| Popis: |
Background The shortage in the supply of benzathine penicillin G (BPG) and other limitations associated with BPG use underscore the need for new therapeutic options for syphilis treatment. Until recently, Treponema pallidum (T. pallidum), the syphilis agent, could not be cultured in vitro, making the screening of antibiotics only possible in vivo, and hence difficult, time-consuming, and expensive. Because a cultivation system for this difficult pathogen is now available, we used an in vitro minimum inhibitory concentration (MIC) assay to screen antibiotics with the potential to provide new treatment options for syphilis. Methods T. pallidum was cultured in vitro in the presence of multiple concentrations of cefixime, dalbavancin, isoniazid, and pyrazinamide in independent experiments. All these antibiotics have adequate pharmacokinetic and pharmacodynamic properties to treat syphilis based on previous data from humans studies in other infections. After seven days in culture, DNA was extracted from the culture wells and T. pallidum growth was compared to no-antibiotic culture wells using qPCR targeting the tp0574 gene. Results Isoniazid and pyrazinamide, both antimycobacterials, had MICs of >500ng/ml and >64μg/ml, respectively. For cefixime, a cephalosporin, and dalbavancin, a glycopeptide antibiotic, the experimental MICs were Conclusion Cefixime and dalbavancin appear to have marked microbicidal activity against T. pallidum with MICs that make them promising candidates for syphilis treatment in place of BPG. Isoniazid and pyrazinamide showed no significant treponemacidal activity in vitro at the concentrations tested. |
