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Published on: April 25, 2014
Phenotypic amikacin resistance may not indicate poor response to amikacin in Mycobacterium avium complex pulmonary
L M Minuk1, S K Brode1,2,3, M Mehrabi4
1Division of Respirology, Department of Medicine, University of Toronto, Toronto, Ontario, Canada.
Abstract:
When using amikacin to treat Mycobacterium avium complex pulmonary disease (MAC-PD), a minimum inhibitory concentration resistance breakpoint of ≥64 mcg/mL is recommended. We explored whether amikacin resistance characterized by phenotypic drug susceptibility testing was associated with clinical outcomes or mutational resistance in a retrospective cohort of patients with MAC-PD. Despite little aminoglycoside exposure, amikacin resistance was common in our MAC-PD patients but was not associated with worse outcomes or rrs gene mutations.
Insights
Amikacin resistance is common in Mycobacterium avium complex pulmonary disease (MAC-PD) patients, even with limited drug exposure. However, this resistance did not correlate with poorer clinical outcomes or specific gene mutations.
Area of Science:
- Microbiology
- Pulmonary Medicine
- Infectious Diseases
Background:
- Mycobacterium avium complex pulmonary disease (MAC-PD) requires effective treatment, often involving amikacin.
- A high minimum inhibitory concentration resistance breakpoint (≥64 mcg/mL) is recommended for amikacin in MAC-PD.
- Understanding amikacin resistance mechanisms and clinical impact is crucial for optimizing MAC-PD therapy.
Purpose of the Study:
- To investigate the association between phenotypic amikacin resistance and clinical outcomes in MAC-PD patients.
- To determine if phenotypic amikacin resistance correlates with genotypic resistance, specifically mutations in the *rrs* gene.
- To assess the prevalence of amikacin resistance in MAC-PD despite potentially low aminoglycoside exposure.
Main Methods:
- Retrospective cohort study of patients diagnosed with MAC-PD.
- Phenotypic drug susceptibility testing (DST) was used to characterize amikacin resistance.
- Analysis of clinical outcomes and *rrs* gene mutations in relation to amikacin resistance.
Main Results:
- Amikacin resistance was frequently observed in the MAC-PD patient cohort.
- Despite the prevalence of resistance, no significant association was found between amikacin resistance and worse clinical outcomes.
- Phenotypic amikacin resistance was not linked to the presence of *rrs* gene mutations in this patient group.
Conclusions:
- Amikacin resistance is common in MAC-PD, irrespective of prior aminoglycoside exposure.
- Current amikacin resistance breakpoints may not accurately predict clinical outcomes in MAC-PD.
- Further research is needed to understand the drivers of amikacin resistance and its clinical relevance in MAC-PD.

