In Vivo Efficacy of Tigecycline-based Therapy Against Vibrio vulnificus Sepsis: Comparison with pre-Existing Regimens

Abstract

BackgroundThe mortality of Vibrio vulnificus sepsis is still high, despite the application of various antibiotic regimens. In-vivo efficacy of tigecycline against V. vulnificus has not been examined.MethodsTime-kill assay was performed to evaluate the presence of in-vitro antibiotic synergism. The cytotoxicity of V. vulnificus was measured by using the lactate dehydrogenase assay, and rtxA1 toxin gene transcription was measured by β-galactosidase assay. Subcutaneous injection of V. vulnificus was performed with 1 × 108 CFU on iron-overloaded female BALB/c mouse, then intraperitoneal antibiotic therapy was initiated 2 hours after bacterial inoculation.ResultsIn vitro time-kill assay reveals synergism between tigecycline and ciprofloxacin. Inhibitory effects of tigecycline on rtx A1 transcription (66%) and cytotoxicity (59%) were comparable to those of ciprofloxacin (64% and 53%), but superior to those of minocycline (76% and 69%) or cefotaxime (86% and 83%; P < 0.05, each). Survival of tigecycline-treated mice were significantly higher than those of mice treated by current regimens (P < 0.05, each; Table). At Vibrio vulnificus sepsis mice inoculating 1 × 109 CFU, survival rate for tigecycline-plus-ciprofloxacin was significantly higher than that of tigecycline (0%; 0/19) or tigecycline-plus-cefotaxime (0%; 0/19) (P < 0.05, each; Table).108 CFU, 96hr survival (%)109 CFU, 96hr survival (%)control0/24 (0%)0/13 (0%)ciprofloxacin14/25 (56%)N.Acefotaxime-minocycline16/25 (64%)N.Atigecycline22/25 (88%)0/19 (0%)tigecycline-cefotaxime21/25 (84%)0/19 (0%)tigecycline-ciprofloxacin21/25 (84%)7/19 (37%)ConclusionTigecycline-plus-ciprofloxacin showed superior in-vivo efficacy to pre-existing regimens.Disclosures All authors: No reported disclosures.