Abstract & Commentary: Do Macrolide Antibiotics Improve Survival in Acute Lung Injury?
Abstract & Commentary
Do Macrolide Antibiotics Improve Survival in Acute Lung Injury?
By David J. Pierson, MD, Editor, Professor Emeritus, Pulmonary and Critical Care Medicine, University of Washington, Seattle, is Editor for Critical Care Alert.
Synopsis: In a retrospective examination of data from the original ARDS Network low-tidal-volume study, patients who had received a macrolide antibiotic had lower 180-day mortality and got off the ventilator faster than patients who did not receive a macrolide; other antibiotics had no detectable association with the study variables.
Source: Walkey AJ, Wiener RS. Macrolide antibiotics and survival in patients with acute lung injury. Chest 2011;Nov 23. [Epub ahead of print.]
This is a report of a secondary analysis of data from the original Acute Respiratory Distress Syndrome (ARDS) Network low-tidal-volume study, which demonstrated improved survival with ventilator tidal volumes of 6 (vs 12) mL/kg predicted body weight in patients meeting the American-European consensus definition of acute lung injury (ALI) or ARDS. In a 2-by-2 factorial design, that original study also investigated the effect of lysophylline in ALI/ARDS. Because no effect of lysophylline was demonstrated, all the data (that is, from both 6- and 12-mL/kg PBW tidal volumes, and both lysophylline and placebo) were used in the present study of the possible effect of macrolide antibiotics (not part of the original study, but recorded in the database) on patient outcomes.
Virtually all of the 235 patients in the study (232/235, 99%) had received one or more antibiotics within 24 hours of study enrollment. Macrolides had been used in 47 (20%) of the patients — erythromycin in 27 (57%), azithromycin in 19 (40%), and clarithromycin in 1 patient. Eleven of the patients who received a macrolide (23%) died prior to the a priori 180-day survival cutoff, as compared to 67/188 (36%) of the patients who did not receive a macrolide. The difference was not significant (P = 0.11), but after adjustment for confounding covariates, mortality in the macrolide group was significantly lower (hazard ratio, 0.46; 95% confidence interval, 0.23-0.92; P = 0.028). In addition, time to discontinuation of mechanical ventilation was significantly lower among patients who received a macrolide (P = 0.009). These associations were unaffected by the diagnosis predisposing to ALI/ARDS or by tidal volume randomization group. The authors could detect no effects of fluoroquinolones in the 90 patients who received this class of antibiotics, nor of cephalosporins in the 93 patients who received them.
COMMENTARY
By no means does this retrospective analysis demonstrate that macrolide antibiotics reduce mortality and shorten the need for mechanical ventilation in ALI/ARDS. That will require much more rigorous, prospective investigation. However, the results of this study are intriguing, both on theoretical grounds and in light of recent studies of this class of antibiotics in other pulmonary disorders.
Macrolides have anti-inflammatory properties in addition to their antimicrobial action. Studies using animal models have shown beneficial effects of macrolide antibiotics against ALI induced by a variety of drugs and toxins. Clinically, macrolides have been shown to be effective in treating diffuse panbronchiolitis, a chronic airway disease seen primarily in Japan and elsewhere in Asia. Studies in cystic fibrosis, non-CF bronchiectasis, bronchiolitis obliterans, and other chronic airway disorders have also produced encouraging preliminary results.1 And, in a study recently reported in the New England Journal of Medicine, daily administration of low-dose azithromycin for 1 year reduced the frequency of exacerbations and improved some measures of quality of life in patients with chronic obstructive pulmonary disease (COPD).2
While it seems a long way from COPD and diffuse panbronchiolitis to ALI/ARDS, there is at least biologic plausibility to the notion that macrolides could be effective in the latter. We should not start treating all our ALI/ARDS patients with macrolides on the basis of the study by Walkey and Wiener, but we should keep our eyes open for further developments.
REFERENCES
- Friedlander AL, Albert RK. Chronic macrolide therapy in inflammatory airways diseases. Chest 2010;138:1202-1212.
- Albert RK, et al for the COPD Clinical Research Network. Azithromycin for prevention of exacerbations of COPD. N Engl J Med 2011;365:689-698.
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