Setting: Rifampin (RMP) resistant Mycobacterium tuberculosis is usually assumed to be resistant to all rifamycins. Increasing evidence indicates, however, that some rpoB mutations, detectable by rapid molecular diagnostics, confer resistance to RMP but not to rifabutin (RBT), suggesting that RBT may be effective for the treatment of M. tuberculosis with these mutations.
Objective: To determine if specific rpoB mutations reliably predict differential phenotypic resistance to RMP and RBT.
Design: We selected 60 clinical M. tuberculosis isolates from a repository of multinational multidrug-resistant tuberculosis isolates and stratified them into two groups: 1) those with rpoB mutations suspected to confer differential resistance to RMP and RBT, and 2) those expected to be cross-resistant to RMP and RBT. These assumptions were tested by comparing the phenotypic susceptibilities of RMP/RBT with those predicted by mutations in the rpoB gene.
Results: Of 20 suspected RMP-resistant/RBT-susceptible isolates, 15 were RMP-resistant but RBT-susceptible, 3 were RMP- and RBT-susceptible, and 2 were cross-resistant to both RMP and RBT. In comparison, 40 of 40 suspected cross-resistant isolates were both RMP- and RBT-resistant.
Conclusion: Our data support the association between specific rpoB mutations and differential resistance of M. tuberculosis to RMP and RBT. Clinical studies are required to investigate the efficacy of RBT in the treatment of M. tuberculosis harboring these mutations.
Download full-text PDF |
Source |
---|---|
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4608372 | PMC |
http://dx.doi.org/10.5588/ijtld.14.0936 | DOI Listing |
Sci Rep
January 2025
Experimental Pathology Department, National Institute of Medical Sciences and Nutrition Salvador Zubiran, Mexico City, Mexico.
It was a general belief that drug resistance in Mycobacterium tuberculosis (Mtb) was associated with lesser virulence, particularly rifampicin resistance, which is usually produced by mutations in the RNA polymerase Beta subunit (RpoB). Interestingly, this kind of bacterial mutations affect gene transcription with significant effects on bacterial physiology and metabolism, affecting also the bacterial antigenic constitution that in consequence can produce diverse immune responses and disease outcome. In the present study, we show the results of the Mtb clinical isolate A96, which is resistant to rifampicin and when used to infect BALB/c mice showed hypervirulence, apparently by rapidly polarization of the Th2 immune response through early and high production of IL-4.
View Article and Find Full Text PDFSci Rep
January 2025
Faculty of Allied Health Sciences, Center of Excellence for Innovative Diagnosis of Antimicrobial Resistance, Chulalongkorn University, Bangkok, 10330, Thailand.
Rifampicin-resistant tuberculosis (RR-TB) is a critical issue with significant implications for patient care, public health, and TB control efforts that necessitate comprehensive strategies for detection. This study presents a novel point-of-care diagnostic tool for RR-TB detection employing a peptide nucleic acid (PNA)-paper-based sensor combined with isothermal recombinase polymerase amplification (RPA). The sensor targets mutations in codons 516, 526, and 531 of the rpoB gene, the top three common mutations associated with rifampicin-resistant strains.
View Article and Find Full Text PDFAntimicrob Agents Chemother
January 2025
Division of Infectious Diseases, Department of Medicine, University of Texas at Tyler School of Medicine, Tyler, Texas, USA.
The impact of heteroresistance on tuberculosis (TB) treatment outcomes is unclear, as is the role of different rifampin and isoniazid exposures on developing resistance mutations. Hollow fiber system model of TB (HFS-TB) units were inoculated with drug-susceptible () and treated with isoniazid and rifampin exposure identified in a clinical trial as leading to treatment failure and acquired drug resistance. Systems were sampled for drug concentration measurements, estimation of total and drug-resistant , and small molecule overlapping reads (SMOR) analysis for the detection of heteroresistance.
View Article and Find Full Text PDFJ Glob Antimicrob Resist
January 2025
Department of Medical Research, No. 5, Ziwaka Rd., Dagon Tsp, 11191, Yangon, Republic of the Union of Myanmar.
Detecting rifampicin resistance is crucial in selecting tuberculosis (TB) treatment. Recently, several studies reported that I491F and V170F rpoB mutations, previously designated as borderline rifampicin-resistance mutations, were found with a varying prevalence. Sputum specimens from first-line tuberculosis treatment failed patients attending Tuberculosis Centers in Yangon Region during 2022 were cultured in solid media.
View Article and Find Full Text PDFMed Microbiol Immunol
January 2025
Research Institute for Medicines (iMed.ULisboa), Faculdade de Farmácia, Universidade de Lisboa, Lisboa, Portugal.
\nKlebsiella pneumoniae is a common pathogen of healthcare-associated infections expressing a plethora of antimicrobial resistance loci, including ADP-ribosyltransferase coding genes (arr), able to mediate rifampicin resistance. The latter has activity against a broad range of microorganisms by inhibiting DNA-dependent RNA polymerases. This study aims to characterise the arr distribution and genetic context in 138 clinical isolates of K.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!