J Kim1, H Sung2, J-S Park2, S-H Choi3, T-S Shim3, M-N Kim2. 1. Department of Asan Medical Center and University of Ulsan College of Medicine, Seoul, Republic of Korea; Department of Laboratory Medicine, Asan Medical Center and University of Ulsan College of Medicine, Seoul, Republic of Korea. 2. Department of Laboratory Medicine, Asan Medical Center and University of Ulsan College of Medicine, Seoul, Republic of Korea. 3. Department of Internal Medicine, Asan Medical Center and University of Ulsan College of Medicine, Seoul, Republic of Korea.
Abstract
BACKGROUND: Treating Mycobacterium abscessus infections with antimicrobials remains difficult, possibly due to drug resistance. OBJECTIVE: To investigate the subspecies distribution of M. abscessus and its correlation with antibiotic susceptibility and the genetics of antibiotic resistance, focusing on macrolides and fluoroquinolones, in the Republic of Korea. DESIGN: A total of 53 M. abscessus isolates were identified to the subspecies level by sequencing of hsp65 and erm(41). The minimal inhibitory concentrations (MICs) of clarithromycin (CLM) and ciprofloxacin (CFX) were determined using Sensititre™ RAPMYCO plates. The rrl, gyrA and gyrB genes were sequenced to elucidate the molecular mechanisms of macrolide and fluoroquinolone resistance. RESULTS: Isolates included 22 M. abscessus subsp. abscessus and 31 M. abscessus subsp. bolletii. erm(41) sequences showing subspecies-specific deletions and sequence variations in the 28th nucleotide were concordant with inducible CLM resistance; however, mutations in rrl were not detected. Low- and high-level CFX resistance was observed in respectively 19 (35.8%) and 10 (18.9%) of the 53 clinical isolates, regardless of subspecies. However, no non-synonymous mutations were detected in gyrA or gyrB. CONCLUSION: Sequencing of the erm gene and subspeciation of M. abscessus may be used to predict inducible macrolide susceptibility. Further studies of the relationship between specific mutations in gyrA or gyrB to MIC change are required.
BACKGROUND: Treating Mycobacterium abscessus infections with antimicrobials remains difficult, possibly due to drug resistance. OBJECTIVE: To investigate the subspecies distribution of M. abscessus and its correlation with antibiotic susceptibility and the genetics of antibiotic resistance, focusing on macrolides and fluoroquinolones, in the Republic of Korea. DESIGN: A total of 53 M. abscessus isolates were identified to the subspecies level by sequencing of hsp65 and erm(41). The minimal inhibitory concentrations (MICs) of clarithromycin (CLM) and ciprofloxacin (CFX) were determined using Sensititre™ RAPMYCO plates. The rrl, gyrA and gyrB genes were sequenced to elucidate the molecular mechanisms of macrolide and fluoroquinolone resistance. RESULTS: Isolates included 22 M. abscessus subsp. abscessus and 31 M. abscessus subsp. bolletii. erm(41) sequences showing subspecies-specific deletions and sequence variations in the 28th nucleotide were concordant with inducible CLM resistance; however, mutations in rrl were not detected. Low- and high-level CFX resistance was observed in respectively 19 (35.8%) and 10 (18.9%) of the 53 clinical isolates, regardless of subspecies. However, no non-synonymous mutations were detected in gyrA or gyrB. CONCLUSION: Sequencing of the erm gene and subspeciation of M. abscessus may be used to predict inducible macrolide susceptibility. Further studies of the relationship between specific mutations in gyrA or gyrB to MIC change are required.