The potential use of rifabutin for treatment of patients diagnosed with rifampicin-resistant tuberculosis

Whitfield, Michael G.; Warren, Robin M.; Mathys, Vanessa; Scott, Lesley; Vos, Elise De; Stevens, Wendy; Streicher, Elizabeth M.; Groenen, Guido; Sirgel, Frederick A.; Rie, Annelies Van

doi:10.1093/jac/dky248

Cited by 18 publications

(26 citation statements)

References 36 publications

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“…collated genotypic and phenotypic susceptibility for rifampicin and rifabutin from 2000 MTB isolates. Among 112 rpoB SNPs identified, 11 were significantly associated with rifabutin susceptibility and six with rifabutin resistance . The 516 GAC→GTC SNP accounted for 70% to 75% of all potentially rifampicin‐resistant rifabutin‐susceptibility from two population‐representative samples, one with high and one with low HIV co‐prevalence .…”

Section: Rifampicin‐resistant Rifabutin‐susceptible Tbmentioning

confidence: 99%

“…Among 112 rpoB SNPs identified, 11 were significantly associated with rifabutin susceptibility and six with rifabutin resistance . The 516 GAC→GTC SNP accounted for 70% to 75% of all potentially rifampicin‐resistant rifabutin‐susceptibility from two population‐representative samples, one with high and one with low HIV co‐prevalence . This SNP, which is detected by both the Hain MTBDR plus line probe assay and Xpert MTB/RIF Ultra molecular beacon assay, could enable accelerated determination of rifampicin‐resistant rifabutin‐susceptible isolates in a programmatic setting.…”

Section: Rifampicin‐resistant Rifabutin‐susceptible Tbmentioning

confidence: 99%

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Global access of rifabutin for the treatment of tuberculosis – why should we prioritize this?

et al. 2019

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Introduction Rifabutin, a rifamycin of equivalent potency to rifampicin, has several advantages in its pharmacokinetic and toxicity profile, particularly in HIV co‐infected patients on combined antiretroviral therapy (cART). In this commentary, we evaluate evidence supporting increased global use of rifabutin and highlight key recommendations for action. Discussion Although extrapolation of data from HIV uninfected patients would suggest non‐inferiority, there has been no randomized controlled study comparing rifabutin versus rifampicin in the outcomes of relapse‐free cure, in drug susceptible tuberculosis (TB), in HIV co‐infected patients on currently utilized cART regimens or in paediatric populations. An important advantage of rifabutin is that compared to the dose adjustments required with rifampicin, it can be co‐administered with the integrase strand transfer inhibitors raltegravir or dolutegravir without the need for dose adjustments. This strategy would be easier to implement in a programmatic setting and would save costs. We have assessed cost incentives to utilize rifabutin and have estimated generic costs for a range of rifabutin dosage scenarios. Where facilities are present for drug re‐challenge and monitoring for drug toxicity and cross‐reactivity, rifabutin offers a switch alternative for adverse drug reactions (ADR)s attributed to rifampicin. This would negate the need to prolong treatment in the absence of a rifamycin as part of short‐course multidrug therapy. There is evidence of incomplete cross‐resistance to rifampicin and rifabutin. Rifabutin may be useful in rifampicin‐resistant TB, in an estimated 20% of cases, based on phenotypic or genotypic rifabutin susceptibility testing. Conclusions Rifabutin should be available globally as a first‐line rifamycin in HIV co‐infected individuals and as a switch option in cases of rifampicin associated ADRs. Further studies are needed to ascertain the utility of rifabutin in rifampicin‐resistant rifabutin‐susceptible TB.

