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Things We Do for No Reason – The “48 Hour Rule-out” for Well-Appearing Febrile Infants
The “Things We Do for No Reason” (TWDFNR) series reviews practices that have become common parts of hospital care but may provide little value to our patients. Practices reviewed in the TWDFNR series do not represent “black and white” conclusions or clinical practice standards but are meant as a starting place for research and active discussions among hospitalists and patients. We invite you to be part of that discussion. https://www.choosingwisely.org/
CASE PRESENTATION
A 3-week-old, full-term term male febrile infant was evaluated in the emergency department (ED). On the day of admission, he was noted to feel warm to the touch and was found to have a rectal temperature of 101.3°F (38.3°C) at home.
In the ED, the patient was well appearing and had normal physical exam findings. His workup in the ED included a normal chest radiograph, complete blood count (CBC) with differential count, cerebrospinal fluid (CSF) analysis (cell count, protein, and glucose), and urinalysis. Blood, CSF, and catheterized urine cultures were collected, and he was admitted to the hospital on parenteral antibiotics. His provider informed the parents that the infant would be observed in the hospital for 48 hours while monitoring the bacterial cultures. Is it necessary for the hospitalization of this child to last a full 48 hours?
INTRODUCTION
Evaluation and management of fever (T ≥ 38°C) is a common cause of emergency department visits and accounts for up to 20% of pediatric emergency visits.2
Why You Might Think Hospitalization for at Least 48 Hours is Necessary
The evaluation and management of fever in infants aged less than 90 days is challenging due to concern for occult serious bacterial infections. In particular, providers may be concerned that the physical exam lacks sensitivity.9
There is also a perceived risk of poor outcomes in young infants if a serious bacterial infection is missed. For these reasons, the evaluation and management of febrile infants has been characterized by practice variability in both outpatient10 and ED3 settings.
Commonly used febrile infant management protocols vary in approach and do not provide clear guidelines on the recommended duration of hospitalization and empiric antimicrobial treatment.11-14 Length of hospitalization was widely studied in infants between 1979 and 1999, and results showed that the majority of clinically important bacterial pathogens can be detected within 48 hours.15-17 Many textbooks and online references, based on this literature, continue to support 48 to 72 hours of observation and empiric antimicrobial treatment for febrile infants.18,19 A 2012 AAP Clinical Report advocated for limiting the antimicrobial treatment in low-risk infants suspected of early-onset sepsis to 48 hours.20
Why Shorten the Period of In-Hospital Observation to a Maximum of 36 Hours of Culture Incubation
Discharge of low-risk infants with negative enhanced urinalysis and negative bacterial cultures at 36 hours or earlier can reduce costs21 and potentially preventable harm (eg, intravenous catheter complications, nosocomial infections) without negatively impacting patient outcomes.22 Early discharge is also patient-centered, given the stress and indirect costs associated with hospitalization, including potential separation of a breastfeeding infant and mother, lost wages from time off work, or childcare for well siblings.23
Initial studies that evaluated the time-to-positivity (TTP) of bacterial cultures in febrile infants predate the use of continuous monitoring systems for blood cultures. Traditional bacterial culturing techniques require direct observation of broth turbidity and subsequent subculturing onto chocolate and sheep blood agar, typically occurring only once daily.24 Current commercially available continuous monitoring bacterial culture systems decrease TTP by immediately alerting laboratory technicians to bacterial growth through the detection of 14CO2 released by organisms utilizing radiolabeled glucose in growth media.24 In addition, many studies supporting the evaluation of febrile infants in the hospital for a 48-hour period include those in ICU settings,25 with medically complex histories,24 and aged < 28 days admitted in the NICU,15 where pathogens with longer incubation times are frequently seen.
In a recent single-center retrospective study, infant blood cultures with TTP longer than 36 hours are 7.8 times more likely to be identified as contaminant bacteria compared with cultures that tested positive in <36 hours.26 Even if bacterial cultures were unexpectedly positive after 36 hours, which occurs in less than 1.1% of all infants and 0.3% of low-risk infants,1 these patients do not have adverse outcomes. Infants who were deemed low risk based on established criteria and who had bacterial cultures positive for pathogenic bacteria were treated at that time and recovered uneventfully.7, 31
CSF and urine cultures are often reviewed only once or twice daily in most institutions, and this practice artificially prolongs the TTP for pathogenic bacteria. Small sample-sized studies have demonstrated the low detection rate of pathogens in CSF and urine cultures beyond 36 hours. Evans et al. found that in infants aged 0-28 days, 0.03% of urine cultures and no CSF cultures tested positive after 36 hours.26 In a retrospective study of infants aged 28-90 days in the ED setting, Kaplan et al. found that 0.9% of urine cultures and no CSF cultures were positive at >24 hours.1 For well-appearing infants who have reassuring initial CSF studies, the risk of meningitis is extremely low.7 Management criteria for febrile infants provide guidance for determining those infants with abnormal CSF results who may benefit from longer periods of observation.
