Inhalational antibiotic therapy for treatment of chronic pulmonary Mycobacterium abscessus disease in mice
Date
2019
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Abstract
Mycobacterium abscessus (M. abscessus) is a nontuberculous mycobacterium that causes chronic pulmonary infections. Due to M. abscessus's intrinsic antibiotic resistance, treatment is often complex with low cure rates. Tigecycline, a glycylcycline class antibiotic, demonstrates bactericidal effects against M. abscessus without eliciting bacterial resistance mechanisms, however, this antibiotic requires intravenous administration and causes significant side effects that limit its use. Here, we tested the hypothesis that tigecycline administered via inhalation has the potential to maximize the bactericidal effect while reducing side effects. GM-CSF knockout mice with pulmonary M. abscessus infection were treated by intrapulmonary tigecycline aerosols in 0.25 mg, 1.25 mg, and 2.50 mg doses for 28 days. Assessment of pulmonary bacterial burden after full treatment duration shows that inhaled tigecycline is highly effective, dose-dependent, and well tolerated. We concluded that inhaled tigecycline represents a viable treatment option for M. abscessus pulmonary disease. Future studies should address the pharmacokinetics, and ultimately, translation into clinical trials.
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Subject
Mycobacterium abscessus
nontuberculous
inhaled therapy
tigecycline
Mycobacterium infection