Shorter Treatment for Community-Acquired Pneumonia as Effective as Longer Course

Although childhood community-acquired pneumonia (CAP) is typically treated with a 10-day antibiotic regimen, a study published in JAMA Pediatrics found a 5-day regimen was superior.

The 5-day treatment demonstrated that clinical response and antibiotic-associated adverse effects were similar to the usual 10-day antibiotic treatment. Additionally, the 5-day version reduced antibiotic exposure and resistance.

According to the study authors, current guidelines recommending the 10-day treatment for uncomplicated outpatient CAP warrant reevaluation.

“Providing the shortest duration of antibiotics necessary to effectively treat an infection is a central tenet of antimicrobial stewardship and a convenient and cost-effective strategy for caregivers,” the authors said. “With an estimated 1.5 million ambulatory visits for CAP annually, reducing treatment from 10 to 5 days for outpatient CAP could result in a reduction of up to 7.5 million antibiotic days in the US each year.”

To come to this finding, they conducted a randomized, double-blind, placebo-controlled clinical trial in outpatient clinic, urgent care, or emergency settings across 8 US cities. The trial included 380 healthy children aged between 6 and 71 months, with 189 children randomized to the 5-day short course of oral β-lactam, and 191 randomized to the 10-day standard treatment course. The mean (SD) age was 35.7 (17.2) months, 194 (51%) children were male, and a large majority of 234 (62%) children were White.

All children had nonsevere CAP and showed early clinical improvement and were prescribed amoxicillin, amoxicillin and clavulanate, or cefdinir at the outpatient clinic, urgent care, or emergency setting they were admitted to, based on standard of care and independent of the trial. They were enrolled between December 2, 2016, and December 16, 2019, and the data were analyzed between January and September 2020.

After 5 days of receiving their originally prescribed therapy, eligible participants were randomized 1:1 to receive either a 5-day course of matching placebo—representing the short course treatment—or an additional 5-day course of the same antibiotic they were originally prescribed.

Success of treatment among participants was measured using an ordinal desirability of outcome ranking (DOOR), which considered clinical response, resolution of symptoms, and frequency of antibiotic-associated adverse effects.

The authors noted the following between the 5-day and 10-day course groups:

• No differences in the proportion of participants reporting antibiotic-associated adverse effects
• No significant differences in the number of participants with persistent symptoms at outcome assessment visit (OAV) 1 or 2
• No significant differences between treatment strategies in proportions of inadequate clinical response at OAV1 or OAV2
• No differences in cumulative risk, regardless of DOOR

However, at OAV2, 96 (51%) children in the 5-day course group and 92 (48%) in the 10-day course group reported an antibiotic-associated adverse effect, and 36 children among both groups reported a moderate-to-severe adverse effect.

The authors further noted the probability of a more desirable DOOR for the 5-day treatment was 0.48 (95% CI, 0.42-0.53), suggesting no difference compared with the 10-day treatment.

The short-course therapy was also superior to the standard-course when taking duration into account, with an estimated probability of a more desirable end-of-treatment response adjusted for duration of antibiotic risk (RADAR) for the short-course therapy of 0.69 (95% CI, 0.63-0.75) at OAV1, and 0.63 (95% CI, 0.57-0.69) at OAV2.

The data also suggest the reduction in β-lactam therapy exposure in linked to fewer antibiotic resistance genes (ARGs) in the respiratory microbiota.

“We do not know how persistent these differences in the resistome are, and the clinical relevance of this finding is incompletely understood,” the authors said. “Nevertheless, these data support our a priori assumption that shorter antibiotic durations are more desirable when clinical outcomes are similar because of reduced antibiotic selective pressure, which is associated with the prevalence of antibiotic resistance.”

The authors encouraged further research with larger populations. In addition, since most of the participants were healthy and did not have underlying conditions, results may not be applicable to children with comorbidities or more severe pneumonia. Nevertheless, they encouraged implementation of the 5-day course, as it can optimize treatment efficacy and reduce unnecessary antibiotic use and prevalence of ARGs among colonizing oropharyngeal flora.

Reference

Williams DJ, Creech CB, Walter EB, et al; The DMID 14-0079 Study Team. Short- vs standard-course outpatient antibiotic therapy for community-acquired pneumonia in children. JAMA Pediatr. Published online January 18, 2022. doi:10.1001/jamapediatrics.2021.5547