QTc interval prolongation associated with inpatient azithromycin therapy for pneumonia

In 2013, the US Food and Drug Administration issued a warning regarding the use of azithromycin and the risk of fatal dysrhythmias after a 14-year retrospective analysis showed increased risk of cardiovascular-related death in patients who had taken a 5-day course of azithromycin compared with those who took amoxicillin, ciprofloxacin, or no antibiotics. At the authors' institution, pneumonia is the most common diagnosis for which azithromycin is used as a treatment for patients who are hospitalized.

To compare corrected QT (QTc) interval measurements on electrocardiogram (ECG) before and after inpatient azithromycin treatment for pneumonia.

The authors retrospectively reviewed the medical records of 642 patients age 18 years and older who were diagnosed with pneumonia and treated with azithromycin at an academic teaching hospital between January 1, 2017 and December 31, 2017. Patients who had an ECG performed both before and after azithromycin treatment were included and divided into 2 groups: those who had 1 dose of azithromycin (Group 1) and those who had 2 doses (Group 2). Patients were excluded if they had a baseline QTc interval on initial ECG greater than or equal to 500 ms, any signs of ischemia or myocardial infarction, any initial dysrhythmia or underlying ECG abnormalities, or absence of pre- and post-ECG results. Outcomes measures included a comparison of QTc intervals on ECG before and after azithromycin, and an analysis of the percentage of patients with a QTc interval measurement greater than 500 ms on ECG after azithromycin treatment. Our primary outcome measurement was the QTc interval measurement on ECG before and after azithromycin in patients treated with azithromycin for community acquired pneumonia. Our secondary outcome measurement was the percentage of patients with a QTc interval measurement of greater than 500 ms on ECG after azithromycin treatment. A Wilcoxon signed-rank test was used to evaluate repeated QTc measures of our primary outcome in Group 1 and Group 2. Our secondary outcome was reported as a percentage of total patients with a QTc interval of greater than 500 ms after azithromycin doses on ECG.

Of 642 patients, 142 had available pre- and post-EGC results available; 100 were included in Group 1 (1 dose) and 42 in Group 2 (2 doses). Mean QTc interval differences after 1 dose of azithromycin exhibited an increase compared to baseline values (424 vs 477 ms). A Wilcoxon signed-rank test indicated a significant QTc prolongation after 1 dose of azithromycin (mean rank, 43.76; Z=-4.921; P<.001). QTc interval differences after 2 doses of azithromycin did not reach statistical significance when compared to baseline values (422 vs 444 ms). A total of 10 patients (10%) in Group 1 and 4 patients (9.5%) in Group 2 had a QTc interval >500 ms after azithromycin. There were no documented dysrhythmias during hospitalization in this study period.

QTc interval increases were observed during inpatient azithromycin therapy for pneumonia, but were not found to be associated with cardiac dysrhythmias during hospitalization.