High rate of reinfection and possible transmission of Mycobacterium avium complex in Northeast Thailand

Boonjetsadaruhk, Wicharajit; Kaewprasert, Orawee; Nithichanon, Arnone; Ananta, Pimjai; Chaimanee, Prajuab; Salao, Kanin; Phoksawat, Wisitsak; Laohaviroj, Marut; Sirichoat, Auttawit; Fong, Yang; Wongwajana, Suwin; Namwat, Wises; Lulitanond, Viraphong; Chetchotisakd, Ploenchan; Faksri, Kiatichai

doi:10.1016/j.onehlt.2022.100374

Cited by 5 publications

(3 citation statements)

References 35 publications

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“…In conclusion, our study evaluated the drug susceptibility of MAC isolates and revealed high rates of resistance to moxifloxacin, followed by linezolid, clarithromycin and amikacin. High resistance rates might be a consequence of the misuse of antibiotics in our region [57]. Specifically, we found an rrs mutation at C464T for amikacin intermediate resistance in M. avium, and two mutations (T250A and G1453T) in amikacin non-susceptible M. intracellulare.…”

Section: Plos Onementioning

confidence: 64%

Phenotypic drug-susceptibility profiles and genetic analysis based on whole-genome sequencing of Mycobacterium avium complex isolates in Thailand

Sirichoat,

Kaewprasert,

Hinwan

et al. 2023

PLoS ONE

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Mycobacterium avium complex (MAC) infections are a significant clinical challenge. Determining drug-susceptibility profiles and the genetic basis of drug resistance is crucial for guiding effective treatment strategies. This study aimed to determine the drug-susceptibility profiles of MAC clinical isolates and to investigate the genetic basis conferring drug resistance using whole-genome sequencing (WGS) analysis. Drug-susceptibility profiles based on minimum inhibitory concentration (MIC) assays were determined for 38 MAC clinical isolates (12 Mycobacterium avium and 26 Mycobacterium intracellulare). Mutations associated with drug resistance were identified through genome analysis of these isolates, and their phylogenetic relationships were also examined. Drug resistance, based on MIC values, was most commonly observed for moxifloxacin (81.6%), followed by linezolid (78.9%), clarithromycin (44.7%) and amikacin (36.8%). We identified specific mutations associated with resistance to amikacin. These include the rrs mutation at C464T in amikacin intermediate-resistance M. avium, and two mutations at T250A and G1453T in amikacin non-susceptible M. intracellulare. Mutations in rrl at A2058G, A2059C and A2059G were potentially linked to clarithromycin resistance. MAC clinical isolates not susceptible to linezolid exhibited mutations in rplC at G237C and C459T, as well as two rplD mutations at G443A and A489G. GyrB substitution Thr521Ala (T521A) was identified in moxifloxacin non-susceptible isolates, which may contribute to this resistance. A phylogeny of our MAC isolates revealed high levels of genetic diversity. Our findings suggest that the standard treatment regimen for MAC infections using moxifloxacin, linezolid, clarithromycin and amikacin may be driving development of resistance, potentially due to specific mutations. The combination of phenotypic and genotypic susceptibility testing can be valuable in guiding the clinical use of drugs for the treatment of MAC infections.

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Section: Plos Onementioning

confidence: 64%

Phenotypic drug-susceptibility profiles and genetic analysis based on whole-genome sequencing of Mycobacterium avium complex isolates in Thailand

Sirichoat,

Kaewprasert,

Hinwan

et al. 2023

PLoS ONE

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“…Mycobacterium avium complex (MAC), which comprises multiple species, such as Mycobacterium avium , Mycobacterium intracellulare , Mycobacterium chimaera , and other minor species, is the most common cause of NTM-PD worldwide [ 4 , 5 ]. MAC pulmonary infection is an emerging pulmonary disease, particularly in immunocompromised patients or immunocompetent patients with chronic pulmonary diseases such as bronchiectasis, chronic obstructive pulmonary disease, cystic fibrosis, emphysema, and previous pulmonary tuberculosis [ 6 , 7 ]. However, the treatment of MAC-PD is challenging due to the emergence of antibiotic resistance and toxic adverse effects related to prolonged antibiotic treatment [ 8 ].…”

