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Journal of Clinical Microbiology, March 2006, p. 811-818, Vol. 44, No. 3
0095-1137/06/$08.00+0     doi:10.1128/JCM.44.3.811-818.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Evaluation of MGIT 960-Based Antimicrobial Testing and Determination of Critical Concentrations of First- and Second-Line Antimicrobial Drugs with Drug-Resistant Clinical Strains of Mycobacterium tuberculosis

Health Protection Agency, Mycobacterium Reference Unit, Clinical Research Centre, Barts and the London School of Medicine, Queen Mary College, University of London, 2 Newark Street, London, United Kingdom E1 2AT,¹ Tartu University Clinics, United Laboratory, Department of Mycobacteriology, Tartu, Estonia²

Received 28 April 2005/ Returned for modification 8 July 2005/ Accepted 31 October 2005

The objectives of this study were to (i) compare agreement of the MGIT 960 system for first-line drugs with a methodology (the resistance ratio method [RRM]) that had been used in clinical trials, relating drug susceptibility to clinical outcome; (ii) compare the performance of the MGIT 960, RRM, and microtiter plate assay (MPA) methodologies for second-line drug testing; and (iii) define critical concentrations for ciprofloxacin and moxifloxacin for liquid-culture-based testing. The large collection of clinical isolates of Mycobacterium tuberculosis (n = 247) used included 176 (71%) multidrug-resistant isolates. The results for MGIT 960 and the RRM for rifampin and isoniazid (n = 200) were in excellent (99 to 100%) agreement for all strains. For streptomycin, 97% of the results at the critical concentration and 92% at high concentration, and for pyrazinamide 92% of results overall, were concordant, but for ethambutol, fewer than 85% (65% for the critical concentration and 84% for the high concentration) of the MGIT-based results were concordant with those for the RRM. The MGIT 960, RRM, and MPA assays (n = 133) correlated well for most second-line drugs tested. For susceptibility to ofloxacin, the MGIT 960 and MPA results were in full agreement. The amikacin and rifabutin results obtained by MGIT 960 agreed with the RRM results in 131 (99%) cases, and for capreomycin, they agreed for 129 of 133 isolates tested (97%). For prothionamide testing, only a limited number of drug-resistant isolates were available for testing and drawing definitive conclusions. We propose critical concentrations of 1.0 µg/ml and 0.125 µg/ml for ciprofloxacin and moxifloxacin, respectively, for liquid-culture-based testing.

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