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Section: Rifampicin‐resistant Rifabutin‐susceptible Tbmentioning

confidence: 99%

Section: Rifampicin‐resistant Rifabutin‐susceptible Tbmentioning

confidence: 99%

Global access of rifabutin for the treatment of tuberculosis – why should we prioritize this?

et al. 2019

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“… [12] , [15] , [16] , [17] , [18] , [19] Almost all studies concluded that isolates with a D435Y mutation are susceptible to rifabutin. [10] , [15] , [16] , [17] , [20] …”

Section: Discussionmentioning

confidence: 99%

“…a higher dose of rifampicin or replacing rifampicin by rifabutin. [10] , [16] , [18] , [20] , [26] The currently recommended dose of rifampicin has been challenged over the last years. [27] , [28] Dosage studies indicate that 35 mg/kg rifampicin instead of 10 mg/kg is well tolerated and more effective than the standard dose.…”

Section: Discussionmentioning

confidence: 99%

Should treatment of low-level rifampicin mono-resistant tuberculosis be different?

Gopie

Commiesie²,

Baldi

et al. 2021

Journal of Clinical Tuberculosis and Other Mycobacterial Diseas

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Background Rifampicin resistant tuberculosis (RR-TB) was frequently detected in Suriname after the introduction of Xpert MTB/RIF in 2012. Subsequent phenotypic drug-susceptibility testing (DST) was not conclusive at that moment, while RR-TB patients treated with first-line tuberculostatics had good treatment outcome. In our study, we analysed this interesting observation. Methods We collected demographic and clinical characteristics and treatment outcome of TB patients from May 2012-December 2018 and performed a univariate and multivariate analysis to assess possible associations with resistance to rifampicin. Secondly, we conducted whole genome sequencing on all available Mycobacterium tuberculosis isolates that had a rifampicin resistance in the Xpert MTB/RIF test and performed phenotypic DST on selected isolates. Findings RR-TB was detected in 59 (9.6%) patients confirmed by Xpert. These patients were treated with rifampicin-containing regimens in most (88%) of the cases. In all 32 samples examined, a D435Y mutation in the rpoB gene was identified; only one isolate revealed an additional isoniazid mutation. Phenotypic DST indicated low-level rifampicin resistance. In multivariate analysis, the Creole ethnicity was a factor associated with rifampicin resistance (aOR 3.5; 95%CI 1.9–6.4). The treatment success rate for patients with RR-TB (78.0%) was comparable to the treatment outcome in non-RR-TB patients 77.8%. Interpretation This study confirms a low-level rifampicin mono-resistance in TB patients of Suriname. These patients could benefit from a first-line regimen with high dose rifampicin (or rifabutin), rather than from the lengthy treatment regimens for rifampicin-resistant and multi-drug resistant TB, a concept of stratified medicine also advocated for the treatment of TB. Funding None.

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“…[71] More recently, we queried the prediction of rifampicin resistance by the Xpert MTB/RIF assay, as MIC testing clearly indicated that not all rpoB mutations confer phenotypic resistance above the critical concentration (1 µg/mL, used to differentiate susceptible from resistant). [72] We have proposed that patients with reduced susceptibility to rifampicin could benefit from either high-dose rifampicin or an alternative rifamycin, namely rifabutin. [73] Clinical trials are now underway to evaluate the efficacy of such regimens but are expected to have great value in certain patients with XDR-TB (http://task.org.za/clinical-trials/).…”

Section: Researchmentioning

confidence: 99%

Tuberculosis research in South Africa over the past 30 years: From bench to bedside

et al. 2019

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This open-access article is distributed under Creative Commons licence CC-BY-NC 4.0. The South African Medical Research Council Centre for Tuberculosis Research has a rich history of high-impact research that has influenced our understating of this hyper-epidemic which is further exacerbated by the emergence and spread of drug-resistant forms of the disease. This review aims to summarise the past 30 years of research conducted in the Centre which has influenced the way that tuberculosis (TB) is diagnosed and treated. The review includes the development of new technologies for rapid screening of people with probable TB and the repurposing of human diagnostics for wildlife conservation.

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The potential use of rifabutin for treatment of patients diagnosed with rifampicin-resistant tuberculosis

Cited by 18 publications

References 36 publications

Global access of rifabutin for the treatment of tuberculosis – why should we prioritize this?

Global access of rifabutin for the treatment of tuberculosis – why should we prioritize this?

Should treatment of low-level rifampicin mono-resistant tuberculosis be different?

Tuberculosis research in South Africa over the past 30 years: From bench to bedside

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