Urinary tract infections are common serious bacterial infections in this age group. Enhanced urinalysis, in which cell count and Gram stain analysis are performed on uncentrifuged urine, shows 96% sensitivity of predicting urinary tract infection and can provide additional reassurance for well-appearing infants who are discharged prior to 48 hours.27
When a Longer Observation Period May Be Warranted
What You Should Do Instead: Limit Hospitalization to a Maximum of 36 Hours
For well-appearing febrile infants between 0–90 days of age hospitalized for observation and awaiting bacterial culture results, providers should consider discharge at 36 hours or less, rather than 48 hours, if blood, urine, and CSF cultures do not show bacterial growth. In a large health system, researchers implemented an evidence-based care process model for febrile infants to provide specific guidelines for laboratory testing, criteria for admission, and recommendation for discontinuation of empiric antibiotics and discharge after 36 hours in infants with negative bacterial cultures. These changes led to a 27% reduction in the length of hospital stay and 23% reduction in inpatient costs without any cases of missed bacteremia.21 The reduction in the in-hospital observation duration to 24 hours of culture incubation for well-appearing febrile infants has been advocated 32 and is a common practice for infants with appropriate follow up and parental assurance. This recommendation is supported by the following:
- Recent data showing the overwhelming majority of pathogens will be identified by blood culture <24 hours in infants aged 0-90 days32 with blood culture TTP in infants aged 0-30 days being either no different26 or potentially shorter32
- Studies showing that infants meeting low-risk clinical and laboratory profiles further reduce the likelihood of identifying serious bacterial infection after 24 hours to 0.3%.1
RECOMMENDATIONS
- Determine if febrile infants aged 0-90 days are at low risk for serious bacterial infection and obtain appropriate bacterial cultures.
- If hospitalized for observation, discharge low-risk febrile infants aged 0–90 days after 36 hours or less if bacterial cultures remain negative.
- If hospitalized for observation, consider reducing the length of inpatient observation for low-risk febrile infants aged 0–90 days with reliable follow-up to 24 hours or less when the culture results are negative.
CONCLUSION
Monitoring patients in the hospital for greater than 36 hours of bacterial culture incubation is unnecessary for patients similar to the 3 week-old full-term infant in the case presentation, who are at low risk for serious bacterial infection based on available scoring systems and have negative cultures. If patients are not deemed low risk, have an incomplete laboratory evaluation, or have had prior antibiotic treatment, longer observation in the hospital may be warranted. Close reassessment of the rare patients whose blood cultures return positive after 36 hours is necessary, but their outcomes are excellent, especially in well-appearing infants.7,33
What do you do?
Do you think this is a low-value practice? Is this truly a “Thing We Do for No Reason”? Let us know what you do in your practice and propose ideas for other “Things We Do for No Reason” topics. Please join in the conversation online at Twitter (#TWDFNR)/Facebook and don’t forget to “Like It” on Facebook or retweet it on Twitter. We invite you to propose ideas for other “Things We Do for No Reason” topics by emailingTWDFNR@hospitalmedicine.org.
Disclosures
There are no conflicts of interest relevant to this work reported by any of the authors.
1. Kaplan RL, Harper MB, Baskin MN, Macone AB, Mandl KD. Time to detection of positive cultures in 28- to 90-day-old febrile infants. Pediatrics 2000;106(6):E74. PubMed
2. Fleisher GR, Ludwig S, Henretig FM. Textbook of Pediatric Emergency Medicine: Lippincott Williams & Wilkins; 2006.
3. Aronson PL, Thurm C, Williams DJ, et al. Association of clinical practice guidelines with emergency department management of febrile infants </=56 days of age. J Hosp Med. 2015;10(6):358-365. PubMed
4. Hui C, Neto G, Tsertsvadze A, et al. Diagnosis and management of febrile infants (0-3 months). Evid Rep Technol Assess. 2012;205:1-297. PubMed
5. Garcia S, Mintegi S, Gomez B, et al. Is 15 days an appropriate cut-off age for considering serious bacterial infection in the management of febrile infants? Pediatr Infect Dis J. 2012;31(5):455-458. PubMed
6. Schwartz S, Raveh D, Toker O, Segal G, Godovitch N, Schlesinger Y. A week-by-week analysis of the low-risk criteria for serious bacterial infection in febrile neonates. Arch Dis Child. 2009;94(4):287-292. PubMed
7. Huppler AR, Eickhoff JC, Wald ER. Performance of low-risk criteria in the evaluation of young infants with fever: review of the literature. Pediatrics 2010;125(2):228-233. PubMed
8. Baskin MN. The prevalence of serious bacterial infections by age in febrile infants during the first 3 months of life. Pediatr Ann. 1993;22(8):462-466. PubMed
9. Nigrovic LE, Mahajan PV, Blumberg SM, et al. The Yale Observation Scale Score and the risk of serious bacterial infections in febrile infants. Pediatrics 2017;140(1):e20170695. PubMed
10. Bergman DA, Mayer ML, Pantell RH, Finch SA, Wasserman RC. Does clinical presentation explain practice variability in the treatment of febrile infants? Pediatrics 2006;117(3):787-795. PubMed
11. Baker MD, Bell LM, Avner JR. Outpatient management without antibiotics of fever in selected infants. N Engl J Med. 1993;329(20):1437-1441. PubMed
12. Jaskiewicz JA, McCarthy CA, Richardson AC, et al. Febrile infants at low risk for serious bacterial infection--an appraisal of the Rochester criteria and implications for management. Febrile Infant Collaborative Study Group. Pediatrics 1994;94(3):390-396. PubMed
13. Baskin MN, O’Rourke EJ, Fleisher GR. Outpatient treatment of febrile infants 28 to 89 days of age with intramuscular administration of ceftriaxone. J Pediatr. 1992;120(1):22-27. PubMed
14. Bachur RG, Harper MB. Predictive model for serious bacterial infections among infants younger than 3 months of age. Pediatrics 2001;108(2):311-316. PubMed
15. Pichichero ME, Todd JK. Detection of neonatal bacteremia. J Pediatr. 1979;94(6):958-960. PubMed
16. Hurst MK, Yoder BA. Detection of bacteremia in young infants: is 48 hours adequate? Pediatr Infect Dis J. 1995;14(8):711-713. PubMed
17. Friedman J, Matlow A. Time to identification of positive bacterial cultures in infants under three months of age hospitalized to rule out sepsis. Paediatr Child Health 1999;4(5):331-334. PubMed
18. Kliegman R, Behrman RE, Nelson WE. Nelson textbook of pediatrics. Edition 20 / ed. Philadelphia, PA: Elsevier; 2016.
19. Fever in infants and children. Merck Sharp & Dohme Corp, 2016. (Accessed 27 Nov 2016, 2016, at https://www.merckmanuals.com/professional/pediatrics/symptoms-in-infants-and-children/fever-in-infants-and-children.)
