitalized during the intervention period, 77 (56%) had a COT greater than 30 hours. Among these 77 patients, 49 (64%) had their final culture incubated between 9
DISCUSSION
Our study aimed to decrease the average COT from 38 hours to 30 hours among hospitalized infants aged 60 days and younger over a period of 12 months. An intervention featuring implementation of an evidence-based guideline through education, laboratory procedure transparency, creation of a standardized EHR order set, and near-time feedback was associated with a shorter average COT of 32 hours, sustained over a 17-month period. No infants with bacteremia or meningitis were inappropriately discharged during this study.
Interpretation
Prior to our improvement efforts, most febrile infants at CCHMC were observed for at least 36 hours based on a prior institutional guideline,6 despite recent evidence suggesting that most pathogens in blood and CSF cultures grow within 24 hours of incubation.7-9 The goal of this improvement initiative was to bridge the gap between emerging evidence and clinical practice by developing and disseminating an updated evidence-based guideline to safely decrease the hospital observation time in febrile infants aged 60 days and younger.
Similar to previous studies aimed at improving diagnosis and management among febrile infants,13-16 generation and structured dissemination of an institutional evidence-based guideline was crucial to safely shortening COT in our population. These prior studies established a goal COT of 36 to 42 hours for hospitalized febrile infants.13,15,16 Our study incorporated emerging evidence and local experience into an updated evidence-based practice guideline to further reduce COT to 32 hours for hospitalized infants. Key factors contributing to our success included multidisciplinary engagement, specifically partnering with nurses and resident physicians in designing and implementing our initiatives. Furthermore, improved transparency of culture monitoring practices allowed clinicians to better understand the recommended observation periods. Finally, we employed a standardized EHR order set as a no-cost, one-time, high-reliability intervention to establish 24 hours of culture monitoring as the default and to enhance transparency around start time for culture incubation.
Average COT remained stable at 32 hours for 17 months after initiation of the intervention. During the intervention period, 64% patients with hospital stays longer than 30 hours had cultures obtained between 9
Limitations
The study has several limitations. First, this single-center study was conducted at a quaternary care medical center with a robust quality improvement infrastructure. Our interventions took advantage of the existing processes in place that ensure timely discharge of medically ready patients.11 Furthermore, microbiology laboratory practices are unique to our institution. These factors limit the generalizability of this work. Second, due to small numbers of eligible infants, analyses were conducted per five patients. Infrequent hospitalizations limited our ability to learn quickly from PDSA cycles. Finally, we did not measure cost savings attributable to shorter hospital stays. However, in addition to financial savings from charges and decreased nonmedical costs such as lost earnings and childcare,17 shorter hospitalizations have many additional benefits, such as promoting bonding and breastfeeding and decreasing exposure to nosocomial infections. Shorter hospitalizations, with clearly communicated discharge times, also serve to optimize patient throughput.
CONCLUSION
Implementation of a clinical practice guideline resulted in reduction of average COT from 38 to 32 hours in febrile infants aged 60 days and younger, with no cases of missed IBI. Engagement of multidisciplinary stakeholders in the generation and structured dissemination of the evidence-based guideline, improved transparency of the microbiological blood and CSF culture process, and standardization of EHR order sets were crucial to the success of this work. Cultures incubated overnight and daily CSF culture-monitoring practices primarily contributed to an average LOS of more than 30 hours.
Future work will include collaboration with emergency physicians to improve evaluation efficiency and decrease LOS in the ED for febrile infants. Additionally, creation of an automated data dashboard of COT and LOS will provide clinicians with real-time feedback on hospitalization practices.
Acknowledgments
The authors thank Dr Jeffrey Simmons, MD, MSc, as well as the members of the 2019 Fever of Uncertain Source Evidence-Based Guideline Committee. We also thank the James M Anderson Center for Health System Excellence and the Rapid Cycle Improvement Collaborative for their support with guideline development as well as design and execution of our improvement efforts.
1. Cruz AT, Mahajan P, Bonsu BK, et al. Accuracy of complete blood cell counts to identify febrile infants 60 days or younger with invasive bacterial infections. JAMA Pediatr. 2017;171(11):e172927. https://doi.org/10.1001/jamapediatrics.2017.2927
2. Kuppermann N, Dayan PS, Levine DA, et al; Febrile Infant Working Group of the Pediatric Emergency Care Applied Research Network (PECARN). A clinical prediction rule to identify febrile infants 60 days and younger at low risk for serious bacterial infections. JAMA Pediatr. 2019;173(4):342-351. https://doi.org/10.1001/jamapediatrics.2018.5501
3. Nigrovic LE, Mahajan PV, Blumberg SM, et al; Febrile Infant Working Group of the Pediatric Emergency Care Applied Research Network (PECARN). The Yale Observation Scale Score and the risk of serious bacterial infections in febrile infants. Pediatrics. 2017;140(1):e20170695. https://doi.org/10.1542/peds.2017-0695
4. De S, Tong A, Isaacs D, Craig JC. Parental perspectives on evaluation and management of fever in young infants: an interview study. Arch Dis Child. 2014;99(8):717-723. https://doi.org/10.1136/archdischild-2013-305736
5. Paxton RD, Byington CL. An examination of the unintended consequences of the rule-out sepsis evaluation: a parental perspective. Clin Pediatr (Phila). 2001;40(2):71-77. https://doi.org/10.1177/000992280104000202
6. FUS Team. Cincinnati Children’s Hospital Medical Center. Evidence-based clinical care guideline for fever of uncertain source in infants 60 days of age or less. Guideline 2. 2010:1-4.
7. Aronson PL, Wang ME, Nigrovic LE, et al; Febrile Young Infant Research Collaborative. Time to pathogen detection for non-ill versus ill-appearing infants ≤60 days old with bacteremia and meningitis. Hosp Pediatr. 2018;8(7):379-384. https://doi.org/10.1542/hpeds.2018-0002
8. Biondi EA, Mischler M, Jerardi KE, et al; Pediatric Research in Inpatient Settings (PRIS) Network. Blood culture time to positivity in febrile infants with bacteremia. JAMA Pediatr. 2014;168(9):844-849. https://doi.org/10.1001/jamapediatrics.2014.895
9. Lefebvre CE, Renaud C, Chartrand C. Time to positivity of blood cultures in infants 0 to 90 days old presenting to the emergency department: is 36 hours enough? J Pediatric Infect Dis Soc. 2017;6(1):28-32. https://doi.org/10.1093/jpids/piv078
10. Unaka N, Statile A, Bensman, R, et al. Cincinnati Children’s Hospital Medical Center. Evidence-based clinical care guideline for evidence-based care guideline for management of infants 0 to 60 days seen in emergency department for fever of unknown source. Guideline 10. 2019;1-42. http://www.cincinnatichildrens.org/service/j/anderson-center/evidence-based-care/recommendations/default/
11. White CM, Statile AM, White DL, et al. Using quality improvement to optimise paediatric discharge efficiency. BMJ Qual Saf. 2014;23(5):428-436. https://doi.org/10.1136/bmjqs-2013-002556
12. Benneyan JC, Lloyd RC, Plsek PE. Statistical process control as a tool for research and healthcare improvement. Qual Saf Health Care. 2003;12(6):458-464. https://doi.org/10.1136/qhc.12.6.458
13. Biondi EA, McCulloh R, Staggs VS, et al; American Academy of Pediatrics’ Revise Collaborative. Reducing variability in the infant sepsis evaluation (REVISE): a national quality initiative. Pediatrics. 2019;144(3): e20182201. https://doi.org/10.1542/peds.2018-2201
14. McCulloh RJ, Commers T, Williams DD, Michael J, Mann K, Newland JG. Effect of combined clinical practice guideline and electronic order set implementation on febrile infant evaluation and management. Pediatr Emerg Care. 2021;37(1):e25-e31. https://doi.org/10.1097/pec.0000000000002012
15. Foster LZ, Beiner J, Duh-Leong C, et al. Implementation of febrile infant management guidelines reduces hospitalization. Pediatr Qual Saf. 2020;5(1):e252. https://doi.org/10.1097/pq9.0000000000000252
16. Byington CL, Reynolds CC, Korgenski K, et al. Costs and infant outcomes after implementation of a care process model for febrile infants. Pediatrics. 2012;130(1):e16-e24. https://doi.org/10.1542/peds.2012-0127
17. Chang LV, Shah AN, Hoefgen ER, et al; H2O Study Group. Lost earnings and nonmedical expenses of pediatric hospitalizations. Pediatrics. 2018;142(3):e20180195. https://doi.org/10.1542/peds.2018-0195
Febrile infants aged 0 to 60 days often undergo diagnostic testing to evaluate for invasive bacterial infections (IBI; ie, bacteremia and meningitis) and are subsequently hospitalized pending culture results. Only 1% to 2% of infants 0 to 60 days old have an IBI,1-3 and most hospitalized infants are discharged once physicians feel confident that pathogens are unlikely to be isolated from blood and cerebrospinal fluid (CSF) cultures. Practice regarding duration of hospitalization while awaiting blood and CSF culture results is not standardized in this population. Longer hospitalizations can lead to increased costs and familial stress, including difficulty with breastfeeding and anxiety in newly postpartum mothers.4,5
In 2010, an institutional evidence-based guideline for the management of febrile infants aged 0 to 60 days recommended discharge after 36 hours of observation if all cultures were negative.6 However, recent studies demonstrate that 85% to 93% of pathogens in blood and CSF cultures grow within 24 hours of incubation.7-9 Assuming a 2% prevalence of IBI, if 15% of pathogens were identified after 24 hours of incubation, only one out of 333 infants would have an IBI identified after 24 hours of hospital observation.7
Furthermore, a review of our institution’s electronic health records (EHR) over the past 5 years revealed that an observation period of 24 hours would have resulted in the discharge of three infants with an IBI. Two infants had bacteremia; both were discharged from the emergency department (ED) without antibiotics, returned to care after cultures were reported positive at 27 hours, and had no adverse outcomes. The third infant had meningitis, but also had an abnormal CSF Gram stain, which led to a longer hospitalization.
In 2019, our institution appraised the emerging literature and institutional data supporting the low absolute risk of missed IBI, and also leveraged local consensus among key stakeholders to update its evidence-based guideline for the evaluation and management of febrile infants aged 60 days and younger. The updated guideline recommends that clinicians consider discharging well-appearing neonates and infants if blood and CSF cultures remain negative at 24 hours.10 The objective of this study was to decrease the average hospital culture observation time (COT; culture incubation to hospital discharge) from 38 to 30 hours over a 12-month period in febrile infants aged 0 to 60 days.
METHODS
Context
Improvement efforts were conducted at Cincinnati Children’s Hospital Medical Center (CCHMC), a large, urban, academic hospital that admitted more than 8,000 noncritically ill patients to the hospital medicine (HM) service from July 1, 2018, through June 30, 2019. Hospital medicine teams, located at both the main and satellite campuses, are staffed by attending physicians, fellows, residents, medical students, and nurse practitioners. The two campuses, which are about 20 miles apart, share clinician providers but have distinct nursing pools.
Microbiology services for all CCHMC patients are provided at the main campus. Blood and CSF cultures at the satellite campus are transported to the main campus for incubation and monitoring via an urgent courier service. The microbiology laboratory at CCHMC uses a continuous monitoring system for blood cultures (BACT/ALERT Virtuo, BioMérieux). The system automatically alerts laboratory technicians of positive cultures; these results are reported to clinical providers within 30 minutes of detection. Laboratory technicians manually evaluate CSF cultures once daily for 5 days.
Improvement Team
Our improvement team included three HM attending physicians; two HM fellows; a pediatric chief resident; two nurses, who represented nursing pools at the main and satellite campuses; and a clinical pharmacist, who is a co-leader of the antimicrobial stewardship program at CCHMC. Supporting members for the improvement team included the CCHMC laboratory director; the microbiology laboratory director; an infectious disease physician, who is a co-leader of the antimicrobial stewardship program; and nursing directors of the HM units at both campuses.
Evidence-Based Guideline
Our improvement initiative was based on recommendations from the updated CCHMC Evidence-Based Care Guideline for Management of Infants 0 to 60 days with Fever of Unknown Source.10 This guideline, published in May 2019, was developed by a multidisciplinary working group composed of key stakeholders from HM, community pediatrics, emergency medicine, the pediatric residency program, infectious disease, and laboratory medicine. Several improvement team members were participants on the committee that published the evidence-based guideline. The committee first performed a systematic literature review and critical appraisal of the literature. Care recommendations were formulated via a consensus process directed by best evidence, patient and family preferences, and clinical expertise; the recommendations were subsequently reviewed and approved by clinical experts who were not involved in the development process.
Based on evidence review and multistakeholder consensus, the updated guideline recommends clinicians consider discharging neonates and infants aged 60 days and younger if there is no culture growth after an observation period of 24 hours (as documented in the EHR) and patients are otherwise medically ready for discharge (ie, well appearing with adequate oral intake).10,11 In addition, prior to discharge, there must be a documented working phone number on file for the patient’s parents/guardians, an established outpatient follow-up plan within 24 hours, and communication with the primary pediatrician who is in agreement with discharge at 24 hours.
Study Population
Infants 0 to 60 days old who had a documented or reported fever without an apparent source based on history and physical exam upon presentation to the ED, and who were subsequently admitted to the HM service at CCHMC between October 30, 2018, and July 10, 2020, were eligible for inclusion. We excluded infants who were admitted to other clinical services (eg, intensive care unit); had organisms identified on blood, urine, or CSF culture within 24 hours of incubation; had positive herpes simplex virus testing; had skin/soft tissue infections or another clearly documented source of bacterial infection; or had an alternative indication for hospitalization (eg, need for intravenous fluid or deep suctioning) after cultures had incubated for 24 hours. Infants who had a positive blood, urine, or CSF culture result after 24 hours of incubation were included in the study population. Organisms were classified as pathogen or contaminant based on treatment decisions made by the care team.
Improvement Activities
Key drivers critical to success of the improvement efforts were: (1) clearly defined standard of care for duration of observation in febrile infants 0 to 60 days old; (2) improved understanding of microbiology lab procedures; (3) effective communication of discharge criteria between providers and nurses; and (4) transparency of data with feedback (Figure 1).
Education and Structured Dissemination of Evidence-Based Guideline
The CCHMC febrile infant guideline10 was disseminated to HM physicians, residents, and nurses via the following means: (1) in-person announcements at staff meetings and educational conferences, (2) published highlights from the guideline in weekly newsletters, and (3) email announcements. Additionally, members of the study team educated HM attending physicians, nursing staff from the medical units at both campuses, and resident physicians about recent studies demonstrating safety of shorter length of stay (LOS) in febrile infants aged 0 to 60 days. The study team also provided residents, physicians, and nurses with data on the number of positive blood and CSF cultures and outcomes of patients at CCHMC within the past 5 years. In addition, team members led a journal club for residents discussing an article7 describing time-to-positivity of blood and CSF cultures in febrile infants. For ongoing engagement, the evidence-based guideline and a detailed explanation of microbiology procedures were published in the resident handbook, an internal resource that includes vital clinical pearls and practice guidelines across specialties. (Each resident receives an updated hard copy each year, and there is also an online link to the resource in the EHR.) Information about the guideline and COT was also included in the monthly chief resident’s orientation script, which is relayed to all residents on the first day of their HM rotation.
