Shorter antibiotic durations are better for some pediatric infections
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Most patients when filling an antibiotic prescription are counseled to “take all of the antibiotic to complete the course, even if you feel better.”
Traditionally, antibiotic durations involve a multiplier of either 5 or 7 days. Before recent studies, recommendations for durations of therapy were largely based on clinical anecdotes and expert opinion. Inappropriate antibiotic use has been associated with a rise in antibiotic resistance and has triggered a global antibiotic stewardship mission. Additionally, emerging research has shown that inappropriate antibiotic use early in life is associated with disrupting the gastrointestinal microbiome, which can lead to increased risk for medical conditions later in life.
A 2010-2011 National Ambulatory Medical Care Survey found the annual antibiotic prescription rate was highest among children aged 2 years and younger. Although there is a large body of literature to suggest shorter durations are noninferior to longer durations in adults, pediatric literature remains scant. However, for certain infections, this evidence is growing.
The circulating paradigm “shorter is better” has prompted studies looking at durations of fewer than 7 days vs. longer durations. The general takeaway from most of these studies has been that the treatment of common infections can be accomplished with shorter durations of therapy, decreasing the risk for antibiotic resistance, adverse effects and cost. Venekamp and colleagues estimated that one in 15 children treated for acute otitis media (AOM) with antibiotics experiences an adverse drug reaction, highlighting that shorter durations of therapy could also help to minimize these occurrences.
Although data remain limited, there has been increasing evidence for shorter durations of therapy in common pediatric infections such as community-acquired pneumonia (CAP), UTIs, otitis media and bacteremia. (The Table includes updated recommendations.)
CAP
Pediatric guidelines recommend a duration of 10 days of therapy for CAP, although they acknowledge shorter durations are likely to be sufficient. More recent studies suggest shorter durations of therapy for uncomplicated cases are as effective as longer courses.
Williams and colleagues recently published the SCOUT-CAP study. This randomized, double-blind, placebo-controlled clinical trial largely in outpatients compared 5 days of therapy vs. 10 days and adverse effects for nonsevere CAP in patients who showed early clinical improvement. This was also the first study to analyze potential associations between treatment duration and its impact on antibiotic resistance in the respiratory microbiome. Results suggest that a shorter course achieved similar clinical response and resolution of symptoms while having comparable antibiotic-associated adverse effects. They also suggested that resistance genes per prokaryotic cell were significantly lower in the short-course strategy compared with the standard course. These findings are similar to previous noninferiority studies that suggested 5 days of therapy resulted in comparable clinical outcomes to 10 days.
UTI
A retrospective observational study of children with pyelonephritis found no significant difference between children treated with a short course of antibiotics (median 8 days) and those treated with a longer course (median 11 days). However, studies that support these findings are often limited to children aged older than 2 years.
International treatment guidelines recommend all infants aged 90 days and younger be admitted to the hospital for IV antibiotic therapy for UTI, but there is a lack of consensus in national guidelines on duration of therapy, as well as when it may be appropriate to swap from IV to oral therapy.
A systematic review by Hikmat and colleagues found a shorter duration of IV antibiotic treatment of 7 days or less for bacteremia secondary to a UTI and 3 days or less for nonbacteremic UTI is not associated with an increased rate of UTI recurrence, all-cause hospitalization or adverse clinical outcomes in infants where meningitis has been excluded and who do not appear septic. The data also suggest shorter IV antibiotic courses can be used in well-appearing infants with concurrent sterile cerebrospinal fluid pleocytosis, and oral antibiotics alone can be considered for UTIs in infants aged 1 to 3 months; however, further studies are needed to confirm that.
AOM
Data surrounding AOM are highly variable, likely as a reflection that most children do not need antibiotic therapy and should receive symptomatic therapy. It has been estimated that for every 20 children treated with antibiotics for AOM, one child is likely to benefit, whereas five will likely experience harm.
Frost and colleagues published a paper describing how providers can rethink their approach to management of AOM. The authors highlighted studies that have supported 5- to 7-day durations of therapy for children aged 2 years or older. Despite these recommendations, more than 94% of children with AOM are prescribed antibiotics for a duration of 10 days. Interventions to decrease the duration of therapy and increase the use of delayed antibiotic prescriptions are needed.
Bacteremia
Data for bacteremia in children are very limited. As mentioned earlier, Hikmat and colleagues suggest for bacteremia secondary to UTI that 7 days is likely sufficient. However, this cannot be extrapolated to other sources of primary infection.
Park and colleagues analyzed short (7 to 10 days) vs. prolonged (more than 10 days) durations of antibiotic therapy for children with uncomplicated gram-negative bacteremia. Their results suggest that treatment for more than 10 days does not reduce the risk for microbiological relapse and may increase risk for candidemia, supporting that short-course therapy may be preferred. The primary source of infection for children in the study were central line-associated infections, followed by UTI, pneumonia, intra-abdominal infections, unknown infections and skin and soft tissue infections.
Conclusion
This growing body of literature supports the movement that children can effectively be treated with shorter durations, therefore decreasing their exposure to potential side effects. As noted, these are reflective of many common pediatric infections. Work is still needed to expand the list of infections in pediatrics where shorter courses are as efficacious as longer courses. For now, increasing awareness that certain common infections can safely be treated with shorter durations is crucial.
- References:
- Fleming-Dutra K, et al. JAMA. 2016;doi:10.1001/jama.2016.4151.
- Fox MT, et al. JAMA Netw Open. 2020;doi:10.1001/jamanetworkopen.2020.3951.
- Frost H, et al. JAMA Pediatrics. 2022;doi:10.1001/jamapediatrics.2021.6575.
- Ginsburg A, et al. N Engl J Med. 2020;doi:10.1056/NEJMoa1912400.
- Good A, et al. Am J Nurs Sci. 2021;doi:10.1097/01.NAJ.0000798052.41204.18.
- Greenberg D, et al. Pediatr Infect Dis J. 2014;doi: 10.1097/INF.0000000000000023.
- Hikmat S, et al. Pediatrics. 2022;10.1542/peds.2021-052466.
- King L, et al. Clin Infect Dis. 2020;doi:10.1093/cid/ciz225.
- Park S, et al. J Antimicrob Chemother. 2014;doi:10.1093/jac/dkt424.
- Pernica J, et al. JAMA Pediatr. 2021;doi:10.1001/jamapediatrics.2020.6735.
- Venekamp R, et al. Cochrane Database Syst Rev. 2015;doi:10.1002/14651858.CD000219.pub4.
- WHO. Revised WHO classification and treatment of pneumonia in children at health facilities: evidence summaries. Accessed July 5, 2022. https://apps.who.int/iris/bitstream/handle/10665/137319/9789241507813_eng.pdf.
- Williams D, et al. JAMA Pediatr. 2022;doi:10.1001/jamapediatrics.2021.5547.
- For more information:
- Alex Craig, PharmD, is a PGY2 infectious diseases pharmacy resident at Denver Health Medical Center.
- Kati Shihadeh, PharmD, BCIDP, is a clinical pharmacy specialist in infectious diseases at Denver Health Medical Center. Shihadeh can be reached at katherine.shihadeh@dhha.org.
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