Document Detail

Pyrazinamide resistance among South African multidrug-resistant Mycobacterium tuberculosis isolates.
MedLine Citation:
PMID:  18753350     Owner:  NLM     Status:  MEDLINE    
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.
Matsie Mphahlele; Heidi Syre; Håvard Valvatne; Ruth Stavrum; Turid Mannsåker; Tshilidzi Muthivhi; Karin Weyer; P Bernard Fourie; Harleen M S Grewal
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2008-08-27
Journal Detail:
Title:  Journal of clinical microbiology     Volume:  46     ISSN:  1098-660X     ISO Abbreviation:  J. Clin. Microbiol.     Publication Date:  2008 Oct 
Date Detail:
Created Date:  2008-10-06     Completed Date:  2008-10-27     Revised Date:  2013-06-05    
Medline Journal Info:
Nlm Unique ID:  7505564     Medline TA:  J Clin Microbiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  3459-64     Citation Subset:  IM    
Section of Microbiology and Immunology, The Gade Institute, University of Bergen, N-5021 Bergen, Norway.
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MeSH Terms
Aged, 80 and over
Amidohydrolases / genetics
Amino Acid Substitution
Antitubercular Agents / pharmacology*
DNA Fingerprinting
DNA, Bacterial / chemistry,  genetics
Drug Resistance, Multiple, Bacterial*
Microbial Sensitivity Tests
Middle Aged
Mutation, Missense
Mycobacterium tuberculosis / classification,  drug effects*,  genetics,  isolation & purification
Point Mutation
Pyrazinamide / pharmacology*
Sequence Analysis, DNA
South Africa
Tuberculosis, Multidrug-Resistant / microbiology*
Tuberculosis, Pulmonary / microbiology*
Reg. No./Substance:
0/Antitubercular Agents; 0/DNA, Bacterial; 98-96-4/Pyrazinamide; EC 3.5.-/Amidohydrolases; EC 3.5.-/PncA protein, Mycobacterium tuberculosis

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