Recently, as clofazimine (CFZ) showed a good therapeutic effect in treating multi-drug-resistant tuberculosis (MDR-TB), the anti-tuberculosis activity and resistance were re-focused. Here, we investigated the CFZ resistance and genetic mutations of drug-resistant Mycobacterium tuberculosis (DR-Mtb) isolates to improve the diagnosis and treatment of drug-resistant TB patients. The minimal inhibitory concentration (MIC) of CFZ was examined by resazurin microtiter assay (REMA) with two reference strains and 122 clinical isolates from Korea. The cause of CFZ resistance was investigated in relation to the therapeutic history of patients. Mutations of Rv0678, Rv1979c and pepQ of CFZ resistant isolates were analyzed by PCR and DNA sequencing. The rate of CFZ resistance with MIC > 1 mg/L was 4.1% in drug-resistant Mtb isolates. The cause of CFZ resistance was not related to treatment with CFZ or bedaquiline. A CFZ susceptibility test should be conducted regardless of dugs use history. The four novel mutation sites were identified in the Rv0678 and pepQ genes related to CFZ resistance in this study.
Download full-text PDF |
Source |
---|---|
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9000149 | PMC |
http://dx.doi.org/10.3390/jcm11071927 | DOI Listing |
BMC Complement Med Ther
January 2025
Department of Clinical Biochemistry, Afzalipour Faculty of Medicine, Kerman University of Medical Sciences, Kerman, Iran.
Objective: This study aimed to investigate the synergistic effects of the chemotherapy drug Carfilzomib (CFZ) and Pistachio hull extract on the SK-BR3 breast cancer cell line.
Methods: In this experimental study, we evaluated the effect of Pistachio hull extract and CFZ as standalone treatments on cell viability using the MTT assay at 24- and 48-hours post-treatment. Following this, we conducted combination therapy analyses to assess the potential synergistic relationship between Pistachio hull extract and CFZ after 24- and 48-hours of treatment on both the SK-BR3 breast cancer cell line and the MCF10A normal cell line.
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 PDFInt J Mol Sci
December 2024
Department of Immunology, Faculty of Health Sciences, University of Pretoria, Pretoria 0001, South Africa.
Multidrug-resistant tuberculosis (MDR-TB) patients are treated with a standardised, short World Health Organization (WHO) regimen which includes clofazimine (CFZ) and bedaquiline (BDQ) antibiotics. These two antibiotics lead to the development of QT prolongation in patients, inhibiting potassium (K) uptake by targeting the voltage-gated K (Kv)11.1 (hERG) channel of the cardiomyocytes (CMs).
View Article and Find Full Text PDFInt Immunopharmacol
January 2025
Medical Complex, School of Medicine & Life Science, Far Eastern Federal University, Vladivostok, Russian Federation 690091. Electronic address:
Rationale: Glioblastoma is one of the most aggressive human brain tumors. The prognosis is unfavorable and treatment effects are relatively low. However, temozolomide (TMZ) chemotherapy may prolong patients' survival.
View Article and Find Full Text PDFClin Microbiol Infect
December 2024
Departments of Medicine and Medical Microbiology/Immunology, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
Objectives: The objective of this study is to assess the frequency of the novel sodium bicarbonate (NaHCO)-responsive phenotype, wherein clinical methicillin-resistant Staphylococcus aureus (MRSA) isolates are rendered susceptible to standard-of-care β-lactams in the presence of NaHCO, in a collection of 103 clinical U.S. MRSA skin and soft-tissue infection (SSTI) isolates and 22 clinical European SSTI isolates.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!