A Phase II study of the sterilising activities of ofloxacin, gatifloxacin and moxifloxacin in pulmonary tuberculosis.
METHODS
Current treatment for pulmonary tuberculosis (TB) might be shortened by the incorporation of fluoroquinolones (FQs).


OBJECTIVE
A Phase II study aimed to assess the sterilising activities of three novel regimens containing FQs before a Phase III trial of a 4-month regimen containing gatifloxacin (GFX).


METHODS
A total of 217 newly diagnosed smear-positive patients were randomly allocated to one of four regimens: isoniazid (INH), pyrazinamide and rifampicin (RMP) with either ethambutol, GFX, moxifloxacin (MFX) or ofloxacin (OFX) for 2 months. At the end of the study, RMP and INH were given for 4 months. The rates of elimination of Mycobacterium tuberculosis were compared in the regimens using non-linear mixed effects modelling of the serial sputum colony counts (SSCC) during the first 8 weeks.


RESULTS
After adjustment for covariates, MFX substitution appeared superior during the early phase of a bi-exponential fall in colony counts, but significant and similar acceleration of bacillary elimination during the late phase occurred with both GFX and MFX (P = 0.002). Substitution of OFX had no effect. These findings were supported by estimates of time to conversion, using Cox regression, but there were no significant differences in proportions culture-negative at 8 weeks.


CONCLUSIONS
GFX and MFX improve the sterilising activity of regimens and might shorten treatment; their progression into Phase III trials therefore seems warranted.
Rustomjee
R
R
Unit for Clinical and Biomedical TB Research, Medical Research Council, Durban, South Africa.
Lienhardt
C
C
Kanyok
T
T
Davies
G R
GR
Levin
J
J
Mthiyane
T
T
Reddy
C
C
Sturm
A W
AW
Sirgel
F A
FA
Allen
J
J
Coleman
D J
DJ
Fourie
B
B
Mitchison
D A
DA
D000293:Adolescent; D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D000995:Antitubercular Agents / Q000627:therapeutic use*; D001372:Aza Compounds / Q000627:therapeutic use*; D015169:Colony Count, Microbial; D004359:Drug Therapy, Combination; D005260:Female; D024841:Fluoroquinolones / Q000627:therapeutic use*; D000077734:Gatifloxacin; D006801:Humans; D007538:Isoniazid / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D000077266:Moxifloxacin; D017711:Nonlinear Dynamics; D015242:Ofloxacin / Q000627:therapeutic use*; D011718:Pyrazinamide / Q000627:therapeutic use; D011804:Quinolines / Q000627:therapeutic use*; D012293:Rifampin / Q000627:therapeutic use; D013183:Sputum / Q000382:microbiology
D000900:Anti-Bacterial Agents; D000995:Antitubercular Agents; D001372:Aza Compounds; D024841:Fluoroquinolones; D011804:Quinolines; D011718:Pyrazinamide; D015242:Ofloxacin; D000077734:Gatifloxacin; D000077266:Moxifloxacin; D007538:Isoniazid; D012293:Rifampin