Aminoglycoside toxicity: daily versus thrice-weekly dosing for treatment of mycobacterial diseases.

Aminoglycoside use is limited by ototoxicity and nephrotoxicity. This study compared the incidences of toxicities associated with 2 recommended dosing regimens. Eighty-seven patients with tuberculosis or nontuberculous mycobacterial infections were prospectively randomized by drug to receive 15 mg/kg per day or 25 mg/kg 3 times per week of intravenous streptomycin, kanamycin, or amikacin. Doses were adjusted to achieve target serum concentrations. The size of the dosage and the frequency of administration were not associated with the incidences of ototoxicity (hearing loss determined by audiogram), vestibular toxicity (determined by the findings of a physical examination), or nephrotoxicity (determined by elevated serum creatinine levels). Risk of ototoxicity (found in 32 [37%] of the patients) was associated with older age and with a larger cumulative dose received. Vestibular toxicity (found in 8 [9%] of the patients) usually resolved, and nephrotoxicity (found in 13 [15%] of the patients) was mild and reversible in all cases. Subjective changes in hearing or balance did not correlate with objective findings. Streptomycin, kanamycin, and amikacin can be administered either daily or 3 times weekly without affecting the likelihood of toxicity.

Treatment and outcome analysis of 205 patients with multidrug-resistant tuberculosis.

Multidrug-resistant tuberculosis, a disease caused by Mycobacterium tuberculosis strains that are resistant at least to rifampin and isoniazid, entails extended treatment, expensive and toxic regimens, and higher rates of treatment failure and death. We retrospectively analyzed the outcomes in 205 patients treated at our center for multidrug-resistant tuberculosis, with strains resistant to a median of six drugs, and compared the results with those of our previous series. Logistic regression and survival analysis were used to evaluate short- and long-term outcomes, respectively. Initial favorable response, defined as at least three consecutive negative sputum cultures over a period of at least 3 months, was 85% compared with 65% in the prior cohort. The current cohort had greater long-term success rates, 75% versus 56%, and lower tuberculosis death rates, 12% versus 22%, than the earlier one. Surgical resection and fluoroquinolone therapy were associated with improved microbiological and clinical outcomes in the 205 patients studied after adjusting for other variables. The improvement was statistically significant for surgery and among older patients for fluoroquinolone therapy.