The rationale for using rifabutin in the treatment of MDR and XDR tuberculosis outbreaks

Sirgel, Frederick A.; Warren, Robin M.; Bottger, Erik C.; Klopper, Marisa; Victor, Thomas C.; Van Helden, Paul D.

The rationale for using rifabutin in the treatment of MDR and XDR tuberculosis outbreaks

dc.contributor.author	Sirgel, Frederick A.	en_ZA
dc.contributor.author	Warren, Robin M.	en_ZA
dc.contributor.author	Bottger, Erik C.	en_ZA
dc.contributor.author	Klopper, Marisa	en_ZA
dc.contributor.author	Victor, Thomas C.	en_ZA
dc.contributor.author	Van Helden, Paul D.	en_ZA
dc.date.accessioned	2016-08-23T09:29:09Z
dc.date.available	2016-08-23T09:29:09Z
dc.date.issued	2015
dc.description	Please cite as follows: Sirgel, F. A., et al. 2015. The rationale for using rifabutin in the treatment of MDR and XDR tuberculosis outbreaks. PLoS ONE, 8(3):1-4, doi:10.1371/journal.pone.0059414
dc.description	The original publication is available at http://journals.plos.org/plosone
dc.description.abstract	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.	en_ZA
dc.description.uri	http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0059414
dc.description.version	Publisher's version
dc.format.extent	4 pages
dc.identifier.citation	Sirgel, F. A., et al. 2015. The rationale for using rifabutin in the treatment of MDR and XDR tuberculosis outbreaks. PLoS ONE, 8(3):1-4, doi:10.1371/journal.pone.0059414
dc.identifier.issn	1932-6203 (online)
dc.identifier.other	doi:10.1371/journal.pone.0059414
dc.identifier.uri	http://hdl.handle.net/10019.1/99438
dc.language.iso	en_ZA	en_ZA
dc.publisher	Public Library of Science
dc.rights.holder	Authors retain copyright
dc.subject	Drug resistant tuberculosis	en_ZA
dc.subject	Multidrug-resistant tuberculosis (MDR-TB)	en_ZA
dc.subject	Extensively multidrug-resistant tuberculosis (XDR-TB)	en_ZA
dc.subject	Mycobacterium tuberculosis -- Treatment	en_ZA
dc.subject	Rifabutin	en_ZA
dc.subject	Rifampin	en_ZA
dc.title	The rationale for using rifabutin in the treatment of MDR and XDR tuberculosis outbreaks	en_ZA
dc.type	Article	en_ZA