Macrolide antibiotics are known to exhibit anti-inflammatory action beyond their antimicrobial activity and have shown to have some clinical benefit in chronic lung diseases such as cystic fibrosis and acute lung injury (animal model only).1-7
Acute lung injury (ALI) can affect 200,000 people per year in the United States and is associated with 30% to 40% mortality rate. Unfortunately, the only strategy (non-pharmacological) known to improve survival in patients with ALI is using the low tidal volume lung-protective ventilation strategy.8
In this issue of CHEST, Walkey and Wiener9 examined the use of pharmacological strategy in patients with ALI. The authors sought to determine whether there is an association between macrolide antibiotic administration and mortality in patients with ALI using available data from the Acute Respiratory Distress Network (ARDSNet) Lisofylline and Respiratory Management of Acute Lung Injury (LARMA) trial. In this trial, patients (n= 235) were randomized in a two-by-two fashion to receive low tidal volume vs. standard tidal volume ventilation and either lisofylline or placebo.10
All patients enrolled were evaluated in terms of receiving a macrolide antibiotic within 24 h of enrollment. A total of 47 of 235 (20%) patients studied received a macrolide antibiotic for a total duration [median (IQR) of 4(2-8) days, erythromycin (57%) and azithromycin (40%) were the most commonly administered drugs.
Interestingly, after the adjustment for confounding variables, patients who received a macrolide antibiotic had a significant reduction in 180-day mortality (hazard ratio [HR]=0.46; 95% CI: 0.23-0.92; P= 0.028) and shorter time to successful discontinuation of mechanical ventilation (HR=1.93; 95% CI: 1.18-3.17; P=0 .009). On the other hand, patients who received a fluoroquinolone or cephalosporin, compared with patients who did not, had no survival benefit, suggesting that this benefit was due to macrolides use.
This study shows intriguing results but is limited by its observational design and the small number of patients who received macrolides. Prospective, randomized controlled clinical trials to definitively address the impact of macrolides on outcomes in patients with ALI are necessary.
1. López-Boado YS, Rubin BK. Macrolides as immunomodulatory medications for the therapy of chronic lung diseases. Curr Opin Pharmacol
2. Altenburg J, de Graaff CS, van der Werf TS, et al. Immunomodulatory effects of macrolide antibiotics–part 1: biological mechanisms. Respiration
3. Wunderink RG, Mandell L. Adjunctive therapy in community-acquired pneumonia. Semin Respir Crit Care Med
4. Wolter J, Seeney S, Bell S, et al. Effect of long term treatment with azithromycin on disease parameters in cystic fibrosis: a randomised trial. Thorax
5. Sato K, Suga M, Akaike T, et al. Therapeutic effect of erythromycin on infl uenza virus-induced lung injury in mice. Am J Respir Crit Care Med
. 1998;157(3 Pt 1):853-857.