Levofloxacin, the active L-isomer of the quinolone ofloxacin, is now widely accepted for treatment of multidrug-resistant tuberculosis. Because the drug is now widely used, we sought to establish susceptibility test conditions for Mycobacterium tuberculosis against levofloxacin by the traditional reference method, agar proportion (AP), the commonly used BACTEC 460 radiometric system, and the newer BACTEC MGIT 960 method. To determine the stability of levofloxacin in the two newer test systems (BACTEC 460 and BACTEC MGIT 960), media containing subinhibitory levels of levofloxacin were prepared and stored at 4 and 37°C for 14 days. The stored media were inoculated with H37Rv, and the drug activity was compared to freshly prepared media. Results show that levofloxacin is stable over the course of testing. Next, optimum levofloxacin test concentrations were determined for AP, BACTEC 460, and BACTEC MGIT 960 methods. MICs were determined for 32 pan-susceptible isolates of M. tuberculosis obtained from presumably untreated patients and 14 quinolone-resistant isolates. The levofloxacin-resistant strains either were isolated from patients who remained culture-positive despite treatment with a quinolone agent (six strains) or contained known mutations in gyrA (eight strains). Levofloxacin MICs resulted in a bimodal pattern with values for resistant strains consistently higher than those for pan-susceptible strains. Results show that levofloxacin concentrations of 2 g/ml (BACTEC 460 and BACTEC MGIT 960) and 1 g/ml (AP) inhibited the growth of all pan-susceptible strains while permitting the growth of all levofloxacin-resistant strains. Confirmatory tests with a subset of pan-susceptible and levofloxacin-resistant isolates validated the selected test concentrations.Increasing reports of multidrug-resistant tuberculosis (MDR-TB) and the emergence of TB in human immunodeficiency virus-infected persons have resulted in the need for new anti-TB agents (3). The fluoroquinolones, especially ofloxacin, have been shown to be highly useful as second-line anti-TB agents against drug-resistant strains. Studies have demonstrated that levofloxacin (LVX), the L-isomer of ofloxacin, is nearly twice as active against Mycobacterium tuberculosis in vitro as its parent compound ofloxacin (8,9,15). Because of its effectiveness, LVX has become widely used as a second-line anti-TB agent to treat patients with MDR-TB.In response to the use of LVX for treatment of MDR-TB, the need to establish laboratory protocols for susceptibility testing of LVX has developed. To address this need, we investigated the conditions necessary to obtain valid LVX susceptibility results with the BACTEC 460 radiometric system (10) and the newer BACTEC MGIT 960 nonradiometric system (13), based on the previously published drug stability studies done by the agar proportion (AP) method (4).Once susceptibility test conditions were determined, critical testing concentration levels for LVX for the three methods were established with fluoroquinolone-resistant and -susceptibl...
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