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Michael Cosimini, MD and Eric Biondi, MD

Pearls:

  • Febrile infants less than 90 days of age who present well appearing but febrile are at risk of serious bacterial infections including urinary tract infections, bacteremia and meningitis.

  • A recent study showed that 91% of all positive blood cultures in febrile infants less than 90 days of age will be positive by 24 hours.

  • Febrile infants less than 90 days of age who present well appearing but febrile are at risk of serious bacterial infections including urinary tract infections, bacteremia and meningitis. Urinary tract infection is the most common around 8%, bacteremia is found in around 2% and meningitis is found in less than 0.5%.

  • These patients are often admitted for 48 hours or more while awaiting culture results. Some of the early research establishing the 48 hour time period was done when blood culture were checked once or twice a day and current technology monitors the cultures much more frequently.

  • New data suggests that less than this classic 48 hours waiting period  may be feasible. A retrospective review of 392 true positive (as determined by the care team) blood cultures obtained at 17 centers in children less than 90 days of age. Excluded were those with significant surgical histories, those with central lines and those, which were obtained in the ICU or obtained in patients who were transferred to the ICU shortly after the blood culture was drawn. This study found that 91% of all these cultures were positive by 24 hours.

Biondi EA et al. Blood culture time to positivity in febrile infants with bacteremia.JAMA Pediatr. 2014 Sep;168(9):844-9. PMID 25048522

  • Why was a study needed on this topic? Much of the literature that has been done on this topic comes out of data samples that include ICU patients, older patients or done with previous blood culture technology. These different patients and technology does not get us a good sense of what the timeline is for this particular group of patients.  With the urine and CSF good preliminary information is available but for the bacteremia all you have is the culture.

  • What about urine culture? Is the Urinalysis (UA) and microscopy enough to say that we don’t suspect UTI. Is this blood culture data alone enough to change our practice? UA is not all you would need to diagnose a urinary tract infection, although there are some new data in that regard, however, suggesting you may not need to keep a child in the hospital just to see if their urine culture turns positive.

  • Are cerebrospinal fluid studies(CSF) enough to say if a child will have meningitis or do we need to know how long it will take for CSF to come back positive? In a case without a pleocytosis the risk of meningitis is very low. In this case you are really waiting for the blood culture data.

  • How long are you keeping these kids inpatient in your practice now? Biondi’s group was keeping patients for 48 hours but has dropped to 36 and he is advocating for 24 hours.

  • Another study supporting a 24 or 36-hour discharge was written by Carrie Byington. This article describes an evidence based care process model implemented in a Utah health system which used a 24 hour discharge for all low-risk infants, as well as those that were high-risk by a modified Rochester criteria who had positive viral testing. They used a 36 hour discharge for those who were high risk by modified Rochester and viral testing negative. This care process was applied to thousands of infants without an increase in hospital readmission after discharge.

Byington CL et al. Costs and infant outcomes after implementation of a care process model for febrile infants. Pediatrics. 2012 Jul;130(1):e16-24. PMID 22732178

Details of the care process models can be found here: Inpatient care process modelEmergency care process model

  • Is there any difference in neonates <30 days old? There is no agreed upon risk number in the infants less than 30 days of age. It seems like they may be higher risk but it is hard to point at a specific number. It seems that it is pretty standard practice to do a full evaluation including lumbar puncture in this group even though strictly following Rochester criteria you do not have to perform an LP.

  • More good information about the management of febrile infants and guidance for standardizing practice will be coming in from  the Value in Inpatient Pediatrics Network from the American Academy of Pediatrics in the summer of 2016. Keep an eye out for the Febrile Infant Project.

Do we need to use ampicillin in addition to a third generation cephalosporin? This is a subject of debate. Ampicillin will cover listeria and enterococcus. Listeria was not found in any of the positive blood cultures in this series and enterococcus was rarely found. Adding ampicillin to a third generation cephalosporin will only help cover 2-4% of positive blood cultures keeping in mind that only 2% of these infants will have a positive blood culture at all. This leads to a very high number needed to treat. Biondi uses Ampicillin and Gentamicin because of concern for the overuse of cephalosporins. The take home is that if you are adding ampicillin it is there to cover enterococcus because Listeria is so uncommon.