azithromycin for pneumonia and decreased mortality

there have been a couple of warning-type articles in the past couple of years about adverse effects of azithromycin, especially cardiac deaths. as i suggested previously (see below), azithromycin is a really important antibiotic, but should be targeted only for significant bacterial infections -- and it seems mostly to be used unnecessarily (see prior blog below). a recent large cohort study did find some increased likelihood of MI but, most significantly, a lower 90-day mortality (see azithromycin decreases mortality in elderly jama 2014 in dropbox, or doi:10.1001/jama.2014.4304).  those on azithro were on combo therapy. others received guideline-concordant therapy. results:

    --retrospective study from 2002-2012 of 73,690 patients older than 65 (mean age 77.8) from 118 VA hospitals who were hospitalized for community-acquired pneumonia, comparing 30- and 90-day outcomes, and matching 31863 on azithromycin vs same number not. high levels of comorbidities: 40% smokers, 52% with COPD, 35% with diabetes, 25% with prior malignancy. 15.9% were admitted to ICU
    --no significant difference in identified potential confounders between groups
    --90-day mortality 27% lower in those on azithro (17.4% on azithro, 22.3% not -- ie, 4.9% absolute diff, with number needed to treat of 21)
    --however, increased odds of MI (17% higher on azithro, 5.1% vs 4.4% -- ie, number needed to harm of 144), though no diff in "any cardiac event", which was 43.0% vs 42.7%, cardiac arrhythmias (25.8% vs 26.0%) or heart failure (26.3% vs 26.2%).

so, very large study, though retrospective. they did try to use propensity score matching to try to control for likely confounders (which, per their analysis, they did well), and as a large study gives lots of support for their conclusions. interesting that there was no increase in arrhythmias in the azithro group, surprising given the likely increase in QTc as suggested below (reminds me of the issue of prolonged QTc with citalopram, also with lack of anticipated clinical endpoints). bottom line: azithro is an important antibiotic to use, but only for significant probable bacterial infections. this also supports the american thoracic society (ATS) and infectious diseases society of america (ISDA) recommendation for patients with comorbidities (as in this study) to use either fluoroquinolone or combo macrolides (azithro is probably the best) with b-lactam (eg high dose amox, amox/clavulanate) to treat community-acquired pneumonia. of note, a couple of studies have found that combo fluoroquinolone/macrolide is better than fluoroquinolone alone, and that b-lactam plus macrolide is better than b-lactam plus fluoroquinolone.  

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