20. Polin RA, Committee on F, Newborn. Management of neonates with suspected or proven early-onset bacterial sepsis. Pediatrics 2012;129(5):1006-1015. PubMed
21. 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. PubMed
22. DeAngelis C, Joffe A, Wilson M, Willis E. Iatrogenic risks and financial costs of hospitalizing febrile infants. Am J Dis Child. 1983;137(12):1146-1149. PubMed
23. Nizam M, Norzila MZ. Stress among parents with acutely ill children. Med J Malaysia. 2001;56(4):428-434. PubMed
24. Rowley AH, Wald ER. The incubation period necessary for detection of bacteremia in immunocompetent children with fever. Implications for the clinician. Clin Pediatr (Phila). 1986;25(10):485-489. PubMed
25. La Scolea LJ, Jr., Dryja D, Sullivan TD, Mosovich L, Ellerstein N, Neter E. Diagnosis of bacteremia in children by quantitative direct plating and a radiometric procedure. J Clin Microbiol. 1981;13(3):478-482. PubMed
26. Evans RC, Fine BR. Time to detection of bacterial cultures in infants aged 0 to 90 days. Hosp Pediatr. 2013;3(2):97-102. PubMed
27. Herr SM, Wald ER, Pitetti RD, Choi SS. Enhanced urinalysis improves identification of febrile infants ages 60 days and younger at low risk for serious bacterial illness. Pediatrics 2001;108(4):866-871. PubMed
28. Nigrovic LE, Kuppermann N, Macias CG, et al. Clinical prediction rule for identifying children with cerebrospinal fluid pleocytosis at very low risk of bacterial meningitis. JAMA. 2007;297(1):52-60. PubMed
29. Doby EH, Stockmann C, Korgenski EK, Blaschke AJ, Byington CL. Cerebrospinal fluid pleocytosis in febrile infants 1-90 days with urinary tract infection. Pediatr Infect Dis J. 2013;32(9):1024-1026. PubMed
30. Bhansali P, Wiedermann BL, Pastor W, McMillan J, Shah N. Management of hospitalized febrile neonates without CSF analysis: A study of US pediatric hospitals. Hosp Pediatr. 2015;5(10):528-533. PubMed
31. Kanegaye JT, Soliemanzadeh P, Bradley JS. Lumbar puncture in pediatric bacterial meningitis: defining the time interval for recovery of cerebrospinal fluid pathogens after parenteral antibiotic pretreatment. Pediatrics 2001;108(5):1169-1174. PubMed
32. Biondi EA, Mischler M, Jerardi KE, et al. Blood culture time to positivity in febrile infants with bacteremia. JAMA Pediatr. 2014;168(9):844-849. PubMed
33. Moher D HC, Neto G, Tsertsvadze A. Diagnosis and Management of Febrile Infants (0–3 Months). Evidence Report/Technology Assessment No. 205. In: Center OE-bP, ed. Rockville, MD: Agency for Healthcare Research and Quality; 2012. PubMed
The “Things We Do for No Reason” (TWDFNR) series reviews practices that have become common parts of hospital care but may provide little value to our patients. Practices reviewed in the TWDFNR series do not represent “black and white” conclusions or clinical practice standards but are meant as a starting place for research and active discussions among hospitalists and patients. We invite you to be part of that discussion. https://www.choosingwisely.org/
CASE PRESENTATION
A 3-week-old, full-term term male febrile infant was evaluated in the emergency department (ED). On the day of admission, he was noted to feel warm to the touch and was found to have a rectal temperature of 101.3°F (38.3°C) at home.
In the ED, the patient was well appearing and had normal physical exam findings. His workup in the ED included a normal chest radiograph, complete blood count (CBC) with differential count, cerebrospinal fluid (CSF) analysis (cell count, protein, and glucose), and urinalysis. Blood, CSF, and catheterized urine cultures were collected, and he was admitted to the hospital on parenteral antibiotics. His provider informed the parents that the infant would be observed in the hospital for 48 hours while monitoring the bacterial cultures. Is it necessary for the hospitalization of this child to last a full 48 hours?
INTRODUCTION
Evaluation and management of fever (T ≥ 38°C) is a common cause of emergency department visits and accounts for up to 20% of pediatric emergency visits.2
Why You Might Think Hospitalization for at Least 48 Hours is Necessary
The evaluation and management of fever in infants aged less than 90 days is challenging due to concern for occult serious bacterial infections. In particular, providers may be concerned that the physical exam lacks sensitivity.9
There is also a perceived risk of poor outcomes in young infants if a serious bacterial infection is missed. For these reasons, the evaluation and management of febrile infants has been characterized by practice variability in both outpatient10 and ED3 settings.
