June 9, 2021
By Razan El Ramahi, MBBS
Community-acquired pneumonia (CAP) is one of the leading diagnoses for adult hospitalization and antibiotic use. Reducing the duration of antimicrobial therapy can impact rates of bacterial resistance and antibiotic side effects.
Described by Dinh et al. in the Lancet, the Pneumonia Short Treatment trial was a double-blind, randomized, placebo-controlled trial set in 16 medical centers in France between December 2013 and February 2018 that looked at the noninferiority of 3 days compared to 8 days of β-lactam (BL) therapy. Eligible participants were adults with non–critical care hospitalizations for moderately severe CAP started on BL therapy and included after meeting prespecified stability criteria after receiving 72 hours of treatment. (More information about the stability criteria used is available in references 4 and 22 from the article.) They were stratified by Pneumonia Severity Index (at the beginning of treatment) and randomized to an additional 5 days of either placebo or BL (amoxicillin 1 g plus clavulanate 125 mg three times daily). Primary outcome was day 15 cure, defined as resolution of fever, resolution or improvement in clinical signs or symptoms, and no additional antibiotic use. Secondary outcomes included day 30 cure and all-cause mortality, and adverse events during the study follow-up period, among others.
During the study period, 706 patients were assessed for eligibility, but 396 were excluded, of whom 31% were due to not meeting day 3 clinical stability. Among 310 included patients, 157 were randomized to placebo and 153 to BL treatment. In the intention-to-treat group, day 15 cure was recorded in 77% of placebo patients and 68% of BL patients (between-group difference of 9.42%, 95% confidence interval [CI], -0.38 to 20.04), meeting noninferiority. In the per-protocol analysis, day 15 cure occurred in 78% of placebo patients and 68% of BL patients (difference of 9.44%, 95% CI, -0.15 to 20.34), also meeting noninferiority. Similar noninferiority results were found for day 30 cure. Mortality at day 30 was not different between the two groups, and there was no difference in reported adverse events between the placebo and BL groups.
The study shows that 3 days of BL therapy in non-immunocompromised, non–critically ill patients with uncomplicated moderately severe CAP who achieved clinical stability after 3 days and followed for 30 days is noninferior to 8 days of BL courses.