Relationship between Antibiotic Susceptibility and Genotype in Mycobacterium abscessus Clinical Isolates

Abstract

This study aimed to determine the antibiotic susceptibility and resistance related genotypes of Mycobacterium abscessus. One hundred sixty-two clinical isolates were collected. Genomic data were obtained by whole genome sequencing. Single nucleotide polymorphism (SNP) analysis was conducted using the NCBI GenBank database and BLAST algorithm. The following genes were of interest: erm(41), rrl and rrs. Erm(41) was further divided into 3 sequevars: erm(41)C28, erm(41)T28, and M type [erm(41) with deletions in nucleotides 64 and 65, or 159 through 432]. Antibiotic susceptibility was assessed at 3 days (early reading time, ERT) and 14 days (late reading time, LRT) after clarithromycin (CLA) treatment. Three patterns of CLA resistance were observed. (1) Fifty-five (acquired resistance) isolates [45 erm(41)T28, 1 erm(41)C28 and 9 M type] exhibited MIC ≥8 mg/L at ERT; among these isolates, 10 had an rrl 2058/2059 mutation. (2) Sixty-two subsp. abscessus and 2 subsp. massiliense (induced resistance) isolates exhibited MIC ≤4 mg/L at ERT, but ≥8 mg/L at LRT. (3) Forty-three (sensitive and intermediate) isolates [14 erm(41)C28, 1 erm(41)T28, and 28 M type] exhibited MIC ≤4 mg/L at both ERT and LRT. No rrs 1408 mutation or other meaningful SNP was found in 3 amikacin-resistant isolates. No correlation was found between rrl, erm(41) or rrs and susceptibility to the 8 other antibiotics tested. The rrl and erm(41) genotypes could predict the CLA resistance of M. abscessus clinical isolates. China has a large number of CLA-resistant M. abscessus isolates with erm(41)T28 sequevar. Treatment of M. abscessus infections should be based upon a comprehensive consideration of factors that include genotype and geographic location.

Antibiograms and Molecular Characterization of Drug Resistance ofMycobacterium abscessuscomplex from Patients with Multidrug-Resistant Pulmonary Tuberculosis (MDR TB) Infection

“…On the other hand, three M. massiliense isolates (MAS04: >16μg/ml, MAS06: >16μg/ml, MAS10: >16μg/ml) exhibited inducible resistance to CLR and AZM on the 14 th day. This is contrast with previous studies (Kim et al , 2015; Koh et al , 2010) which demonstrated that inducible resistance to CLR was only present in M. abscessus and not in M. massiliense. Nevertheless, our results support the findings of Li et al .…”

“…Susceptibility rates of M. abscessus complex isolates in the present study showed that MXF has better in vitro activity against M. abscessus (81.8% susceptible) and M. massiliense (60% susceptible) compared to CIP against M. abscessus (9.1% susceptible) and M. massiliense (20% susceptible). This is consistent with other studies showing that MXF has better in vitro activity against M. abscessus and M. massiliense compared to CIP (Kim et al , 2015; Lee et al , 2014; Koh et al , 2010). On the other hand, DOX was found to be more potent against M. abscessus (72.7% susceptible) isolates compared to its activity against M. massiliense (10% susceptible).…”

“…These are in conformity with the results of the study of Nie et al in 2014 which showed that the susceptibility rate of M. abscesuss to AMK was 98%. Likewise, Park et al (2008) reported a 99% susceptibility rate of M. abscessus to AMK, while Kim et al (2015) reported the susceptibility rate of M. abscessus and M. massiliense to AMK as 91.2% and 100%, respectively. The susceptibility of all isolates to amikacin in the present study may be attributed to the current treatment regimen for MDR-TB in the country which is comprised of kanamycin and not amikacin.…”

“…Mycobacterium abscessus isolate MAB09 showed inducible resistance to both CLR (>16μg/ml) and AZM (>16μg/ml) on the 14 th day of incubation. Inducible resistance in M. abscessus was expected since they have a functional erm(41) gene (Kim et al , 2015; Koh et al , 2010; Nash et al , 2009). On the other hand, three M. massiliense isolates (MAS04: >16μg/ml, MAS06: >16μg/ml, MAS10: >16μg/ml) exhibited inducible resistance to CLR and AZM on the 14 th day.…”

Clinical Efficacy and Adverse Effects of Antibiotics Used to Treat Mycobacterium abscessus Pulmonary Disease

“…The anti- M. abscessus activity of imipenem in vitro is variable; bacterial resistance was over 60% in some studies (12, 17, 18). Imipenem was efficacious, however, in treating pulmonary M. abscessus disease in our study.…”