Clinical use of Levofloxacin in the long-term treatment of drug resistant tuberculosis.
Multidrug-resistant (MDR) tuberculosis (TB) is a form of TB that is resistant to some of the first-line drugs used for the treatment of the disease. It is associated both with a higher incidence of treatment failures and of disease recurrence, as well as with higher mortality than forms of TB sensitive to first-line drugs. Levofloxacin (LFX) represents one of the few second-line drugs recently introduced in the therapeutic regimens for MDR TB. We report our experience concerning in vitro activity and clinical safety of LFX in long term second-line regimens for MDR TB.
The in vitro activity of ciprofloxacin, ofloxacin and LFX was studied on 28 strains belonging to different species of Mycobacteria. In Dubos medium, LFX inhibited the growth of both library and MDR clinical Mycobacteria strains in a range of 0.25-1 mcg/ml. In International Union Tuberculosis Medium (IUTM) the minimum inhibitory concentrations (MIC) were slightly higher, but LFX activity was not affected by the higher complexity of the medium.


METHODS
Four patients with MDR TB were treated with a second-line regimen comprising oral LFX 500 mg twice daily, for at least 9 months. Two isolates obtained from the patients reported here showed multi resistance to isoniazid and rifampin, one to rifampin and streptomycin and one to isoniazid and ethambutol. During therapy, no significant alteration of either liver function tests, blood tests or any other described side effect of the fluoroquinolone class was observed. The 3 patients with pulmonary MDR TB showed radiologic and clinical improvement.


CONCLUSIONS
We confirm the higher in vitro activity of LFX compared to older fluoroquinolones. Furthermore, in a limited number of MDR TB patients, second-line regimens comprising LFX 500 mg b.i.d. administered in a range of 9-24 months were well tolerated and safe.
Richeldi
L
L
Clinica di Malattie dell'Apparato Respiratorio, Università degli Studi di Modena e Reggio Emilia, Italy. richeldi.luca@unimo.it
Covi
M
M
Ferrara
G
G
Franco
F
F
Vailati
P
P
Meschiari
E
E
Fabbri
L M
LM
Velluti
G
G
D000328:Adult; D000368:Aged; D000890:Anti-Infective Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000633:toxicity; D005260:Female; D006801:Humans; D064704:Levofloxacin; D008297:Male; D008826:Microbial Sensitivity Tests; D009161:Mycobacterium / Q000187:drug effects*; D015242:Ofloxacin / Q000008:administration & dosage* / Q000009:adverse effects / Q000633:toxicity; D014384:Tuberculosis, Female Genital / Q000188:drug therapy*; D018088:Tuberculosis, Multidrug-Resistant / Q000188:drug therapy*; D014397:Tuberculosis, Pulmonary / Q000188:drug therapy*
D000890:Anti-Infective Agents; D064704:Levofloxacin; D015242:Ofloxacin