title: A Phase II study of the sterilising activities of ofloxacin, gatifloxacin and moxifloxacin in pulmonary tuberculosis.
abstract: 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.
authors.affiliation: Unit for Clinical and Biomedical TB Research, Medical Research Council, Durban, South Africa.
authors.forename: R
authors.initials: R
authors.lastname: Rustomjee
authors.forename: C
authors.initials: C
authors.lastname: Lienhardt
authors.forename: T
authors.initials: T
authors.lastname: Kanyok
authors.forename: G R
authors.initials: GR
authors.lastname: Davies
authors.forename: J
authors.initials: J
authors.lastname: Levin
authors.forename: T
authors.initials: T
authors.lastname: Mthiyane
authors.forename: C
authors.initials: C
authors.lastname: Reddy
authors.forename: A W
authors.initials: AW
authors.lastname: Sturm
authors.forename: F A
authors.initials: FA
authors.lastname: Sirgel
authors.forename: J
authors.initials: J
authors.lastname: Allen
authors.forename: D J
authors.initials: DJ
authors.lastname: Coleman
authors.forename: B
authors.initials: B
authors.lastname: Fourie
authors.forename: D A
authors.initials: DA
authors.lastname: Mitchison
mesh_terms: 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
chemical_list: 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