Commonly used febrile infant management protocols vary in approach and do not provide clear guidelines on the recommended duration of hospitalization and empiric antimicrobial treatment.11-14 Length of hospitalization was widely studied in infants between 1979 and 1999, and results showed that the majority of clinically important bacterial pathogens can be detected within 48 hours.15-17 Many textbooks and online references, based on this literature, continue to support 48 to 72 hours of observation and empiric antimicrobial treatment for febrile infants.18,19 A 2012 AAP Clinical Report advocated for limiting the antimicrobial treatment in low-risk infants suspected of early-onset sepsis to 48 hours.20
Why Shorten the Period of In-Hospital Observation to a Maximum of 36 Hours of Culture Incubation
Discharge of low-risk infants with negative enhanced urinalysis and negative bacterial cultures at 36 hours or earlier can reduce costs21 and potentially preventable harm (eg, intravenous catheter complications, nosocomial infections) without negatively impacting patient outcomes.22 Early discharge is also patient-centered, given the stress and indirect costs associated with hospitalization, including potential separation of a breastfeeding infant and mother, lost wages from time off work, or childcare for well siblings.23
Initial studies that evaluated the time-to-positivity (TTP) of bacterial cultures in febrile infants predate the use of continuous monitoring systems for blood cultures. Traditional bacterial culturing techniques require direct observation of broth turbidity and subsequent subculturing onto chocolate and sheep blood agar, typically occurring only once daily.24 Current commercially available continuous monitoring bacterial culture systems decrease TTP by immediately alerting laboratory technicians to bacterial growth through the detection of 14CO2 released by organisms utilizing radiolabeled glucose in growth media.24 In addition, many studies supporting the evaluation of febrile infants in the hospital for a 48-hour period include those in ICU settings,25 with medically complex histories,24 and aged < 28 days admitted in the NICU,15 where pathogens with longer incubation times are frequently seen.
In a recent single-center retrospective study, infant blood cultures with TTP longer than 36 hours are 7.8 times more likely to be identified as contaminant bacteria compared with cultures that tested positive in <36 hours.26 Even if bacterial cultures were unexpectedly positive after 36 hours, which occurs in less than 1.1% of all infants and 0.3% of low-risk infants,1 these patients do not have adverse outcomes. Infants who were deemed low risk based on established criteria and who had bacterial cultures positive for pathogenic bacteria were treated at that time and recovered uneventfully.7, 31
CSF and urine cultures are often reviewed only once or twice daily in most institutions, and this practice artificially prolongs the TTP for pathogenic bacteria. Small sample-sized studies have demonstrated the low detection rate of pathogens in CSF and urine cultures beyond 36 hours. Evans et al. found that in infants aged 0-28 days, 0.03% of urine cultures and no CSF cultures tested positive after 36 hours.26 In a retrospective study of infants aged 28-90 days in the ED setting, Kaplan et al. found that 0.9% of urine cultures and no CSF cultures were positive at >24 hours.1 For well-appearing infants who have reassuring initial CSF studies, the risk of meningitis is extremely low.7 Management criteria for febrile infants provide guidance for determining those infants with abnormal CSF results who may benefit from longer periods of observation.
Urinary tract infections are common serious bacterial infections in this age group. Enhanced urinalysis, in which cell count and Gram stain analysis are performed on uncentrifuged urine, shows 96% sensitivity of predicting urinary tract infection and can provide additional reassurance for well-appearing infants who are discharged prior to 48 hours.27
When a Longer Observation Period May Be Warranted
What You Should Do Instead: Limit Hospitalization to a Maximum of 36 Hours
For well-appearing febrile infants between 0–90 days of age hospitalized for observation and awaiting bacterial culture results, providers should consider discharge at 36 hours or less, rather than 48 hours, if blood, urine, and CSF cultures do not show bacterial growth. In a large health system, researchers implemented an evidence-based care process model for febrile infants to provide specific guidelines for laboratory testing, criteria for admission, and recommendation for discontinuation of empiric antibiotics and discharge after 36 hours in infants with negative bacterial cultures. These changes led to a 27% reduction in the length of hospital stay and 23% reduction in inpatient costs without any cases of missed bacteremia.21 The reduction in the in-hospital observation duration to 24 hours of culture incubation for well-appearing febrile infants has been advocated 32 and is a common practice for infants with appropriate follow up and parental assurance. This recommendation is supported by the following:
- Recent data showing the overwhelming majority of pathogens will be identified by blood culture <24 hours in infants aged 0-90 days32 with blood culture TTP in infants aged 0-30 days being either no different26 or potentially shorter32
- Studies showing that infants meeting low-risk clinical and laboratory profiles further reduce the likelihood of identifying serious bacterial infection after 24 hours to 0.3%.1
RECOMMENDATIONS
- Determine if febrile infants aged 0-90 days are at low risk for serious bacterial infection and obtain appropriate bacterial cultures.
- If hospitalized for observation, discharge low-risk febrile infants aged 0–90 days after 36 hours or less if bacterial cultures remain negative.
- If hospitalized for observation, consider reducing the length of inpatient observation for low-risk febrile infants aged 0–90 days with reliable follow-up to 24 hours or less when the culture results are negative.
CONCLUSION
Monitoring patients in the hospital for greater than 36 hours of bacterial culture incubation is unnecessary for patients similar to the 3 week-old full-term infant in the case presentation, who are at low risk for serious bacterial infection based on available scoring systems and have negative cultures. If patients are not deemed low risk, have an incomplete laboratory evaluation, or have had prior antibiotic treatment, longer observation in the hospital may be warranted. Close reassessment of the rare patients whose blood cultures return positive after 36 hours is necessary, but their outcomes are excellent, especially in well-appearing infants.7,33
What do you do?
