Evolving rifampicin and isoniazid mono-resistance in a high multidrug-resistant and extensively drug-resistant tuberculosis region: a retrospective data analysis

Abstract

ObjectivesSouth Africa ranks among the highest drug-resistant tuberculosis (DR-TB) burdened countries in the world. This study assessed the changes in resistance levels in culture confirmed Mycobacterium tuberculosis (MTB) in the highest burdened province of South Africa during a period where major changes in diagnostic algorithm were implemented.SettingThis study was conducted at the central academic laboratory of the KwaZulu-Natal province of South Africa.ParticipantsWe analysed data for all MTB cultures performed in the KwaZulu-Natal province between 2011 and 2014. The data were collected from the laboratory information system.ResultsOut of 88 559 drug susceptibility results analysed, 18 352 (20.7%) were resistant to rifampicin (RIF) and 19 190 (21.7%) showed resistance to isoniazid (INH). The proportion of rifampicin resistant cases that were mono-resistant increased from 15.3% in 2011 to 21.4% in 2014 while INH mono-resistance (IMR) showed a range between 13.8% and 21.1%. The multidrug-resistant tuberculosis (MDR-TB) rates increased from 18.8% to 23.9% and the proportion of MDR-TB cases that had extensively drug-resistant tuberculosis remained between 10.2% and 11.1%. Most drug resistance was found in females between the ages of 15 and 44 years and the northern districts bordering high MDR-TB regions had the highest MDR-TB rates.ConclusionOur findings show increasing RIF mono-resistance (RMR) and a substantial amount of IMR. This highlights a need for an initial test that detects resistance to both these drugs so as to avoid using RIF monotherapy during continuous phase of treatment in patients with IMR. Furthermore, addition of INH will benefit patients with RMR. Although DR-TB is widespread, HIV and migration influence its distribution; therefore, TB control strategies should include interventions that target these aspects.

A data compendium of Mycobacterium tuberculosis antibiotic resistance

“…South Africa and Nigeria contributed a significantly higher number of RMR isolates, as a proportion of rifampicin resistant isolates, than that of the total dataset at 17.5% (p <0.00001) and 27.3% (p = 0.00534) respectively. We note that countries may have oversampled for solo resistance, but the higher contribution of RMR isolates from South Africa is consistent with previous studies [44].…”

“…Around 1% of TB cases are rifampicin mono-resistant (RMR) and the frequency is increasing (1, 43). The WHO does not recommend isoniazid for RMR treatment, despite it being effective; this is likely due to the reliance on assays such as Xpert® MTB/RIF which cannot distinguish between RMR and MDR.…”

“…A widely used, WHO-endorsed diagnostic tool, the Xpert® MTB/RIF assay, uses a proxy whereby any SNP detected in the "rifampicin-resistance determining region" (RRDR) of rpoB results in a prediction of MDR. However, the suitability of the proxy is dependent upon prevalence of RMR in the population [44]. We tested the reliability of this on the 4,655 rifampicin resistant isolates in our dataset that had a phenotype for isoniazid (Fig.…”

Rifampicin Mono-Resistant Tuberculosis—A Review of an Uncommon But Growing Challenge for Global Tuberculosis Control

“…Most recently, among 88 559 M. tuberculosis cultures with DST results in KwaZulu-Natal between 2011 and 2014, 18 352 (20.7%) were RIF resistant and 19 190 (21.7%) were INH resistant. The proportion of RR-TB cases increased from 15.3% in 2011 to 21.4% in 2014, similar to increases seen for INH mono-resistant and MDR disease [ 26 ].…”

Low-Level Rifampin Resistance and rpoB Mutations in Mycobacterium tuberculosis: an Analysis of Whole-Genome Sequencing and Drug Susceptibility Test Data in New York

“…Resistance-conferring rpoB mutations were detected most commonly in MDR and XDR strains; however, a significant portion (9/53 [17%]) of RIF-resistant strains were found to be RIF monoresistant. The incidence of RIF monoresistance varies considerably by setting, ranging from 0% in some settings to as high as 21.4% in South Africa (19,(36)(37)(38)(39). Reported incidences of RIF monoresistance may be underestimated if lowlevel resistant strains are undetected or were excluded from analysis as a result of using critical-concentration MGIT DST.…”