Clear Communication of Microbiology Procedures
Team members created a detailed process map describing the processing protocols for blood and CSF cultures collected at both CCHMC campuses. This information was shared with HM attending physicians and nurses via in-person announcements at staff meetings, flyers in team workrooms, and email communications. Residents received information on microbiology protocols via in-person announcements at educational conferences and dissemination in the weekly residency newsletter.Important information communicated included:
1. Definition of culture start time. We conveyed that there may be a delay of up to 4 hours between culture collection at the satellite campus and culture incubation at the main campus laboratory. As a result, the time of blood or CSF sample arrival to the main campus laboratory was a more accurate reflection of the culture incubation start time than the culture collection time.
2. Explanation of CSF culture processing. We discussed the process by which these cultures are plated upon arrival at the microbiology laboratory and read once per day in the morning. Therefore, a culture incubated at midnight would be evaluated once at 9 hours and not again until 33 hours.
Modification of Febrile Infant Order Set
Enhancements to the febrile infant order set improved communication and cultivated a shared mental model regarding discharge goals among all members of the care team. The EHR order set for febrile infants was updated as follows: (1) mandatory free-text fields that established the culture start time for blood and CSF cultures were added, (2) culture start time was clearly defined (ie, the time culture arrives at the main campus laboratory), and (3) a change was made in the default discharge criteria11 to “culture observation for 24 hours,” with the ability to modify COT (Appendix Figure 1). We embedded hyperlinks to the guideline and microbiology process map within the updated order set, which allowed providers to easily access this information and refresh their knowledge of the recommendations (Appendix Figure 1).
Identification of Failures and Follow-up With Near-Time Feedback
All cases of febrile infants were tracked weekly. For infants hospitalized longer than 24 hours, the study team contacted the discharging clinicians to discuss reasons for prolonged hospitalization, with an emphasis on identifying system-level barriers to earlier discharge.
Study of the Interventions
The institutional microbiology database was queried weekly to identify all infants 0 to 60 days old who had a blood culture obtained and were hospitalized on the HM service. Study team members conducted targeted EHR review to determine whether patients met exclusion criteria and to identify reasons for prolonged COT. Baseline data were collected retrospectively for a 3-month period prior to initiation of improvement activities. During the study period, queries were conducted weekly and reviewed by study team members to evaluate the impact of improvement activities and to inform new interventions.
Measures
Our primary outcome measure was COT, defined as the hours between final culture incubation and hospital discharge. The operational definition for “final culture incubation” was the documented time of arrival of the last collected culture to the microbiology laboratory. Our goal COT was 30 hours to account for a subset of patients whose blood and/or CSF culture were obtained overnight (ie, after 9
Analysis
Measures were evaluated using statistical process control charts and run charts, and Western Electric rules were employed to determine special cause variation.12 Annotated X-bar S control charts tracked the impact of improvement activities on average COT and LOS for all infants. Given that a relatively small number of patients (ie, two to four) met inclusion criteria each week, average COT was calculated per five patients.
This study was considered exempt from review by the CCHMC Institutional Review Board.
RESULTS
Of the 184 infants in this study, 46 were included as part of baseline data collection, and 138 were included during the intervention period. The median age was 26.6 days (range, 3-59 days); 52% of patients were female; two-thirds were non-Hispanic White; 22% were Black, and 5% were Hispanic (Appendix Table).
Average COT decreased from 38 hours to 32 hours with improvement activities (Figure 2) and was sustained for a total of 17 months. There were small decreases in COT after initial education was provided to attendings, nurses, and residents.
After the launch of the updated order set, median usage of the EHR order set increased from 50% to 80%. Medical discharge criteria were entered for 80 (96%) of the 83 patients for whom the updated order set was applied; culture incubation start times were entered for 78 (94%) of these patients.
No infants in our cohort were found to have IBI after hospital discharge. There were no ED revisits within 48 hours of discharge, and there were no hospital readmissions within 7 days of index discharge. Furthermore, none of the patients included in the study had growth of a pathogenic organism after 24 hours.
Of the 138 infants hospitalized during the intervention period, 77 (56%) had a COT greater than 30 hours. Among these 77 patients, 49 (64%) had their final culture incubated between 9
DISCUSSION
Our study aimed to decrease the average COT from 38 hours to 30 hours among hospitalized infants aged 60 days and younger over a period of 12 months. An intervention featuring implementation of an evidence-based guideline through education, laboratory procedure transparency, creation of a standardized EHR order set, and near-time feedback was associated with a shorter average COT of 32 hours, sustained over a 17-month period. No infants with bacteremia or meningitis were inappropriately discharged during this study.
Interpretation
Prior to our improvement efforts, most febrile infants at CCHMC were observed for at least 36 hours based on a prior institutional guideline,6 despite recent evidence suggesting that most pathogens in blood and CSF cultures grow within 24 hours of incubation.7-9 The goal of this improvement initiative was to bridge the gap between emerging evidence and clinical practice by developing and disseminating an updated evidence-based guideline to safely decrease the hospital observation time in febrile infants aged 60 days and younger.
Similar to previous studies aimed at improving diagnosis and management among febrile infants,13-16 generation and structured dissemination of an institutional evidence-based guideline was crucial to safely shortening COT in our population. These prior studies established a goal COT of 36 to 42 hours for hospitalized febrile infants.13,15,16 Our study incorporated emerging evidence and local experience into an updated evidence-based practice guideline to further reduce COT to 32 hours for hospitalized infants. Key factors contributing to our success included multidisciplinary engagement, specifically partnering with nurses and resident physicians in designing and implementing our initiatives. Furthermore, improved transparency of culture monitoring practices allowed clinicians to better understand the recommended observation periods. Finally, we employed a standardized EHR order set as a no-cost, one-time, high-reliability intervention to establish 24 hours of culture monitoring as the default and to enhance transparency around start time for culture incubation.
Average COT remained stable at 32 hours for 17 months after initiation of the intervention. During the intervention period, 64% patients with hospital stays longer than 30 hours had cultures obtained between 9
Limitations
The study has several limitations. First, this single-center study was conducted at a quaternary care medical center with a robust quality improvement infrastructure. Our interventions took advantage of the existing processes in place that ensure timely discharge of medically ready patients.11 Furthermore, microbiology laboratory practices are unique to our institution. These factors limit the generalizability of this work. Second, due to small numbers of eligible infants, analyses were conducted per five patients. Infrequent hospitalizations limited our ability to learn quickly from PDSA cycles. Finally, we did not measure cost savings attributable to shorter hospital stays. However, in addition to financial savings from charges and decreased nonmedical costs such as lost earnings and childcare,17 shorter hospitalizations have many additional benefits, such as promoting bonding and breastfeeding and decreasing exposure to nosocomial infections. Shorter hospitalizations, with clearly communicated discharge times, also serve to optimize patient throughput.
CONCLUSION
Implementation of a clinical practice guideline resulted in reduction of average COT from 38 to 32 hours in febrile infants aged 60 days and younger, with no cases of missed IBI. Engagement of multidisciplinary stakeholders in the generation and structured dissemination of the evidence-based guideline, improved transparency of the microbiological blood and CSF culture process, and standardization of EHR order sets were crucial to the success of this work. Cultures incubated overnight and daily CSF culture-monitoring practices primarily contributed to an average LOS of more than 30 hours.
Future work will include collaboration with emergency physicians to improve evaluation efficiency and decrease LOS in the ED for febrile infants. Additionally, creation of an automated data dashboard of COT and LOS will provide clinicians with real-time feedback on hospitalization practices.
Acknowledgments
The authors thank Dr Jeffrey Simmons, MD, MSc, as well as the members of the 2019 Fever of Uncertain Source Evidence-Based Guideline Committee. We also thank the James M Anderson Center for Health System Excellence and the Rapid Cycle Improvement Collaborative for their support with guideline development as well as design and execution of our improvement efforts.
Febrile infants aged 0 to 60 days often undergo diagnostic testing to evaluate for invasive bacterial infections (IBI; ie, bacteremia and meningitis) and are subsequently hospitalized pending culture results. Only 1% to 2% of infants 0 to 60 days old have an IBI,1-3 and most hospitalized infants are discharged once physicians feel confident that pathogens are unlikely to be isolated from blood and cerebrospinal fluid (CSF) cultures. Practice regarding duration of hospitalization while awaiting blood and CSF culture results is not standardized in this population. Longer hospitalizations can lead to increased costs and familial stress, including difficulty with breastfeeding and anxiety in newly postpartum mothers.4,5
In 2010, an institutional evidence-based guideline for the management of febrile infants aged 0 to 60 days recommended discharge after 36 hours of observation if all cultures were negative.6 However, recent studies demonstrate that 85% to 93% of pathogens in blood and CSF cultures grow within 24 hours of incubation.7-9 Assuming a 2% prevalence of IBI, if 15% of pathogens were identified after 24 hours of incubation, only one out of 333 infants would have an IBI identified after 24 hours of hospital observation.7
Furthermore, a review of our institution’s electronic health records (EHR) over the past 5 years revealed that an observation period of 24 hours would have resulted in the discharge of three infants with an IBI. Two infants had bacteremia; both were discharged from the emergency department (ED) without antibiotics, returned to care after cultures were reported positive at 27 hours, and had no adverse outcomes. The third infant had meningitis, but also had an abnormal CSF Gram stain, which led to a longer hospitalization.
In 2019, our institution appraised the emerging literature and institutional data supporting the low absolute risk of missed IBI, and also leveraged local consensus among key stakeholders to update its evidence-based guideline for the evaluation and management of febrile infants aged 60 days and younger. The updated guideline recommends that clinicians consider discharging well-appearing neonates and infants if blood and CSF cultures remain negative at 24 hours.10 The objective of this study was to decrease the average hospital culture observation time (COT; culture incubation to hospital discharge) from 38 to 30 hours over a 12-month period in febrile infants aged 0 to 60 days.
METHODS
Context
Improvement efforts were conducted at Cincinnati Children’s Hospital Medical Center (CCHMC), a large, urban, academic hospital that admitted more than 8,000 noncritically ill patients to the hospital medicine (HM) service from July 1, 2018, through June 30, 2019. Hospital medicine teams, located at both the main and satellite campuses, are staffed by attending physicians, fellows, residents, medical students, and nurse practitioners. The two campuses, which are about 20 miles apart, share clinician providers but have distinct nursing pools.
Microbiology services for all CCHMC patients are provided at the main campus. Blood and CSF cultures at the satellite campus are transported to the main campus for incubation and monitoring via an urgent courier service. The microbiology laboratory at CCHMC uses a continuous monitoring system for blood cultures (BACT/ALERT Virtuo, BioMérieux). The system automatically alerts laboratory technicians of positive cultures; these results are reported to clinical providers within 30 minutes of detection. Laboratory technicians manually evaluate CSF cultures once daily for 5 days.
Improvement Team
Our improvement team included three HM attending physicians; two HM fellows; a pediatric chief resident; two nurses, who represented nursing pools at the main and satellite campuses; and a clinical pharmacist, who is a co-leader of the antimicrobial stewardship program at CCHMC. Supporting members for the improvement team included the CCHMC laboratory director; the microbiology laboratory director; an infectious disease physician, who is a co-leader of the antimicrobial stewardship program; and nursing directors of the HM units at both campuses.
Evidence-Based Guideline
Our improvement initiative was based on recommendations from the updated CCHMC Evidence-Based Care Guideline for Management of Infants 0 to 60 days with Fever of Unknown Source.10 This guideline, published in May 2019, was developed by a multidisciplinary working group composed of key stakeholders from HM, community pediatrics, emergency medicine, the pediatric residency program, infectious disease, and laboratory medicine. Several improvement team members were participants on the committee that published the evidence-based guideline. The committee first performed a systematic literature review and critical appraisal of the literature. Care recommendations were formulated via a consensus process directed by best evidence, patient and family preferences, and clinical expertise; the recommendations were subsequently reviewed and approved by clinical experts who were not involved in the development process.
Based on evidence review and multistakeholder consensus, the updated guideline recommends clinicians consider discharging neonates and infants aged 60 days and younger if there is no culture growth after an observation period of 24 hours (as documented in the EHR) and patients are otherwise medically ready for discharge (ie, well appearing with adequate oral intake).10,11 In addition, prior to discharge, there must be a documented working phone number on file for the patient’s parents/guardians, an established outpatient follow-up plan within 24 hours, and communication with the primary pediatrician who is in agreement with discharge at 24 hours.
Study Population
Infants 0 to 60 days old who had a documented or reported fever without an apparent source based on history and physical exam upon presentation to the ED, and who were subsequently admitted to the HM service at CCHMC between October 30, 2018, and July 10, 2020, were eligible for inclusion. We excluded infants who were admitted to other clinical services (eg, intensive care unit); had organisms identified on blood, urine, or CSF culture within 24 hours of incubation; had positive herpes simplex virus testing; had skin/soft tissue infections or another clearly documented source of bacterial infection; or had an alternative indication for hospitalization (eg, need for intravenous fluid or deep suctioning) after cultures had incubated for 24 hours. Infants who had a positive blood, urine, or CSF culture result after 24 hours of incubation were included in the study population. Organisms were classified as pathogen or contaminant based on treatment decisions made by the care team.
Improvement Activities
Key drivers critical to success of the improvement efforts were: (1) clearly defined standard of care for duration of observation in febrile infants 0 to 60 days old; (2) improved understanding of microbiology lab procedures; (3) effective communication of discharge criteria between providers and nurses; and (4) transparency of data with feedback (Figure 1).
Education and Structured Dissemination of Evidence-Based Guideline
The CCHMC febrile infant guideline10 was disseminated to HM physicians, residents, and nurses via the following means: (1) in-person announcements at staff meetings and educational conferences, (2) published highlights from the guideline in weekly newsletters, and (3) email announcements. Additionally, members of the study team educated HM attending physicians, nursing staff from the medical units at both campuses, and resident physicians about recent studies demonstrating safety of shorter length of stay (LOS) in febrile infants aged 0 to 60 days. The study team also provided residents, physicians, and nurses with data on the number of positive blood and CSF cultures and outcomes of patients at CCHMC within the past 5 years. In addition, team members led a journal club for residents discussing an article7 describing time-to-positivity of blood and CSF cultures in febrile infants. For ongoing engagement, the evidence-based guideline and a detailed explanation of microbiology procedures were published in the resident handbook, an internal resource that includes vital clinical pearls and practice guidelines across specialties. (Each resident receives an updated hard copy each year, and there is also an online link to the resource in the EHR.) Information about the guideline and COT was also included in the monthly chief resident’s orientation script, which is relayed to all residents on the first day of their HM rotation.
