Macrolide-based regimens and mortality in hospitalized patients with community-acquired pneumonia: a systematic
Leyla Asadi1, Wendy I Sligl, Dean T Eurich
1Division of Infectious Diseases, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Canada.
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.
Insights
Macrolide antibiotics may reduce mortality in community-acquired pneumonia (CAP) patients. However, this survival benefit was not observed in randomized trials or with guideline-concordant treatments, suggesting adherence to guidelines is key.
Area of Science:
- Medical Research
- Infectious Diseases
- Pharmacology
Background:
- Macrolides are frequently prescribed for community-acquired pneumonia (CAP).
- Growing antimicrobial resistance raises concerns about macrolide efficacy.
- Macrolides possess immunomodulatory properties that may influence CAP outcomes.
Purpose of the Study:
- To systematically review studies on macrolide use and mortality in hospitalized CAP patients.
- To compare mortality rates between macrolide and non-macrolide treatments for CAP.
- To analyze outcomes based on guideline concordance and study design.
Main Methods:
- Systematic review of randomized controlled trials (RCTs) and observational studies.
- Inclusion of studies comparing macrolides to other regimens in adult CAP patients.
- Primary analysis of any macrolide use vs. non-macrolide use; secondary analysis of guideline-concordant macrolide/beta-lactam combinations vs. fluoroquinolones.
Main Results:
- 23 studies and 137,574 patients were included.
- Overall, macrolide use was linked to a significant mortality reduction (RR 0.78; P=.01).
- No survival advantage was found in RCTs or for guideline-concordant treatments.
Conclusions:
- Macrolide-based regimens showed a significant mortality reduction in observational studies of CAP.
- The observed mortality benefit was not evident in RCTs or with guideline-concordant therapy.
- Findings emphasize the importance of guideline adherence over specific antibiotic choice in CAP management.
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