The antimycobacterial susceptibility test was performed and minimal inhibitory concentration (MIC) to drugs was determined in 98 strains of Mycobacteium tuberculosis (MTB) isolated in Tokyo from 2000 to 2003, to find which were resistant to any of the four main anti-MTB drugs, isoniazid (INH), rifampicin (RFP), streptomycin (SM), and ethambutol (EMB). 27strains of them were resistant only to SM, and 16 strains were resistant only to INH. 51 strains of them were resistant to not only INH but also other drugs. 38 strains were resistant to both INH and RFP. 19 strains were resistant to all four drugs, including 7 strains resistant to new quinolon anti-biotics also. Nucleotide or amino-acid mutations in drug resistant MTB genome were determined by DNA sequencing method. Mutation of codon 516, 526, or 531 of rpoB gene was detected in 98% of MTBs resistant to RFP. Deletion or insertion of katG gene or nucleotide mutation at regulatory region of ahpC gene was detected in MTBs highly resistant to INH. Amino acid mutation of katG gene, especially at codon 315, was detected in MTBs resistant to INH intermediate. Nucleotide mutations at regulatory region of inhA gene were detected in MTBs resistant to INH at low level. Amino acid mutation at codon 43 or 88 of rpsL gene was detected in MTBs highly resistant to SM, and nucleotide mutation at 512, 513, or 516 of rrs gene was detected in MTBs resistant to SM at low level. Amino acid mutation at codon 306 of embB gene was detected in 87% of MTBs resistant to EMB.
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http://dx.doi.org/10.11150/kansenshogakuzasshi1970.79.388 | DOI Listing |
Antimicrob Agents Chemother
December 2024
Public Health Agency of Sweden, Solna, Sweden.
This comparative study aimed at qualifying a broth microdilution (BMD) assay for phenotypic drug susceptibility testing (pDST) of complex (MTBC) strains for implementation in a routine DST workflow. The assay was developed based on the EUCAST (European Committee on Antimicrobial Susceptibility Testing) reference protocol for determination of the minimum inhibitory concentration (MIC) of 14 anti-tuberculous drugs (isoniazid [INH], rifampicin [RIF], ethambutol [EMB], amikacin [AMI], moxifloxacin [MFX], levofloxacin [LFX], bedaquiline [BDQ], clofazimine [CFZ], delamanid [DLM], pretomanid [PA], para-aminosalicylic acid [PAS], linezolid [LZD], ethionamide [ETH], and cycloserine [CS]). Forty MTBC strains with various drug resistance profiles were tested to determine the agreement between MIC results and genotypic drug susceptibility testing (gDST) results derived from whole-genome sequencing (WGS).
View Article and Find Full Text PDFCell Biochem Funct
December 2024
Center for Biotechnology, Siksha 'O' Anusandhan (Deemed to be University), Bhubaneswar, Odisha, India.
Tuberculosis (TB) remains a significant global health challenge, exacerbated by the emergence of drug-resistant strains of Mycobacterium tuberculosis (M. tb). The complex biology of M.
View Article and Find Full Text PDFEur J Pharm Sci
December 2024
Centro de Química Estrutural, Institute of Molecular Sciences, Departamento de Química e Bioquímica, Faculdade de Ciências, Universidade de Lisboa, 1749-016 Campo Grande, Portugal. Electronic address:
Tuberculosis is one of the leading causes of mortality worldwide due to the growth of multi-drug resistant strains unsusceptible to currently available therapies. Four compounds, isoniazid (INH), and three derivatives, N'-decanoylisonicotinohydrazide (INH-C10), N'-(E)-(4-phenoxybenzylidene)isonicotinohydrazide (N34) and N'-(4-phenoxybenzyl)isonicotinohydrazide (N34red), were studied. Owing to their advantageous in vitro selectivity index against the primary mutation responsible for drug resistance in Mycobacterium tuberculosis (Mtb), as well as their suitable lipophilicity and interaction with human serum albumin, INH-C10 and N34 were deemed promising antitubercular compounds.
View Article and Find Full Text PDFMicrobiol Spectr
December 2024
Department of Bacteriology and Immunology, Beijing Chest Hospital, Capital Medical University/Beijing Tuberculosis & Thoracic Tumor Research Institute, Beijing, China.
Sitafloxacin is a quinolone broad-spectrum antimicrobial agent, and its pharmacologic properties and data demonstrate that sitafloxacin has a potent killing effect against , including drug-resistant strains, which is superior to that of other available quinolones. However, its efficacy in patients with primary-sensitive tuberculosis is unclear. This study aims to evaluate the early bactericidal activity (EBA) of sitafloxacin in patients with primary drug-susceptible tuberculosis.
View Article and Find Full Text PDFBMC Infect Dis
December 2024
Department of Immunology and Molecular Biology, School of Biomedical Sciences, College of Health Sciences, Makerere University, P.O. Box 7072, Kampala, Uganda.
Background: Efforts toward tuberculosis management and control are challenged by the emergence of Mycobacterium tuberculosis (MTB) resistance to existing anti-TB drugs. This study aimed to explore the potential of machine learning algorithms in predicting drug resistance of four anti-TB drugs (rifampicin, isoniazid, streptomycin, and ethambutol) in MTB using whole-genome sequence and clinical data from Uganda. We also assessed the model's generalizability on another dataset from South Africa.
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