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

Abstract

Abstract Background 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. Methods 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. Results 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%). Conclusions 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.

Keywords

• Aminoglycosides
• Therapeutic drug monitoring
• Hearing loss
• Tuberculosis
• Pharmacokinetics
• Pharmacodynamics