Groningen, The Netherlands—The recommended treatment for tuberculosis (TB) might be effective against the respiratory disease, but, depending on the dosage, it can cause significant hearing loss and kidney damage.
Now, new research published in Antimicrobial Agents and Chemotherapy, a journal of the American Society for Microbiology, finds that the dosage of aminoglycosides can be reduced in a carefully calculated manner, thereby reducing hearing loss without compromising effectiveness against TB.
The study began as a multidisciplinary effort to provide better care for patients, said principal investigator Jan-Willem C. Alffenaar, PhD, PharmD, associate professor in the Department of Clinical Pharmacy and Pharmacology at the University of Groningen in the Netherlands. The concern was that the usual medication dose caused hearing loss in 40% of patients.
By monitoring the concentration of the recommended drug strength in patients' blood, researchers were able to determine whether it was too high or too low and how effective it was against the bacteria. “If the bacteria are more susceptible to the antibiotic than normal, we can use a lower dose,” said Alffenaar explained.
Ultimately, personalized dosages were able to be reduced to as little as one-third of the current standard in some patients, reducing hearing loss from 40% to 10%.
“The dosage applied in our study is two-fold lower than the 15 mg/kg recommended by the
World Health Organization, yet outcome was favorable in the vast majority of patients, and in those with unfavorable outcome, aminoglycoside dosage appeared unrelated to those outcomes,” study authors conclude.
Overall, two-thirds of the 57 patients had successful outcomes, with TB eradicated over 2 years’ follow-up, and low percentages of hearing loss.
“At a median dose of 6.5 mg/kg a correlation was found between the dose per kg bodyweight during daily dosing and the extent of hearing loss in dB at 8000 Hz,” according to the researchers. “This study suggests that the efficacy at this lower dosage is maintained with limited toxicity. A randomized controlled trial should provide final proof of the safety and efficacy of [therapeutic drug monitoring]-guided use of aminoglycosides in MDR-TB treatment.”
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