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J Antimicrob Chemother. 2015 Mar;70(3):686-96. doi: 10.1093/jac/dku438. Epub 2014 Nov 11.

Revisiting susceptibility testing in MDR-TB by a standardized quantitative phenotypic assessment in a European multicentre study.

Author information

1
AP-HP, Hôpital Lariboisière, Service de Bactériologie, Centre National de Référence des Mycobactéries et de la Résistance des Mycobactéries aux Antituberculeux; IAME UMR1137, INSERM, Université Paris Diderot, 75010 Paris, France emmanuelle.cambau@lrb.aphp.fr.
2
Grupo de Micobactérias, Unidade de Microbiologia Médica, Instituto de Higiene e Medicina Tropical, Universidade Nova de Lisboa (IHMT/UNL), Rua da Junqueira 100, 1349-008 Lisboa, Portugal.
3
AP-HP, Hôpital Lariboisière, Service de Bactériologie, Centre National de Référence des Mycobactéries et de la Résistance des Mycobactéries aux Antituberculeux; IAME UMR1137, INSERM, Université Paris Diderot, 75010 Paris, France.
4
Institut für Medizinische Mikrobiologie, Nationales Zentrum für Mykobakterien, Universität Zürich, Zürich, Switzerland.
5
IRCCS San Raffaele Scientific Institute, Emerging Bacterial Pathogens Unit Supranational Reference Laboratory, via Olgettina 60, 20132 Milan, Italy.
6
National Reference Centre of Tuberculosis and Mycobacteria, Communicable and Infectious Diseases, Scientific Institute of Public Health (WIV-ISP), Brussels, Belgium.
7
Department of Microbiology, Public Health Agency of Sweden and Department of Microbiology, Cell and Tumor Biology, Karolinska Institute, Stockholm, Sweden.
8
National Reference Center for Mycobacteria, Forschungszentrum Borstel, Borstel, Germany.
9
Servicio de Microbiología, CH Universitario de Santiago, Centro de Referencia de Micobacterias de Galicia, Choupana S/N, 15705 Santiago de Compostela, Spain.
10
Tuberculosis Reference Laboratory, National Institute for Public Health and the Environment (RIVM), PO Box 1, 3720 BA Bilthoven, The Netherlands Department of Pulmonary Diseases/Department of Clinical Microbiology, Radboud University Medical Centre, PO Box 9101, Nijmegen, The Netherlands.

Abstract

OBJECTIVES:

Treatment outcome of MDR-TB is critically dependent on the proper use of second-line drugs as per the result of in vitro drug susceptibility testing (DST). We aimed to establish a standardized DST procedure based on quantitative determination of drug resistance and compared the results with those of genotypes associated with drug resistance.

METHODS:

The protocol, based on MGIT 960 and the TB eXiST software, was evaluated in nine European reference laboratories. Resistance detection at a screening drug concentration was followed by determination of resistance levels and estimation of the resistance proportion. Mutations in 14 gene regions were investigated using established techniques.

RESULTS:

A total of 139 Mycobacterium tuberculosis isolates from patients with MDR-TB and resistance beyond MDR-TB were tested for 13 antituberculous drugs: isoniazid, rifampicin, rifabutin, ethambutol, pyrazinamide, streptomycin, para-aminosalicylic acid, ethionamide, amikacin, capreomycin, ofloxacin, moxifloxacin and linezolid. Concordance between phenotypic and genotypic resistance was >80%, except for ethambutol. Time to results was short (median 10 days). High-level resistance, which precludes the therapeutic use of an antituberculous drug, was observed in 49% of the isolates. The finding of a low or intermediate resistance level in 16% and 35% of the isolates, respectively, may help in designing an efficient personalized regimen for the treatment of MDR-TB patients.

CONCLUSIONS:

The automated DST procedure permits accurate and rapid quantitative resistance profiling of first- and second-line antituberculous drugs. Prospective validation is warranted to determine the impact on patient care.

KEYWORDS:

DST; MGIT; TB eXiST; antibiotic susceptibility testing; antituberculous drugs

PMID:
25587993
DOI:
10.1093/jac/dku438
[Indexed for MEDLINE]
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