Around the world, inexpensive antibiotics known as aminoglycosides have been used for the past 60 years in the battles against acute infections and tuberculosis as antibacterial prophylaxis in cystic fibrosis patients and in other conditions. But for all of the good they do, the drugs also have been widely linked to irreversible hearing loss.
Now, researchers at the University of Michigan's Kresge Hearing Research Institute and their Chinese colleagues, working under the leadership of Jochen Schacht, Ph.D., and Su-Hua Sha, M.D., have found that the hearing loss can be prevented in many people with the use of another inexpensive, widely available medication: aspirin. The results appear in the April 27 issue of the New England Journal of Medicine.
The researchers studied 195 patients in China who received 80 to 160 milligrams of gentamicin (a type of aminoglycoside) intravenously twice daily, typically for five to seven days. Of those, 89 patients were given aspirin along with the antibiotic, and 106 were given placebos along with the antibiotic. The results were dramatic: The incidence of hearing loss in the group that was given placebos was 13 percent, while in the aspirin group it was just 3 percent, or 75 percent lower.
"We would like to see the word get around to the medical community around the world that you can take some precautions to minimize the risk to your patients. Aspirin is available everywhere, and it's cheap," says senior author Schacht, professor of biological chemistry in otolaryngology at the University of Michigan Medical School and director of the U-M Health System's Kresge Hearing Research Institute. Gentamicin is not commonly used in the United States.
He notes that this research builds on earlier U-M studies that showed promise in combating drug-induced hearing loss in the laboratory. "Previously we found that such a treatment works well in mice, but I am very excited that this worked so well in humans," says Schacht. "Translating animal studies into clinical practice is not an easy thing to do. We were fortunate that our extrapolation from mice to men and women worked in the first trial."
The research is exciting, says lead author Sha, because hearing loss caused by these antibiotics is so prevalent. The incidence of aminoglycoside-induced hearing loss averages 8 percent but the numbers may be higher in developing countries, she notes, where aminoglycosides are frequently the only affordable antibiotics and are sold over the counter. No therapy currently exists to prevent ototoxicity.
This research began in 1999 with a collaboration with Chinese hospitals. Working with Schacht, Sha -- associate laboratory director of U-M's Kresge Hearing Research Institute's Biochemistry Laboratory -- got in touch with her colleagues in China. The two traveled to China and presented their ideas, and ultimately began a partnership with the Fourth Military Medical University in Xi'an, China. The third author on the paper, Jian-Hua Qiu, M.D., represents the colleagues of the Fourth Military Medical University.
After receiving approvals from institutional review boards at U-M and the Fourth Military Medical University, the otolaryngology department in Xi'an conducted the prospective, randomized, double-blind trial at Xijing Hospital and Airforce Chengdu Hospital from 1999 to 2003. All of the participants were ages 18 to 65, and were inpatients who were scheduled for treatment with gentamicin. Hearing damage, or ototoxicity, was defined as a shift from a person's baseline hearing by at least 15 decibels at both the 6 and 8 kHz frequencies, which are the first affected by the drugs. The effectiveness of the gentamicin as an antibiotic did not lessen when it was paired with aspirin.
Schacht notes that even though gentamicin has been linked widely with hearing loss, and its use has been declining in industrial countries, it is not practical to think that it will be replaced in the near future by other antibiotics because it has specific applications and is so inexpensive and available, especially in poor countries. While aspirin shows promise, and he hopes that health care providers pair it with gentamicin, he also notes it is not yet the perfect solution because of the potential side effects of aspirin, including gastric bleeding. And he notes that this is an off-label use of aspirin, which may inhibit some practitioners from giving it to patients in such instances.
He hopes that further studies will lead to the development of new and safer antibiotics, or another drug that can be paired with gentamicin that has fewer side effects than aspirin. He and Sha are exploring partnerships with other countries to conduct future research.
Funding for the research came from George and Christine Strumbos and the Kent and Carol Landsberg Foundation.
Citation: New England Journal of Medicine, Volume 354, Issue 17: April 27, 2006.
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