Do you think this is a low-value practice? Is this truly a “Thing We Do for No Reason”? Let us know what you do in your practice and propose ideas for other “Things We Do for No Reason” topics. Please join in the conversation online at Twitter (#TWDFNR)/Facebook and don’t forget to “Like It” on Facebook or retweet it on Twitter. We invite you to propose ideas for other “Things We Do for No Reason” topics by emailingTWDFNR@hospitalmedicine.org.
Disclosures
There are no conflicts of interest relevant to this work reported by any of the authors.
The “Things We Do for No Reason” (TWDFNR) series reviews practices that have become common parts of hospital care but may provide little value to our patients. Practices reviewed in the TWDFNR series do not represent “black and white” conclusions or clinical practice standards but are meant as a starting place for research and active discussions among hospitalists and patients. We invite you to be part of that discussion. https://www.choosingwisely.org/
CASE PRESENTATION
A 3-week-old, full-term term male febrile infant was evaluated in the emergency department (ED). On the day of admission, he was noted to feel warm to the touch and was found to have a rectal temperature of 101.3°F (38.3°C) at home.
In the ED, the patient was well appearing and had normal physical exam findings. His workup in the ED included a normal chest radiograph, complete blood count (CBC) with differential count, cerebrospinal fluid (CSF) analysis (cell count, protein, and glucose), and urinalysis. Blood, CSF, and catheterized urine cultures were collected, and he was admitted to the hospital on parenteral antibiotics. His provider informed the parents that the infant would be observed in the hospital for 48 hours while monitoring the bacterial cultures. Is it necessary for the hospitalization of this child to last a full 48 hours?
INTRODUCTION
Evaluation and management of fever (T ≥ 38°C) is a common cause of emergency department visits and accounts for up to 20% of pediatric emergency visits.2
Why You Might Think Hospitalization for at Least 48 Hours is Necessary
The evaluation and management of fever in infants aged less than 90 days is challenging due to concern for occult serious bacterial infections. In particular, providers may be concerned that the physical exam lacks sensitivity.9
There is also a perceived risk of poor outcomes in young infants if a serious bacterial infection is missed. For these reasons, the evaluation and management of febrile infants has been characterized by practice variability in both outpatient10 and ED3 settings.
Commonly used febrile infant management protocols vary in approach and do not provide clear guidelines on the recommended duration of hospitalization and empiric antimicrobial treatment.11-14 Length of hospitalization was widely studied in infants between 1979 and 1999, and results showed that the majority of clinically important bacterial pathogens can be detected within 48 hours.15-17 Many textbooks and online references, based on this literature, continue to support 48 to 72 hours of observation and empiric antimicrobial treatment for febrile infants.18,19 A 2012 AAP Clinical Report advocated for limiting the antimicrobial treatment in low-risk infants suspected of early-onset sepsis to 48 hours.20
Why Shorten the Period of In-Hospital Observation to a Maximum of 36 Hours of Culture Incubation
Discharge of low-risk infants with negative enhanced urinalysis and negative bacterial cultures at 36 hours or earlier can reduce costs21 and potentially preventable harm (eg, intravenous catheter complications, nosocomial infections) without negatively impacting patient outcomes.22 Early discharge is also patient-centered, given the stress and indirect costs associated with hospitalization, including potential separation of a breastfeeding infant and mother, lost wages from time off work, or childcare for well siblings.23
Initial studies that evaluated the time-to-positivity (TTP) of bacterial cultures in febrile infants predate the use of continuous monitoring systems for blood cultures. Traditional bacterial culturing techniques require direct observation of broth turbidity and subsequent subculturing onto chocolate and sheep blood agar, typically occurring only once daily.24 Current commercially available continuous monitoring bacterial culture systems decrease TTP by immediately alerting laboratory technicians to bacterial growth through the detection of 14CO2 released by organisms utilizing radiolabeled glucose in growth media.24 In addition, many studies supporting the evaluation of febrile infants in the hospital for a 48-hour period include those in ICU settings,25 with medically complex histories,24 and aged < 28 days admitted in the NICU,15 where pathogens with longer incubation times are frequently seen.
In a recent single-center retrospective study, infant blood cultures with TTP longer than 36 hours are 7.8 times more likely to be identified as contaminant bacteria compared with cultures that tested positive in <36 hours.26 Even if bacterial cultures were unexpectedly positive after 36 hours, which occurs in less than 1.1% of all infants and 0.3% of low-risk infants,1 these patients do not have adverse outcomes. Infants who were deemed low risk based on established criteria and who had bacterial cultures positive for pathogenic bacteria were treated at that time and recovered uneventfully.7, 31
CSF and urine cultures are often reviewed only once or twice daily in most institutions, and this practice artificially prolongs the TTP for pathogenic bacteria. Small sample-sized studies have demonstrated the low detection rate of pathogens in CSF and urine cultures beyond 36 hours. Evans et al. found that in infants aged 0-28 days, 0.03% of urine cultures and no CSF cultures tested positive after 36 hours.26 In a retrospective study of infants aged 28-90 days in the ED setting, Kaplan et al. found that 0.9% of urine cultures and no CSF cultures were positive at >24 hours.1 For well-appearing infants who have reassuring initial CSF studies, the risk of meningitis is extremely low.7 Management criteria for febrile infants provide guidance for determining those infants with abnormal CSF results who may benefit from longer periods of observation.
