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Journal of Clinical Microbiology, November 2009, p. 3501-3506, Vol. 47, No. 11
0095-1137/09/$08.00+0     doi:10.1128/JCM.01209-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Mycobacterium tuberculosis Strains with Highly Discordant Rifampin Susceptibility Test Results{triangledown}

A. Van Deun,1* L. Barrera,2 I. Bastian,3 L. Fattorini,4 H. Hoffmann,5 K. M. Kam,6 L. Rigouts,1 S. Rüsch-Gerdes,7 and A. Wright8

Mycobacteriology Unit, Institute of Tropical Medicine, Nationalestraat 155, 2000 Antwerp, Belgium,1 Supra-National Tuberculosis Reference Laboratory, Servicio Micobacterias, INEI ANLIS Dr CG Malbran, Buenos Aires, Argentina,2 Supra-National Tuberculosis Reference Laboratory, Institute of Medical and Veterinary Science, Adelaide, Australia,3 Supra-National Tuberculosis Reference Laboratory, Istituto Superiore di Sanità, Rome, Italy,4 Supra-National Tuberculosis Reference Laboratory, IML-Gauting, Germany,5 Supra-National Tuberculosis Reference Laboratory, Centre for Health Protection, Hong Kong, China,6 Supra-National Tuberculosis Reference Laboratory, Forschungszentrum Borstel, Borstel, Germany,7 World Health Organization, Geneva, Switzerland8

Received 17 June 2009/ Returned for modification 6 August 2009/ Accepted 7 September 2009

The objectives of this study were to investigate the origin of highly discordant rifampin (rifampicin) (RMP) drug susceptibility test results obtained for Mycobacterium tuberculosis strains during proficiency testing. Nine Supra-National Tuberculosis Reference Laboratories tested the RMP susceptibilities of 19 selected M. tuberculosis strains, using standard culture-based methods. The strains were classified as definitely resistant (R) (n = 6) or susceptible (S) (n = 2) or probably resistant (PR) (n = 8) or susceptible (PS) (n = 3) based on rpoB mutations and treatment outcome. All methods yielded a susceptible result for the two S and three PS strains lacking an rpoB mutation and a resistant result for one R strain with a Ser531Leu mutation and one PR strain with a double mutation. Although the remaining 12 R and PR strains had rpoB mutations (four Asp516Tyr, three Leu511Pro, two Leu533Pro, one each His526Leu/Ser, and one Ile572Phe), they were all susceptible by the radiometric Bactec 460TB or Bactec 960 MGIT methods. In contrast, only one was susceptible by the proportion method on Löwenstein-Jensen medium and two on Middlebrook 7H10 agar. Low-level but probably clinically relevant RMP resistance linked to specific rpoB mutations is easily missed by standard growth-based methods, particularly the automated broth-based systems. Further studies are required to confirm these findings, to determine the frequency of these low-level-resistant isolates, and to identify technical improvements that may identify such strains.

* Corresponding author. Mailing address: Mycobacteriology Unit, Institute of Tropical Medicine, Nationalestraat 155, 2000-Antwerp, Belgium. Phone: 32 3 2476548. Fax: 32 3 2476333. E-mail: avdeun{at}itg.be

{triangledown} Published ahead of print on 16 September 2009.

Journal of Clinical Microbiology, November 2009, p. 3501-3506, Vol. 47, No. 11
0095-1137/09/$08.00+0     doi:10.1128/JCM.01209-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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