Low-dose amikacin in the treatment of Multidrug-resistant Tuberculosis (MDR-TB)

摘要

The World Health Organization recommends intravenous amikacin for the treatment of MDR-TB at a dose of 15?mg/kg. However, higher doses are associated with significant toxicity. Patients with MDR-TB treated at our institution receive amikacin at 8–10?mg/kg, with dose adjustment based on therapeutic drug monitoring. We conducted a retrospective cohort study of patients with MDR-TB who received amikacin between 2010 and 2016. Forty-nine patients were included in the study. The median starting dose of amikacin was 8.9?mg/kg (IQR 8, 10), and target therapeutic drug levels were achieved at a median of 12?days (IQR 5, 26). The median duration of amikacin treatment was 7.2?months (IQR 5.7, 8), and median time to sputum culture conversion was 1?month (IQR 1,2). Six patients (12.2%) experienced hearing loss based on formal audiometry testing (95% CI 4.6–24.8%); 22.2% had subjective hearing loss (95% CI 11.2–37.1%) and 31.9% subjective tinnitus (95% CI 19.1–47.1%). Ten patients (23%) had a significant rise in serum creatinine (95% CI 11.8–38.6%), but only 5 patients had a GFR ?60 at treatment completion. 84% of patients had a successful treatment outcome (95% CI 84–99%). Low dose amikacin is associated with relatively low rates of aminoglycoside-related adverse events. We hypothesize that low-dose amikacin can be used as a safe and effective treatment for MDR-TB in situations where an adequate regimen cannot be constructed with Group A and B drugs, and where careful monitoring for adverse events is feasible.