Optimal duration of antibiotic treatment for community-acquired pneumonia in adults: a systematic review and duration-effect meta-analysis

ABSTRACT Importance Community-acquired pneumonia (CAP) is a leading cause of morbidity and mortality globally. The optimal duration of antimicrobial therapy remains unclear and controversial. Objective To find the optimal treatment duration with antibiotics for CAP in adults. Data Sources MEDLINE, Embase and CENTRAL from inception to present (25 August, 2021). Study Selection All randomized controlled trials comparing the same antibiotics used at the same daily dosage but for different durations for CAP in adults. We included any antibiotics, administered orally or intravenously. We included both outpatients and inpatients but not those admitted to intensive care unit. Data Extraction and Synthesis Two review authors independently screened and extracted data. We conducted random-effects, one-stage duration-effect meta-analysis with restricted cubic splines. We tested the non-inferiority with the pre-specified non-inferiority margin of 10% examined against 10 days using intention-to-treat dataset. Main Outcomes and Measures The primary outcome was clinical improvement at day 15 (range 7-45 days). Secondary outcomes were all-cause mortality, serious adverse events, and clinical improvement at day 30 (15-60 days). We calculated odds ratios. Results We included 9 trials (2399 patients with a mean [SD] age of 61.2 [22.1]; 39% women). The duration-effect curve was monotonic with longer duration leading to lower probability of improvement, and the lower 95%CI curve was constantly above the prespecified non-inferiority margin throughout the examined duration. Harmful outcome curves indicated no association. The average percentage of clinical improvement rate at day 15 in the 10-day treatment arms was 68%. Using that average, we computed the absolute clinical improvement rates at the following durations: a 3-day treatment 75% (95%CI: 68 to 81%), 5-day treatment 72% (66 to 78%), and 7-day treatment 69% (61 to 76%). Conclusions and Relevance Shorter treatment duration probably achieves the optimal balance between efficacy and treatment burden for treating CAP in adults. However, the small number of included studies and the overall moderate to high risk of bias may compromise the certainty of the results. Further research focusing on the shorter duration range is required. Registration PROSPERO (CRD 42021273357). KEY POINTS Question What is the optimal treatment duration of antibiotics for community-acquired pneumonia (CAP) in adults.? Findings This systematic review and duration-effect meta-analysis of 9 trials with 2399 patients found that the shorter treatment duration (3-9 days) was likely to be non-inferior to the standard treatment duration (10 days) for CAP in adults if they achieved clinical stability. Meaning Shorter antibiotic treatment duration probably achieves the optimal balance between efficacy and treatment burden for CAP in adults.