Chest
Volume 141, Issue 5, May 2012, Pages 1153-1159
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Original Research
Critical Care
Macrolide Antibiotics and Survival in Patients With Acute Lung Injury

https://doi.org/10.1378/chest.11-1908Get rights and content

Background

Animal models suggest that immunomodulatory properties of macrolide antibiotics have therapeutic value for patients with acute lung injury (ALI). We investigated the association between receipt of macrolide antibiotics and clinical outcomes in patients with ALI.

Methods

Secondary analysis of multicenter, randomized controlled trial data from the Acute Respiratory Distress Syndrome Network Lisofylline and Respiratory Management of Acute Lung Injury Trial, which collected detailed data regarding antibiotic use among participants with ALI.

Results

Forty-seven of 235 participants (20%) received a macrolide antibiotic within 24 h of trial enrollment. Among patients who received a macrolide, erythromycin was the most common (57%), followed by azithromycin (40%). The median duration of macrolide use after study enrollment was 4 days (interquartile range, 2-8 days). Eleven of the 47 (23%) patients who received macrolides died, compared with 67 of the 188 (36%) who did not receive a macrolide (P = .11). Participants administered macrolides were more likely to have pneumonia as an ALI risk factor, were less likely to have nonpulmonary sepsis or to be randomized to low tidal volume ventilation, and had a shorter length of stay prior to trial enrollment. After adjusting for potentially confounding covariates, use of macrolide was associated with lower 180-day mortality (hazard ratio [HR], 0.46; 95% CI, 0.23-0.92; P = .028) and shorter time to successful discontinuation of mechanical ventilation (HR, 1.93; 95% CI, 1.18-3.17; P = .009). In contrast, fluoroquinolone (n = 90) and cephalosporin antibiotics (n = 93) were not associated with improved outcomes.

Conclusions

Receipt of macrolide antibiotics was associated with improved outcomes in patients with ALI.

Section snippets

Data Source

We used deidentified, open-access data from subjects previously enrolled in the ARDSNet LARMA trial, during which antibiotic type and timing was recorded in detail for all participants. Details of LARMA have been published previously.8 Briefly, participants were enrolled from 21 hospitals across the United States within 36 h of meeting ALI consensus criteria21 and were randomized via 2 × 2 factorial design to receive 6 mL or 12 mL/kg tidal volumes (as part of the Respiratory Management of ALI

Results

The characteristics of the 235 study participants stratified by macrolide exposure are shown in Table 1. Analogous results for fluoroquinolone use are shown in Table 2.

An antibiotic was administered to 232 of 235 trial participants (99%) within 24 h of enrollment. Macrolide antibiotics were used in 47 trial participants (20%). The most common macrolide received was erythromycin (n = 27, 57%), followed by azithromycin (n = 19, 40%); one participant received clarithromycin. The median duration of

Discussion

The analysis suggests an association between macrolide antibiotic use and improved outcomes in ALI. We observed increased survival and decreased time to successful discontinuation of mechanical ventilation associated with receipt of a macrolide early during the course of ALI. Our analyses did not demonstrate an association between fluoroquinolone or cephalosporin use and ALI survival. These findings suggest that macrolide antibiotics hold promise as a potential therapy early in the course of

Conclusions

In conclusion, this analysis suggests a novel association between macrolide use and increased survival in patients with ALI. Further studies to investigate potential therapeutic benefits for macrolides in ALI are warranted.

Acknowledgments

Author contributions: Dr Walkey had full access to the data and takes full responsibility for the contents of this manuscript.Dr Walkey: contributed to the study concept, statistical analyses, results interpretation, and drafting of the manuscript.Dr Wiener: contributed to the results interpretation and drafting of the manuscript.

Financial/nonfinancial disclosures: The authors have reported to CHEST that no potential conflicts of interest exist with any companies/organizations whose products or

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    Funding/Support: Dr Wiener is supported by a career development award through the National Cancer Institute [K07 CA138772] and by the Department of Veterans Affairs.

    Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (http://www.chestpubs.org/site/misc/reprints.xhtml).

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