Clear Communication of Microbiology Procedures
Team members created a detailed process map describing the processing protocols for blood and CSF cultures collected at both CCHMC campuses. This information was shared with HM attending physicians and nurses via in-person announcements at staff meetings, flyers in team workrooms, and email communications. Residents received information on microbiology protocols via in-person announcements at educational conferences and dissemination in the weekly residency newsletter.Important information communicated included:
1. Definition of culture start time. We conveyed that there may be a delay of up to 4 hours between culture collection at the satellite campus and culture incubation at the main campus laboratory. As a result, the time of blood or CSF sample arrival to the main campus laboratory was a more accurate reflection of the culture incubation start time than the culture collection time.
2. Explanation of CSF culture processing. We discussed the process by which these cultures are plated upon arrival at the microbiology laboratory and read once per day in the morning. Therefore, a culture incubated at midnight would be evaluated once at 9 hours and not again until 33 hours.
Modification of Febrile Infant Order Set
Enhancements to the febrile infant order set improved communication and cultivated a shared mental model regarding discharge goals among all members of the care team. The EHR order set for febrile infants was updated as follows: (1) mandatory free-text fields that established the culture start time for blood and CSF cultures were added, (2) culture start time was clearly defined (ie, the time culture arrives at the main campus laboratory), and (3) a change was made in the default discharge criteria11 to “culture observation for 24 hours,” with the ability to modify COT (Appendix Figure 1). We embedded hyperlinks to the guideline and microbiology process map within the updated order set, which allowed providers to easily access this information and refresh their knowledge of the recommendations (Appendix Figure 1).
Identification of Failures and Follow-up With Near-Time Feedback
All cases of febrile infants were tracked weekly. For infants hospitalized longer than 24 hours, the study team contacted the discharging clinicians to discuss reasons for prolonged hospitalization, with an emphasis on identifying system-level barriers to earlier discharge.
Study of the Interventions
The institutional microbiology database was queried weekly to identify all infants 0 to 60 days old who had a blood culture obtained and were hospitalized on the HM service. Study team members conducted targeted EHR review to determine whether patients met exclusion criteria and to identify reasons for prolonged COT. Baseline data were collected retrospectively for a 3-month period prior to initiation of improvement activities. During the study period, queries were conducted weekly and reviewed by study team members to evaluate the impact of improvement activities and to inform new interventions.
Measures
Our primary outcome measure was COT, defined as the hours between final culture incubation and hospital discharge. The operational definition for “final culture incubation” was the documented time of arrival of the last collected culture to the microbiology laboratory. Our goal COT was 30 hours to account for a subset of patients whose blood and/or CSF culture were obtained overnight (ie, after 9
Analysis
Measures were evaluated using statistical process control charts and run charts, and Western Electric rules were employed to determine special cause variation.12 Annotated X-bar S control charts tracked the impact of improvement activities on average COT and LOS for all infants. Given that a relatively small number of patients (ie, two to four) met inclusion criteria each week, average COT was calculated per five patients.
This study was considered exempt from review by the CCHMC Institutional Review Board.
RESULTS
Of the 184 infants in this study, 46 were included as part of baseline data collection, and 138 were included during the intervention period. The median age was 26.6 days (range, 3-59 days); 52% of patients were female; two-thirds were non-Hispanic White; 22% were Black, and 5% were Hispanic (Appendix Table).
Average COT decreased from 38 hours to 32 hours with improvement activities (Figure 2) and was sustained for a total of 17 months. There were small decreases in COT after initial education was provided to attendings, nurses, and residents.
After the launch of the updated order set, median usage of the EHR order set increased from 50% to 80%. Medical discharge criteria were entered for 80 (96%) of the 83 patients for whom the updated order set was applied; culture incubation start times were entered for 78 (94%) of these patients.
No infants in our cohort were found to have IBI after hospital discharge. There were no ED revisits within 48 hours of discharge, and there were no hospital readmissions within 7 days of index discharge. Furthermore, none of the patients included in the study had growth of a pathogenic organism after 24 hours.
Of the 138 infants hospitalized during the intervention period, 77 (56%) had a COT greater than 30 hours. Among these 77 patients, 49 (64%) had their final culture incubated between 9
DISCUSSION
Our study aimed to decrease the average COT from 38 hours to 30 hours among hospitalized infants aged 60 days and younger over a period of 12 months. An intervention featuring implementation of an evidence-based guideline through education, laboratory procedure transparency, creation of a standardized EHR order set, and near-time feedback was associated with a shorter average COT of 32 hours, sustained over a 17-month period. No infants with bacteremia or meningitis were inappropriately discharged during this study.
Interpretation
Prior to our improvement efforts, most febrile infants at CCHMC were observed for at least 36 hours based on a prior institutional guideline,6 despite recent evidence suggesting that most pathogens in blood and CSF cultures grow within 24 hours of incubation.7-9 The goal of this improvement initiative was to bridge the gap between emerging evidence and clinical practice by developing and disseminating an updated evidence-based guideline to safely decrease the hospital observation time in febrile infants aged 60 days and younger.
Similar to previous studies aimed at improving diagnosis and management among febrile infants,13-16 generation and structured dissemination of an institutional evidence-based guideline was crucial to safely shortening COT in our population. These prior studies established a goal COT of 36 to 42 hours for hospitalized febrile infants.13,15,16 Our study incorporated emerging evidence and local experience into an updated evidence-based practice guideline to further reduce COT to 32 hours for hospitalized infants. Key factors contributing to our success included multidisciplinary engagement, specifically partnering with nurses and resident physicians in designing and implementing our initiatives. Furthermore, improved transparency of culture monitoring practices allowed clinicians to better understand the recommended observation periods. Finally, we employed a standardized EHR order set as a no-cost, one-time, high-reliability intervention to establish 24 hours of culture monitoring as the default and to enhance transparency around start time for culture incubation.
Average COT remained stable at 32 hours for 17 months after initiation of the intervention. During the intervention period, 64% patients with hospital stays longer than 30 hours had cultures obtained between 9
Limitations
The study has several limitations. First, this single-center study was conducted at a quaternary care medical center with a robust quality improvement infrastructure. Our interventions took advantage of the existing processes in place that ensure timely discharge of medically ready patients.11 Furthermore, microbiology laboratory practices are unique to our institution. These factors limit the generalizability of this work. Second, due to small numbers of eligible infants, analyses were conducted per five patients. Infrequent hospitalizations limited our ability to learn quickly from PDSA cycles. Finally, we did not measure cost savings attributable to shorter hospital stays. However, in addition to financial savings from charges and decreased nonmedical costs such as lost earnings and childcare,17 shorter hospitalizations have many additional benefits, such as promoting bonding and breastfeeding and decreasing exposure to nosocomial infections. Shorter hospitalizations, with clearly communicated discharge times, also serve to optimize patient throughput.
CONCLUSION
Implementation of a clinical practice guideline resulted in reduction of average COT from 38 to 32 hours in febrile infants aged 60 days and younger, with no cases of missed IBI. Engagement of multidisciplinary stakeholders in the generation and structured dissemination of the evidence-based guideline, improved transparency of the microbiological blood and CSF culture process, and standardization of EHR order sets were crucial to the success of this work. Cultures incubated overnight and daily CSF culture-monitoring practices primarily contributed to an average LOS of more than 30 hours.
Future work will include collaboration with emergency physicians to improve evaluation efficiency and decrease LOS in the ED for febrile infants. Additionally, creation of an automated data dashboard of COT and LOS will provide clinicians with real-time feedback on hospitalization practices.
Acknowledgments
The authors thank Dr Jeffrey Simmons, MD, MSc, as well as the members of the 2019 Fever of Uncertain Source Evidence-Based Guideline Committee. We also thank the James M Anderson Center for Health System Excellence and the Rapid Cycle Improvement Collaborative for their support with guideline development as well as design and execution of our improvement efforts.
1. Cruz AT, Mahajan P, Bonsu BK, et al. Accuracy of complete blood cell counts to identify febrile infants 60 days or younger with invasive bacterial infections. JAMA Pediatr. 2017;171(11):e172927. https://doi.org/10.1001/jamapediatrics.2017.2927
2. Kuppermann N, Dayan PS, Levine DA, et al; Febrile Infant Working Group of the Pediatric Emergency Care Applied Research Network (PECARN). A clinical prediction rule to identify febrile infants 60 days and younger at low risk for serious bacterial infections. JAMA Pediatr. 2019;173(4):342-351. https://doi.org/10.1001/jamapediatrics.2018.5501
3. Nigrovic LE, Mahajan PV, Blumberg SM, et al; Febrile Infant Working Group of the Pediatric Emergency Care Applied Research Network (PECARN). The Yale Observation Scale Score and the risk of serious bacterial infections in febrile infants. Pediatrics. 2017;140(1):e20170695. https://doi.org/10.1542/peds.2017-0695
4. De S, Tong A, Isaacs D, Craig JC. Parental perspectives on evaluation and management of fever in young infants: an interview study. Arch Dis Child. 2014;99(8):717-723. https://doi.org/10.1136/archdischild-2013-305736
5. Paxton RD, Byington CL. An examination of the unintended consequences of the rule-out sepsis evaluation: a parental perspective. Clin Pediatr (Phila). 2001;40(2):71-77. https://doi.org/10.1177/000992280104000202
6. FUS Team. Cincinnati Children’s Hospital Medical Center. Evidence-based clinical care guideline for fever of uncertain source in infants 60 days of age or less. Guideline 2. 2010:1-4.
7. Aronson PL, Wang ME, Nigrovic LE, et al; Febrile Young Infant Research Collaborative. Time to pathogen detection for non-ill versus ill-appearing infants ≤60 days old with bacteremia and meningitis. Hosp Pediatr. 2018;8(7):379-384. https://doi.org/10.1542/hpeds.2018-0002
8. Biondi EA, Mischler M, Jerardi KE, et al; Pediatric Research in Inpatient Settings (PRIS) Network. Blood culture time to positivity in febrile infants with bacteremia. JAMA Pediatr. 2014;168(9):844-849. https://doi.org/10.1001/jamapediatrics.2014.895
9. Lefebvre CE, Renaud C, Chartrand C. Time to positivity of blood cultures in infants 0 to 90 days old presenting to the emergency department: is 36 hours enough? J Pediatric Infect Dis Soc. 2017;6(1):28-32. https://doi.org/10.1093/jpids/piv078
10. Unaka N, Statile A, Bensman, R, et al. Cincinnati Children’s Hospital Medical Center. Evidence-based clinical care guideline for evidence-based care guideline for management of infants 0 to 60 days seen in emergency department for fever of unknown source. Guideline 10. 2019;1-42. http://www.cincinnatichildrens.org/service/j/anderson-center/evidence-based-care/recommendations/default/
11. White CM, Statile AM, White DL, et al. Using quality improvement to optimise paediatric discharge efficiency. BMJ Qual Saf. 2014;23(5):428-436. https://doi.org/10.1136/bmjqs-2013-002556
12. Benneyan JC, Lloyd RC, Plsek PE. Statistical process control as a tool for research and healthcare improvement. Qual Saf Health Care. 2003;12(6):458-464. https://doi.org/10.1136/qhc.12.6.458
13. Biondi EA, McCulloh R, Staggs VS, et al; American Academy of Pediatrics’ Revise Collaborative. Reducing variability in the infant sepsis evaluation (REVISE): a national quality initiative. Pediatrics. 2019;144(3): e20182201. https://doi.org/10.1542/peds.2018-2201
14. McCulloh RJ, Commers T, Williams DD, Michael J, Mann K, Newland JG. Effect of combined clinical practice guideline and electronic order set implementation on febrile infant evaluation and management. Pediatr Emerg Care. 2021;37(1):e25-e31. https://doi.org/10.1097/pec.0000000000002012
15. Foster LZ, Beiner J, Duh-Leong C, et al. Implementation of febrile infant management guidelines reduces hospitalization. Pediatr Qual Saf. 2020;5(1):e252. https://doi.org/10.1097/pq9.0000000000000252
16. Byington CL, Reynolds CC, Korgenski K, et al. Costs and infant outcomes after implementation of a care process model for febrile infants. Pediatrics. 2012;130(1):e16-e24. https://doi.org/10.1542/peds.2012-0127
17. Chang LV, Shah AN, Hoefgen ER, et al; H2O Study Group. Lost earnings and nonmedical expenses of pediatric hospitalizations. Pediatrics. 2018;142(3):e20180195. https://doi.org/10.1542/peds.2018-0195
1. Cruz AT, Mahajan P, Bonsu BK, et al. Accuracy of complete blood cell counts to identify febrile infants 60 days or younger with invasive bacterial infections. JAMA Pediatr. 2017;171(11):e172927. https://doi.org/10.1001/jamapediatrics.2017.2927
2. Kuppermann N, Dayan PS, Levine DA, et al; Febrile Infant Working Group of the Pediatric Emergency Care Applied Research Network (PECARN). A clinical prediction rule to identify febrile infants 60 days and younger at low risk for serious bacterial infections. JAMA Pediatr. 2019;173(4):342-351. https://doi.org/10.1001/jamapediatrics.2018.5501
3. Nigrovic LE, Mahajan PV, Blumberg SM, et al; Febrile Infant Working Group of the Pediatric Emergency Care Applied Research Network (PECARN). The Yale Observation Scale Score and the risk of serious bacterial infections in febrile infants. Pediatrics. 2017;140(1):e20170695. https://doi.org/10.1542/peds.2017-0695
4. De S, Tong A, Isaacs D, Craig JC. Parental perspectives on evaluation and management of fever in young infants: an interview study. Arch Dis Child. 2014;99(8):717-723. https://doi.org/10.1136/archdischild-2013-305736
5. Paxton RD, Byington CL. An examination of the unintended consequences of the rule-out sepsis evaluation: a parental perspective. Clin Pediatr (Phila). 2001;40(2):71-77. https://doi.org/10.1177/000992280104000202
6. FUS Team. Cincinnati Children’s Hospital Medical Center. Evidence-based clinical care guideline for fever of uncertain source in infants 60 days of age or less. Guideline 2. 2010:1-4.
