Risk factors, molecular analysis and treatment outcomes of amikacin-resistant Mycobacterium avium complex pulmonary disease.

Abstract

Background: Although the incidence of amikacin (AMK)-resistant Mycobacterium avium complex (MAC) pulmonary disease (PD) is suspected to have increased, limited data are available on AMK-resistant MAC-PD. This study evaluated the risk factors associated with AMK resistance, the molecular characteristics of the AMK-resistant isolates, and treatment outcomes of patients with AMK-resistant MAC-PD.

Methods: This retrospective case-control study included 73 patients with severe and refractory MAC-PD who had a history of aminoglycoside drug use. Patients with initial and repeat AMK minimum inhibitory concentration (MIC) ≥64 μg·mL^-1 were classified as AMK-resistant. To clarify the clinical outcomes and prognosis, an observational study was conducted. 21 patients with AMK resistance (AMK-resistant) and 52 controls (AMK-susceptible) were analysed.

Results: In all cases of AMK resistance where previous isolates were available, the AMK MICs were elevated compared to the levels prior to aminoglycoside administration. In the multivariate analysis of risk factors, clarithromycin resistance (OR 6.31, 95% CI 1.68-23.7) and >12 months of total duration of aminoglycoside use (OR 4.69, 95% CI 1.09-20.2) were identified as independent risk factors for AMK resistance. 12 (57%) out of 21 AMK-resistant isolates were found to have mutations in the rrs region. There was a significant difference between the AMK-resistant and AMK-susceptible groups in terms of worsening outcomes, including the introduction of home oxygen therapy (38% versus 12%; p=0.01) and 3-year mortality (33% versus 10%; p=0.02).

Conclusions: Better management strategies for patients with severe and refractory MAC-PD are crucial. This includes placing a strong emphasis on preventing AMK resistance.