Drug Susceptibility Profiling and Genetic Determinants ofDrug Resistance in Mycobacterium simiae isolates obtained fromRegional Tuberculosis Reference Laboratories of Iran

Background and Aim : Among Non-tuberculous mycobacteria (NTM) which generally causeopportunistic infections, especially in immunocompromised hosts, Mycobacterium simiae (M.simiae) is one of the most important NTM, associated with pulmonary disease. The main concernabout M. simiae infections is the extreme resistance of this NTM to antibiotics. There are limitedstudies about drug susceptibility testing (DST) and the causes of drug resistance in M. simiae.Hence, the current study aimed to identify the M. simiae isolates and to assess the drug resistanceof the isolates using phenotypic and molecular methods.Methods : In this study, ۵۰ clinical pulmonary isolates suspected of NTM were collected fromregional tuberculosis reference laboratories of Iran. The isolates were identified as M. simiae byusing standard biochemical tests and molecular methods. DST was performed for identified M.simiae isolates and additional ۳۵ M. simiae isolates from the department archive, against eightdrugs. The mutations in gyrA, gyrB, and rrl genes in clarithromycin and moxifloxacin resistantisolates were investigated by polymerase chain reaction (PCR) followed by sequencing.Results : Out of ۵۰ suspected NTM isolates, ۲۵ isolates were detected as M. simiae species basedon the biochemical tests, and ۱۸ isolates were verified based on the rpoB gene sequence analysisto achieve a total of ۵۳ isolates when the archive isolates were included. DST results showed thatall ۵۳ isolates were resistant to isoniazid, rifampin, and clofazimine. The rate of resistance toethambutol and linezolid were ۳۴ (۶۴%), and ۴۰ (۷۶%) respectively. The highest susceptibilityrate was demonstrated for amikacin ۵۳ (۱۰۰%) and clarithromycin ۴۵(۸۵%), followed bymoxifloxacin ۳۵(۶۶%). Sequence analysis showed mutations in positions ۲۰۵۸ and ۲۰۵۹ of the rrlgene, as well non-synonymous mutation at codons ۳۸۹, ۴۴۴, and ۵۷۱ of the gyrB gene. Sequenceanalysis showed no mutation in the gyrA gene. drug-resistant isolates with mutations showedhigher MICs compared to non-mutant-resistant isolates.Conclusion : This study revealed amikacin, clarithromycin, and moxifloxacin as the mosteffective antibiotics. However, since M. simiae exhibited a high level of antibiotic resistance invitro, therefore, species identification and determining the antibiotic susceptibility pattern of theisolates are essential before treatment.

کلیدواژه ها:

Antibiotic resistance ، Iran ، Mycobacterium simiae