There is considerable variation in the approach to infants presenting to the emergency department and outpatient clinics with fever without a source. We set out to describe the current clinical practice regarding culture acquisition on febrile young infants and review the outcomes of infants with and without cultures obtained.
This study analyzed Kaiser Permanente Northern California’s electronic medical record to identify all febrile, full term, previously healthy infants born between July 1, 2010, and June 30, 2013, presenting for care between 7 and 90 days of age.
During this 3-year study, 96 156 full-term infants were born at Kaiser Permanente Northern California. A total of 1380 infants presented for care with a fever with an incidence rate of 14.4 (95% confidence interval: 13.6–15.1) per 1000 full term births. Fifty-nine percent of infants 7 to 28 days old had a full evaluation compared with 25% of infants 29 to 60 days old and 5% of infants 61 to 90 days old. Older infants with lower febrile temperatures presenting to an office setting were less likely to have a culture. In the 30 days after fevers, 1% of infants returned with a urinary tract infection. No infants returned with bacteremia or meningitis.
Fever in a medical setting occurred in 1.4% of infants in this large cohort. Forty-one percent of febrile infants did not have any cultures including 24% less than 28 days. One percent returned in the following month with a urinary tract infection. There was no delayed identification of bacteremia or meningitis.
Management of Fever in Infants. Is The Glass Half Empty? Half Full? Or Both?
I congratulate Drs. Greenhow, Hung and Pantell for presenting their data on a large cohort of febrile, full-term infants 7 to 90 days old (1). Serious bacterial infection (SBI), defined as UTI, bacteremia or meningitis, occurred in 195 of 1380 infants (14%). Specifically, 183 (13.2%) of febrile infants had UTI, 36 (2.6%) had bacteremia, and 4 (0.3%) had meningitis. A few patients with UTI also had bacteremia and one had bacteremia plus meningitis. Among the neonates 7-28 days old, SBI rates were highest, with 57 cases of UTI, 18 cases of bacteremia and 1 case of meningitis. A “full evaluation” -- cultures of urine, blood and CSF—was completed in 59% of those 7-28 days old, 25% of the 29-60 day olds, and 5% of those 61-90 days old.
Of the 442 children (32%) with no cultures or in those with only selected cultures done (urine, blood, and CSF cultures were per obtained in 60%, 64%, and 29% of children, respectively), 5 (1%) were diagnosed in the next 30 days to have a febrile UTI; additionally, 5 children who initially had negative urine cultures also were found to have UTI in the next 30 days. Importantly, no child with less than the full complement of cultures was later found to have bacteremia or meningitis in the next month. While this is reassuring, it must be noted that many children lacking the full evaluation were treated with antibiotics at presentation. This may have cured some bacterial infections. Additionally, some asymptomatic bacteremias may have resolved without treatment. It is unlikely, though, that subsequent cases of meningitis were missed.
A commentary (Management of Fever in Young Infants: Evidence Versus Practice) (2) on this valuable article by Greenhow et al. was written by Drs. Baker and Avner, academicians trained in Emergency Medicine and well-known for their publications on the topic of SBIs in febrile infants. They emphasize that:
1. Multiple studies confirm that rates of bacteremia (about 1%) and bacterial meningitis (about 0.4%) are low in this population of febrile infants under 90 days of age;
2. There is a low but definite rate of SBIs in young febrile infants (6-7%) even when a viral infection is confirmed to be present.; and
3. Well-appearing febrile infants judged to be at low risk of SBI by experienced practitioners can on occasion have SBI.
Drs. Baker and Avner advocate performing complete evaluations on most, if not all, febrile infants under three months old, and especially in those under a month of age, to ensure that all children with SBI are detected and treated. They are disconcerted by what they feel is the dismissal by many practitioners of the established scientific evidence which, they believe, compels practioners to perform full evaluations. They see a “disconnect” between evidence and clinical practice.
