Susceptibility to levofloxacin of Myocobacterium tuberculosis isolates from patients with HIV-related tuberculosis and characterization of a strain with levofloxacin monoresistance. Community Programs for Clinical Research on AIDS 019 and the AIDS Clinical Trials Group 222 Protocol Team

Abstract

Objective: To characterize the susceptibility to levofloxacin of clinical isolates of Mycobacterium tuberculosis (MTB) obtained from patients with HIV-related tuberculosis and to characterize the molecular genetics of levofloxacin resistance.

Design and methods: Isolates from culture-positive patients in a United States multicenter trial of HIV-related TB were tested for susceptibility to levofloxacin by minimum inhibitory concentration (MIC) determinations in Bactec 7H12 broth. Automated sequencing of the resistance determining region of gyrA was performed.

Results: Of the 135 baseline MTB isolates tested, 134 (99%; 95% exact binomial confidence interval, 95.9-99.9%) were susceptible to levofloxacin with an MIC < or = 1.0 microg/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 patient with AIDS who had received ofloxacin for 8 months prior to the diagnosis of tuberculosis.

Conclusions: Clinical MTB isolates from HIV-infected patients were generally susceptible to levofloxacin. However, the identification of a clinical isolate with mono-resistance to levofloxacin highlights the need for circumspection in the use of fluoroquinolones in the setting of potential HIV-related tuberculosis and for monitoring of rates of resistance of MTB isolates to fluoroquinolones.