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J. Clin. Microbiol. doi:10.1128/JCM.00973-08
Copyright (c) 2008, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Pyrazinamide resistance among South African multi-drug resistant Mycobacterium tuberculosis isolates

The Gade Institute, Section of Microbiology and Immunology, University of Bergen, N-5021, Bergen, Norway; Medical Research Council, Pretoria, South Africa; National Reference Laboratory for Mycobacteria, Norwegian Institute of Public Health, Oslo, Norway; Medicine in Need, MRC Building, Pretoria, South Africa; Department of Microbiology and Immunology, Haukeland University Hospital, N-5021, Bergen, Norway

^* To whom correspondence should be addressed. Email: Harleen.Grewal{at}Gades.uib.no.

	Abstract

Pyrazinamide is important in tuberculosis treatment, as it is bactericidal to semi-dormant mycobacteria not killed by other anti-tuberculosis drugs. Pyrazinamide is also one of the cornerstone drugs retained in the treatment of multi-drug resistant tuberculosis (MDR-TB). However, due to technical difficulties, routine drug susceptibility testing of Mycobacterium tuberculosis for pyrazinamide is in many laboratories not performed. The objective of our study was to generate information on pyrazinamide susceptibility among South African multi-drug resistant (MDR) and susceptible M. tuberculosis isolates from pulmonary tuberculosis patients.

Seventy-one MDR and 59 fully susceptible M. tuberculosis isolates collected during the national surveillance study (2001-2002, by the Medical Research Council, South Africa) were examined for pyrazinamide susceptibility by the radiometric BACTEC 460 TB system, pyrazinamidase activity (Wayne's assay) and sequencing of the pncA gene.

The frequency of pyrazinamide resistance (by BACTEC) among the MDR M. tuberculosis isolates was 37 of 71 (52.1%) and 6 of 59 (10.2%) among fully sensitive isolates. A total of 25 unique mutations in the pncA gene were detected. The majority of these were point mutations that resulted in amino acid substitutions. Twenty-eight isolates had identical mutations in the pncA gene, but could be differentiated from each other by a combination of spoligotype pattern and 12 MIRU loci.

A high proportion of South African MDR M. tuberculosis isolates were resistant to pyrazinamide, suggesting a reconsideration of its role in patients treated previously for tuberculosis as well as the treatment of MDR-TB.