• E Cambau, M Viveiros, D Machado, L Raskine, C Ritter, E Tortoli, V Matthys, S Hoffner, E Richter, M L Perez Del Molino, D M Cirillo, D van Soolingen, and E C Böttger.
• 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.
• J. Antimicrob. Chemother. 2015 Mar 1; 70 (3): 686-96.

ObjectivesTreatment 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.MethodsThe 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.ResultsA 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.ConclusionsThe 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.© The Author 2014. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

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