Urinary tract infections are common serious bacterial infections in this age group. Enhanced urinalysis, in which cell count and Gram stain analysis are performed on uncentrifuged urine, shows 96% sensitivity of predicting urinary tract infection and can provide additional reassurance for well-appearing infants who are discharged prior to 48 hours.27
When a Longer Observation Period May Be Warranted
What You Should Do Instead: Limit Hospitalization to a Maximum of 36 Hours
For well-appearing febrile infants between 0–90 days of age hospitalized for observation and awaiting bacterial culture results, providers should consider discharge at 36 hours or less, rather than 48 hours, if blood, urine, and CSF cultures do not show bacterial growth. In a large health system, researchers implemented an evidence-based care process model for febrile infants to provide specific guidelines for laboratory testing, criteria for admission, and recommendation for discontinuation of empiric antibiotics and discharge after 36 hours in infants with negative bacterial cultures. These changes led to a 27% reduction in the length of hospital stay and 23% reduction in inpatient costs without any cases of missed bacteremia.21 The reduction in the in-hospital observation duration to 24 hours of culture incubation for well-appearing febrile infants has been advocated 32 and is a common practice for infants with appropriate follow up and parental assurance. This recommendation is supported by the following:
- Recent data showing the overwhelming majority of pathogens will be identified by blood culture <24 hours in infants aged 0-90 days32 with blood culture TTP in infants aged 0-30 days being either no different26 or potentially shorter32
- Studies showing that infants meeting low-risk clinical and laboratory profiles further reduce the likelihood of identifying serious bacterial infection after 24 hours to 0.3%.1
RECOMMENDATIONS
- Determine if febrile infants aged 0-90 days are at low risk for serious bacterial infection and obtain appropriate bacterial cultures.
- If hospitalized for observation, discharge low-risk febrile infants aged 0–90 days after 36 hours or less if bacterial cultures remain negative.
- If hospitalized for observation, consider reducing the length of inpatient observation for low-risk febrile infants aged 0–90 days with reliable follow-up to 24 hours or less when the culture results are negative.
CONCLUSION
Monitoring patients in the hospital for greater than 36 hours of bacterial culture incubation is unnecessary for patients similar to the 3 week-old full-term infant in the case presentation, who are at low risk for serious bacterial infection based on available scoring systems and have negative cultures. If patients are not deemed low risk, have an incomplete laboratory evaluation, or have had prior antibiotic treatment, longer observation in the hospital may be warranted. Close reassessment of the rare patients whose blood cultures return positive after 36 hours is necessary, but their outcomes are excellent, especially in well-appearing infants.7,33
What do you do?
Do you think this is a low-value practice? Is this truly a “Thing We Do for No Reason”? Let us know what you do in your practice and propose ideas for other “Things We Do for No Reason” topics. Please join in the conversation online at Twitter (#TWDFNR)/Facebook and don’t forget to “Like It” on Facebook or retweet it on Twitter. We invite you to propose ideas for other “Things We Do for No Reason” topics by emailingTWDFNR@hospitalmedicine.org.
Disclosures
There are no conflicts of interest relevant to this work reported by any of the authors.
1. Kaplan RL, Harper MB, Baskin MN, Macone AB, Mandl KD. Time to detection of positive cultures in 28- to 90-day-old febrile infants. Pediatrics 2000;106(6):E74. PubMed
2. Fleisher GR, Ludwig S, Henretig FM. Textbook of Pediatric Emergency Medicine: Lippincott Williams & Wilkins; 2006.
3. Aronson PL, Thurm C, Williams DJ, et al. Association of clinical practice guidelines with emergency department management of febrile infants </=56 days of age. J Hosp Med. 2015;10(6):358-365. PubMed
4. Hui C, Neto G, Tsertsvadze A, et al. Diagnosis and management of febrile infants (0-3 months). Evid Rep Technol Assess. 2012;205:1-297. PubMed
5. Garcia S, Mintegi S, Gomez B, et al. Is 15 days an appropriate cut-off age for considering serious bacterial infection in the management of febrile infants? Pediatr Infect Dis J. 2012;31(5):455-458. PubMed
6. Schwartz S, Raveh D, Toker O, Segal G, Godovitch N, Schlesinger Y. A week-by-week analysis of the low-risk criteria for serious bacterial infection in febrile neonates. Arch Dis Child. 2009;94(4):287-292. PubMed
7. Huppler AR, Eickhoff JC, Wald ER. Performance of low-risk criteria in the evaluation of young infants with fever: review of the literature. Pediatrics 2010;125(2):228-233. PubMed
8. Baskin MN. The prevalence of serious bacterial infections by age in febrile infants during the first 3 months of life. Pediatr Ann. 1993;22(8):462-466. PubMed
9. Nigrovic LE, Mahajan PV, Blumberg SM, et al. The Yale Observation Scale Score and the risk of serious bacterial infections in febrile infants. Pediatrics 2017;140(1):e20170695. PubMed
10. Bergman DA, Mayer ML, Pantell RH, Finch SA, Wasserman RC. Does clinical presentation explain practice variability in the treatment of febrile infants? Pediatrics 2006;117(3):787-795. PubMed
11. Baker MD, Bell LM, Avner JR. Outpatient management without antibiotics of fever in selected infants. N Engl J Med. 1993;329(20):1437-1441. PubMed
12. Jaskiewicz JA, McCarthy CA, Richardson AC, et al. Febrile infants at low risk for serious bacterial infection--an appraisal of the Rochester criteria and implications for management. Febrile Infant Collaborative Study Group. Pediatrics 1994;94(3):390-396. PubMed
13. Baskin MN, O’Rourke EJ, Fleisher GR. Outpatient treatment of febrile infants 28 to 89 days of age with intramuscular administration of ceftriaxone. J Pediatr. 1992;120(1):22-27. PubMed
14. Bachur RG, Harper MB. Predictive model for serious bacterial infections among infants younger than 3 months of age. Pediatrics 2001;108(2):311-316. PubMed
15. Pichichero ME, Todd JK. Detection of neonatal bacteremia. J Pediatr. 1979;94(6):958-960. PubMed
16. Hurst MK, Yoder BA. Detection of bacteremia in young infants: is 48 hours adequate? Pediatr Infect Dis J. 1995;14(8):711-713. PubMed
17. Friedman J, Matlow A. Time to identification of positive bacterial cultures in infants under three months of age hospitalized to rule out sepsis. Paediatr Child Health 1999;4(5):331-334. PubMed
