Shorter Course of Treatment for CAP in Children Demonstrates Success

In 2019 the World Health Organization listed antimicrobial resistance as a top 10 threat to global health and echoed the same concern in a 2021 document.^1,2

Historical teaching regarding antimicrobial therapy pushed for longer treatment courses. There was a commonly held myth that premature cessation or prescription of a short course of antibiotics could select for more resistant pathogens, thereby resulting in incomplete treatment and possibly exacerbating the illness.¹ Infectious Diseases Society of America and Pediatric Infectious Diseases Society guidelines for the management of community-acquired pneumonia (CAP) in children older than 3 months were updated most recently in 2011.²

Those guidelines indicate that treatment courses of 10 days have been best studied but noted that complicated infections or those caused by certain pathogens, notably community-acquired methicillin resistant Staphylococcus aureus, may require longer treatment than those caused by Streptococcus pneumoniae.

Use of shorter courses of antibiotics for uncomplicated bacterial CAP in children has been a continued area of interest, with multiple studies published in recent years. Same and colleagues assessed the association of shorter antibiotic duration with successful treatment of children hospitalized with CAP.³ In this retrospective cohort study from January 2012 through December 2018, clinical review and diagnostic codes were used to identify all children 6 months and older with uncomplicated CAP. Among the 439 patients who met eligibility criteria, 168 (38%) received short-course (5-7 days), and 271 (62%) received prolonged-course (8-14 days) antibiotic therapy. In the propensity-weighted cohort, 20 children (4%) experienced treatment failure within 30 days of discontinuing antibiotics and there was no difference in treatment failure between patients who received short or long courses of antibiotic therapy (odds ratio, 0.48; 95% CI, 0.18-1.30). The results remained consistent when all patients with any posi-tive respiratory viral tests were excluded.

A systematic review by Kuitunen and colleagues on the treatment duration in outpatient children over aged 6 months in high-income countries found that shortened antibiotic courses of 3 to 5 days were effective and safe compared with those receiving the recommended durations of 7 to 10 days.⁴ This comprehensive review looked at 4 retrospective studies, evaluating treatment failure, defined as retreatment or hospitalization within 1 month. A total of 1541 children were identified in this review and assessed for treatment failure; a risk difference of 0.1% (CI –3.0% to 2.0%) was seen. The authors concluded that a shorter course of antibiotics can be implemented in the treatment of uncomplicated pediatric CAP. As part of the previous systematic review, the SCOUT-CAP randomized clinical trial (NCT02891915), Williams and colleagues looked to address the remaining question of short (5-day) vs standard (10-day) antibiotic treatment strategy for CAP in a pediatric population.⁵ This double-blind, placebo-controlled, randomized clinical trial in outpatient clinics studied 380 children aged 6 to 71 months with nonsevere CAP demonstrating early clinical improvement. On day 6 of their originally prescribed therapy, participants were randomly assigned 1:1 to receive 5 days of a matching placebo or 5 additional days of the same antibiotic. Their primary end point was the end-of-treatment response adjusted for duration of antibiotic risk (RADAR), a composite end point that ranks each child’s clinical response, resolution of symptoms, and antibiotic associated adverse effects (AEs) in an ordinal desirability of outcome ranking. When evaluating the results, Williams and colleagues found that the short-course strategy had a 69% probability (95% CI, 63%-75%) of a more desirable RADAR outcome compared with the standard-course strategy. This study concluded that in patients responding to initial therapy for outpatient CAP, a 5-day antibiotic strategy was more favorable compared with a 10-day strategy. Shortened courses of antibiotics resulted in similar clinical responses and antibiotic-associated AEs, while reducing antibiotic exposure and resistance.

As more data are collected and clinical practice evolves, care teams should be aware of the accumulating evidence favoring shorter courses of antibiotics, especially in patients with pneumonia. The decision to shorten therapy can be made based on a multitude of factors, including but not limited to acuity of presentation, inflammatory markers, oral intake, oxygen markers, respiratory rate, and temperature.

References

1. Langford BJ, Morris AM. Is it time to stop counselling patients to “finish the course of antibiotics”? Can Pharm J (Ott). 2017;150(6):349-350. doi:10.1177/1715163517735549

2. Bradley JS, Byington CL, Shah SS, et al; Pediatric Infectious Diseases Society and the Infectious Diseases Society of America. The management of community-acquired pneumonia in infants and children older than 3 months of age: clinical practice guidelines by the Pediatric Infectious Diseases Society and the Infectious Diseases Society of America. Clin Infect Dis. 2011;53(7):e25-76. doi:10.1093/cid/cir531

3. Same R, Amoah J, Hsu A, et al. The association of antibiotic duration with successful treatment of community-acquired pneumonia in children. J Pediatric Infect Dis Soc. 2021;10(3):267-273. doi:10.1093/jpids/piaa055

4. Kuitunen I, Jääskeläinen J, Korppi M, Renko M. Antibiotic treatment duration for community acquired pneumonia in outpatient children in high-income countries - a systematic review and meta-analysis. Clin Infect Dis. 2022;ciac374. Published online May 17, 2022. doi:10.1093/cid/ciac374

5. Williams DJ, Creech CB, Walter EB, et al. Short- vs standard-course outpatient antibiotic therapy for community-acquired pneumonia in children: the SCOUT-CAP randomized clinical trial. JAMA Pediatr.2022;176(3):253-261. doi:10.1001/ jamapediatrics.2021.5547

About the Authors

Morgan Anderson, PharmD, BCIDP, is the medical science liaison at Sanofi Vaccines based in Chicago, Illinois, for Illinois, Michigan, and eastern Wisconsin.

Kevin Nguyen, PharmD, is a PGY-2 infectious diseases pharmacy resident at Boston Medical Center in Massachusetts.