Despite U.S. Food and Drug Administration warnings about fatal arrhythmias with azithromycin, macrolide antibiotics do not appear to increase the risk of ventricular arrhythmia in older adults.
“We would recommend the FDA carefully consider all available evidence, including the findings from this study, to decide if a change in its warning with respect to macrolide antibiotics and the risk of ventricular arrhythmia is warranted,” Dr. Amit Garg from Western University in London, Ontario, Canada, told Reuters Health by email.
Dr. Garg’s team used linked health care databases in Ontario province to investigate whether azithromycin, clarithromycin, or erythromycin were associated with a higher 30-day risk of ventricular arrhythmia than the nonmacrolide antibiotics amoxicillin, cefuroxime, and levofloxacin in adults aged 65 years and older.
In the matched analysis of more than 500,000 pairs of macrolide and nonmacrolide users, the 30-day risk of ventricular arrhythmia was the same for both groups (0.03 percent; p=0.6). Use of macrolide antibiotics was associated with an 18 percent lower risk of all-cause mortality compared with use of nonmacrolide antibiotics (p<0.001). Results were similar in the overall analysis of 616,359 macrolide users and 705,132 nonmacrolide users, the researchers report in a paper online in CMAJ. Results were similar across all subgroups (with and without chronic kidney disease, congestive heart failure, coronary artery disease, or concurrent use of a QT-prolonging drug).
“Worldwide there are several hundred million outpatient prescriptions written for these antibiotics each year,” Dr. Garg said. “While regulatory agencies warn that macrolide antibiotics increase the risk of ventricular arrhythmia, it is reassuring that the findings from our study, along with other studies, suggest this is not a meaningful risk in routine care.”
Dr. Jiun-Ling Wang from National Taiwan University, Taipei, recently reported a slightly increased risk of ventricular arrhythmia and cardiovascular death associated with azithromycin and moxifloxacin.
He told Reuters Health by email, “This study suggests macrolides can still be appropriately used in respiratory tract infection in the elderly due to similar risk of ventricular arrhythmia and better all-cause mortality as compared with other commonly used antibiotics.”
“This study mixed all macrolides (erythromycin, clarithromycin and azithromycin) into one group,” Dr. Wang said. “As previous data showed that azithromycin was associated with the highest risk among all macrolides, a head-to-head comparison between individual macrolide and beta-lactam oral antibiotics may provide important information.”
Dr. Chia-Hsuin Chang, coauthor of Dr. Wang’s report, added, “I would also like to point out that in contrast to this research paper, a recently published Hong Kong study by Wong AYS and colleagues showed that clarithromycin, a macrolide, as compared to amoxicillin, is associated with an increased short-term risk of all-cause, cardiac, and non-cardiac mortality, as well as arrhythmia. The inconsistent results from different studies may be due to substantial variations in practicing behavior and patients’ characteristics in different healthcare systems, implying that unmeasured confounding by indication/contra-indication, comorbidities, and disease severity play a major role.”
“It is strongly recommended to conduct a multinational study to define study populations, exposure, outcomes, and analytic methods with a common protocol, leverage differences in healthcare systems in the assessment of unmeasured confounding, and further examine the heterogeneity across diverse populations,” Dr. Chang concluded.
The study was funded by the Academic Medical Organization of Southwestern Ontario. Dr. Garg declared that his institution received unrestricted research funding from Pfizer.