The efficacy of rifabutin for rifabutin-susceptible, multidrug-resistant tuberculosis

Jo, Kyung‐Wook; Ji, Wonjun; Hong, Yoonki; Lee, Sang‐Do; Kim, Woo Sung; Kim, Dong Soon; Shim, Tae Sun

doi:10.1016/j.rmed.2012.10.021

Cited by 32 publications

(29 citation statements)

References 23 publications

(30 reference statements)

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“…These studies suggest that low-level RIF-resistance can be overcome by the use of higher RIF doses or alternatively, by replacing RIF with RFB [9], [10]. A retrospective study in South Korea showed an 85.7% (12/14) treatment success in patients with RFB-susceptible MDR-TB infections who received RFB as an additional drug [19]. In our study, the MIC distribution for RFB was above the ECOFF, but below the standard CC.…”

Section: Discussionmentioning

confidence: 45%

The Rationale for Using Rifabutin in the Treatment of MDR and XDR Tuberculosis Outbreaks

et al. 2013

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Genetically related Mycobacterium tuberculosis strains with alterations at codon 516 in the rpoB gene were observed amongst a substantial number of patients with drug resistant tuberculosis in the Eastern Cape Province (ECP) of South Africa. Mutations at codon 516 are usually associated with lower level rifampicin (RIF) resistance, while susceptibility to rifabutin (RFB) remains intact. This study was conducted to assess the rationale for using RFB as a substitution for RIF in the treatment of MDR and XDR tuberculosis outbreaks. Minimum inhibitory concentrations (MICs) of 34 drug resistant clinical isolates of M tuberculosis were determined by MGIT 960 and correlated with rpoB mutations. RFB MICs ranged from 0.125 to 0.25 µg/ml in the 34 test isolates thereby confirming phenotypic susceptibility as per critical concentration (CC) of 0.5 µg/ml. The corresponding RIF MICs ranged between 5 and 15 µg/ml, which is well above the CC of 1.0 µg/ml. Molecular-based drug susceptibility testing provides important pharmacogenetic insight by demonstrating a direct correlation between defined rpoB mutation and the level of RFB susceptibility. We suggest that isolates with marginally reduced susceptibility as compared to the epidemiological cut-off for wild-type strains (0.064 µg/ml), but lower than the current CC (≤0.5 µg/ml), are categorised as intermediate. Two breakpoints (0.064 µg/ml and 0.5 µg/ml) are recommended to distinguish between susceptible, intermediate and RFB resistant strains. This concept may assist clinicians and policy makers to make objective therapeutic decisions, especially in situations where therapeutic options are limited. The use of RFB in the ECP may improve therapeutic success and consequently minimise the risk of ongoing transmission of drug resistant M. tuberculosis strains.

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Section: Discussionmentioning

confidence: 45%

The Rationale for Using Rifabutin in the Treatment of MDR and XDR Tuberculosis Outbreaks

et al. 2013

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“…Studies from low HIV settings have reported that 13–26% of MDR-TB isolates show sensitivity to RFB (Chen et al, 2012; Jo et al, 2013; Schon et al, 2013). However, there is limited information on the frequency of RFB susceptibility among MDR-TB isolates in an HIV endemic region.…”

Section: Introductionmentioning

confidence: 99%

Correlation of rpoB Mutations with Minimal Inhibitory Concentration of Rifampin and Rifabutin in Mycobacterium tuberculosis in an HIV/AIDS Endemic Setting, South Africa

Rukasha

Said

Omar³

et al. 2016

Front. Microbiol.

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Treatment of tuberculosis (TB) and HIV co-infections is often complicated by drug-to-drug interactions between anti-mycobacterial and anti-retroviral agents. Rifabutin (RFB) is an alternative to rifampin (RIF) for TB regimens and is recommended for HIV patients concurrently receiving protease inhibitors because of reduced induction of CYP3A4. This study sought to determine the proportion of RFB susceptible isolates among RIF-resistant strains in a high HIV prevalence setting in South Africa. In addition, the study explored the association between rpoB mutations and minimum inhibitory concentrations (MIC) of RIF and RFB. A total of 189 multidrug resistant (MDR) Mycobacterium tuberculosis isolates from the Centre for Tuberculosis repository were analyzed. The MICs were determined using a MYCOTB Sensititre plate method and the rpoB gene was sequenced. Of the 189 MDR isolates, 138 (73%) showed resistance to both RIF and RFB, while 51 (27%) isolates were resistant to RIF but retained susceptibility to RFB. The S531L was the most frequent rpoB point mutation in 105/189 (56%) isolates, followed by H526Y in 27/189 (14%) isolates. Resistance to both RIF and RFB was found predominantly in association with mutations S531L (91/105, 87%), H526Y (20/27, 74%), and H526D (15/19, 79%), while D516V (15/17, 88%), and L533P (3/4, 75%) were found in RIF-resistant, RFB-susceptible isolates. This study has shown that up to 27% of MDR-TB patients in South Africa may benefit from a treatment regimen that includes RFB.

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“…Although this was a small retrospective study, the findings are encouraging given their support of the clinical relevance of differential RFB/RIF resistance. 31 More clinical trials are needed to confirm the effectiveness of RFB in RFB-susceptible RIF-resistant TB.…”

Section: Discussionmentioning

confidence: 99%

Predicting differential rifamycin resistance in clinical <I>Mycobacterium tuberculosis</I> isolates by specific <I>rpo</I>B mutations

ElMaraachli

Slater

Berrada

et al. 2015

int j tuberc lung dis

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Setting Rifampin (RIF)-resistant Mycobacterium tuberculosis (Mtb) 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 RIF but not rifabutin (RFB), suggesting RFB may be effective for treatment of Mtb with these mutations. Objective To determine if specific rpoB mutations reliably predict differential phenotypic resistance to RIF and RFB. Design We selected 60 clinical Mtb isolates from a repository of multinational MDR-TB isolates and stratified them into two groups: 1) Those with rpoB mutations suspected to confer differential resistance to RIF and RFB and 2) Those expected to be cross-resistant to RIF and RFB. These assumptions were tested by comparing the phenotypic susceptibilities of RIF/RFB with those predicted by mutations in the rpoB gene. Results Of 20 suspected RIF-resistant/RFB-susceptible isolates, 15 were RIF resistant but RFB susceptible, 3 were RIF and RFB sensitive, and 2 were cross-resistant to both RIF and RFB. In comparison, 40 of 40 suspected cross-resistant isolates were both RIF and RFB resistant. Conclusion Our data supports the association between specific rpoB mutations and differential resistance of Mtb to RIF and RFB. Clinical studies are required to investigate the efficacy of RFB for treatment of Mtb harboring these mutations.

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The efficacy of rifabutin for rifabutin-susceptible, multidrug-resistant tuberculosis

Abstract: RFB is useful as an additional drug in the treatment of MDR-TB in patients with RFB-susceptible MDR-TB.

Cited by 32 publications

References 23 publications

The Rationale for Using Rifabutin in the Treatment of MDR and XDR Tuberculosis Outbreaks

The Rationale for Using Rifabutin in the Treatment of MDR and XDR Tuberculosis Outbreaks

Correlation of rpoB Mutations with Minimal Inhibitory Concentration of Rifampin and Rifabutin in Mycobacterium tuberculosis in an HIV/AIDS Endemic Setting, South Africa

Predicting differential rifamycin resistance in clinical <I>Mycobacterium tuberculosis</I> isolates by specific <I>rpo</I>B mutations

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