Section: Introductionmentioning

confidence: 99%

Bigger problems from smaller colonies: emergence of antibiotic-tolerant small colony variants of Mycobacterium avium complex in MAC-pulmonary disease patients

Park,

Kim,

Trinh

et al. 2024

Ann Clin Microbiol Antimicrob

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Background Mycobacterium avium complex (MAC) is a group of slow-growing mycobacteria that includes Mycobacterium avium and Mycobacterium intracellulare. MAC pulmonary disease (MAC-PD) poses a threat to immunocompromised individuals and those with structural pulmonary diseases worldwide. The standard treatment regimen for MAC-PD includes a macrolide in combination with rifampicin and ethambutol. However, the treatment failure and disease recurrence rates after successful treatment remain high. Results In the present study, we investigated the unique characteristics of small colony variants (SCVs) isolated from patients with MAC-PD. Furthermore, revertant (RVT) phenotype, emerged from the SCVs after prolonged incubation on 7H10 agar. We observed that SCVs exhibited slower growth rates than wild-type (WT) strains but had higher minimum inhibitory concentrations (MICs) against multiple antibiotics. However, some antibiotics showed low MICs for the WT, SCVs, and RVT phenotypes. Additionally, the genotypes were identical among SCVs, WT, and RVT. Based on the MIC data, we conducted time-kill kinetic experiments using various antibiotic combinations. The response to antibiotics varied among the phenotypes, with RVT being the most susceptible, WT showing intermediate susceptibility, and SCVs displaying the lowest susceptibility. Conclusions In conclusion, the emergence of the SCVs phenotype represents a survival strategy adopted by MAC to adapt to hostile environments and persist during infection within the host. Additionally, combining the current drugs in the treatment regimen with additional drugs that promote the conversion of SCVs to RVT may offer a promising strategy to improve the clinical outcomes of patients with refractory MAC-PD.

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“…Water supply chains such as shower heads, plumbs, and heater-cooler devices were traced as the sources of clinical isolates [ 16 , 17 ]. The possible transmission of the MAC strain from human to human was proposed since clusters of genetically close clinical isolates obtained from different patients were identified [ 18 ]. However, the case of transmission is hardly distinguished from the acquisition of the strain from the same source.…”

Section: Introductionmentioning

confidence: 99%

Variability of Mycobacterium avium Complex Isolates Drug Susceptibility Testing by Broth Microdilution

Zimenkov

2022

Antibiotics

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Non-tuberculous mycobacteria are widely distributed in environments and are capable of infecting humans, particularly those with a compromised immune system. The most prevalent species that cause nontuberculous mycobacterial lung diseases are slow-growing bacteria from the Mycobacterium avium complex (MAC), mainly M. avium or M. intracellulare. The key treatment of MAC infections includes macrolides, ethambutol, and rifampicin; however, the therapy outcomes are unsatisfactory. Phenotypic drug susceptibility testing is a conditional recommendation prior to treatment, and critical concentrations for clarithromycin, amikacin, moxifloxacin, and linezolid have been established. In this review, data from studies on the determination of MIC of clinical isolates using the broth microdilution method were summarized. A significant variation in the MIC distributions from different studies was found. The main reasons could impact the findings: insufficient reproducibility of the phenotypic testing and variation in species lineages identified in different laboratories, which could have various intrinsic susceptibility to drugs. For most of the drugs analyzed, the MICs are too high, which could undermine the treatment efficiency. Further improvement of treatment outcomes demands the validation of microbiological resistance criteria together with the identification of molecular mechanisms of resistance.

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High rate of reinfection and possible transmission of Mycobacterium avium complex in Northeast Thailand

Cited by 5 publications

References 35 publications

Phenotypic drug-susceptibility profiles and genetic analysis based on whole-genome sequencing of Mycobacterium avium complex isolates in Thailand

Phenotypic drug-susceptibility profiles and genetic analysis based on whole-genome sequencing of Mycobacterium avium complex isolates in Thailand

Bigger problems from smaller colonies: emergence of antibiotic-tolerant small colony variants of Mycobacterium avium complex in MAC-pulmonary disease patients

Variability of Mycobacterium avium Complex Isolates Drug Susceptibility Testing by Broth Microdilution

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