Macrolide-Based Regimens and Mortality in Hospitalized Patients With Community-Acquired Pneumonia: A Systematic Review and Meta-analysis

Background. Macrolides are used to treat pneumonia despite increasing antimicrobial resistance. However, the immunomodulatory properties of macrolides may have a favorable effect on pneumonia outcomes. Therefore, we systematically reviewed all studies of macrolide use and mortality among patients hospitalized with community-acquired pneumonia (CAP). Methods. All randomized control trials (RCTs) and observational studies comparing macrolides to other treatment regimens in adults hospitalized with CAP were identified through electronic databases and gray literature searches. Primary analysis examined any macrolide use and mortality; secondary analysis compared Infectious Diseases Society of America/American Thoracic Society guideline-concordant macrolide/beta-lactam combinations vs respiratory fluoroquinolones. Random effects models were used to generate pooled risk ratios (RRs) and evaluate heterogeneity (I-2). Results. We included 23 studies and 137 574 patients. Overall, macrolide use was associated with a statistically significant mortality reduction compared with nonmacrolide use (3.7% [1738 of 47 071] vs 6.5% [5861 of 90 503]; RR, 0.78; 95% confidence interval [CI], .64-.95; P = .01; I-2 = 85%). There was no survival advantage and heterogeneity was reduced when analyses were restricted to RCTs (4.6% [22 of 479] vs 4.1% [25 of 613]; RR, 1.13; 95% CI, .65-1.98; P = .66; I-2 = 0%) or to patients treated with guideline-concordant antibiotics (macrolide/beta-lactam, 5.3% [297 of 5574] vs respiratory fluoroquinolones, 5.8% [408 of 7050]; RR, 1.17; 95% CI, .91-1.50; P = .22; I-2 = 43%). Conclusions. In hospitalized patients with CAP, macrolide-based regimens were associated with a significant 22% reduction in mortality compared with nonmacrolides; however, this benefit did not extend to patients studied in RCTs or patients that received guideline-concordant antibiotics. Our findings suggest guideline concordance is more important than choice of antibiotic when treating CAP.