title: An in vitro investigation of the bioactivities of ciprofloxacin and the new fluoroquinolone agents clinafloxacin (CI-960) and PD 131628 against Mycobacterium tuberculosis in human macrophages.
abstract: In this study the intracellular bioactivity of ciprofloxacin and the new fluoroquinolone agents clinafloxacin (CI-960) and PD 131628 against Mycobacterium tuberculosis (H37Rv) was compared with rifampicin using human macrophages. Monocyte-derived macrophages were infected with M. tuberculosis in the presence of 10% autologous serum and treated with the antibiotics for 2 days, either immediately after infection or 3 days post-infection. The survival of the intracellular microorganisms was determined using the BACTEC tuberculosis system. Clinafloxacin, although not as active, compared favourably with rifampicin at concentrations ranging from 0.1 to 5 micrograms/ml in both systems, whereas PD 131628 performed reasonably well only when added directly after infection. However, ciprofloxacin was relatively unimpressive with intracellular bioactivity detected only with the highest concentration used (5 micrograms/ml). The ability of clinafloxacin, but not PD 131628, to inhibit mycobacteria after most of the organisms have escaped from the fused phagosomes emphasizes the importance of using a prolonged incubation time after infection when screening new antituberculosis drugs for intracellular bioactivity.
authors.affiliation: Medical Research Council Unit for Inflammation and Immunity, Institute for Pathology, University of Pretoria, South Africa.
authors.forename: C E
authors.initials: CE
authors.lastname: Van Rensburg
authors.forename: G K
authors.initials: GK
authors.lastname: Jooné
authors.forename: R
authors.initials: R
authors.lastname: Anderson
mesh_terms: D000890:Anti-Infective Agents / Q000494:pharmacology*; D000904:Antibiotics, Antitubercular / Q000494:pharmacology; D002939:Ciprofloxacin / Q000494:pharmacology*; D024841:Fluoroquinolones; D006801:Humans; D008264:Macrophages / Q000382:microbiology*; D008826:Microbial Sensitivity Tests; D009000:Monocytes / Q000382:microbiology; D009169:Mycobacterium tuberculosis / Q000187:drug effects*; D009287:Naphthyridines / Q000494:pharmacology*; D010587:Phagocytosis; D015363:Quinolones / Q000494:pharmacology*; D012293:Rifampin / Q000494:pharmacology
chemical_list: D000890:Anti-Infective Agents; D000904:Antibiotics, Antitubercular; D024841:Fluoroquinolones; D009287:Naphthyridines; D015363:Quinolones; C068217:PD 131628; D002939:Ciprofloxacin; C057477:clinafloxacin; D012293:Rifampin