Safety and effectiveness of low-dose amikacin in nontuberculous mycobacterial pulmonary disease treated in Toronto, Canada

Abstract

Background Treatment guidelines suggest either a low-dose or high-dose approach when prescribing amikacin for nontuberculous mycobacterial pulmonary disease (NTM PD), but data supporting the low-dose approach are limited. The purpose of this study was to describe the safety and efficacy of the use of a low-dose of intravenous amikacin in a cohort of patients with NTM PD. Methods We retrospectively reviewed all patients with NTM PD who received amikacin at our institution between July 1, 2003 and February 28, 2017. Demographics, clinical, microbiological and radiological data, indication and dose of amikacin, and adverse drug effects were recorded. Results A total of 107 patients received a regimen containing amikacin for a median (IQR) of 7 (4–11) months. Seventy (65.4%) were female and the mean age (SD) was 58.3 (14.9) years. Amikacin was started at a median dose of 9.9 (2.5) mg/kg/day. Ototoxicity was observed in 30/77 (39%) patients and it was related to female sex (OR 4.96, 95%CI 1.24–19.87), and total dose of amikacin per bodyweight (OR 1.62, 95%CI 1.08–2.43). Patients of East Asian ethnicity were less likely to develop ototoxicity (0.24, 95%CI 0.06–0.95). Out of 96 patients who received amikacin for more than 3 months, 65 (67.7%) experienced symptom improvement and 30/62 (49.2%) converted their sputum to culture negative within a year. Conclusions Patients with NTM PD treated with low-dose intravenous amikacin frequently developed ototoxicity, which was associated with female sex, and total dose of amikacin per bodyweight. Physicians should carefully consider dose, treatment duration, and long term prognosis in balancing risks and benefits of intravenous amikacin in NTM PD.

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“…Current standard of care (SOC) regimens usually result in unsatisfactory treatment outcomes due to the nature of NTM's multi-drug resistance 14 . Furthermore, SOC regimens for NTM-related infections are typically prescribed with Amikacin (aminoglycoside antibiotic); however, 39% of patients experienced ototoxicity after 5.5 months (median) of Amikacin in a recent study 12 , 15 . Though these guidelines provide recommended drug combinations against NTM, further optimization in the design of combination therapies against NTM may lead to the discovery of unforeseen drug interactions and improved clinical outcomes 16 , 17 .…”