Macrolides usage as anti-inflammatory agents in the treatment of community-acquired pneumonia and ventilator-associated pneumonia: a systematic review and meta-analysis

BACKGROUND: Community-acquired pneumonia (CAP) and ventilator-associated pneumonia (VAP) require effective treatment strategies. In addition to their antimicrobial role, macrolides may have a potential anti-inflammatory role in CAP and VAP. The purpose of this systematic review is to explore the use of macrolides as anti-inflammatory drugs in CAP and VAP and to assess their impact on mortality and hospital length of stay while adhering to treatment guidelines. METHODS: A comprehensive search was conducted. Inclusion criteria were determined based on the PICOS (Population, Intervention, Comparison, Outcome, and Study Design) framework. The PICOS framework was used to define study eligibility and was not applied as a weighting or scoring system. Only observational studies, non-randomized studies, and randomized controlled trials (RCTs) meeting these criteria were included. A standardized eligibility screening form was employed by three independent reviewers, adhering to the established Cochrane guidelines and utilizing specialized software for analysis. RESULTS: Among 11,960 identified records, 13 studies met the inclusion criteria and underwent qualitative synthesis. Nine studies underwent meta-analysis. Of these, 25% exhibited a low risk of bias, and approximately 50% presented a moderate risk of bias. Meta-analysis showed that macrolide's use was associated with a significant reduction in in-hospital mortality (OR 0.42, 95% CI 0.25-0.71) and post-discharge mortality (OR 0.52, 95% CI 0.31-0.87). A non-significant reduction in length of hospital stay was also observed (MD - 0.68, 95% CI - 1.67 to 0.32). However, the limited number of RCTs reduces the overall quality of the available evidence. CONCLUSIONS: Macrolides demonstrate potential anti-inflammatory benefits in CAP and VAP, leading to improved clinical outcomes. However, further well-designed RCTs are needed to strengthen the evidence and confirm these findings. SYSTEMATIC REVIEW REGISTRATION: This review was registered in PROSPERO (registration number: CRD42018088203).