Empiric Listeria monocytogenes antibiotic coverage for febrile infants (age, 0-90 days)
© 2017 Society of Hospital Medicine
Multicenter studies have reported similar results. In a study of 6 hospital systems in geographically diverse areas of the United States, Biondi et al.12 examined all positive blood cultures (N = 181) for febrile infants younger than 90 days admitted to a general pediatric ward, and found no listeriosis. Mischler et al.13 examined all positive blood cultures (N = 392) for otherwise healthy febrile infants 0 to 90 days old admitted to a hospital in 1 of 17 geographically diverse healthcare systems and found no cases of Listeria. A recent meta-analysis of studies that reported SBI rates for febrile infants 0 to 90 days old found the weighted prevalence of Listeria bacteremia to be 0.03% (2/20,703) and that of meningitis to be 0.02% (3/13,375).14 Veesenmeyer and Edmonson15 used a national inpatient database to identify all Listeria cases among infants over a 6-year period and estimated listeriosis rates for the US population. Over the 6 years, there were 212 total cases, which were extrapolated to 344 in the United States during that period, yielding a pooled annual incidence rate of 1.41 in 100,000 births.
Ampicillin offers no significant improvement in coverage for GBS or E coli beyond other β-lactam antibiotics, such as cefotaxime. Therefore, though the cost and potential harms of 24 to 48 hours of intravenous ampicillin are low for the individual patient, there is almost no potential benefit. Using the weighted prevalence of 0.03% for Listeria bacteremia reported in the recent meta-analysis,14 the number needed to treat to cover 1 case of Listeria bacteremia would be 3333. In addition, the increasing incidence of ampicillin resistance, particularly among gram-negative organisms,4,7,9 argues strongly for better antibiotic stewardship on a national level. A number of expert authors have advocated dropping empiric Listeria coverage as part of the treatment of febrile infants, particularly infants 29 to 90 days old.16,17 Some authors continue to advocate empiric Listeria coverage.6 It is interesting to note, however, that the incidence of Staph aureus bacteremia in recent case series is much higher than that reported for Listeria, accounting for 6-9% of bacteremia cases.9,11,13 Yet few if any authors advocate for empiric S. aureus coverage.
WHEN EMPIRIC AMPICILLIN COVERAGE MAY BE REASONABLE
The rate of listeriosis remains low across age groups in recent studies, but the rate is slightly higher in very young infants. In the recent national database study of listeriosis cases over a 6-year period, almost half involved infants younger than 7 days, and most of these infants showed no evidence of meningitis.15 Therefore, it may be reasonable to include empiric Listeria coverage in febrile infants younger than 7 days, though the study authors estimated 22.5 annual cases of Listeria in this age range in the United States. Eighty percent of the Listeria cases were in infants younger than 28 days, but more than 85% of infants 7 to 28 days old had meningitis. Therefore, broad antimicrobial coverage for infants with CSF pleocytosis and/or a high bacterial meningitis score is reasonable, especially for infants younger than 28 days.
Other potential indications for ampicillin are enterococcal infections. Though enteroccocal SBI rates in febrile infants are also quite low,7-9,11,12 if Enterococcus were highly suspected, such as in an infant with pyuria and gram positive organisms on gram stain, ampicillin offers good additional coverage. In the case of a local outbreak of listeriosis, or a specific exposure to Listeria-contaminated products on a patient history, antibiotics with efficacy against Listeria should be used. Last, in cases in which gentamicin is used as empiric coverage for gram-negative organisms, ampicillin offers important additional coverage for GBS.
Some practitioners advocate ampicillin and gentamicin over cefotaxime regimens on the basis of an often cited study that found a survival benefit for febrile neonates in the intensive care setting.18 There are a number of reasons that this study should not influence care for typical infants admitted with possible sepsis. First, the study was retrospective and limited by its use of administrative data. The authors acknowledged that a potential explanation for their results is unmeasured confounding. Second, the patients included in the study were dramatically different from the group of well infants admitted with possible sepsis; the study included neonatal critical care unit patients treated with antibiotics within the first 3 days of life. Third, the study’s results have not been replicated in otherwise healthy febrile infants.
WHAT YOU SHOULD USE INSTEAD OF AMPICILLIN FOR EMPIRIC LISTERIA COVERAGE
For febrile children 0 to 90 days old, empiric antibiotic coverage should be aimed at covering the current predominant pathogens, which include E coli and GBS. Therefore, for most children and US regions, a third-generation cephalosporin (eg, cefotaxime) is sufficient.