I have great respect for the knowledge and experience of Drs. Baker and Avner, yet have a somewhat different perspective on this issue. The authors see the evidence through the eyes of Emergency Medicine physicians, focusing on large numbers of children of whom a certain (small) percent will undoubtedly have SBIs. However, another approach to these same data, which I endorse, is to see the issue one patient at a time. Instead of pooling children into larger groups based on age, each infant’s case is considered individually. The question asked is not “What is the risk of a child of THIS AGE having an SBI?”; instead, one asks “What is the risk for THIS infant?” I am certain that an experienced pediatrician can, after evaluating a child, either find a lower risk of SBI than the aggregate 14% found by Greenhow et al., or else conclude that it is much higher. Treatment decisions can then be based on a more accurate risk assessment.
In those less than 90 days old, great effort should be made to ensure that UTIs are not missed. Either the urine should be examined at the time of presentation (in cases when the source of infection is unclear) or within 2-3 days (in cases where there is an obvious source, such as a viral illness, but fever persists). Since UTIs comprise over 90% of SBI’s in small infants, when UTI’s are removed from the equation the incidence of serious infections such as bacteremia and bacterial meningitis in febrile infants is quite low.
Among 7-28 day old febrile infants in Greenhow’s study, bacteremia was present in 7% of those with blood cultures and meningitis was found in 0.5% of those with CSF cultures. In those 1-3 months old, the incidence of bacteremia and bacterial meningitis in those who were cultured was 2.9% and 1.6% respectively. Very likely, these numbers would be lower if every child included in the study had received all cultures, since ill appearing infants were much more likely to have cultures obtained than others.
In children under 90 days of age with fever and documented viral infections, the risk of bacteremia (1%, or 5 of 491) and meningitis (no cases found) is also quite low (3).
The rate of SBI in well-appearing infants, too, is very small. Baker and Avner (4) studied 126 febrile infants 4-8 weeks old, with cultures of blood and CSF obtained in all. Of 91 children rated “well-appearing” there was one child (1.1%) with a positive blood culture and no case of meningitis.
Many practioners (myself included), looking at the same facts as Drs. Baker and Avner, come to the conclusion that not all febrile infants under 90 days of age need to have cultures obtained. The rate of bacteremia and meningitis is very low. Children who are ill-appearing and irritable do get a full evaluation. Children who are not ill-appearing or irritable are carefully evaluated by the clinician. A urine culture is obtained on those infants without an obvious source, while in those with obvious viral infections a plan for obtaining a culture is made for those still febrile in another 2-3 days. Children who look well or are assessed to have a viral illness may be observed without cultures or antibiotics, with close follow up assured. Following this algorithm for children 7-90 days of age, the risk of missing a case of bacteremia or meningitis is likely lower than rates noted by Drs. Baker and Avner (bacteremia—1%, meningitis—0.4%)
Follow up of patients is an important part of the process. In pediatric practice (but not necessarily in ER settings), follow up of patients is typically available and reliable. Parents can call the doctor if their child’s condition worsens or if there is no improvement. Pediatricians can see such patients again to reassess their status.
Neither Drs. Baker and Avner’s position nor that of those who practice as I do can claim to be absolutely right; likewise neither is absolutely wrong. Different thoughtful pediatricians reading the same literature cited above can come to different conclusions based on how much weight they place on each piece of the equation. Is the effort to miss no case of serious illness a higher priority than doing sepsis workups (with possible hospital admission and precautionary antibiotics) on over 90 febrile infants for every one case of bacteremia or meningitis diagnosed? Excellent and caring pediatricians can decide what is most important to them and can render good care whichever position they favor. No pediatrician wants to “ignore the evidence” and put infants at risk of poor outcomes.
1. Greehow, TL, Hung YY, Pantell RH. Management and Outcomes of Previously Healthy, Full-Term, Febrile Infants Ages 7 to 90 Days. Pediatrics. 2016; 138(6):e20160270.
2. Baker MD, Avner JR. Management of Fever in Young Infants: Evidence Versus Common Practice. Pediatrics. 2016; 138(6):e20162085.
3. Byington CL, Enriquez FR, Hoff C, et al. Serious Bacterial Infections in Febrile Infants 1 to 90 Days Old With and Without Viral Infections. Pediatrics. 2004; 113(6): 1662-1666.
4. Baker MD, Avner JR, Bell LM. Failure of Infant Observation Scales in Detecting Serious Illness in Febrile, 4- to 8-Week Old Infants. Pediatrics. 1990; 85(6):1040-1043.
Harold S. Raucher, M.D.
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