SUSCEPTIBILITY TO LEVOFLOXACIN OF MYCOBACTERIUM-TUBERCULOSIS ISOLATESFROM PATIENTS WITH HIV-RELATED TUBERCULOSIS AND CHARACTERIZATION OF ASTRAIN WITH LEVOFLOXACIN MONORESISTANCE

Objective: To characterize the susceptibility to levofloxacin of clini cal isolates of Mycobacterium tuberculosis (MTB) obtained from patient s with HIV-related tuberculosis and to characterize the molecular gene tics of levofloxacin resistance. Design and methods: Isolates from cul ture-positive patients in a United States multicenter trial of HIV-rel ated TB were tested for susceptibility to levofloxacin by minimum inhi bitory concentration (MIG) determinations in Bactec 7H12 broth. Automa ted sequencing of the resistance determining region of gyrA was perfor med. Results: Of the 135 baseline MTB isolates tested, 134 (99%; 95% e xact binomial confidence interval, 95.9-99.9%) were susceptible to lev ofloxacin with an MIC less than or equal to 1.0 mu g/ml. We identified a previously unrecognized mis-sense mutation occurring at codon 88 of gyrA in a levofloxacin mono-resistant MTB isolate obtained from a pat ient with AIDS who had received ofloxacin for 8 months prior to the di agnosis of tuberculosis. Conclusions: Clinical MTB isolates from HIV-i nfected patients were generally susceptible to levofloxacin. However, the identification of a clinical isolate with mono-resistance to levof loxacin highlights the need for circumspection in the use of fluoroqui nolones in the setting of potential HIV-related tuberculosis and for m onitoring of rates of resistance of MTB isolates to fluoroquinolones.