Letters To The Editor

Reply to Azithromycin: Short Course with Long Duration

© 2018 Society of Hospital Medicine

We appreciate the interest in our review of antibiotic duration in hospitalized patients. Drs. Sikkens and van Agtmael comment that drug pharmacokinetics can alter true treatment duration.1,2 Specifically, azithromycin has a long half-life in tissues.3 We did not consider pharmacokinetics in our prespecified protocol for study inclusion, nor require that studies compare the same drug between treatment groups. This is consistent with a systematic review of antibiotic duration in community-acquired pneumonia, which included 3 of the 4 studies comparing short-course azithromycin to a longer course of another antibiotic.4 Similarly, in a recent pilot study of antibiotic duration in bloodstream infections, only treatment duration was prespecified.5 We agree that the differing pharmacokinetics between drugs is a limitation to our findings.

To assess whether the inclusion of studies using short-course azithromycin biased our conclusions, we performed an additional meta-analysis for clinical efficacy excluding the 4 studies that compared azithromycin with another drug. This subgroup included 9 trials comprising 1270 patients. The overall risk difference was 0.3% (95% CI −2.7%, 3.3%), consistent with the primary findings that short-course antibiotic treatment is non-inferior to long-course antibiotic treatment. None of these 4 studies examined mortality; thus, the meta-analyses for short-term and long-term mortality are unaffected.


Dr. Royer holds stock in Pfizer. The authors have no other potential financial conflicts of interest to report.


This work was supported by K08 GM115859 [HCP]. This manuscript does not necessarily represent the position or policy of the US government or the Department of Veterans Affairs.


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