A Strategy for Early Discontinuation of Antibiotics in Febrile Infants
By Philip R. Fischer, MD, DTM&H
Professor of Pediatrics, Department of Pediatric and Adolescent Medicine, Mayo Clinic.
Dr. Fischer reports no financial relationships in this field of study.
Approximately half of blood cultures taken from febrile infants with bacteremia turn positive within 15 hours of sampling. By 24 hours, 91% have become positive, and 96% have become positive by 36 hours. Understanding time to culture positivity can help judicious clinicians avoid unnecessarily prolonged antibiotic courses.
: Biondi EA, et al. Blood culture time to positivity in febrile infants with bacteremia. JAMA Pediatrics published online July 21, 2014, doi:10.1001/jamapediatrics.2014.895.
Infants with life-threatening bacteremia often present with fever without localized signs. To avoid delays in life-saving treatment, most pediatricians obtain culture samples and treat febrile infants with parenteral antibiotics for two or more days pending culture results. Approximately 99% of these infants do not have serious infection for which antibiotics are needed, but "overtreatment" is accepted as necessary to prevent undertreatment of the few individuals who actually need antibiotics. Effective means to shorten the duration of antibiotic use could be an important aspect of antimicrobial stewardship programs.
Collaborators at 17 hospital systems in the United States reviewed data from 392 pathogenic blood cultures obtained from febrile infants admitted to general care units. The mean time to culture positivity was 15.4 hours. Ninety-one percent of cultures that ultimately yielded pathogens were identifiably positive by 24 hours, 96% by 36 hours, and 99% by 48 hours.
The authors suggest new standardized protocols for antibiotic treatment of otherwise healthy-seeming febrile infants while awaiting culture results. They note that 91% of pathogens are identified within 24 hours. Shortening the coverage with antibiotics from 48 to 24 hours would decrease the environmental load of resistance-promoting antibiotic exposures.
Currently, admissions for these febrile infants cost an average of $6613; a shortened stay would decrease costs. Shorter durations of administration of intravenous antibiotics would also decrease the risks of infiltration and adverse medication effects. It is estimated that the incidence of hospital-acquired infection is one per 1000 patient days on general pediatric hospital units. Comparing statistics, the authors suggest that for each febrile infant who is identified to be bacteremic with a pathogen after 24 hours, there would be one infant affected by a hospital acquired infection.
COMMENTARY
What should pediatricians do? The authors advocate shortening the "usual" admission for "rule out sepsis" from 48 to 24 hours.
A dictionary defines "stewardship" as "the careful and responsible management of something entrusted to one’s care." While antimicrobial stewardship often focuses on avoiding the development of resistance (and is sometimes perceived as a punitive program designed to regulate physician behaviors), true stewardship should also involve the responsible use of antimicrobial agents in view of benefits, costs, and complications as experienced by patients. As discussed by Biondi and colleagues, shortening the duration of antibiotic use for a common pediatric condition (the febrile newborn) would decrease costs, prevent adverse effects, and avoid complications all without increasing risk to the child. And, this could also slow the development of antimicrobial resistance. Focusing on what is actually best for patients could lead to shorter courses of therapy. As noted by Pavia and colleagues, physicians respond well to concerns about risks and benefits, and such arguments can serve helpfully in discussions of antimicrobial stewardship.1
Appropriate antibiotic use depends on accurate diagnostic strategies. With automated systems electronically identifying growth in liquid culture media before it would be visible by a human eye, blood cultures become positive more rapidly than they did in previous generations. Biondi and colleagues in the Pediatric Research in Inpatient Settings Network collaborated to show that current laboratory techniques used in the United States lead to positive blood cultures within 24 hours in the vast majority of truly infected individuals. Similarly, studies in hospitalized newborns more than a decade ago showed that 77% and 89% of blood cultures were positive by 24 and 36 hours.2 Likewise, in a study of outpatient children, 87% and 92% of cultures were positive by 24 and 36 hours.3 Treatment decisions should be modified to keep pace with diagnostic sensitivity.
At the same time, however, there are still diagnostic problems. In Biondi’s study, 1447 of 2103 (69%) positive cultures were not considered to be pathogens. In the outpatient study, 52% of positive cultures only revealed germs considered to be contaminants.3 In a separate study of febrile infants in the United States, 74% of positive cultures were not treated as pathogenic..4 Decreasing the proportion of positive cultures that are due to non-pathogenic contamination of samples should be a priority in our efforts for antibiotic stewardship.
How long should children who actually do have serious bacterial infections continue to receive antibiotics? A careful review recently challenged current practice and suggested that data do not necessarily support the current fixed durations of parenteral therapy for meningitis, bacteremia, urinary tract infection, and osteomyelitis.5 Part of antimicrobial stewardship should involve considering patient factors, and such consideration might lead to more judicious (ie, less) antimicrobial use.
References
- Hersh AL, et al. Lessons learned in antibiotic stewardship: fluoroquinolone use in pediatrics. J Pediatr Infect Dis Soc 2014; doi:10.1093/jpids/piu044
- Garcia-Prats JA, et al. Rapid detection of microorganisms in blood cultures of newborn infants utilizing an automated blood culture system. Pediatrics 2000;105:523-527.
- McGowan KL, et al. Outpatient pediatric blood cultures: time to positivity. Pediatrics 2000;106:251-255.
- Biondi E, et al. Epidemiology of bacteremia in febrile infants in the Unites States. Pediatrics 2013;132:990-996.
- Schroeder AR, et al. Intravenous antibiotic durations for common bacterial infections i-n children: When is enough enough? J Hospital Med 2014;doi:10.1002/jhm.2239.
