Neil M. Ampel, MD reviewing Olivier KN et al. Am J Respir Crit Care Med 2017 Mar 15.
Liposomal amikacin for inhalation resulted in higher sputum conversion rates and increased exercise tolerance.
Treatment for patients with pulmonary nontuberculous mycobacterial (PNTM) disease is often unsatisfactory. The addition of parenteral aminoglycosides, such as amikacin, to oral therapy is limited because of systemic toxicity. Liposomal amikacin for inhalation (LAI) is a novel formulation that allows for direct delivery of the drug to infected pulmonary macrophages with reduced toxicity.
To examine the efficacy and safety of LAI for PNTM, investigators conducted a multicenter, randomized, double-blind, placebo-controlled, phase II, trial involving 89 PNTM patients with positive sputum cultures who had received multidrug therapy for ≥6 months prior to screening. Patients received a multidrug regimen plus either LAI or placebo by nebulizer once daily for 84 days. An additional 84 days of open-label therapy was given to consenting subjects. Among all patients, 64% had predominantly Mycobacterium avium complex infection, 36% had predominantly Mycobacterium abscessus infection, and 19% had cystic fibrosis.
Although patients receiving LAI versus placebo did not achieve a significantly greater decline in a semiquantitative scale for sputum mycobacterial growth after 84 days (the primary outcome; P=0.072), significantly more LAI recipients had a negative sputum culture (32% vs. 9%; P=0.006). LAI recipients also demonstrated a significant improvement in the 6-minute walk test versus placebo recipients (mean change in distance, +20.6 vs. −25.0 meters; P<0.017). However, LAI use did not result in culture clearance if the isolate was amikacin resistant (minimum inhibitory concentration >64 µg/mL). Also, serious adverse events, most commonly worsening bronchiectasis and pneumonia, occurred at a higher rate in the LAI group (18% vs. 9%).
CITATION(S):
Olivier KN et al. Randomized trial of liposomal amikacin for inhalation in nontuberculous mycobacterial lung disease. Am J Respir Crit Care Med 2017 Mar 15; 195:814.
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