7. Aronson PL, Wang ME, Nigrovic LE, et al; Febrile Young Infant Research Collaborative. Time to pathogen detection for non-ill versus ill-appearing infants ≤60 days old with bacteremia and meningitis. Hosp Pediatr. 2018;8(7):379-384. https://doi.org/10.1542/hpeds.2018-0002
8. Biondi EA, Mischler M, Jerardi KE, et al; Pediatric Research in Inpatient Settings (PRIS) Network. Blood culture time to positivity in febrile infants with bacteremia. JAMA Pediatr. 2014;168(9):844-849. https://doi.org/10.1001/jamapediatrics.2014.895
9. Lefebvre CE, Renaud C, Chartrand C. Time to positivity of blood cultures in infants 0 to 90 days old presenting to the emergency department: is 36 hours enough? J Pediatric Infect Dis Soc. 2017;6(1):28-32. https://doi.org/10.1093/jpids/piv078
10. Unaka N, Statile A, Bensman, R, et al. Cincinnati Children’s Hospital Medical Center. Evidence-based clinical care guideline for evidence-based care guideline for management of infants 0 to 60 days seen in emergency department for fever of unknown source. Guideline 10. 2019;1-42. http://www.cincinnatichildrens.org/service/j/anderson-center/evidence-based-care/recommendations/default/
11. White CM, Statile AM, White DL, et al. Using quality improvement to optimise paediatric discharge efficiency. BMJ Qual Saf. 2014;23(5):428-436. https://doi.org/10.1136/bmjqs-2013-002556
12. Benneyan JC, Lloyd RC, Plsek PE. Statistical process control as a tool for research and healthcare improvement. Qual Saf Health Care. 2003;12(6):458-464. https://doi.org/10.1136/qhc.12.6.458
13. Biondi EA, McCulloh R, Staggs VS, et al; American Academy of Pediatrics’ Revise Collaborative. Reducing variability in the infant sepsis evaluation (REVISE): a national quality initiative. Pediatrics. 2019;144(3): e20182201. https://doi.org/10.1542/peds.2018-2201
14. McCulloh RJ, Commers T, Williams DD, Michael J, Mann K, Newland JG. Effect of combined clinical practice guideline and electronic order set implementation on febrile infant evaluation and management. Pediatr Emerg Care. 2021;37(1):e25-e31. https://doi.org/10.1097/pec.0000000000002012
15. Foster LZ, Beiner J, Duh-Leong C, et al. Implementation of febrile infant management guidelines reduces hospitalization. Pediatr Qual Saf. 2020;5(1):e252. https://doi.org/10.1097/pq9.0000000000000252
16. Byington CL, Reynolds CC, Korgenski K, et al. Costs and infant outcomes after implementation of a care process model for febrile infants. Pediatrics. 2012;130(1):e16-e24. https://doi.org/10.1542/peds.2012-0127
17. Chang LV, Shah AN, Hoefgen ER, et al; H2O Study Group. Lost earnings and nonmedical expenses of pediatric hospitalizations. Pediatrics. 2018;142(3):e20180195. https://doi.org/10.1542/peds.2018-0195
© 2021 Society of Hospital Medicine
Improving the Transition of Intravenous to Enteral Antibiotics in Pediatric Patients with Pneumonia or Skin and Soft Tissue Infections
Intravenous (IV) antibiotics are commonly used in hospitalized pediatric patients to treat bacterial infections. Antimicrobial stewardship guidelines published by the Infectious Diseases Society of America (IDSA) recommend institutions develop a systematic plan to convert from IV to enteral antibiotics, as early transition may reduce healthcare costs, decrease length of stay (LOS), and avoid prolonged IV access complications1 such as extravasation, thrombosis, and catheter-associated infections.2-5
Pediatric patients with community-acquired pneumonia (CAP) and mild skin and soft tissue infections (SSTI) may not require IV antibiotics, even if the patient is hospitalized.6 Although national guidelines for pediatric CAP and SSTI recommend IV antibiotics for hospitalized patients, these guidelines state that mild infections may be treated with enteral antibiotics and emphasize discontinuation of IV antibiotics when the patient meets discharge criteria.7,8 Furthermore, several enteral antibiotics used for the treatment of CAP and SSTI, such as cephalexin and clindamycin,9 have excellent bioavailability (>90%) or can achieve sufficient concentrations to attain the pharmacodynamic target (ie, amoxicillin and trimethoprim–sulfamethoxazole).10,11 Nonetheless, the guidelines do not explicitly outline criteria regarding the transition from IV to enteral antibiotics.7,8
At our institution, patients admitted to Hospital Medicine (HM) often remained on IV antibiotics until discharge. Data review revealed that antibiotic treatment of CAP and SSTI posed the greatest opportunity for early conversion to enteral therapy based on the high frequency of admissions and the ability of commonly used enteral antibiotics to attain pharmacodynamic targets. We sought to change practice culture by decoupling transition to enteral antibiotics from discharge and use administration of other enteral medications as an objective indicator for transition. Our aim was to increase the proportion of enterally administered antibiotic doses for HM patients aged >60 days admitted with uncomplicated CAP or SSTI from 44% to 75% in eight months.
METHODS
Context
Cincinnati Children’s Hospital Medical Center (CCHMC) is a large, urban, academic hospital. The HM division has 45 attendings and admits >8,000 general pediatric patients annually. The five HM teams at the main campus consist of attendings, fellows, residents, and medical students. One HM team serves as the resident quality improvement (QI) team where residents collaborate in a longitudinal study under the guidance of QI-trained coaches. The focus of this QI initiative was determined by resident consensus and aligned with a high-value care curriculum.12
To identify the target patient population, we investigated IV antimicrobials frequently used in HM patients. Ampicillin and clindamycin are commonly used IV antibiotics, most frequently corresponding with the diagnoses of CAP and SSTI, respectively, accounting for half of all antibiotic use on the HM service. Amoxicillin, the enteral equivalent of ampicillin, can achieve sufficient concentrations to attain the pharmacodynamic target at infection sites, and clindamycin has high bioavailability, making them ideal options for early transition. Our institution’s robust antimicrobial stewardship program has published local guidelines on using amoxicillin as the enteral antibiotic of choice for uncomplicated CAP, but it does not provide guidance on the timing of transition for either CAP or SSTI; the clinical team makes this decision.
HM attendings were surveyed to determine the criteria used to transition from IV to enteral antibiotics for patients with CAP or SSTI. The survey illustrated practice variability with providers using differing clinical criteria to signal the timing of transition. Additionally, only 49% of respondents (n = 37) rated themselves as “very comfortable” with residents making autonomous decisions to transition to enteral antibiotics. We chose to use the administration of other enteral medications, instead of discharge readiness, as an objective indicator of a patient’s readiness to transition to enteral antibiotics, given the low-risk patient population and the ability of the enteral antibiotics commonly used for CAP and SSTI to achieve pharmacodynamic targets.
The study population included patients aged >60 days admitted to HM with CAP or SSTI treated with any antibiotic. We excluded patients with potential complications or significant progression of their disease process, including patients with parapneumonic effusions or chest tubes, patients who underwent bronchoscopy, and patients with osteomyelitis, septic arthritis, or preseptal or orbital cellulitis. Past medical history and clinical status on admission were not used to exclude patients.
Interventions
Our multidisciplinary team, formed in January 2017, included HM attendings, HM fellows, pediatric residents, a critical care attending, a pharmacy resident, and an antimicrobial stewardship pharmacist. Under the guidance of QI coaches, the residents on the HM QI team developed and tested all interventions on their team and then determined which interventions would spread to the other four teams. The nursing director of our primary HM unit disseminated project updates to bedside nurses. A simplified failure mode and effects analysis identified areas for improvement and potential interventions. Interventions focused on the following key drivers (Figure 1): increased prescriber awareness of medication charge, standardization of conversion from IV to enteral antibiotics, clear definition of the patients ready for transition, ongoing evaluation of the antimicrobial plan, timely recognition by prescribers of patients ready for transition, culture shift regarding the appropriate administration route in the inpatient setting, and transparency of data. The team implemented sequential Plan-Do-Study-Act (PDSA) cycles13 to test the interventions.
Charge Table
To improve knowledge about the increased charge for commonly used IV medications compared with enteral formulations, a table comparing relative charges was shared during monthly resident morning conferences and at an HM faculty meeting. The table included charge comparisons between ampicillin and amoxicillin and IV and enteral clindamycin.
Standardized Language in Electronic Health Record (EHR) Antibiotic Plan on Rounds
Standardized language to document antibiotic transition plans was added to admission and progress note templates in the EHR. The standard template prompted residents to (1) define clinical transition criteria, (2) discuss attending comfort with transition overnight (based on survey results), and (3) document patient preference of solid or liquid dosage forms. Plans were reviewed and updated daily. We hypothesized that since residents use the information in the daily progress notes, including assessments and plans, to present on rounds, inclusion of the transition criteria in the note would prompt transition plan discussions.
Communication Bundle
To promote early transition to enteral antibiotics, we standardized the discussion about antibiotic transition between residents and attendings. During a weekly preexisting meeting, the resident QI team reviewed preferences for transitions with the new service attending. By identifying attending preferences early, residents were able to proactively transition patients who met the criteria (eg, antibiotic transition in the evening instead of waiting until morning rounds). This discussion also provided an opportunity to engage service attendings in the QI efforts, which were also shared at HM faculty meetings quarterly.
Recognizing that in times of high census, discussion of patient plans may be abbreviated during rounds, residents were asked to identify all patients on IV antibiotics while reviewing patient medication orders prior to rounds. As part of an existing daily prerounds huddle to discuss rounding logistics, residents listed all patients on IV antibiotics and discussed which patients were ready for transition. If patients could not be transitioned immediately, the team identified the transition criteria.
At preexisting evening huddles between overnight shift HM residents and the evening HM attending, residents identified patients who were prescribed IV antibiotics and discussed readiness for enteral transition. If a patient could be transitioned overnight, enteral antibiotic orders were placed. Overnight residents were also encouraged to review the transition criteria with families upon admission.
Real-time Identification of Failures and Feedback
For two weeks, the EHR was queried daily to identify patients admitted for uncomplicated CAP and SSTI who were on antibiotics as well as other enteral medications. A failure was defined as an IV antibiotic dose given to a patient who was administered any enteral medication. Residents on the QI team approached residents on other HM teams whenever patients were identified as a failed transition to learn about failure reasons.
Study of the Interventions
Data for HM patients who met the inclusion criteria were collected weekly from January 2016 through June 2018 via EHR query. We initially searched for diagnoses that fit under the disease categories of pneumonia and SSTI in the EHR, which generated a list of International Classification of Disease-9 and -10 Diagnosis codes (Appendix Figure 1). The query identified patients based on these codes and reported whether the identified patients took a dose of any enteral medication, excluding nystatin, sildenafil, tacrolimus, and mouthwashes, which are commonly continued during NPO status due to no need for absorption or limited parenteral options. It also reported the ordered route of administration for the queried antibiotics (Appendix Figure 1).
The 2016 calendar year established our baseline to account for seasonal variability. Data were reported weekly and reviewed to evaluate the impact of PDSA cycles and inform new interventions.
Measures
Our process measure was the total number of enteral antibiotic doses divided by all antibiotic doses in patients receiving any enteral medication. We reasoned that if patients were well enough to take medications enterally, they could be given an enteral antibiotic that is highly bioavailable or readily achieves concentrations that attain pharmacodynamic targets. This practice change was a culture shift, decoupling the switch to enteral antibiotics from discharge readiness. Our EHR query reported only the antibiotic doses given to patients who took an enteral medication on the day of antibiotic administration and excluded patients who received only IV medications.
Outcome measures included antimicrobial costs per patient encounter using average wholesale prices, which were reported in our EHR query, and LOS. To ensure that transitions of IV to enteral antibiotics were not negatively impacting patient outcomes, patient readmissions within seven days served as a balancing measure.
Analysis
An annotated statistical process control p-chart tracked the impact of interventions on the proportion of antibiotic doses that were enterally administered during hospitalization. An x-bar and an s-chart tracked the impact of interventions on antimicrobial costs per patient encounter and on LOS. A p-chart and an encounters-between g-chart were used to evaluate the impact of our interventions on readmissions. Control chart rules for identifying special cause were used for center line shifts.14
Ethical Considerations
This study was part of a larger study of the residency high-value care curriculum,12 which was deemed exempt by the CCHMC IRB.
RESULTS
The baseline data collected included 372 patients and the postintervention period in 2017 included 326 patients (Table). Approximately two-thirds of patients had a diagnosis of CAP.
The percentage of antibiotic doses given enterally increased from 44% to 80% within eight months (Figure 2). When studying the impact of interventions, residents on the HM QI team found that the standard EHR template added to daily notes did not consistently prompt residents to discuss antibiotic plans and thus was abandoned. Initial improvement coincided with standardizing discussions between residents and attendings regarding transitions. Furthermore, discussion of all patients on IV antibiotics during the prerounds huddle allowed for reliable, daily communication about antibiotic plans and was subsequently spread to and adopted by all HM teams. The percentage of enterally administered antibiotic doses increased to >75% after the evening huddle, which involved all HM teams, and real-time identification of failures on all HM teams with provider feedback. Despite variability when the total number of antibiotic doses prescribed per week was low (<10), we demonstrated sustainability for 11 months (Figure 2), during which the prerounds and evening huddle discussions were continued and an updated control chart was shown monthly to residents during their educational conferences.
Residents on the QI team spoke directly with other HM residents when there were missed opportunities for transition. Based on these discussions and intermittent chart reviews, common reasons for failure to transition in patients with CAP included admission for failed outpatient enteral treatment, recent evaluation by critical care physicians for possible transfer to the intensive care unit, and difficulty weaning oxygen. For patients with SSTI, hand abscesses requiring drainage by surgery and treatment failure with other antibiotics constituted many of the IV antibiotic doses given to patients on enteral medications.
Antimicrobial costs per patient encounter decreased by 70% over one year; the shift in costs coincided with the second shift in our process measure (Appendix Figure 2A). Based on an estimate of 350 patients admitted per year for uncomplicated CAP or SSTI, this translates to an annual cost savings of approximately $29,000. The standard deviation of costs per patient encounter decreased by 84% (Appendix Figure 2B), suggesting a decrease in the variability of prescribing practices.
The average LOS in our patient population prior to intervention was 2.1 days and did not change (Appendix Figure 2C), but the standard deviation decreased by >50% (Appendix Figure 2D). There was no shift in the mean seven-day readmission rate or the number of encounters between readmissions (2.6% and 26, respectively; Appendix Figure 3). In addition, the hospital billing department did not identify an increase in insurance denials related to the route of antibiotic administration.
DISCUSSION
Summary
Using improvement science, we promoted earlier transition to enteral antibiotics for children hospitalized with uncomplicated CAP and SSTI by linking the decision for transition to the ability to take other enteral medications, rather than to discharge readiness. We increased the percentage of enterally administered antibiotic doses in this patient population from 44% to 80% in eight months. Although we did not observe a decrease in LOS as previously noted in a cost analysis study comparing pediatric patients with CAP treated with oral antibiotics versus those treated with IV antibiotics,15 we did find a decrease in LOS variability and in antimicrobial costs to our patients. These cost savings did not include potential savings from nursing or pharmacy labor. In addition, we noted a decrease in the variability in antibiotic prescribing practice, which demonstrates provider ability and willingness to couple antibiotic route transition to an objective characteristic (administration of other enteral medications).
A strength of our study was that residents, the most frequent prescribers of antibiotics on our HM service, were highly involved in the QI initiative, including defining the SMART aim, identifying key drivers, developing interventions, and completing sequential PDSA cycles. Under the guidance of QI-trained coaches, residents developed feasible interventions and assessed their success in real time. Consistent with other studies,16,17 resident buy-in and involvement led to the success of our improvement study.
