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.

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.