Evaluation of the efficacy of doxycycline, ciprofloxacin, levofloxacin, and co-trimoxazole using in vitro and in vivo models of Q fever

Q fever, caused by the intracellular pathogen Coxiella burnetii, is traditionally treated using tetracycline antibiotics, such as doxycycline. Doxycycline is often poorly tolerated, and antibiotic-resistant strains have been isolated. In this study, we have evaluated a panel of antibiotics (doxycycline, ciprofloxacin, levofloxacin, and co-trimoxazole) against C. burnetii using in vitro methods (determination of MIC using liquid and solid media; efficacy assessment in a THP cell infection model) and in vivo methods (wax moth larvae and mouse models of infection). In addition, the schedule for antibiotic treatment has been evaluated, with therapy initiated at 24 h pre- or postchallenge. Both doxycycline and levofloxacin limited overt clinical signs during treatment in the AJ mouse model of aerosol infection, but further studies are required to investigate the possibility of disease relapse or incomplete bacterial clearance after the antibiotics are stopped. Levofloxacin was well tolerated and therefore warrants further investigation as an alternative to the current recommended treatment with doxycycline.