Inducible Resistance to Amikacin in Mycobacterium abscessus Isolated in Beijing, China
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Zhijian Zhang1, Wei Wang2, Yufeng Wang3
1Department of Respiratory and Critical Care Medicine, the Second Medical Center of Chinese PLA General Hospital, Beijing, 100036, People's Republic of China.
Abstract:
We aimed to determine the prevalence of amikacin (AMK) resistance of clinical Mycobacterium abscessus (MAB) isolates and to investigate if AMK resistance was induced by AMK exposure. A total of 75 MAB isolates underwent susceptibility testing for AMK after 3 and 14 days of incubation, respectively. The partial fragment of the rrs gene conferring AMK resistance was sequenced. The MIC values for AMK ranged from 0.5 to 128 μg/mL, with MIC50 and MIC90 values of 2 and 32 μg/mL, respectively. In addition, 9.3% of isolates (7/75) were resistant to AMK, all of which harbored a mutation within the rrs locus, including six with A1408G mutation and one with a C1409T mutation. Of note, the MICs of three isolates were significantly increased from 2 μg/mL to 64 μg/mL (one isolate) and 2 μg/mL to 128 μg/mL (two isolates), suggesting that three of the MAB isolates had inducible resistance to AMK. In conclusion, our data demonstrate that approximately one-tenth of clinical MAB isolates in Beijing harbored AMK resistance due to the acquisition of rrs mutations. Additionally, we firstly identified that intrinsic AMK resistance is inducible in MAB isolates, highlighting the urgent need to establish a proper method for the in vitro detection of AMK susceptibility in MAB.
Insights
Approximately 10% of clinical Mycobacterium abscessus isolates in Beijing show amikacin resistance due to rrs gene mutations. This study also reveals inducible amikacin resistance in MAB, necessitating improved susceptibility testing methods.
Area of Science:
- Microbiology
- Genetics
- Antimicrobial Resistance
Background:
- Mycobacterium abscessus (MAB) is an opportunistic pathogen.
- Amikacin (AMK) is a critical antibiotic for treating MAB infections.
- Understanding AMK resistance mechanisms in MAB is crucial for effective treatment.
Purpose of the Study:
- To determine the prevalence of amikacin resistance in clinical MAB isolates.
- To investigate if AMK resistance can be induced by AMK exposure.
- To identify genetic mutations associated with AMK resistance.
Main Methods:
- Susceptibility testing of 75 MAB isolates to AMK after 3 and 14 days.
- Sequencing of the rrs gene fragment associated with AMK resistance.
- Analysis of Minimum Inhibitory Concentration (MIC) values.
Main Results:
- AMK MIC values ranged from 0.5 to 128 μg/mL (MIC50=2, MIC90=32).
- 9.3% of isolates (7/75) exhibited AMK resistance, all with rrs mutations (A1408G or C1409T).
- Three isolates showed inducible resistance, with MICs increasing significantly after prolonged exposure.
Conclusions:
- About 10% of clinical MAB isolates in Beijing possess AMK resistance linked to rrs mutations.
- Inducible AMK resistance in MAB is identified for the first time.
- There is an urgent need for improved in vitro methods to detect AMK susceptibility in MAB.
