Analysis of drug-susceptibility patterns and gene sequences associated with clarithromycin and amikacin resistance in serial Mycobacterium abscessus isolates from clinical specimens from Northeast Thailand

Abstract

Mycobacterium abscessus is an important infectious agent highly associated with drug resistance and treatment failure. We investigated the drug resistance situation of M. abscessus in Northeast Thailand and the possible genetic basis for this. Sixty-eight M. abscessus clinical isolates were obtained from 26 patients at Srinagarind Hospital during 2012-2016. Drug susceptibility tests and sequencing of erm(41), rrl and rrs genes were performed. Mycobacterium abscessus was resistant to 11/15 antibiotics (nearly 100% resistance in each case). Partial susceptibility to four antibiotics was found (amikacin, tigecycline, clarithromycin and linezolid). Non-massiliense subspecies were significantly associated with clarithromycin resistance (p<0.0001) whereas massiliense subspecies were associated with tigecycline resistance (p = 0.028). Inducible clarithromycin resistance was seen in 22/68 (32.35%) isolates: 21 of these isolates (95.45%) belonged to non-massiliense subspecies and resistance was explicable by the T28C mutation in erm(41). Inducible clarithromycin resistance was found in one isolate of the massiliense subspecies. Acquired clarithromycin resistance explicable by the A2271G/C mutation of rrl was seen in only 7/16 (43.75%) of strains. Inducible and acquired resistance mechanisms can be interchangeable during the course of infection. Rrs mutations were not associated with amikacin resistance in our study. Antibiotic resistance in subspecies of M. abscessus was reported from Northeast Thailand. Known resistance-associated mutations cannot explain all of the resistance patterns observed.

Fig 1. Drug susceptibility patterns of M. abscessus serially isolated from individual patients (P#1-P#26).

Only susceptible (green letters) or intermediate (purple letters) levels of drug sensitivity are shown, except for “CLA” for which “IR” (inducible resistance) and “R” (acquired resistance) are shown. Organ sites are shown except pulmonary sites. Reinfection or recolonization strains (different strain among serial isolates– 2 patients) are excluded. “NONE” refers to resistance to all 15 antibiotics. The timeline shows number of days between successive samplings. ^a These cases were defined as colonization. AMK = Amikacin, FOX = Cefoxitin, CLA = Clarithromycin, DOX = Doxycycline, LZD = Linezolid, MFX = Moxifloxacin, Min = Minocycline, TGC = Tigecycline.