Interpretation
Despite emerging evidence regarding the timing of transition to enteral antibiotics, several factors impeded early transition at our institution, including physician culture, variable practice habits, and hospital workflow. Evidence supports the use of enteral antibiotics in immunocompetent children hospitalized for uncomplicated CAP who do not have chronic lung disease, are not in shock, and have oxygen saturations >85%.6 Although existing literature suggests that in pediatric patients admitted for SSTIs not involving the eye or bone, IV antibiotics may be transitioned when clinical improvement, evidenced by a reduction in fever or erythema, is noted,6 enteral antibiotics that achieve appropriate concentrations to attain pharmacodynamic targets should have the same efficacy as that of IV antibiotics.9 Using the criterion of administration of any medication enterally to identify a patient’s readiness to transition, we were able to overcome practice variation among providers who may have differing opinions of what constitutes clinical improvement. Of note, new evidence is emerging on predictors of enteral antibiotic treatment failure in patients with CAP and SSTI to guide transition timing, but these studies have largely focused on the adult population or were performed in the outpatient and emergency department (ED) settings.18,19 Regardless, the stable number of encounters between readmissions in our patient population likely indicates that treatment failure in these patients was rare.
Rising healthcare costs have led to concerns around sustainability of the healthcare system;20,21 tackling overuse in clinical practice, as in our study, is one mitigation strategy. Several studies have used QI methods to facilitate the provision of high-value care through the decrease of continuous monitor overuse and extraneous ordering of electrolytes.22,23 Our QI study adds to the high-value care literature by safely decreasing the use of IV antibiotics. One retrospective study demonstrated that a one-day decrease in the use of IV antibiotics in pneumonia resulted in decreased costs without an increase in readmissions, similar to our findings.24 In adults, QI initiatives aimed at improving early transition of antibiotics utilized electronic trigger tools.25,26 Fischer et al. used active orders for scheduled enteral medications or an enteral diet as indication that a patient’s IV medications could be converted to enteral form.26
Our work is not without limitations. The list of ICD-9 and -10 codes used to query the EHR did not capture all diagnoses that would be considered as uncomplicated CAP or SSTI. However, we included an extensive list of diagnoses to ensure that the majority of patients meeting our inclusion criteria were captured. Our process measure did not account for patients on IV antibiotics who were not administered other enteral medications but tolerating an enteral diet. These patients were not identified in our EHR query and were not included in our process measure as a failure. However, in latter interventions, residents identified all patients on IV antibiotics, so that patients not identified by our EHR query benefited from our work. Furthermore, this QI study was conducted at a single institution and several interventions took advantage of preexisting structured huddles and a resident QI curriculum, which may not exist at other institutions. Our study does highlight that engaging frontline providers, such as residents, to review antibiotic orders consistently and question the appropriateness of the administration route is key to making incremental changes in prescribing practices.
CONCLUSIONS
Through a partnership between HM and Pharmacy and with substantial resident involvement, we improved the transition of IV antibiotics in patients with CAP or SSTI by increasing the percentage of enterally administered antibiotic doses and reducing antimicrobial costs and variability in antibiotic prescribing practices. This work illustrates how reducing overuse of IV antibiotics promotes high-value care and aligns with initiatives to prevent avoidable harm.27 Our work highlights that standardized discussions about medication orders to create consensus around enteral antibiotic transitions, real-time feedback, and challenging the status quo can influence practice habits and effect change.
Next steps include testing automated methods to notify providers of opportunities for transition from IV to enteral antibiotics through embedded clinical decision support, a method similar to the electronic trigger tools used in adult QI studies.25,26 Since our prerounds huddle includes identifying all patients on IV antibiotics, studying the transition to enteral antibiotics and its effect on prescribing practices in other diagnoses (ie, urinary tract infection and osteomyelitis) may contribute to spreading these efforts. Partnering with our ED colleagues may be an important next step, as several patients admitted to HM on IV antibiotics are given their first dose in the ED.
Acknowledgments
The authors would like to thank the faculty of the James M. Anderson Center for Health Systems Excellence Intermediate Improvement Science Series for their guidance in the planning of this project. The authors would also like to thank Ms. Ursula Bradshaw and Mr. Michael Ponti-Zins for obtaining the hospital data on length of stay and readmissions. The authors acknowledge Dr. Philip Hagedorn for his assistance with the software that queries the electronic health record and Dr. Laura Brower and Dr. Joanna Thomson for their assistance with statistical analysis. The authors are grateful to all the residents and coaches on the QI Hospital Medicine team who contributed ideas on study design and interventions.
1. Dellit TH, Owens RC, McGowan JE, Jr, et al. Infectious diseases society of America and the society for healthcare epidemiology of America guidelines for developing an institutional program to enhance antimicrobial stewardship. Clin Infect Dis. 2007;44(2):159-177. https://doi.org/10.1086/510393.
2. Shah SS, Srivastava R, Wu S, et al. Intravenous Versus oral antibiotics for postdischarge treatment of complicated pneumonia. Pediatrics. 2016;138(6). https://doi.org/10.1542/peds.2016-1692.
3. Keren R, Shah SS, Srivastava R, et al. Comparative effectiveness of intravenous vs oral antibiotics for postdischarge treatment of acute osteomyelitis in children. JAMA Pediatr. 2015;169(2):120-128. https://doi.org/10.1001/jamapediatrics.2014.2822.
4. Jumani K, Advani S, Reich NG, Gosey L, Milstone AM. Risk factors for peripherally inserted central venous catheter complications in children. JAMA Pediatr. 2013;167(5):429-435.https://doi.org/10.1001/jamapediatrics.2013.775.
5. Zaoutis T, Localio AR, Leckerman K, et al. Prolonged intravenous therapy versus early transition to oral antimicrobial therapy for acute osteomyelitis in children. Pediatrics. 2009;123(2):636-642. https://doi.org/10.1542/peds.2008-0596.
6. McMullan BJ, Andresen D, Blyth CC, et al. Antibiotic duration and timing of the switch from intravenous to oral route for bacterial infections in children: systematic review and guidelines. Lancet Infect Dis. 2016;16(8):e139-e152. https://doi.org/10.1016/S1473-3099(16)30024-X.
7. Bradley JS, Byington CL, Shah SS, et al. The management of community-acquired pneumonia in infants and children older than 3 months of age: clinical practice guidelines by the Pediatric Infectious Diseases Society and the Infectious Diseases Society of America. Clin Infect Dis. 2011;53(7):e25-e76. https://doi.org/10.1093/cid/cir531.
8. Stevens DL, Bisno AL, Chambers HF, et al. Executive summary: practice guidelines for the diagnosis and management of skin and soft tissue infections: 2014 update by the infectious diseases society of America. Clin Infect Dis. 2014;59(2):147-159. https://doi.org/10.1093/cid/ciu444.
9. MacGregor RR, Graziani AL. Oral administration of antibiotics: a rational alternative to the parenteral route. Clin Infect Dis. 1997;24(3):457-467. https://doi.org/10.1093/clinids/24.3.457.
10. Downes KJ, Hahn A, Wiles J, Courter JD, Vinks AA. Dose optimisation of antibiotics in children: application of pharmacokinetics/pharmacodynamics in paediatrics. Int J Antimicrob Agents. 2014;43(3):223-230. https://doi.org/10.1016/j.ijantimicag.2013.11.006.
11. Autmizguine J, Melloni C, Hornik CP, et al. Population pharmacokinetics of trimethoprim-sulfamethoxazole in infants and children. Antimicrob Agents Chemother. 2018;62(1):e01813-e01817. https://doi.org/10.1128/AAC.01813-17.
12. Dewan M, Herrmann LE, Tchou MJ, et al. Development and evaluation of high-value pediatrics: a high-value care pediatric resident curriculum. Hosp Pediatr. 2018;8(12):785-792. https://doi.org/10.1542/hpeds.2018-0115
13. Langley GJ, Moen RD, Nolan KM, Nolan TW, Norman CL, Provost LP. The Improvement Guide: A Practical Approach to Enhancing Organizational Performance. New Jersey, US: John Wiley & Sons; 2009.
14. Benneyan JC. Use and interpretation of statistical quality control charts. Int J Qual Health Care. 1998;10(1):69-73. https://doi.org/10.1093/intqhc/10.1.69.
15. Lorgelly PK, Atkinson M, Lakhanpaul M, et al. Oral versus i.v. antibiotics for community-acquired pneumonia in children: a cost-minimisation analysis. Eur Respir J. 2010;35(4):858-864. https://doi.org/10.1183/09031936.00087209.
16. Vidyarthi AR, Green AL, Rosenbluth G, Baron RB. Engaging residents and fellows to improve institution-wide quality: the first six years of a novel financial incentive program. Acad Med. 2014;89(3):460-468. https://doi.org/10.1097/ACM.0000000000000159.
17. Stinnett-Donnelly JM, Stevens PG, Hood VL. Developing a high value care programme from the bottom up: a programme of faculty-resident improvement projects targeting harmful or unnecessary care. BMJ Qual Saf. 2016;25(11):901-908. https://doi.org/10.1136/bmjqs-2015-004546.
18. Peterson D, McLeod S, Woolfrey K, McRae A. Predictors of failure of empiric outpatient antibiotic therapy in emergency department patients with uncomplicated cellulitis. Acad Emerg Med. 2014;21(5):526-531. https://doi.org/10.1111/acem.12371.
19. Yadav K, Suh KN, Eagles D, et al. Predictors of oral antibiotic treatment failure for non-purulent skin and soft tissue infections in the emergency department. Acad Emerg Med. 2018;20(S1):S24-S25. https://doi.org/10.1017/cem.2018.114.
20. Organisation for Economic Co-operation and Development. Healthcare costs unsustainable in advanced economies without reform. http://www.oecd.org/health/healthcarecostsunsustainableinadvancedeconomieswithoutreform.htm. Accessed June 28, 2018; 2015.
21. Berwick DM, Hackbarth AD. Eliminating waste in US health care. JAMA. 2012;307(14):1513-1516. https://doi.org/10.1001/jama.2012.362.
22. Schondelmeyer AC, Simmons JM, Statile AM, et al. Using quality improvement to reduce continuous pulse oximetry use in children with wheezing. Pediatrics. 2015;135(4):e1044-e1051. https://doi.org/10.1542/peds.2014-2295.
23. Tchou MJ, Tang Girdwood S, Wormser B, et al. Reducing electrolyte testing in hospitalized children by using quality improvement methods. Pediatrics. 2018;141(5). https://doi.org/10.1542/peds.2017-3187.
24. Christensen EW, Spaulding AB, Pomputius WF, Grapentine SP. Effects of hospital practice patterns for antibiotic administration for pneumonia on hospital lengths of stay and costs. J Pediatr Infect Dis Soc. 2019;8(2):115-121. https://doi.org/10.1093/jpids/piy003.
25. Berrevoets MAH, Pot JHLW, Houterman AE, et al. An electronic trigger tool to optimise intravenous to oral antibiotic switch: a controlled, interrupted time series study. Antimicrob Resist Infect Control. 2017;6:81. https://doi.org/10.1186/s13756-017-0239-3.
26. Fischer MA, Solomon DH, Teich JM, Avorn J. Conversion from intravenous to oral medications: assessment of a computerized intervention for hospitalized patients. Arch Intern Med. 2003;163(21):2585-2589. https://doi.org/10.1001/archinte.163.21.2585.
27. Schroeder AR, Harris SJ, Newman TB. Safely doing less: a missing component of the patient safety dialogue. Pediatrics. 2011;128(6):e1596-e1597. https://doi.org/10.1542/peds.2011-2726.
Intravenous (IV) antibiotics are commonly used in hospitalized pediatric patients to treat bacterial infections. Antimicrobial stewardship guidelines published by the Infectious Diseases Society of America (IDSA) recommend institutions develop a systematic plan to convert from IV to enteral antibiotics, as early transition may reduce healthcare costs, decrease length of stay (LOS), and avoid prolonged IV access complications1 such as extravasation, thrombosis, and catheter-associated infections.2-5
Pediatric patients with community-acquired pneumonia (CAP) and mild skin and soft tissue infections (SSTI) may not require IV antibiotics, even if the patient is hospitalized.6 Although national guidelines for pediatric CAP and SSTI recommend IV antibiotics for hospitalized patients, these guidelines state that mild infections may be treated with enteral antibiotics and emphasize discontinuation of IV antibiotics when the patient meets discharge criteria.7,8 Furthermore, several enteral antibiotics used for the treatment of CAP and SSTI, such as cephalexin and clindamycin,9 have excellent bioavailability (>90%) or can achieve sufficient concentrations to attain the pharmacodynamic target (ie, amoxicillin and trimethoprim–sulfamethoxazole).10,11 Nonetheless, the guidelines do not explicitly outline criteria regarding the transition from IV to enteral antibiotics.7,8
At our institution, patients admitted to Hospital Medicine (HM) often remained on IV antibiotics until discharge. Data review revealed that antibiotic treatment of CAP and SSTI posed the greatest opportunity for early conversion to enteral therapy based on the high frequency of admissions and the ability of commonly used enteral antibiotics to attain pharmacodynamic targets. We sought to change practice culture by decoupling transition to enteral antibiotics from discharge and use administration of other enteral medications as an objective indicator for transition. Our aim was to increase the proportion of enterally administered antibiotic doses for HM patients aged >60 days admitted with uncomplicated CAP or SSTI from 44% to 75% in eight months.
METHODS
Context
Cincinnati Children’s Hospital Medical Center (CCHMC) is a large, urban, academic hospital. The HM division has 45 attendings and admits >8,000 general pediatric patients annually. The five HM teams at the main campus consist of attendings, fellows, residents, and medical students. One HM team serves as the resident quality improvement (QI) team where residents collaborate in a longitudinal study under the guidance of QI-trained coaches. The focus of this QI initiative was determined by resident consensus and aligned with a high-value care curriculum.12
To identify the target patient population, we investigated IV antimicrobials frequently used in HM patients. Ampicillin and clindamycin are commonly used IV antibiotics, most frequently corresponding with the diagnoses of CAP and SSTI, respectively, accounting for half of all antibiotic use on the HM service. Amoxicillin, the enteral equivalent of ampicillin, can achieve sufficient concentrations to attain the pharmacodynamic target at infection sites, and clindamycin has high bioavailability, making them ideal options for early transition. Our institution’s robust antimicrobial stewardship program has published local guidelines on using amoxicillin as the enteral antibiotic of choice for uncomplicated CAP, but it does not provide guidance on the timing of transition for either CAP or SSTI; the clinical team makes this decision.
HM attendings were surveyed to determine the criteria used to transition from IV to enteral antibiotics for patients with CAP or SSTI. The survey illustrated practice variability with providers using differing clinical criteria to signal the timing of transition. Additionally, only 49% of respondents (n = 37) rated themselves as “very comfortable” with residents making autonomous decisions to transition to enteral antibiotics. We chose to use the administration of other enteral medications, instead of discharge readiness, as an objective indicator of a patient’s readiness to transition to enteral antibiotics, given the low-risk patient population and the ability of the enteral antibiotics commonly used for CAP and SSTI to achieve pharmacodynamic targets.