18. Kliegman R, Behrman RE, Nelson WE. Nelson textbook of pediatrics. Edition 20 / ed. Philadelphia, PA: Elsevier; 2016.
19. Fever in infants and children. Merck Sharp & Dohme Corp, 2016. (Accessed 27 Nov 2016, 2016, at https://www.merckmanuals.com/professional/pediatrics/symptoms-in-infants-and-children/fever-in-infants-and-children.)
20. Polin RA, Committee on F, Newborn. Management of neonates with suspected or proven early-onset bacterial sepsis. Pediatrics 2012;129(5):1006-1015. PubMed
21. 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. PubMed
22. DeAngelis C, Joffe A, Wilson M, Willis E. Iatrogenic risks and financial costs of hospitalizing febrile infants. Am J Dis Child. 1983;137(12):1146-1149. PubMed
23. Nizam M, Norzila MZ. Stress among parents with acutely ill children. Med J Malaysia. 2001;56(4):428-434. PubMed
24. Rowley AH, Wald ER. The incubation period necessary for detection of bacteremia in immunocompetent children with fever. Implications for the clinician. Clin Pediatr (Phila). 1986;25(10):485-489. PubMed
25. La Scolea LJ, Jr., Dryja D, Sullivan TD, Mosovich L, Ellerstein N, Neter E. Diagnosis of bacteremia in children by quantitative direct plating and a radiometric procedure. J Clin Microbiol. 1981;13(3):478-482. PubMed
26. Evans RC, Fine BR. Time to detection of bacterial cultures in infants aged 0 to 90 days. Hosp Pediatr. 2013;3(2):97-102. PubMed
27. Herr SM, Wald ER, Pitetti RD, Choi SS. Enhanced urinalysis improves identification of febrile infants ages 60 days and younger at low risk for serious bacterial illness. Pediatrics 2001;108(4):866-871. PubMed
28. Nigrovic LE, Kuppermann N, Macias CG, et al. Clinical prediction rule for identifying children with cerebrospinal fluid pleocytosis at very low risk of bacterial meningitis. JAMA. 2007;297(1):52-60. PubMed
29. Doby EH, Stockmann C, Korgenski EK, Blaschke AJ, Byington CL. Cerebrospinal fluid pleocytosis in febrile infants 1-90 days with urinary tract infection. Pediatr Infect Dis J. 2013;32(9):1024-1026. PubMed
30. Bhansali P, Wiedermann BL, Pastor W, McMillan J, Shah N. Management of hospitalized febrile neonates without CSF analysis: A study of US pediatric hospitals. Hosp Pediatr. 2015;5(10):528-533. PubMed
31. Kanegaye JT, Soliemanzadeh P, Bradley JS. Lumbar puncture in pediatric bacterial meningitis: defining the time interval for recovery of cerebrospinal fluid pathogens after parenteral antibiotic pretreatment. Pediatrics 2001;108(5):1169-1174. PubMed
32. Biondi EA, Mischler M, Jerardi KE, et al. Blood culture time to positivity in febrile infants with bacteremia. JAMA Pediatr. 2014;168(9):844-849. PubMed
33. Moher D HC, Neto G, Tsertsvadze A. Diagnosis and Management of Febrile Infants (0–3 Months). Evidence Report/Technology Assessment No. 205. In: Center OE-bP, ed. Rockville, MD: Agency for Healthcare Research and Quality; 2012. PubMed
1. Kaplan RL, Harper MB, Baskin MN, Macone AB, Mandl KD. Time to detection of positive cultures in 28- to 90-day-old febrile infants. Pediatrics 2000;106(6):E74. PubMed
