Abstract
BackgroundIn multidrug regimens, including an intravenous aminoglycoside (e.g. amikacin [AMK]) is recommended for difficult-to-treat non-tuberculous mycobacterial (NTM) lung diseases. We aimed to evaluate the efficacy, safety, and feasibility of inhaled AMK therapy in patients with difficult-to-treat NTM lung diseases in a retrospective chart review.MethodsThe study population consisted of patients with NTM lung diseases who received combination therapy, including inhaled AMK therapy, at Keio University Hospital (Tokyo, Japan), from January 2014 through May 2016. A total of 26 cases, consisting of 23 Mycobacterium avium complex (MAC) and three Mycobacterium abscessus complex (MABC) infections cases, were included in this study. The efficacy, safety, and feasibility of inhaled AMK therapy were retrospectively investigated. The Research Ethics Committee of Keio University Hospital approved this study, and informed consent was obtained from all patients.ResultsAll 26 patients were culture-positive at enrolment. Twenty-three of the 26 patients (88.5%), including 21/23 MAC patients (91.3%) and 2/3 MABC patients (66.7%), were administered inhaled AMK therapy for >3 months. The proportion of patients who had clinical symptoms, including, cough and sputum, declined after inhalation AMK therapy. Ten of the 23 patients (43.5%) who received AMK inhalation, including 8/21 MAC (38.1%) and 2/2 MABC patients (100%), showed sputum conversion, defined as at least three consecutive negative sputum cultures. Seven of the 23 patients, including, 5/21 MAC and 2/2 MABC patients, showed improvements in high-resolution computed tomography imaging of the chest. In addition, the serum AMK trough levels before the second inhalation were <1.2 μg/mL in all 26 patients, with no occurrence of severe adverse events, such as renal toxicity. One patient (3.8%) experienced auditory toxicity, in the form of tinnitus. However, this symptom was reversible, after temporary interruption of AMK, the patient was able to safely resume the therapy.ConclusionsInhaled AMK therapy is an effective and feasible therapy for difficult-to-treat NTM lung disease.
Highlights
In multidrug regimens, including an intravenous aminoglycoside is recommended for difficult-to-treat non-tuberculous mycobacterial (NTM) lung diseases
The current treatment statement for NTM lung diseases recommends using long-term multidrug regimens, for example, a regimen of clarithromycin (CLA) or azithromycin (AZM), rifampin (RIP) and ethambutol (EMB) for Mycobacterium avium complex (MAC) lung disease [6], but no consensus recommendations have been reached for the treatment of Mycobacterium abscessus complex (MABC) lung disease
All 26 patients had a positive culture at the beginning of AMK inhalation, with 23 patients (88.5%) having a MAC infection and three patients (11.5%) a MABC infection
Summary
In multidrug regimens, including an intravenous aminoglycoside (e.g. amikacin [AMK]) is recommended for difficult-to-treat non-tuberculous mycobacterial (NTM) lung diseases. In addition to the unpredictability of the efficacy of treatment for NTM lung diseases, drug toxicity, drug-drug interactions, intolerance to long-term treatment with multiple antimicrobial agents and resistance to macrolide antibiotics are challenges associated with the management of NTM lung diseases [6,7,8,9]. The intravenous administration of aminoglycoside antibiotics, including amikacin (AMK) and streptomycin, is recommended for patients who have rapidly growing mycobacterial or extensive cavitary MAC lung disease, and for those whose treatment with the standard multidrug regimen comprising CLA or AZM, RIP and EMB has failed [6]. Inhaled aminoglycoside therapy achieving high drug concentrations within the lungs could be beneficial for reducing systemic toxicity and drug-drug interactions
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