TY - JOUR T1 - Revisiting susceptibility testing in MDR-TB by a standardized quantitative phenotypic assessment in a European multicentre study9 JF - J.Antimicrob.Chemother. Y1 - 2015 A1 - Cambau,E. A1 - Viveiros,M. A1 - Machado,D. A1 - Raskine,L. A1 - Ritter,C. A1 - Tortoli,E. A1 - Vanessa Mathys A1 - S Hoffner A1 - Richter,E. A1 - Perez Del Molino,M.L. A1 - D M. Cirillo A1 - D. van Soolingen A1 - Bottger,E.C. KW - 0 KW - a KW - acid KW - Agent KW - Agents KW - Amikacin KW - an KW - Antitubercular Agents KW - article KW - AS KW - assessment KW - at KW - Belgium KW - Biology KW - Brussels KW - care KW - Cell KW - Clinical KW - Concordance KW - de KW - detection KW - disease KW - Diseases KW - DRUG KW - drug effects KW - Drug Resistance KW - drugs KW - e KW - electronic KW - environment KW - Establish KW - estimation KW - ET KW - Ethionamide KW - Europe KW - European KW - EVALUATION KW - France KW - gene KW - genetics KW - Genotype KW - Genotyping Techniques KW - Germany KW - growth & development KW - health KW - Help KW - Humans KW - im KW - Impact KW - Infectious KW - Infectious diseases KW - Institute KW - IS KW - isolation & purification KW - ITALY KW - journal KW - Laboratories KW - LEVEL KW - levels KW - medical KW - method KW - methods KW - Microbial Sensitivity Tests KW - microbiology KW - Mutation KW - Mycobacterium KW - Mycobacterium tuberculosis KW - national KW - Netherlands KW - objectives KW - observed KW - ON KW - outcome KW - paris KW - pathogen KW - Patient KW - Patient Care KW - patients KW - pharmacology KW - portugal KW - proportion KW - protocol KW - public KW - public health KW - Public-health KW - Pulmonary KW - Pyrazinamide KW - region KW - resistance KW - result KW - results KW - SB - IM KW - SCREENING KW - Service KW - Short KW - SOFTWARE KW - Spain KW - standards KW - Streptomycin KW - study KW - Sweden KW - Switzerland KW - Technique KW - TESTING KW - The Netherlands KW - therapeutic use KW - time KW - treatment KW - Treatment Outcome KW - Tuberculosis KW - Tuberculosis,Multidrug-Resistant KW - tumor KW - Universities KW - university KW - use KW - VALIDATION KW - WIV-ISP AB - 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 VL - 70 CP - 3 U1 - 9 M3 - dku438 [pii];10.1093/jac/dku438 [doi] ER -