Empiric Listeria monocytogenes antibiotic coverage for febrile infants (age, 0-90 days)

The “Things We Do for No Reason” series reviews practices which have become common parts of hospital care but which 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/

Evaluation and treatment of the febrile infant 0 to 90 days of age are common clinical issues in pediatrics, family medicine, emergency medicine, and pediatric hospital medicine. Traditional teaching has been that Listeria monocytogenes is 1 of the 3 most common pathogens causing neonatal sepsis. Many practitioners routinely use antibiotic regimens, including ampicillin, to specifically target Listeria. However, a large body of evidence, including a meta-analysis and several multicenter studies, has shown that listeriosis is extremely rare in the United States. The practice of empiric ampicillin thus exposes the patient to harms and costs with little if any potential benefit, while increasing pressure on the bacterial flora in the community to generate antibiotic resistance. Empiric ampicillin for all infants admitted for sepsis evaluation is a tradition-based practice no longer founded on the best available evidence.

A 32-day-old, full-term, previously healthy girl presented with fever of 1 day’s duration. Her parents reported she had appeared well until the evening before admission, when she became a bit less active and spent less time breastfeeding. The morning of admission, she was fussier than usual. Rectal temperature, taken by her parents, was 101°F. There were no other symptoms and no sick contacts.

On examination, the patient’s rectal temperature was 101.5°F. Her other vitals and the physical examination findings were unremarkable. Laboratory test results included a normal urinalysis and a peripheral white blood cell (WBC) count of 21,300 cells/µL. Cerebrospinal fluid (CSF) analysis revealed normal protein and glucose levels with 3 WBCs/µL and a negative gram stain. Due to stratifying at higher risk for serious bacterial infection (SBI), the child was admitted and started on ampicillin and cefotaxime while awaiting culture results.

Evaluation and treatment of febrile infants are common clinical issues in pediatrics, emergency medicine, and general practice. Practice guidelines for evaluation of febrile infants recommend hospitalization and parenteral antibiotics for children younger than 28 days and children 29 to 90 days old if stratified at high risk for SBI.^1,2 Recommendations for empiric antibiotic regimens include ampicillin in addition to either gentamicin or cefotaxime.^1,2

WHY YOU MIGHT THINK AMPICILLIN IS HELPFUL

Generations of pediatrics students have been taught that the 3 pathogens most likely to cause bacterial sepsis in infants are group B Streptococcus (GBS), Escherichia coli, and Listeria monocytogenes. This teaching is still espoused in the latest editions of pediatrics textbooks.³ Ampicillin is specifically recommended for covering Listeria, and studies have found that 62% to 78% of practitioners choose empiric ampicillin-containing antibiotic regimens for the treatment of febrile infants.^4-6

WHY EMPIRIC AMPICILLIN IS UNNECESSARY

In the past, Listeria was a potential though still uncommon infant pathogen. Over the past few decades, however, the epidemiology of infant sepsis has changed significantly. Estimates of the rate of infection with Listeria now range from extremely rare to nonexistent across multiple studies^4,7-15 (Table). In a 4-year retrospective case series at a single urban academic center in Washington, DC, Sadow et al.⁴ reported no instances of Listeria among 121 positive bacterial cultures in infants younger than 60 days seen in the emergency department (ED). Byington et al.⁷ examined all positive cultures for infants 0 to 90 days old at a large academic referral center in Utah over a 3-year period and reported no cases of Listeria (1298 patients, 105 SBI cases). A study at a North Carolina academic center found 1 case of Listeria meningitis among 72 SBIs (668 febrile infants) without a localizing source.⁸ At a large group-practice in northern California, Greenhow et al.⁹ examined all blood cultures (N = 4255) performed over 4 years for otherwise healthy infants 1 week to 3 months old and found no cases of Listeria. In a follow-up study, the same authors examined all blood (n = 5396), urine (n = 4599), and CSF (n = 1796) cultures in the same population and found no Listeria cases.¹⁰ Hassoun et al.¹¹ studied SBI rates among infants younger than 28 days with any blood, urine, or CSF culture performed over 4 years at two Michigan EDs. One (0.08%) of the 1192 infants evaluated had bacteremia caused by Listeria.