Pyrazinamide resistance in Mycobacterium tuberculosis arises after rifampicin and fluoroquinolone resistance

A K Alame-Emane; P Xu; C Pierre-Audigier; V Cadet-Daniel; X Shen; M Sraouia; J F Djoba Siawaya; H Takiff; Q Gao; B Gicquel

doi:10.5588/ijtld.14.0768

Pyrazinamide resistance in Mycobacterium tuberculosis arises after rifampicin and fluoroquinolone resistance

Int J Tuberc Lung Dis. 2015 Jun;19(6):679-84. doi: 10.5588/ijtld.14.0768.

Authors

A K Alame-Emane¹, P Xu², C Pierre-Audigier³, V Cadet-Daniel⁴, X Shen⁵, M Sraouia⁶, J F Djoba Siawaya⁷, H Takiff⁸, Q Gao², B Gicquel⁹

Affiliations

¹ Unité de Génétique Mycobactérienne, Institut Pasteur, Paris, France; Research and Specialised Diagnostics Unit, National Laboratory of Public Health, Libreville, Gabon.
² Key Laboratory of Medical Molecular Virology, Institutes of Biomedical Sciences and Institute of Medical Microbiology, Shanghai Medical College, Fudan University, Shanghai, China.
³ Unité de Génétique Mycobactérienne, Institut Pasteur, Paris, France; Laboratoire de Bactériologie, Bichat-Claude Bernard Hospital, Paris, France.
⁴ Unité de Génétique Mycobactérienne, Institut Pasteur, Paris, France.
⁵ Department of Tuberculosis Control, Shanghai Municipal Center for Disease Control and Prevention, Shanghai, China.
⁶ Laboratoire de Bactériologie, Bichat-Claude Bernard Hospital, Paris, France.
⁷ Research and Specialised Diagnostics Unit, National Laboratory of Public Health, Libreville, Gabon.
⁸ Laboratorio de Genética Molecular, Centro de Microbiologıa y Biologıa Celular, Instituto Venezolano de Investigaciones Cientificas, Caracas, Venezuela.
⁹ Unité de Génétique Mycobactérienne, Institut Pasteur, Paris, France; Emerging Bacterial Pathogens Laboratory, Institut Pasteur of Shanghai, Shanghai, China.

PMID: 25946359
DOI: 10.5588/ijtld.14.0768

Abstract

Background: Multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains of Mycobacterium tuberculosis (TB) constitute a major public health concern.

Objective: To determine the timing of pncA mutations that confer pyrazinamide (PZA) resistance in relation to mutations conferring resistance to isoniazid (INH) and rifampicin (RMP).

Design: Isolates from two major urban centres--Paris (101 strains) and Shanghai (171 strains)--were investigated for the association of pncA mutations with resistance to drugs other than PZA.

Results: The proportion of pncA mutations found in INH-monoresistant strains was not increased.

Conclusion: pncA mutations associated with PZA resistance were found almost exclusively in MDR-TB strains, underlining the importance of determining PZA resistance when treating MDR- or XDR-TB.

Publication types

Comparative Study
Multicenter Study
Research Support, Non-U.S. Gov't

MeSH terms

Amidohydrolases / genetics
Antitubercular Agents / therapeutic use*
China / epidemiology
DNA Mutational Analysis
DNA, Bacterial / genetics
Drug Resistance, Multiple, Bacterial* / genetics
Extensively Drug-Resistant Tuberculosis / diagnosis
Extensively Drug-Resistant Tuberculosis / drug therapy
Extensively Drug-Resistant Tuberculosis / epidemiology
Extensively Drug-Resistant Tuberculosis / microbiology
Fluoroquinolones / therapeutic use*
Gene Frequency
Genotype
Humans
Microbial Sensitivity Tests
Mutation
Mycobacterium tuberculosis / drug effects*
Mycobacterium tuberculosis / genetics
Mycobacterium tuberculosis / isolation & purification
Paris / epidemiology
Phenotype
Pyrazinamide / therapeutic use*
Rifampin / therapeutic use*
Tuberculosis, Multidrug-Resistant / diagnosis
Tuberculosis, Multidrug-Resistant / drug therapy*
Tuberculosis, Multidrug-Resistant / epidemiology
Tuberculosis, Multidrug-Resistant / microbiology*

Substances

Antitubercular Agents
DNA, Bacterial
Fluoroquinolones
Pyrazinamide
Amidohydrolases
PncA protein, Mycobacterium tuberculosis
Rifampin