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Risk factors, molecular analysis and treatment outcomes of amikacin-resistant Mycobacterium avium complex pulmonary
Tatsuya Kodama1,2,3, Akio Aono3, Keiji Fujiwara1,2,3
1Respiratory Disease Center, Fukujuji Hospital, Japan Anti-Tuberculosis Association, Tokyo, Japan.
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.
Insights
Amikacin resistance in Mycobacterium avium complex pulmonary disease is linked to prior clarithromycin resistance and prolonged aminoglycoside use. This resistance is associated with poorer patient outcomes and increased mortality.
Area of Science:
- Pulmonary Medicine
- Infectious Diseases
- Microbiology
Background:
- Limited data exist on amikacin (AMK)-resistant Mycobacterium avium complex (MAC) pulmonary disease (PD), despite suspected increases in incidence.
- This study investigates risk factors, molecular characteristics, and treatment outcomes for AMK-resistant MAC-PD.
Purpose of the Study:
- To identify risk factors for amikacin resistance in MAC-PD.
- To characterize the molecular basis of AMK resistance in MAC isolates.
- To evaluate the clinical outcomes and prognosis of patients with AMK-resistant MAC-PD.
Main Methods:
- Retrospective case-control and observational study of 73 patients with severe/refractory MAC-PD and prior aminoglycoside use.
- AMK resistance defined as minimum inhibitory concentration (MIC) ≥64 μg·mL⁻¹.
- Analysis of risk factors, molecular mutations (rrs region), and clinical outcomes (oxygen therapy, mortality).
Main Results:
- Clarithromycin resistance (OR 6.31) and >12 months of aminoglycoside use (OR 4.69) were independent risk factors for AMK resistance.
- Mutations in the rrs region were found in 57% of AMK-resistant isolates.
- AMK-resistant group showed significantly worse outcomes: increased home oxygen therapy (38% vs 12%) and 3-year mortality (33% vs 10%).
Conclusions:
- Preventing AMK resistance is crucial for managing severe and refractory MAC-PD.
- Enhanced strategies are needed to mitigate the development of AMK resistance in MAC-PD patients.