The study population included patients aged >60 days admitted to HM with CAP or SSTI treated with any antibiotic. We excluded patients with potential complications or significant progression of their disease process, including patients with parapneumonic effusions or chest tubes, patients who underwent bronchoscopy, and patients with osteomyelitis, septic arthritis, or preseptal or orbital cellulitis. Past medical history and clinical status on admission were not used to exclude patients.
Interventions
Our multidisciplinary team, formed in January 2017, included HM attendings, HM fellows, pediatric residents, a critical care attending, a pharmacy resident, and an antimicrobial stewardship pharmacist. Under the guidance of QI coaches, the residents on the HM QI team developed and tested all interventions on their team and then determined which interventions would spread to the other four teams. The nursing director of our primary HM unit disseminated project updates to bedside nurses. A simplified failure mode and effects analysis identified areas for improvement and potential interventions. Interventions focused on the following key drivers (Figure 1): increased prescriber awareness of medication charge, standardization of conversion from IV to enteral antibiotics, clear definition of the patients ready for transition, ongoing evaluation of the antimicrobial plan, timely recognition by prescribers of patients ready for transition, culture shift regarding the appropriate administration route in the inpatient setting, and transparency of data. The team implemented sequential Plan-Do-Study-Act (PDSA) cycles13 to test the interventions.
Charge Table
To improve knowledge about the increased charge for commonly used IV medications compared with enteral formulations, a table comparing relative charges was shared during monthly resident morning conferences and at an HM faculty meeting. The table included charge comparisons between ampicillin and amoxicillin and IV and enteral clindamycin.
Standardized Language in Electronic Health Record (EHR) Antibiotic Plan on Rounds
Standardized language to document antibiotic transition plans was added to admission and progress note templates in the EHR. The standard template prompted residents to (1) define clinical transition criteria, (2) discuss attending comfort with transition overnight (based on survey results), and (3) document patient preference of solid or liquid dosage forms. Plans were reviewed and updated daily. We hypothesized that since residents use the information in the daily progress notes, including assessments and plans, to present on rounds, inclusion of the transition criteria in the note would prompt transition plan discussions.
Communication Bundle
To promote early transition to enteral antibiotics, we standardized the discussion about antibiotic transition between residents and attendings. During a weekly preexisting meeting, the resident QI team reviewed preferences for transitions with the new service attending. By identifying attending preferences early, residents were able to proactively transition patients who met the criteria (eg, antibiotic transition in the evening instead of waiting until morning rounds). This discussion also provided an opportunity to engage service attendings in the QI efforts, which were also shared at HM faculty meetings quarterly.
Recognizing that in times of high census, discussion of patient plans may be abbreviated during rounds, residents were asked to identify all patients on IV antibiotics while reviewing patient medication orders prior to rounds. As part of an existing daily prerounds huddle to discuss rounding logistics, residents listed all patients on IV antibiotics and discussed which patients were ready for transition. If patients could not be transitioned immediately, the team identified the transition criteria.
At preexisting evening huddles between overnight shift HM residents and the evening HM attending, residents identified patients who were prescribed IV antibiotics and discussed readiness for enteral transition. If a patient could be transitioned overnight, enteral antibiotic orders were placed. Overnight residents were also encouraged to review the transition criteria with families upon admission.
Real-time Identification of Failures and Feedback
For two weeks, the EHR was queried daily to identify patients admitted for uncomplicated CAP and SSTI who were on antibiotics as well as other enteral medications. A failure was defined as an IV antibiotic dose given to a patient who was administered any enteral medication. Residents on the QI team approached residents on other HM teams whenever patients were identified as a failed transition to learn about failure reasons.
Study of the Interventions
Data for HM patients who met the inclusion criteria were collected weekly from January 2016 through June 2018 via EHR query. We initially searched for diagnoses that fit under the disease categories of pneumonia and SSTI in the EHR, which generated a list of International Classification of Disease-9 and -10 Diagnosis codes (Appendix Figure 1). The query identified patients based on these codes and reported whether the identified patients took a dose of any enteral medication, excluding nystatin, sildenafil, tacrolimus, and mouthwashes, which are commonly continued during NPO status due to no need for absorption or limited parenteral options. It also reported the ordered route of administration for the queried antibiotics (Appendix Figure 1).
The 2016 calendar year established our baseline to account for seasonal variability. Data were reported weekly and reviewed to evaluate the impact of PDSA cycles and inform new interventions.
Measures
Our process measure was the total number of enteral antibiotic doses divided by all antibiotic doses in patients receiving any enteral medication. We reasoned that if patients were well enough to take medications enterally, they could be given an enteral antibiotic that is highly bioavailable or readily achieves concentrations that attain pharmacodynamic targets. This practice change was a culture shift, decoupling the switch to enteral antibiotics from discharge readiness. Our EHR query reported only the antibiotic doses given to patients who took an enteral medication on the day of antibiotic administration and excluded patients who received only IV medications.
Outcome measures included antimicrobial costs per patient encounter using average wholesale prices, which were reported in our EHR query, and LOS. To ensure that transitions of IV to enteral antibiotics were not negatively impacting patient outcomes, patient readmissions within seven days served as a balancing measure.
Analysis
An annotated statistical process control p-chart tracked the impact of interventions on the proportion of antibiotic doses that were enterally administered during hospitalization. An x-bar and an s-chart tracked the impact of interventions on antimicrobial costs per patient encounter and on LOS. A p-chart and an encounters-between g-chart were used to evaluate the impact of our interventions on readmissions. Control chart rules for identifying special cause were used for center line shifts.14
Ethical Considerations
This study was part of a larger study of the residency high-value care curriculum,12 which was deemed exempt by the CCHMC IRB.
RESULTS
The baseline data collected included 372 patients and the postintervention period in 2017 included 326 patients (Table). Approximately two-thirds of patients had a diagnosis of CAP.
The percentage of antibiotic doses given enterally increased from 44% to 80% within eight months (Figure 2). When studying the impact of interventions, residents on the HM QI team found that the standard EHR template added to daily notes did not consistently prompt residents to discuss antibiotic plans and thus was abandoned. Initial improvement coincided with standardizing discussions between residents and attendings regarding transitions. Furthermore, discussion of all patients on IV antibiotics during the prerounds huddle allowed for reliable, daily communication about antibiotic plans and was subsequently spread to and adopted by all HM teams. The percentage of enterally administered antibiotic doses increased to >75% after the evening huddle, which involved all HM teams, and real-time identification of failures on all HM teams with provider feedback. Despite variability when the total number of antibiotic doses prescribed per week was low (<10), we demonstrated sustainability for 11 months (Figure 2), during which the prerounds and evening huddle discussions were continued and an updated control chart was shown monthly to residents during their educational conferences.
Residents on the QI team spoke directly with other HM residents when there were missed opportunities for transition. Based on these discussions and intermittent chart reviews, common reasons for failure to transition in patients with CAP included admission for failed outpatient enteral treatment, recent evaluation by critical care physicians for possible transfer to the intensive care unit, and difficulty weaning oxygen. For patients with SSTI, hand abscesses requiring drainage by surgery and treatment failure with other antibiotics constituted many of the IV antibiotic doses given to patients on enteral medications.
Antimicrobial costs per patient encounter decreased by 70% over one year; the shift in costs coincided with the second shift in our process measure (Appendix Figure 2A). Based on an estimate of 350 patients admitted per year for uncomplicated CAP or SSTI, this translates to an annual cost savings of approximately $29,000. The standard deviation of costs per patient encounter decreased by 84% (Appendix Figure 2B), suggesting a decrease in the variability of prescribing practices.
The average LOS in our patient population prior to intervention was 2.1 days and did not change (Appendix Figure 2C), but the standard deviation decreased by >50% (Appendix Figure 2D). There was no shift in the mean seven-day readmission rate or the number of encounters between readmissions (2.6% and 26, respectively; Appendix Figure 3). In addition, the hospital billing department did not identify an increase in insurance denials related to the route of antibiotic administration.
DISCUSSION
Summary
Using improvement science, we promoted earlier transition to enteral antibiotics for children hospitalized with uncomplicated CAP and SSTI by linking the decision for transition to the ability to take other enteral medications, rather than to discharge readiness. We increased the percentage of enterally administered antibiotic doses in this patient population from 44% to 80% in eight months. Although we did not observe a decrease in LOS as previously noted in a cost analysis study comparing pediatric patients with CAP treated with oral antibiotics versus those treated with IV antibiotics,15 we did find a decrease in LOS variability and in antimicrobial costs to our patients. These cost savings did not include potential savings from nursing or pharmacy labor. In addition, we noted a decrease in the variability in antibiotic prescribing practice, which demonstrates provider ability and willingness to couple antibiotic route transition to an objective characteristic (administration of other enteral medications).
A strength of our study was that residents, the most frequent prescribers of antibiotics on our HM service, were highly involved in the QI initiative, including defining the SMART aim, identifying key drivers, developing interventions, and completing sequential PDSA cycles. Under the guidance of QI-trained coaches, residents developed feasible interventions and assessed their success in real time. Consistent with other studies,16,17 resident buy-in and involvement led to the success of our improvement study.
Interpretation
Despite emerging evidence regarding the timing of transition to enteral antibiotics, several factors impeded early transition at our institution, including physician culture, variable practice habits, and hospital workflow. Evidence supports the use of enteral antibiotics in immunocompetent children hospitalized for uncomplicated CAP who do not have chronic lung disease, are not in shock, and have oxygen saturations >85%.6 Although existing literature suggests that in pediatric patients admitted for SSTIs not involving the eye or bone, IV antibiotics may be transitioned when clinical improvement, evidenced by a reduction in fever or erythema, is noted,6 enteral antibiotics that achieve appropriate concentrations to attain pharmacodynamic targets should have the same efficacy as that of IV antibiotics.9 Using the criterion of administration of any medication enterally to identify a patient’s readiness to transition, we were able to overcome practice variation among providers who may have differing opinions of what constitutes clinical improvement. Of note, new evidence is emerging on predictors of enteral antibiotic treatment failure in patients with CAP and SSTI to guide transition timing, but these studies have largely focused on the adult population or were performed in the outpatient and emergency department (ED) settings.18,19 Regardless, the stable number of encounters between readmissions in our patient population likely indicates that treatment failure in these patients was rare.
Rising healthcare costs have led to concerns around sustainability of the healthcare system;20,21 tackling overuse in clinical practice, as in our study, is one mitigation strategy. Several studies have used QI methods to facilitate the provision of high-value care through the decrease of continuous monitor overuse and extraneous ordering of electrolytes.22,23 Our QI study adds to the high-value care literature by safely decreasing the use of IV antibiotics. One retrospective study demonstrated that a one-day decrease in the use of IV antibiotics in pneumonia resulted in decreased costs without an increase in readmissions, similar to our findings.24 In adults, QI initiatives aimed at improving early transition of antibiotics utilized electronic trigger tools.25,26 Fischer et al. used active orders for scheduled enteral medications or an enteral diet as indication that a patient’s IV medications could be converted to enteral form.26
Our work is not without limitations. The list of ICD-9 and -10 codes used to query the EHR did not capture all diagnoses that would be considered as uncomplicated CAP or SSTI. However, we included an extensive list of diagnoses to ensure that the majority of patients meeting our inclusion criteria were captured. Our process measure did not account for patients on IV antibiotics who were not administered other enteral medications but tolerating an enteral diet. These patients were not identified in our EHR query and were not included in our process measure as a failure. However, in latter interventions, residents identified all patients on IV antibiotics, so that patients not identified by our EHR query benefited from our work. Furthermore, this QI study was conducted at a single institution and several interventions took advantage of preexisting structured huddles and a resident QI curriculum, which may not exist at other institutions. Our study does highlight that engaging frontline providers, such as residents, to review antibiotic orders consistently and question the appropriateness of the administration route is key to making incremental changes in prescribing practices.
CONCLUSIONS
Through a partnership between HM and Pharmacy and with substantial resident involvement, we improved the transition of IV antibiotics in patients with CAP or SSTI by increasing the percentage of enterally administered antibiotic doses and reducing antimicrobial costs and variability in antibiotic prescribing practices. This work illustrates how reducing overuse of IV antibiotics promotes high-value care and aligns with initiatives to prevent avoidable harm.27 Our work highlights that standardized discussions about medication orders to create consensus around enteral antibiotic transitions, real-time feedback, and challenging the status quo can influence practice habits and effect change.
Next steps include testing automated methods to notify providers of opportunities for transition from IV to enteral antibiotics through embedded clinical decision support, a method similar to the electronic trigger tools used in adult QI studies.25,26 Since our prerounds huddle includes identifying all patients on IV antibiotics, studying the transition to enteral antibiotics and its effect on prescribing practices in other diagnoses (ie, urinary tract infection and osteomyelitis) may contribute to spreading these efforts. Partnering with our ED colleagues may be an important next step, as several patients admitted to HM on IV antibiotics are given their first dose in the ED.
Acknowledgments
The authors would like to thank the faculty of the James M. Anderson Center for Health Systems Excellence Intermediate Improvement Science Series for their guidance in the planning of this project. The authors would also like to thank Ms. Ursula Bradshaw and Mr. Michael Ponti-Zins for obtaining the hospital data on length of stay and readmissions. The authors acknowledge Dr. Philip Hagedorn for his assistance with the software that queries the electronic health record and Dr. Laura Brower and Dr. Joanna Thomson for their assistance with statistical analysis. The authors are grateful to all the residents and coaches on the QI Hospital Medicine team who contributed ideas on study design and interventions.
Intravenous (IV) antibiotics are commonly used in hospitalized pediatric patients to treat bacterial infections. Antimicrobial stewardship guidelines published by the Infectious Diseases Society of America (IDSA) recommend institutions develop a systematic plan to convert from IV to enteral antibiotics, as early transition may reduce healthcare costs, decrease length of stay (LOS), and avoid prolonged IV access complications1 such as extravasation, thrombosis, and catheter-associated infections.2-5
Pediatric patients with community-acquired pneumonia (CAP) and mild skin and soft tissue infections (SSTI) may not require IV antibiotics, even if the patient is hospitalized.6 Although national guidelines for pediatric CAP and SSTI recommend IV antibiotics for hospitalized patients, these guidelines state that mild infections may be treated with enteral antibiotics and emphasize discontinuation of IV antibiotics when the patient meets discharge criteria.7,8 Furthermore, several enteral antibiotics used for the treatment of CAP and SSTI, such as cephalexin and clindamycin,9 have excellent bioavailability (>90%) or can achieve sufficient concentrations to attain the pharmacodynamic target (ie, amoxicillin and trimethoprim–sulfamethoxazole).10,11 Nonetheless, the guidelines do not explicitly outline criteria regarding the transition from IV to enteral antibiotics.7,8
At our institution, patients admitted to Hospital Medicine (HM) often remained on IV antibiotics until discharge. Data review revealed that antibiotic treatment of CAP and SSTI posed the greatest opportunity for early conversion to enteral therapy based on the high frequency of admissions and the ability of commonly used enteral antibiotics to attain pharmacodynamic targets. We sought to change practice culture by decoupling transition to enteral antibiotics from discharge and use administration of other enteral medications as an objective indicator for transition. Our aim was to increase the proportion of enterally administered antibiotic doses for HM patients aged >60 days admitted with uncomplicated CAP or SSTI from 44% to 75% in eight months.
