Combination of aspirin plus macrolides in patients with severe community-acquired pneumonia: a hypothesis-generating study

Objectives. While the inflammatory response to severe pneumonia is paramount in reining in and resolving the infection, the excessive inflammation can lead to deleterious effects. We theorized that patients with severe community-acquired pneumonia (CAP), treated with macrolides and aspirin, would receive benefit beyond conventional antibiotic therapy. Methods. An observational study was conducted on patients with severe CAP. All patients were admitted to 5 teaching hospitals (in Italy, USA, Japan, and China), and data were gathered from their electronic medical records. Severe pneumonia was defined according to ATS/IDSA criteria. Patients were divided in 4 groups: 1) Aspirin only (ASG), 2) Macrolides only (MG), 3) combination Aspirin + Macrolides (ASMG), or 4) neither (NASMG). Survival among the 4 groups was evaluated after adjustment for confounders, and after weighting by propensity score. Results. A total of 1295 patients were included in the analysis. There were 237 (18.3%) patients in the ASG, 294 (22.7%) in the MG, 148 (11.4%) in the ASMG, and 616 (47.6%) in the NASMG. Mortality at 30 days was 15.5% in the ASMG, compared to 28.2% of the NASMG, 23.8% of the MG, and 21.1% of the ASG. After propensity score analysis, receipt of aspirin plus macrolide (Hazard Ratio 0.71, 95% Confidence Interval 0.58-0.88, p=0.002) was associated with higher 30-day survival. Conclusions. This is a hypothesis generating a study in which data suggest that combination of aspirin plus a macrolide improves 30-day survival of patients with severe CAP. Further randomized studies will need to be undertaken to confirm this phenomenon