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

Objectives: To find the optimal treatment duration with antibiotics for community-acquired pneumonia (CAP) in adults.
Design: Systematic review and duration-effect meta-analysis.
Data Sources: MEDLINE, Embase and CENTRAL through 25 August 2021.
Eligibility Criteria: All randomised controlled trials comparing the same antibiotics used at the same daily dosage but for different durations for CAP in adults. Both outpatients and inpatients were included but not those admitted to intensive care units. We imposed no date, language or publication status restriction.
Data Extraction and Synthesis: Data extraction by two independent reviewers. We conducted a random-effects, one-stage duration-effect meta-analysis with restricted cubic splines. We tested the non-inferiority with the prespecified non-inferiority margin of 10% examined against 10 days . The primary outcome was clinical improvement on day 15 (range 7-45 days).
Secondary Outcomes: all-cause mortality, serious adverse events and clinical improvement on day 30 (15-60 days).
Results: We included nine 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 a lower probability of improvement, and shorter treatment duration (3-9 days) was likely to be non-inferior to 10-day treatment. Harmful outcome curves indicated no association. The weighted average percentage of the primary outcome in the 10-day treatment arms was 68%. Using that average, the absolute clinical improvement rates of the following durations were: 3-day treatment 75% (95% CI: 68% to 81%), 5-day treatment 72% (95% CI: 66% to 78%) and 7-day treatment 69% (95% CI: 61% to 76%).
Conclusions: Shorter treatment duration (3-5 days) probably offers the optimal balance between efficacy and treatment burden for treating CAP in adults if they achieved clinical stability. 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 on the shorter duration range is required.
Prospero Registration Number: CRD 42021273357.
Competing Interests: Competing interests: YL is receiving a Grant-in-Aid for JSPS Fellow (KAKENHI Grant Number 21J15050). SF has a research grant from JSPS KAKENHI Grant Number JP 20K18964 and the KDDI Foundation. AO obtained speakers fees from Chugai Pharmaceutical, Asahi Kasei Corporation, Eli Lilly, AbbVie GK, Pfizer, Mitsubishi Tanabe Pharma Corporation and GlaxoSmithKline, and research grants from Advantest and JSPS KAKENHI outside the submitted work. EO has received research and consultancy fees from Angelini Pharma. EO is supported by the National Institute for Health Research (NIHR) Research Professorship to Professor Andrea Cipriani (grant RP-2017-08-ST2-006), by the NIHR Applied Research Collaboration (ARC) Oxford and Thames Valley, by the NIHR Oxford Cognitive Health Clinical Research Facility and by the NIHR Oxford Health Biomedical Research Centre (grant BRC-1215-20005). TAF reports grants and personal fees from Mitsubishi-Tanabe, personal fees from MSD, personal fees from Shionogi, personal fees from Sony, outside the submitted work; in addition, TAF has a patent 2018-177688 concerning smartphone CBT applications pending, and intellectual properties for Kokoro-application licensed to Mitsubishi-Tanabe. YK received a research grant from the Systematic Review Workshop Peer Support Group, the Japan Osteoporosis Foundation and Yasuda Memorial Medical Foundation for other research purposes. YF and TH declare no conflicts of interest.
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