METHODS
Context
Cincinnati Children’s Hospital Medical Center (CCHMC) is a large, urban, academic hospital. The HM division has 45 attendings and admits >8,000 general pediatric patients annually. The five HM teams at the main campus consist of attendings, fellows, residents, and medical students. One HM team serves as the resident quality improvement (QI) team where residents collaborate in a longitudinal study under the guidance of QI-trained coaches. The focus of this QI initiative was determined by resident consensus and aligned with a high-value care curriculum.12
To identify the target patient population, we investigated IV antimicrobials frequently used in HM patients. Ampicillin and clindamycin are commonly used IV antibiotics, most frequently corresponding with the diagnoses of CAP and SSTI, respectively, accounting for half of all antibiotic use on the HM service. Amoxicillin, the enteral equivalent of ampicillin, can achieve sufficient concentrations to attain the pharmacodynamic target at infection sites, and clindamycin has high bioavailability, making them ideal options for early transition. Our institution’s robust antimicrobial stewardship program has published local guidelines on using amoxicillin as the enteral antibiotic of choice for uncomplicated CAP, but it does not provide guidance on the timing of transition for either CAP or SSTI; the clinical team makes this decision.
HM attendings were surveyed to determine the criteria used to transition from IV to enteral antibiotics for patients with CAP or SSTI. The survey illustrated practice variability with providers using differing clinical criteria to signal the timing of transition. Additionally, only 49% of respondents (n = 37) rated themselves as “very comfortable” with residents making autonomous decisions to transition to enteral antibiotics. We chose to use the administration of other enteral medications, instead of discharge readiness, as an objective indicator of a patient’s readiness to transition to enteral antibiotics, given the low-risk patient population and the ability of the enteral antibiotics commonly used for CAP and SSTI to achieve pharmacodynamic targets.
The study population included patients aged >60 days admitted to HM with CAP or SSTI treated with any antibiotic. We excluded patients with potential complications or significant progression of their disease process, including patients with parapneumonic effusions or chest tubes, patients who underwent bronchoscopy, and patients with osteomyelitis, septic arthritis, or preseptal or orbital cellulitis. Past medical history and clinical status on admission were not used to exclude patients.
Interventions
Our multidisciplinary team, formed in January 2017, included HM attendings, HM fellows, pediatric residents, a critical care attending, a pharmacy resident, and an antimicrobial stewardship pharmacist. Under the guidance of QI coaches, the residents on the HM QI team developed and tested all interventions on their team and then determined which interventions would spread to the other four teams. The nursing director of our primary HM unit disseminated project updates to bedside nurses. A simplified failure mode and effects analysis identified areas for improvement and potential interventions. Interventions focused on the following key drivers (Figure 1): increased prescriber awareness of medication charge, standardization of conversion from IV to enteral antibiotics, clear definition of the patients ready for transition, ongoing evaluation of the antimicrobial plan, timely recognition by prescribers of patients ready for transition, culture shift regarding the appropriate administration route in the inpatient setting, and transparency of data. The team implemented sequential Plan-Do-Study-Act (PDSA) cycles13 to test the interventions.
Charge Table
To improve knowledge about the increased charge for commonly used IV medications compared with enteral formulations, a table comparing relative charges was shared during monthly resident morning conferences and at an HM faculty meeting. The table included charge comparisons between ampicillin and amoxicillin and IV and enteral clindamycin.
Standardized Language in Electronic Health Record (EHR) Antibiotic Plan on Rounds
Standardized language to document antibiotic transition plans was added to admission and progress note templates in the EHR. The standard template prompted residents to (1) define clinical transition criteria, (2) discuss attending comfort with transition overnight (based on survey results), and (3) document patient preference of solid or liquid dosage forms. Plans were reviewed and updated daily. We hypothesized that since residents use the information in the daily progress notes, including assessments and plans, to present on rounds, inclusion of the transition criteria in the note would prompt transition plan discussions.
Communication Bundle
To promote early transition to enteral antibiotics, we standardized the discussion about antibiotic transition between residents and attendings. During a weekly preexisting meeting, the resident QI team reviewed preferences for transitions with the new service attending. By identifying attending preferences early, residents were able to proactively transition patients who met the criteria (eg, antibiotic transition in the evening instead of waiting until morning rounds). This discussion also provided an opportunity to engage service attendings in the QI efforts, which were also shared at HM faculty meetings quarterly.
Recognizing that in times of high census, discussion of patient plans may be abbreviated during rounds, residents were asked to identify all patients on IV antibiotics while reviewing patient medication orders prior to rounds. As part of an existing daily prerounds huddle to discuss rounding logistics, residents listed all patients on IV antibiotics and discussed which patients were ready for transition. If patients could not be transitioned immediately, the team identified the transition criteria.
At preexisting evening huddles between overnight shift HM residents and the evening HM attending, residents identified patients who were prescribed IV antibiotics and discussed readiness for enteral transition. If a patient could be transitioned overnight, enteral antibiotic orders were placed. Overnight residents were also encouraged to review the transition criteria with families upon admission.
Real-time Identification of Failures and Feedback
For two weeks, the EHR was queried daily to identify patients admitted for uncomplicated CAP and SSTI who were on antibiotics as well as other enteral medications. A failure was defined as an IV antibiotic dose given to a patient who was administered any enteral medication. Residents on the QI team approached residents on other HM teams whenever patients were identified as a failed transition to learn about failure reasons.
Study of the Interventions
Data for HM patients who met the inclusion criteria were collected weekly from January 2016 through June 2018 via EHR query. We initially searched for diagnoses that fit under the disease categories of pneumonia and SSTI in the EHR, which generated a list of International Classification of Disease-9 and -10 Diagnosis codes (Appendix Figure 1). The query identified patients based on these codes and reported whether the identified patients took a dose of any enteral medication, excluding nystatin, sildenafil, tacrolimus, and mouthwashes, which are commonly continued during NPO status due to no need for absorption or limited parenteral options. It also reported the ordered route of administration for the queried antibiotics (Appendix Figure 1).
The 2016 calendar year established our baseline to account for seasonal variability. Data were reported weekly and reviewed to evaluate the impact of PDSA cycles and inform new interventions.
Measures
Our process measure was the total number of enteral antibiotic doses divided by all antibiotic doses in patients receiving any enteral medication. We reasoned that if patients were well enough to take medications enterally, they could be given an enteral antibiotic that is highly bioavailable or readily achieves concentrations that attain pharmacodynamic targets. This practice change was a culture shift, decoupling the switch to enteral antibiotics from discharge readiness. Our EHR query reported only the antibiotic doses given to patients who took an enteral medication on the day of antibiotic administration and excluded patients who received only IV medications.
Outcome measures included antimicrobial costs per patient encounter using average wholesale prices, which were reported in our EHR query, and LOS. To ensure that transitions of IV to enteral antibiotics were not negatively impacting patient outcomes, patient readmissions within seven days served as a balancing measure.
Analysis
An annotated statistical process control p-chart tracked the impact of interventions on the proportion of antibiotic doses that were enterally administered during hospitalization. An x-bar and an s-chart tracked the impact of interventions on antimicrobial costs per patient encounter and on LOS. A p-chart and an encounters-between g-chart were used to evaluate the impact of our interventions on readmissions. Control chart rules for identifying special cause were used for center line shifts.14
Ethical Considerations
This study was part of a larger study of the residency high-value care curriculum,12 which was deemed exempt by the CCHMC IRB.
RESULTS
The baseline data collected included 372 patients and the postintervention period in 2017 included 326 patients (Table). Approximately two-thirds of patients had a diagnosis of CAP.
The percentage of antibiotic doses given enterally increased from 44% to 80% within eight months (Figure 2). When studying the impact of interventions, residents on the HM QI team found that the standard EHR template added to daily notes did not consistently prompt residents to discuss antibiotic plans and thus was abandoned. Initial improvement coincided with standardizing discussions between residents and attendings regarding transitions. Furthermore, discussion of all patients on IV antibiotics during the prerounds huddle allowed for reliable, daily communication about antibiotic plans and was subsequently spread to and adopted by all HM teams. The percentage of enterally administered antibiotic doses increased to >75% after the evening huddle, which involved all HM teams, and real-time identification of failures on all HM teams with provider feedback. Despite variability when the total number of antibiotic doses prescribed per week was low (<10), we demonstrated sustainability for 11 months (Figure 2), during which the prerounds and evening huddle discussions were continued and an updated control chart was shown monthly to residents during their educational conferences.
Residents on the QI team spoke directly with other HM residents when there were missed opportunities for transition. Based on these discussions and intermittent chart reviews, common reasons for failure to transition in patients with CAP included admission for failed outpatient enteral treatment, recent evaluation by critical care physicians for possible transfer to the intensive care unit, and difficulty weaning oxygen. For patients with SSTI, hand abscesses requiring drainage by surgery and treatment failure with other antibiotics constituted many of the IV antibiotic doses given to patients on enteral medications.
Antimicrobial costs per patient encounter decreased by 70% over one year; the shift in costs coincided with the second shift in our process measure (Appendix Figure 2A). Based on an estimate of 350 patients admitted per year for uncomplicated CAP or SSTI, this translates to an annual cost savings of approximately $29,000. The standard deviation of costs per patient encounter decreased by 84% (Appendix Figure 2B), suggesting a decrease in the variability of prescribing practices.
The average LOS in our patient population prior to intervention was 2.1 days and did not change (Appendix Figure 2C), but the standard deviation decreased by >50% (Appendix Figure 2D). There was no shift in the mean seven-day readmission rate or the number of encounters between readmissions (2.6% and 26, respectively; Appendix Figure 3). In addition, the hospital billing department did not identify an increase in insurance denials related to the route of antibiotic administration.
DISCUSSION
Summary
Using improvement science, we promoted earlier transition to enteral antibiotics for children hospitalized with uncomplicated CAP and SSTI by linking the decision for transition to the ability to take other enteral medications, rather than to discharge readiness. We increased the percentage of enterally administered antibiotic doses in this patient population from 44% to 80% in eight months. Although we did not observe a decrease in LOS as previously noted in a cost analysis study comparing pediatric patients with CAP treated with oral antibiotics versus those treated with IV antibiotics,15 we did find a decrease in LOS variability and in antimicrobial costs to our patients. These cost savings did not include potential savings from nursing or pharmacy labor. In addition, we noted a decrease in the variability in antibiotic prescribing practice, which demonstrates provider ability and willingness to couple antibiotic route transition to an objective characteristic (administration of other enteral medications).
A strength of our study was that residents, the most frequent prescribers of antibiotics on our HM service, were highly involved in the QI initiative, including defining the SMART aim, identifying key drivers, developing interventions, and completing sequential PDSA cycles. Under the guidance of QI-trained coaches, residents developed feasible interventions and assessed their success in real time. Consistent with other studies,16,17 resident buy-in and involvement led to the success of our improvement study.
Interpretation
Despite emerging evidence regarding the timing of transition to enteral antibiotics, several factors impeded early transition at our institution, including physician culture, variable practice habits, and hospital workflow. Evidence supports the use of enteral antibiotics in immunocompetent children hospitalized for uncomplicated CAP who do not have chronic lung disease, are not in shock, and have oxygen saturations >85%.6 Although existing literature suggests that in pediatric patients admitted for SSTIs not involving the eye or bone, IV antibiotics may be transitioned when clinical improvement, evidenced by a reduction in fever or erythema, is noted,6 enteral antibiotics that achieve appropriate concentrations to attain pharmacodynamic targets should have the same efficacy as that of IV antibiotics.9 Using the criterion of administration of any medication enterally to identify a patient’s readiness to transition, we were able to overcome practice variation among providers who may have differing opinions of what constitutes clinical improvement. Of note, new evidence is emerging on predictors of enteral antibiotic treatment failure in patients with CAP and SSTI to guide transition timing, but these studies have largely focused on the adult population or were performed in the outpatient and emergency department (ED) settings.18,19 Regardless, the stable number of encounters between readmissions in our patient population likely indicates that treatment failure in these patients was rare.
Rising healthcare costs have led to concerns around sustainability of the healthcare system;20,21 tackling overuse in clinical practice, as in our study, is one mitigation strategy. Several studies have used QI methods to facilitate the provision of high-value care through the decrease of continuous monitor overuse and extraneous ordering of electrolytes.22,23 Our QI study adds to the high-value care literature by safely decreasing the use of IV antibiotics. One retrospective study demonstrated that a one-day decrease in the use of IV antibiotics in pneumonia resulted in decreased costs without an increase in readmissions, similar to our findings.24 In adults, QI initiatives aimed at improving early transition of antibiotics utilized electronic trigger tools.25,26 Fischer et al. used active orders for scheduled enteral medications or an enteral diet as indication that a patient’s IV medications could be converted to enteral form.26
Our work is not without limitations. The list of ICD-9 and -10 codes used to query the EHR did not capture all diagnoses that would be considered as uncomplicated CAP or SSTI. However, we included an extensive list of diagnoses to ensure that the majority of patients meeting our inclusion criteria were captured. Our process measure did not account for patients on IV antibiotics who were not administered other enteral medications but tolerating an enteral diet. These patients were not identified in our EHR query and were not included in our process measure as a failure. However, in latter interventions, residents identified all patients on IV antibiotics, so that patients not identified by our EHR query benefited from our work. Furthermore, this QI study was conducted at a single institution and several interventions took advantage of preexisting structured huddles and a resident QI curriculum, which may not exist at other institutions. Our study does highlight that engaging frontline providers, such as residents, to review antibiotic orders consistently and question the appropriateness of the administration route is key to making incremental changes in prescribing practices.
CONCLUSIONS
Through a partnership between HM and Pharmacy and with substantial resident involvement, we improved the transition of IV antibiotics in patients with CAP or SSTI by increasing the percentage of enterally administered antibiotic doses and reducing antimicrobial costs and variability in antibiotic prescribing practices. This work illustrates how reducing overuse of IV antibiotics promotes high-value care and aligns with initiatives to prevent avoidable harm.27 Our work highlights that standardized discussions about medication orders to create consensus around enteral antibiotic transitions, real-time feedback, and challenging the status quo can influence practice habits and effect change.
Next steps include testing automated methods to notify providers of opportunities for transition from IV to enteral antibiotics through embedded clinical decision support, a method similar to the electronic trigger tools used in adult QI studies.25,26 Since our prerounds huddle includes identifying all patients on IV antibiotics, studying the transition to enteral antibiotics and its effect on prescribing practices in other diagnoses (ie, urinary tract infection and osteomyelitis) may contribute to spreading these efforts. Partnering with our ED colleagues may be an important next step, as several patients admitted to HM on IV antibiotics are given their first dose in the ED.
