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Popular Antibiotic May Raise Risk of Sudden Death
The increased odds of death are small, but significant enough that the authors of the study say doctors should consider prescribing a different drug, like amoxicillin, for high-risk patients who need antibiotics. People at high risk include those with heart failure, diabetes or a previous heart attack, and those who have undergone bypass surgery or have had stents implanted. In such patients, the drug may cause abnormal heart rhythms that can be fatal. Just how the drug might disrupt heart rhythm is not known, the researchers said.
The concerns do not apply to children, because most have very little risk of heart disease, according to the lead author of the study, Wayne A. Ray, a professor of preventive medicine at Vanderbilt University. The study is being published on Thursday in The New England Journal of Medicine.
Azithromycin is used to treat bacterial infections, including bronchitis, pneumonia, sore throats and earaches. It is familiar to many people as the “Z-Pak,” to be taken for five days, and part of its appeal is its convenience; many other antibiotics must be taken for 10 days or longer. Last year, doctors wrote 55. 3 million prescriptions for azithromycin in the United States, and sales were $464.6 million, according to IMS Health, a health care information and services company. Global sales were $1.8 billion.
Two related antibiotics, erythromycin and clarithromycin, were already known to raise the risk of sudden death. But azithromycin was thought to be safer.
Experts outside the study gave it differing reviews.
Dr. John G. Bartlett, a professor of medicine at Johns Hopkins University School of Medicine and a former president of the Infectious Diseases Society of America, said, “I’m inclined to agree with Dr. Ray.”
He said he was convinced by the study because it included data on a huge number of patients and because the findings were biologically plausible, given that related drugs had also been found capable of disrupting heart rhythm. For patients at high risk, he would prescribe a different drug, he said, adding that there are plenty of alternatives.
Dr. Bartlett also said that the study provided another reason to curb overuse of antibiotics, which are too often prescribed for colds and other viral infections that they cannot treat. The overuse has contributed to the emergence of dangerous, drug-resistant strains of bacteria.
“We use azithromycin for an awful lot of things, and we abuse it terribly,” Dr. Bartlett said. “It’s very convenient. Patients love it. ‘Give me the Z-Pak.’ For most of where we use it, probably the best option is not to give an antibiotic, quite frankly.”
Dr. Lori Mosca, director of preventive cardiology at NewYork-Presbyterian Hospital/Columbia University Medical Center, advised caution in interpreting the study, because of its methodology and because azithromycin’s benefits may outweigh the small risks suggested by the study.
Dr. Mosca noted that the study was observational, meaning that the researchers looked back at medical records, rather than setting up an experiment in which patients were assigned at random to one treatment or another and then monitored. Even the most careful observational study can be misleading, she said: results that appear related to treatment may really be due to basic, undetected differences between groups of patients. She said a more rigorous study should be done to verify these new findings.
In the meantime, she said: “It would be crazy to think we can’t use azithromycin. It’s bad to undertreat infections.”
Dr. Roy M. Gulick, the chief of infectious diseases at NewYork-Presbyterian/Weill Cornell, also said that more research was needed. But, he said, “in someone with significant cardiovascular risks or documented disease, the results of this study would be one factor that would help you choose among the antibiotics.”
Dr. Ray and his team analyzed the medical records of about 540,000 Medicaid patients ages 30 to 74 in Tennessee from 1992 to 2006. The researchers looked at cardiovascular deaths while people were taking various antibiotics and during comparable periods in which they were taking none: about 350,000 prescriptions for azithromycin, 1.4 million matched periods with no treatment, 1.4 million prescriptions for amoxicillin, 265,000 for ciprofloxacin and 194,000 for levofloxacin. By comparing people taking other antibiotics, the researchers hoped to control for the possibility that the infections they were being treated for were the cause of sudden death.
Over all, there were few sudden deaths during these specified periods, fewer than 100 combined among those taking azithromycin, amoxicillin or no antibiotic. But when the researchers calculated the rates of sudden death per million courses of treatment (or untreated control periods), azithromycin stood out, with 64.6 deaths per million courses, as opposed to 21.8 for amoxicillin and 24 when there was no treatment. The death rates with azithromycin and levofloxacin were about the same (earlier studies have linked levofloxacin to abnormal heart rhythms), and were higher than the rate with ciprofloxacin.
The people who had the greatest baseline risk for heart disease had the highest risk from taking azithromycin.
“Any antibiotic is going to have risks and benefits,” Dr. Ray said. “We think this is an important piece of information about risks.”