edoc

Rifampicin mono-resistant tuberculosis is not the same as multidrug-resistant tuberculosis: a descriptive study from Khayelitsha, South Africa

Salaam-Dreyer, Z. and Streicher, E. M. and Sirgel, F. A. and Menardo, F. and Borrell, S. and Reinhard, M. and Doetsch, A. and Cudahy, P. G. T. and Mohr-Holland, E. and Daniels, J. and Dippenaar, A. and Nicol, M. P. and Gagneux, S. and Warren, R. M. and Cox, H.. (2021) Rifampicin mono-resistant tuberculosis is not the same as multidrug-resistant tuberculosis: a descriptive study from Khayelitsha, South Africa. Antimicrob Agents Chemother, 65 (11). e0036421.

[img] PDF - Published Version
Available under License CC BY (Attribution).

386Kb

Official URL: https://edoc.unibas.ch/89368/

Downloads: Statistics Overview

Abstract

Rifampicin mono-resistant TB (RMR-TB, rifampicin resistance and isoniazid susceptibility) constitutes 38% of all rifampicin-resistant TB (RR-TB) in South Africa and is increasing. We aimed to compare RMR-TB with multidrug-resistant TB (MDR-TB) within a high TB, RR-TB and HIV burden setting. Patient-level clinical data and stored RR-TB isolates from 2008-2017 with available whole genome sequencing (WGS) data were used to describe risk factors associated with RMR-TB and to compare rifampicin-resistance (RR) conferring mutations between RMR-TB and MDR-TB. A subset of isolates with particular RR-conferring mutations were subjected to semi-quantitative rifampicin phenotypic drug susceptibility testing. Among 2,041 routinely diagnosed RR-TB patients, 463 (22.7%) had RMR-TB. HIV-positive individuals (adjusted Odds Ratio 1.4, 95% CI 1.1-1.9) and diagnosis between 2013-2017 versus 2008-2012 (aOR 1.3, 1.1-1.7) were associated with RMR-TB. Among 1,119 (54.8%) patients with available WGS data showing RR-TB, significant differences in the distribution of rpoB RR-conferring mutations between RMR-TB and MDR-TB isolates were observed. Mutations associated with high-level RR were more commonly found among MDR-TB isolates (811/889, 90.2% versus 162/230, 70.4% among RMR-TB, p<0.0001). In particular, the rpoB L430P mutation, conferring low-level RR, was identified in 32/230 (13.9%) RMR-TB versus 10/889 (1.1%) in MDR-TB (p<0.0001). Among 10 isolates with an rpoB L430P mutation, 7 were phenotypically susceptible using the critical concentration of 0.5 mug/ml (range 0.125-1 mug/ml). The majority (215/230, 93.5%) of RMR-TB isolates showed susceptibility to all other TB drugs, highlighting the potential benefits of WGS for simplified treatment. These data suggest that the evolution of RMR-TB differs from MDR-TB with a potential contribution from HIV infection.
Faculties and Departments:09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH)
09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH) > Department of Medical Parasitology and Infection Biology (MPI) > Tuberculosis Ecology and Evolution Unit (Gagneux)
UniBasel Contributors:Menardo, Fabrizio and Borrell Farnov, Sonia and Reinhard, Miriam and Gagneux, Sebastien
Item Type:Article, refereed
Article Subtype:Research Article
ISSN:1098-6596 (Electronic)0066-4804 (Linking)
Note:Publication type according to Uni Basel Research Database: Journal article
Language:English
Related URLs:
Identification Number:
edoc DOI:
Last Modified:21 Dec 2022 09:57
Deposited On:21 Dec 2022 09:57

Repository Staff Only: item control page