Acknowledgments
The authors would like to thank the faculty of the James M. Anderson Center for Health Systems Excellence Intermediate Improvement Science Series for their guidance in the planning of this project. The authors would also like to thank Ms. Ursula Bradshaw and Mr. Michael Ponti-Zins for obtaining the hospital data on length of stay and readmissions. The authors acknowledge Dr. Philip Hagedorn for his assistance with the software that queries the electronic health record and Dr. Laura Brower and Dr. Joanna Thomson for their assistance with statistical analysis. The authors are grateful to all the residents and coaches on the QI Hospital Medicine team who contributed ideas on study design and interventions.
1. Dellit TH, Owens RC, McGowan JE, Jr, et al. Infectious diseases society of America and the society for healthcare epidemiology of America guidelines for developing an institutional program to enhance antimicrobial stewardship. Clin Infect Dis. 2007;44(2):159-177. https://doi.org/10.1086/510393.
2. Shah SS, Srivastava R, Wu S, et al. Intravenous Versus oral antibiotics for postdischarge treatment of complicated pneumonia. Pediatrics. 2016;138(6). https://doi.org/10.1542/peds.2016-1692.
3. Keren R, Shah SS, Srivastava R, et al. Comparative effectiveness of intravenous vs oral antibiotics for postdischarge treatment of acute osteomyelitis in children. JAMA Pediatr. 2015;169(2):120-128. https://doi.org/10.1001/jamapediatrics.2014.2822.
4. Jumani K, Advani S, Reich NG, Gosey L, Milstone AM. Risk factors for peripherally inserted central venous catheter complications in children. JAMA Pediatr. 2013;167(5):429-435.https://doi.org/10.1001/jamapediatrics.2013.775.
5. Zaoutis T, Localio AR, Leckerman K, et al. Prolonged intravenous therapy versus early transition to oral antimicrobial therapy for acute osteomyelitis in children. Pediatrics. 2009;123(2):636-642. https://doi.org/10.1542/peds.2008-0596.
6. McMullan BJ, Andresen D, Blyth CC, et al. Antibiotic duration and timing of the switch from intravenous to oral route for bacterial infections in children: systematic review and guidelines. Lancet Infect Dis. 2016;16(8):e139-e152. https://doi.org/10.1016/S1473-3099(16)30024-X.
7. Bradley JS, Byington CL, Shah SS, et al. The management of community-acquired pneumonia in infants and children older than 3 months of age: clinical practice guidelines by the Pediatric Infectious Diseases Society and the Infectious Diseases Society of America. Clin Infect Dis. 2011;53(7):e25-e76. https://doi.org/10.1093/cid/cir531.
8. Stevens DL, Bisno AL, Chambers HF, et al. Executive summary: practice guidelines for the diagnosis and management of skin and soft tissue infections: 2014 update by the infectious diseases society of America. Clin Infect Dis. 2014;59(2):147-159. https://doi.org/10.1093/cid/ciu444.
9. MacGregor RR, Graziani AL. Oral administration of antibiotics: a rational alternative to the parenteral route. Clin Infect Dis. 1997;24(3):457-467. https://doi.org/10.1093/clinids/24.3.457.
10. Downes KJ, Hahn A, Wiles J, Courter JD, Vinks AA. Dose optimisation of antibiotics in children: application of pharmacokinetics/pharmacodynamics in paediatrics. Int J Antimicrob Agents. 2014;43(3):223-230. https://doi.org/10.1016/j.ijantimicag.2013.11.006.
11. Autmizguine J, Melloni C, Hornik CP, et al. Population pharmacokinetics of trimethoprim-sulfamethoxazole in infants and children. Antimicrob Agents Chemother. 2018;62(1):e01813-e01817. https://doi.org/10.1128/AAC.01813-17.
12. Dewan M, Herrmann LE, Tchou MJ, et al. Development and evaluation of high-value pediatrics: a high-value care pediatric resident curriculum. Hosp Pediatr. 2018;8(12):785-792. https://doi.org/10.1542/hpeds.2018-0115
13. Langley GJ, Moen RD, Nolan KM, Nolan TW, Norman CL, Provost LP. The Improvement Guide: A Practical Approach to Enhancing Organizational Performance. New Jersey, US: John Wiley & Sons; 2009.
14. Benneyan JC. Use and interpretation of statistical quality control charts. Int J Qual Health Care. 1998;10(1):69-73. https://doi.org/10.1093/intqhc/10.1.69.
15. Lorgelly PK, Atkinson M, Lakhanpaul M, et al. Oral versus i.v. antibiotics for community-acquired pneumonia in children: a cost-minimisation analysis. Eur Respir J. 2010;35(4):858-864. https://doi.org/10.1183/09031936.00087209.
16. Vidyarthi AR, Green AL, Rosenbluth G, Baron RB. Engaging residents and fellows to improve institution-wide quality: the first six years of a novel financial incentive program. Acad Med. 2014;89(3):460-468. https://doi.org/10.1097/ACM.0000000000000159.
17. Stinnett-Donnelly JM, Stevens PG, Hood VL. Developing a high value care programme from the bottom up: a programme of faculty-resident improvement projects targeting harmful or unnecessary care. BMJ Qual Saf. 2016;25(11):901-908. https://doi.org/10.1136/bmjqs-2015-004546.
18. Peterson D, McLeod S, Woolfrey K, McRae A. Predictors of failure of empiric outpatient antibiotic therapy in emergency department patients with uncomplicated cellulitis. Acad Emerg Med. 2014;21(5):526-531. https://doi.org/10.1111/acem.12371.
19. Yadav K, Suh KN, Eagles D, et al. Predictors of oral antibiotic treatment failure for non-purulent skin and soft tissue infections in the emergency department. Acad Emerg Med. 2018;20(S1):S24-S25. https://doi.org/10.1017/cem.2018.114.
20. Organisation for Economic Co-operation and Development. Healthcare costs unsustainable in advanced economies without reform. http://www.oecd.org/health/healthcarecostsunsustainableinadvancedeconomieswithoutreform.htm. Accessed June 28, 2018; 2015.
21. Berwick DM, Hackbarth AD. Eliminating waste in US health care. JAMA. 2012;307(14):1513-1516. https://doi.org/10.1001/jama.2012.362.
22. Schondelmeyer AC, Simmons JM, Statile AM, et al. Using quality improvement to reduce continuous pulse oximetry use in children with wheezing. Pediatrics. 2015;135(4):e1044-e1051. https://doi.org/10.1542/peds.2014-2295.
23. Tchou MJ, Tang Girdwood S, Wormser B, et al. Reducing electrolyte testing in hospitalized children by using quality improvement methods. Pediatrics. 2018;141(5). https://doi.org/10.1542/peds.2017-3187.
24. Christensen EW, Spaulding AB, Pomputius WF, Grapentine SP. Effects of hospital practice patterns for antibiotic administration for pneumonia on hospital lengths of stay and costs. J Pediatr Infect Dis Soc. 2019;8(2):115-121. https://doi.org/10.1093/jpids/piy003.
25. Berrevoets MAH, Pot JHLW, Houterman AE, et al. An electronic trigger tool to optimise intravenous to oral antibiotic switch: a controlled, interrupted time series study. Antimicrob Resist Infect Control. 2017;6:81. https://doi.org/10.1186/s13756-017-0239-3.
26. Fischer MA, Solomon DH, Teich JM, Avorn J. Conversion from intravenous to oral medications: assessment of a computerized intervention for hospitalized patients. Arch Intern Med. 2003;163(21):2585-2589. https://doi.org/10.1001/archinte.163.21.2585.
27. Schroeder AR, Harris SJ, Newman TB. Safely doing less: a missing component of the patient safety dialogue. Pediatrics. 2011;128(6):e1596-e1597. https://doi.org/10.1542/peds.2011-2726.
1. Dellit TH, Owens RC, McGowan JE, Jr, et al. Infectious diseases society of America and the society for healthcare epidemiology of America guidelines for developing an institutional program to enhance antimicrobial stewardship. Clin Infect Dis. 2007;44(2):159-177. https://doi.org/10.1086/510393.
2. Shah SS, Srivastava R, Wu S, et al. Intravenous Versus oral antibiotics for postdischarge treatment of complicated pneumonia. Pediatrics. 2016;138(6). https://doi.org/10.1542/peds.2016-1692.
3. Keren R, Shah SS, Srivastava R, et al. Comparative effectiveness of intravenous vs oral antibiotics for postdischarge treatment of acute osteomyelitis in children. JAMA Pediatr. 2015;169(2):120-128. https://doi.org/10.1001/jamapediatrics.2014.2822.
4. Jumani K, Advani S, Reich NG, Gosey L, Milstone AM. Risk factors for peripherally inserted central venous catheter complications in children. JAMA Pediatr. 2013;167(5):429-435.https://doi.org/10.1001/jamapediatrics.2013.775.
5. Zaoutis T, Localio AR, Leckerman K, et al. Prolonged intravenous therapy versus early transition to oral antimicrobial therapy for acute osteomyelitis in children. Pediatrics. 2009;123(2):636-642. https://doi.org/10.1542/peds.2008-0596.
6. McMullan BJ, Andresen D, Blyth CC, et al. Antibiotic duration and timing of the switch from intravenous to oral route for bacterial infections in children: systematic review and guidelines. Lancet Infect Dis. 2016;16(8):e139-e152. https://doi.org/10.1016/S1473-3099(16)30024-X.
7. Bradley JS, Byington CL, Shah SS, et al. The management of community-acquired pneumonia in infants and children older than 3 months of age: clinical practice guidelines by the Pediatric Infectious Diseases Society and the Infectious Diseases Society of America. Clin Infect Dis. 2011;53(7):e25-e76. https://doi.org/10.1093/cid/cir531.
8. Stevens DL, Bisno AL, Chambers HF, et al. Executive summary: practice guidelines for the diagnosis and management of skin and soft tissue infections: 2014 update by the infectious diseases society of America. Clin Infect Dis. 2014;59(2):147-159. https://doi.org/10.1093/cid/ciu444.
9. MacGregor RR, Graziani AL. Oral administration of antibiotics: a rational alternative to the parenteral route. Clin Infect Dis. 1997;24(3):457-467. https://doi.org/10.1093/clinids/24.3.457.
10. Downes KJ, Hahn A, Wiles J, Courter JD, Vinks AA. Dose optimisation of antibiotics in children: application of pharmacokinetics/pharmacodynamics in paediatrics. Int J Antimicrob Agents. 2014;43(3):223-230. https://doi.org/10.1016/j.ijantimicag.2013.11.006.
11. Autmizguine J, Melloni C, Hornik CP, et al. Population pharmacokinetics of trimethoprim-sulfamethoxazole in infants and children. Antimicrob Agents Chemother. 2018;62(1):e01813-e01817. https://doi.org/10.1128/AAC.01813-17.
12. Dewan M, Herrmann LE, Tchou MJ, et al. Development and evaluation of high-value pediatrics: a high-value care pediatric resident curriculum. Hosp Pediatr. 2018;8(12):785-792. https://doi.org/10.1542/hpeds.2018-0115
13. Langley GJ, Moen RD, Nolan KM, Nolan TW, Norman CL, Provost LP. The Improvement Guide: A Practical Approach to Enhancing Organizational Performance. New Jersey, US: John Wiley & Sons; 2009.
14. Benneyan JC. Use and interpretation of statistical quality control charts. Int J Qual Health Care. 1998;10(1):69-73. https://doi.org/10.1093/intqhc/10.1.69.
15. Lorgelly PK, Atkinson M, Lakhanpaul M, et al. Oral versus i.v. antibiotics for community-acquired pneumonia in children: a cost-minimisation analysis. Eur Respir J. 2010;35(4):858-864. https://doi.org/10.1183/09031936.00087209.
16. Vidyarthi AR, Green AL, Rosenbluth G, Baron RB. Engaging residents and fellows to improve institution-wide quality: the first six years of a novel financial incentive program. Acad Med. 2014;89(3):460-468. https://doi.org/10.1097/ACM.0000000000000159.
17. Stinnett-Donnelly JM, Stevens PG, Hood VL. Developing a high value care programme from the bottom up: a programme of faculty-resident improvement projects targeting harmful or unnecessary care. BMJ Qual Saf. 2016;25(11):901-908. https://doi.org/10.1136/bmjqs-2015-004546.
18. Peterson D, McLeod S, Woolfrey K, McRae A. Predictors of failure of empiric outpatient antibiotic therapy in emergency department patients with uncomplicated cellulitis. Acad Emerg Med. 2014;21(5):526-531. https://doi.org/10.1111/acem.12371.
19. Yadav K, Suh KN, Eagles D, et al. Predictors of oral antibiotic treatment failure for non-purulent skin and soft tissue infections in the emergency department. Acad Emerg Med. 2018;20(S1):S24-S25. https://doi.org/10.1017/cem.2018.114.
20. Organisation for Economic Co-operation and Development. Healthcare costs unsustainable in advanced economies without reform. http://www.oecd.org/health/healthcarecostsunsustainableinadvancedeconomieswithoutreform.htm. Accessed June 28, 2018; 2015.
21. Berwick DM, Hackbarth AD. Eliminating waste in US health care. JAMA. 2012;307(14):1513-1516. https://doi.org/10.1001/jama.2012.362.
22. Schondelmeyer AC, Simmons JM, Statile AM, et al. Using quality improvement to reduce continuous pulse oximetry use in children with wheezing. Pediatrics. 2015;135(4):e1044-e1051. https://doi.org/10.1542/peds.2014-2295.
23. Tchou MJ, Tang Girdwood S, Wormser B, et al. Reducing electrolyte testing in hospitalized children by using quality improvement methods. Pediatrics. 2018;141(5). https://doi.org/10.1542/peds.2017-3187.
24. Christensen EW, Spaulding AB, Pomputius WF, Grapentine SP. Effects of hospital practice patterns for antibiotic administration for pneumonia on hospital lengths of stay and costs. J Pediatr Infect Dis Soc. 2019;8(2):115-121. https://doi.org/10.1093/jpids/piy003.
25. Berrevoets MAH, Pot JHLW, Houterman AE, et al. An electronic trigger tool to optimise intravenous to oral antibiotic switch: a controlled, interrupted time series study. Antimicrob Resist Infect Control. 2017;6:81. https://doi.org/10.1186/s13756-017-0239-3.
26. Fischer MA, Solomon DH, Teich JM, Avorn J. Conversion from intravenous to oral medications: assessment of a computerized intervention for hospitalized patients. Arch Intern Med. 2003;163(21):2585-2589. https://doi.org/10.1001/archinte.163.21.2585.
27. Schroeder AR, Harris SJ, Newman TB. Safely doing less: a missing component of the patient safety dialogue. Pediatrics. 2011;128(6):e1596-e1597. https://doi.org/10.1542/peds.2011-2726.
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