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Journal of Clinical Microbiology, October 2008, p. 3459-3464, Vol. 46, No. 10
0095-1137/08/$08.00+0     doi:10.1128/JCM.00973-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Pyrazinamide Resistance among South African Multidrug-Resistant Mycobacterium tuberculosis Isolates{triangledown}

Matsie Mphahlele,1,2 Heidi Syre,1,5 Håvard Valvatne,1 Ruth Stavrum,1,5 Turid Mannsåker,3 Tshilidzi Muthivhi,2 Karin Weyer,2 P. Bernard Fourie,4 and Harleen M. S. Grewal1,5*

The Gade Institute, Section of Microbiology and Immunology, University of Bergen, N-5021 Bergen, Norway,1 Medical Research Council, Pretoria, South Africa,2 National Reference Laboratory for Mycobacteria, Norwegian Institute of Public Health, Oslo, Norway,3 Medicine in Need, MRC Building, Pretoria, South Africa,4 Department of Microbiology and Immunology, Haukeland University Hospital, N-5021 Bergen, Norway5

Received 21 May 2008/ Returned for modification 6 July 2008/ Accepted 19 August 2008

Pyrazinamide is important in tuberculosis treatment, as it is bactericidal to semidormant mycobacteria not killed by other antituberculosis drugs. Pyrazinamide is also one of the cornerstone drugs retained in the treatment of multidrug-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 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 to 2002, by the Medical Research Council, South Africa) were examined for pyrazinamide susceptibility by the radiometric Bactec 460 TB system, pyrazinamidase activity (by Wayne's assay), and sequencing of the pncA gene. The frequency of pyrazinamide resistance (by the Bactec system) 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 the spoligotype patterns and 12 mycobacterial interspersed repetitive-unit loci. A high proportion of South African MDR M. tuberculosis isolates were resistant to pyrazinamide, suggesting an evaluation of its role in patients treated previously for tuberculosis as well as its role in the treatment of MDR-TB.

* Corresponding author. Mailing address: Section of Microbiology and Immunology, The Gade Institute, University of Bergen and Haukeland University Hospital, N-5021 Bergen, Norway. Phone: 47-55974631. Fax: 47-55974979. E-mail: Harleen.Grewal{at}Gades.uib.no

{triangledown} Published ahead of print on 27 August 2008.

Journal of Clinical Microbiology, October 2008, p. 3459-3464, Vol. 46, No. 10
0095-1137/08/$08.00+0     doi:10.1128/JCM.00973-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Valvatne, H., Syre, H., Kross, M., Stavrum, R., Ti, T., Phyu, S., Grewal, H. M. S. (2009). Isoniazid and rifampicin resistance-associated mutations in Mycobacterium tuberculosis isolates from Yangon, Myanmar: implications for rapid molecular testing. J Antimicrob Chemother 64: 694-701 [Abstract] [Full Text]  


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