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Macrolides and Mortality in Critically Ill Patients with Community-Acquired Pneumonia: a Systematic Review and Meta-Analysis
Study Question: Do critically ill patients treated with macrolides for community-acquired pneumonia (CAP) have better outcomes?
Study Description: A comprehensive database search found 28 observational studies to be included in the meta-analysis. Eligible studies met the following criteria: patient sample comprised of critically ill adults with CAP, and a comparison of macrolide exposure to no exposure (comparison group). The primary analysis examined the effect of macrolides on all-cause mortality at one month. Additionally, the efficacy of macrolide monotherapy or combination therapy was compared to non-macrolide regimens.
Results: A majority of the studies were small but all were scored as high-quality, non-randomized studies, 61% were multicenter, and 54% were retrospective. The primary analysis included 9,850 patients; 41% received macrolide therapy. Mortality was lower with macrolide use as compared to non-macrolide use (21% vs. 24% [RR 0.82, 95% CI 0.7-0.97, p = 0.02]). Of note, the meta-analysis’ heterogeneity was 63%. Combination macrolide therapy was associated with a lower mortality compared to non-macrolide combination (21% vs. 23%, p = 0.05). Furthermore, critically ill patients receiving beta-lactam/macrolide versus beta-lactam/fluoroquinolone therapies had a trend towards reduced mortality (20% vs. 23% [RR 0.83, 95% CI 0.67-1.03, p = 0.09]). In a subgroup analysis of prospective studies, there was no significant mortality difference (macrolide 24% vs. non-macrolide 23%). Likewise, macrolide use was not associated with a statistically significant mortality reduction in septic shock (p = 0.45) or critically ill patients with pneumococcal CAP (p = 0.48).
Conclusion: This meta-analysis supports the use of macrolides as first line combination therapy in critically ill patients with severe CAP and reinforces the current treatment guidelines.
Perspective: The analysis had major limitations including significant heterogeneity, lack of detailed patient demographics, no data on comparator treatments or microbiology, and many of the studies did not discuss concomitant, immune-modulating therapies. This analysis does provide slight support for macrolide use in critically ill patients as monotherapy or in combination, but it failed to demonstrate a significant mortality benefit in patients with septic shock.