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.
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.


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.
Perlman
D C
DC
Beth Israel Medical Center, New York, NY 10003, USA.
El Sadr
W M
WM
Heifets
L B
LB
Nelson
E T
ET
Matts
J P
JP
Chirgwin
K
K
Salomon
N
N
Telzak
E E
EE
Klein
O
O
Kreiswirth
B N
BN
Musser
J M
JM
Hafner
R
R
D017088:AIDS-Related Opportunistic Infections / Q000188:drug therapy* / Q000382:microbiology* / Q000473:pathology; D000890:Anti-Infective Agents / Q000627:therapeutic use*; D000904:Antibiotics, Antitubercular / Q000008:administration & dosage / Q000627:therapeutic use; D000995:Antitubercular Agents / Q000008:administration & dosage / Q000627:therapeutic use; D004352:Drug Resistance, Microbial / Q000235:genetics; D004359:Drug Therapy, Combination; D004977:Ethambutol / Q000008:administration & dosage / Q000627:therapeutic use; D006801:Humans; D066298:In Vitro Techniques; D007538:Isoniazid / Q000008:administration & dosage / Q000627:therapeutic use; D064704:Levofloxacin; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D015242:Ofloxacin / Q000627:therapeutic use*; D011718:Pyrazinamide / Q000008:administration & dosage / Q000627:therapeutic use; D012293:Rifampin / Q000008:administration & dosage / Q000627:therapeutic use; D013183:Sputum / Q000382:microbiology; D014376:Tuberculosis / Q000150:complications / Q000188:drug therapy* / Q000382:microbiology
D000890:Anti-Infective Agents; D000904:Antibiotics, Antitubercular; D000995:Antitubercular Agents; D011718:Pyrazinamide; D064704:Levofloxacin; D004977:Ethambutol; D015242:Ofloxacin; D007538:Isoniazid; D012293:Rifampin