Things We Do for No Reason – The “48 Hour Rule-out” for Well-Appearing Febrile Infants
Fever, defined as a rectal temperature of ≥38°C (100.4°F), is a common reason for hospital admission of infants aged ≤ 90 days. Febrile infants are often admitted to the hospital due to risk for serious bacterial infections, such as urinary tract infection, bacteremia, and meningitis. The traditional observation time is 48 hours following the collection of blood, urine, and cerebrospinal fluid cultures. In the majority of these infants, bacterial infection is not the source of fever. When a bacterial source is identified, less than 0.3% of the bacteria will be detected more than 24 hours after the cultures were obtained in low-risk infants.1 Recent studies show that the traditional 48 hour hospital observation period is unnecessary for infants aged ≤ 90 days who are at low risk for serious bacterial infection based on available scoring systems.
© 2018 Society of Hospital Medicine
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
