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.
BackgroundNontuberculous mycobacterial (NTM) infection is increasing worldwide. Current epidemiological data and knowledge of risk factors for this disease are limited. We investigated the trends in and risk of NTM infection in Northeast Thailand during 2012–2016.MethodsPatient demographics, infection site(s), and underlying disease or conditions from 530 suspected cases of NTM infections were retrieved from medical records, reviewed and analyzed. A diagnosis of true NTM infection was accepted in 150 cases. Risk factor analyses were done for extrapulmonary NTM infections compared to pulmonary NTM infections and for Mycobacterium abscessus compared to members of the Mycobacterium avium complex (MAC). Trend analysis among NTM species causing NTM infections was performed.ResultsThe most common species of NTMs causing extrapulmonary (n = 114) and pulmonary (n = 36) NTM infections in Northeast Thailand were M. abscessus (25.4% of extrapulmonary infected cases and 27.8% of pulmonary cases) followed by MAC (14.9% of extrapulmonary and 13.9% of pulmonary cases). Presence of anti-IFN-γ autoantibodies was the major risk factor for extrapulmonary (odds ratio (OR) = 20.75, 95%CI [2.70–159.24]) compared to pulmonary NTM infection. M. abscessus infection was less likely (OR = 0.17; 95%CI [0.04–0.80]) to be found in patients with HIV infection than was MAC infection. The prevalence of NTM infection, especially M. abscessus, in Northeast Thailand has recently increased. Extrapulmonary NTM and complicated NTM infections have increased in concordance with the recent trend of increasing frequency of anti-IFN-γ autoantibodies in the population.ConclusionsM. abscessus was the commonest NTM pathogen followed by MAC. The prevalence of NTM infections and anti-IFN-γ are showing an upward trend. Autoimmune disease due to anti-IFN-γ is the major risk factor for extrapulmonary NTM infection in Northeast Thailand.
Background Infection with Mycobacterium abscessus is usually chronic and is associated with clarithromycin resistance. Increasing drug resistance is a major public-health problem and has led to the search for new antimycobacterial agents. We evaluated the antimycobacterial activity, toxicity, and synergistic effects of several plant secondary metabolites against M. abscessus. Methods Twenty-three compounds were evaluated for antimycobacterial activity against thirty M. abscessus clinical isolates by broth microdilution to determine their minimum inhibitory concentration (MIC) values. Toxicity was evaluated using red and white blood cells (RBCs and WBCs). The compounds were used in combination with clarithromycin to investigate the possibility of synergistic activity. Results Five out of twenty-three compounds (RL008, RL009, RL011, RL012 and RL013) exhibited interesting antimycobacterial activity against M. abscessus, with MIC values ranging from <1 to >128 μg/mL. These extracts did not induce hemolytic effect on RBCs and displayed low toxicity against WBCs. The five least-toxic compounds were tested for synergism with clarithromycin against seven isolates with inducible clarithromycin resistance and seven with acquired clarithromycin resistance. The best synergistic results against these isolates were observed for RL008 and RL009 (8/14 isolates; 57%). Conclusions This study demonstrated antimycobacterial and synergistic activities of pure compounds extracted from medicinal plants against clarithromycin-resistant M. abscessus. This synergistic action, together with clarithromycin, may be effective for treating infections and should be further studied for the development of novel antimicrobial agents.
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