amoxicillin-potassium-clavulanate-combination and Pulmonary-Fibrosis

Topics: Adult; Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Azathioprine; Azithromycin; Fatal Outcome; Glucocorticoids; Humans; Immunosuppressive Agents; Male; Prednisolone; Pulmonary Fibrosis; Respiratory Function Tests; Thoracoscopy; Tomography, X-Ray Computed

The activity of amoxycillin, amoxycillin/clavulanic acid and two tetracycline antibiotics was investigated against three strains of Chlamydia trachomatis in vitro. McCoy cells were infected and single doses of antibiotic administered 24 h after infection. The percentage of infected cells was calculated at intervals up to 72 h after infection. Amoxycillin and clavulanic acid, alone and in combination, reduced the incidence of inclusion formation of all three strains. Particularly good activity was observed against the laboratory-adapted strain C. trachomatis Sa2f and a clinical isolate C. trachomatis LB1, where a progressive reduction in numbers of inclusions was observed with time. Minocycline and oxytetracycline were the most active agents tested. In an experimental animal model, mice were inoculated intranasally with C. trachomatis MoPn (ATCC VR123) which caused a fatal pneumonia within 16 days, and treated orally for four days commencing at 24 h after infection. At doses producing clinically achievable serum concentrations, amoxycillin (10 mg/kg), amoxycillin/clavulanic acid (10 + 5 mg/kg) and minocycline (5 mg/kg) all protected the mice over a 21-day period. The majority of the animals treated with clavulanic acid alone (20 mg/kg) survived the infection. Treatment with oxytetracycline was less effective, a dose of 160 mg/kg being required to protect 70% of the mice. The results indicate that amoxycillin and amoxycillin/clavulanic acid were more effective against C. trachomatis MoPn in vivo than might be predicted from in-vitro data, suggesting that amoxycillin/clavulanic acid may have potential for the treatment of polymicrobial infections involving C. trachomatis.

Topics: Amoxicillin; Amoxicillin-Potassium Clavulanate Combination; Animals; Chlamydia Infections; Chlamydia trachomatis; Clavulanic Acids; Drug Evaluation, Preclinical; Drug Therapy, Combination; Female; Mice; Microbial Sensitivity Tests; Oxytetracycline; Pulmonary Fibrosis; Tetracycline