2. Fleisher GR, Ludwig S, Henretig FM. Textbook of Pediatric Emergency Medicine: Lippincott Williams & Wilkins; 2006.
3. Aronson PL, Thurm C, Williams DJ, et al. Association of clinical practice guidelines with emergency department management of febrile infants </=56 days of age. J Hosp Med. 2015;10(6):358-365. PubMed
4. Hui C, Neto G, Tsertsvadze A, et al. Diagnosis and management of febrile infants (0-3 months). Evid Rep Technol Assess. 2012;205:1-297. PubMed
5. Garcia S, Mintegi S, Gomez B, et al. Is 15 days an appropriate cut-off age for considering serious bacterial infection in the management of febrile infants? Pediatr Infect Dis J. 2012;31(5):455-458. PubMed
6. Schwartz S, Raveh D, Toker O, Segal G, Godovitch N, Schlesinger Y. A week-by-week analysis of the low-risk criteria for serious bacterial infection in febrile neonates. Arch Dis Child. 2009;94(4):287-292. PubMed
7. Huppler AR, Eickhoff JC, Wald ER. Performance of low-risk criteria in the evaluation of young infants with fever: review of the literature. Pediatrics 2010;125(2):228-233. PubMed
8. Baskin MN. The prevalence of serious bacterial infections by age in febrile infants during the first 3 months of life. Pediatr Ann. 1993;22(8):462-466. PubMed
9. Nigrovic LE, Mahajan PV, Blumberg SM, et al. The Yale Observation Scale Score and the risk of serious bacterial infections in febrile infants. Pediatrics 2017;140(1):e20170695. PubMed
10. Bergman DA, Mayer ML, Pantell RH, Finch SA, Wasserman RC. Does clinical presentation explain practice variability in the treatment of febrile infants? Pediatrics 2006;117(3):787-795. PubMed
11. Baker MD, Bell LM, Avner JR. Outpatient management without antibiotics of fever in selected infants. N Engl J Med. 1993;329(20):1437-1441. PubMed
12. Jaskiewicz JA, McCarthy CA, Richardson AC, et al. Febrile infants at low risk for serious bacterial infection--an appraisal of the Rochester criteria and implications for management. Febrile Infant Collaborative Study Group. Pediatrics 1994;94(3):390-396. PubMed
13. Baskin MN, O’Rourke EJ, Fleisher GR. Outpatient treatment of febrile infants 28 to 89 days of age with intramuscular administration of ceftriaxone. J Pediatr. 1992;120(1):22-27. PubMed
14. Bachur RG, Harper MB. Predictive model for serious bacterial infections among infants younger than 3 months of age. Pediatrics 2001;108(2):311-316. PubMed
15. Pichichero ME, Todd JK. Detection of neonatal bacteremia. J Pediatr. 1979;94(6):958-960. PubMed
16. Hurst MK, Yoder BA. Detection of bacteremia in young infants: is 48 hours adequate? Pediatr Infect Dis J. 1995;14(8):711-713. PubMed
17. Friedman J, Matlow A. Time to identification of positive bacterial cultures in infants under three months of age hospitalized to rule out sepsis. Paediatr Child Health 1999;4(5):331-334. PubMed
18. Kliegman R, Behrman RE, Nelson WE. Nelson textbook of pediatrics. Edition 20 / ed. Philadelphia, PA: Elsevier; 2016.
19. Fever in infants and children. Merck Sharp & Dohme Corp, 2016. (Accessed 27 Nov 2016, 2016, at https://www.merckmanuals.com/professional/pediatrics/symptoms-in-infants-and-children/fever-in-infants-and-children.)
20. Polin RA, Committee on F, Newborn. Management of neonates with suspected or proven early-onset bacterial sepsis. Pediatrics 2012;129(5):1006-1015. PubMed
21. 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. PubMed
22. DeAngelis C, Joffe A, Wilson M, Willis E. Iatrogenic risks and financial costs of hospitalizing febrile infants. Am J Dis Child. 1983;137(12):1146-1149. PubMed
23. Nizam M, Norzila MZ. Stress among parents with acutely ill children. Med J Malaysia. 2001;56(4):428-434. PubMed
24. Rowley AH, Wald ER. The incubation period necessary for detection of bacteremia in immunocompetent children with fever. Implications for the clinician. Clin Pediatr (Phila). 1986;25(10):485-489. PubMed
25. La Scolea LJ, Jr., Dryja D, Sullivan TD, Mosovich L, Ellerstein N, Neter E. Diagnosis of bacteremia in children by quantitative direct plating and a radiometric procedure. J Clin Microbiol. 1981;13(3):478-482. PubMed
26. Evans RC, Fine BR. Time to detection of bacterial cultures in infants aged 0 to 90 days. Hosp Pediatr. 2013;3(2):97-102. PubMed
27. Herr SM, Wald ER, Pitetti RD, Choi SS. Enhanced urinalysis improves identification of febrile infants ages 60 days and younger at low risk for serious bacterial illness. Pediatrics 2001;108(4):866-871. PubMed
28. Nigrovic LE, Kuppermann N, Macias CG, et al. Clinical prediction rule for identifying children with cerebrospinal fluid pleocytosis at very low risk of bacterial meningitis. JAMA. 2007;297(1):52-60. PubMed
29. Doby EH, Stockmann C, Korgenski EK, Blaschke AJ, Byington CL. Cerebrospinal fluid pleocytosis in febrile infants 1-90 days with urinary tract infection. Pediatr Infect Dis J. 2013;32(9):1024-1026. PubMed
30. Bhansali P, Wiedermann BL, Pastor W, McMillan J, Shah N. Management of hospitalized febrile neonates without CSF analysis: A study of US pediatric hospitals. Hosp Pediatr. 2015;5(10):528-533. PubMed
31. Kanegaye JT, Soliemanzadeh P, Bradley JS. Lumbar puncture in pediatric bacterial meningitis: defining the time interval for recovery of cerebrospinal fluid pathogens after parenteral antibiotic pretreatment. Pediatrics 2001;108(5):1169-1174. PubMed
32. Biondi EA, Mischler M, Jerardi KE, et al. Blood culture time to positivity in febrile infants with bacteremia. JAMA Pediatr. 2014;168(9):844-849. PubMed
33. Moher D HC, Neto G, Tsertsvadze A. Diagnosis and Management of Febrile Infants (0–3 Months). Evidence Report/Technology Assessment No. 205. In: Center OE-bP, ed. Rockville, MD: Agency for Healthcare Research and Quality; 2012. PubMed
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