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Rifampicin-resistant and rifabutin-susceptible Mycobacterium tuberculosis strains: a breakpoint artefact?
Linköping University, Department of Clinical and Experimental Medicine, Medical Microbiology. Linköping University, Faculty of Health Sciences. Kalmar County Hospital, Sweden .
Swedish Institute Communicable Disease Control SMI, Sweden .
Karolinska University Hospital, Sweden .
Karolinska University Hospital, Sweden .
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2013 (English)In: Journal of Antimicrobial Chemotherapy, ISSN 0305-7453, E-ISSN 1460-2091, Vol. 68, no 9, 2074-2077 p.Article in journal (Refereed) Published
Abstract [en]

It has long been assumed that some rifampicin-resistant Mycobacterium tuberculosis strains are susceptible to, and thus treatable with, rifabutin. However, clinical breakpoints for susceptibility testing of rifabutin as well as the evidence for a clinical effect of rifabutin in rifampicin-resistant strains remains poorly defined. The objective of this study was to re-evaluate the breakpoint for rifabutin in relation to its MIC wild-type distribution and the presence of mutations in rpoB. less thanbrgreater than less thanbrgreater thanThe MIC in 7H10 Middlebrook medium was determined for clinical isolates of M. tuberculosis (n95), where a majority were multidrug resistant. Additionally, all strains were screened for rpoB mutations by sequencing and the GenoType MTBDRplus assay. less thanbrgreater than less thanbrgreater thanRifampicin resistance was confirmed by genotypical and/or phenotypical tests in 73 isolates (76.8). Nineteen isolates, defined as rifampicin resistant and rifabutin susceptible according to the present breakpoint, exhibited significantly higher MICs of rifabutin (0.0640.5 mg/L) than rifabutin-susceptible isolates without any detectable mutations in rpoB (P0.001). These 19 isolates were clearly resistant to rifampicin (MIC 2256 mg/L) and all but one had mutations in rpoB, with 9 (47.4) specifically in Asp516Val. less thanbrgreater than less thanbrgreater thanOur results indicate that rifampicin-resistant but rifabutin-susceptible isolates according to the present breakpoints harbour rpoB mutations and have a rifabutin MIC significantly higher than strains without any detectable mutations in rpoB. So far there are no clinical, pharmacological or microbiological data to confirm that such isolates can be treated with rifabutin and we suggest a revision of the current breakpoints.

Place, publisher, year, edition, pages
Oxford University Press (OUP): Policy B - Oxford Open Option B , 2013. Vol. 68, no 9, 2074-2077 p.
Keyword [en]
epidemiological cut-offs, ECOFFs, minimal inhibitory concentrations, MICs, multidrug-resistant tuberculosis, MDR, HIV, rpoB
National Category
Medical and Health Sciences
URN: urn:nbn:se:liu:diva-97436DOI: 10.1093/jac/dkt150ISI: 000323424100018OAI: diva2:647893

Funding Agencies|Wallenberg Foundation||Swedish Medical Association||Swedish Society of Antimicrobial Chemotherapy (SSAC)||Research Council of South East Sweden (FORSS)||

Available from: 2013-09-12 Created: 2013-09-12 Last updated: 2013-09-12

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