Background: The aim of our study was to investigate the efficacy of combination treatment of caspofungin (CAS) or voriconazole (VRC) with sefoperazone/sulbactam (CPZ/SAM) and piperacillin/tazobactam (PIP/TAZ) both in vitro and in vivo. Methods: The interaction was tested in vitro by chequerboard analysis and fractional inhibitory concentration index (FICI). For in vivo experiments, all mice were done neutropenic with cyclophosphamide and then infected with standard Candida albicans strain. Control group included infected but not treated mice. Treatment groups were divided into six groups: Group 1 (CAS alone) group 2 (CAS plus CPZ/SAM), Group 3 (CAS plus PIP/TAZ), group 4 (VRC alone); group 5 (VRC plus CPZ/SAM) and group 6 (VRC plus PIP/TAZ). All groups included 12 mice. Treatment was started at 24 h of infection. Three mice from each treatment groups were sacrified with 24 h intervals untill the fifth day of infection. The cytokine (TNF-α , INF-γ , IL-23 and IL-17) levels were determined by ELISA. Results: The in vitro synergistic interaction between CAS and antibiotics namely CPZ/SAM (FICI=0.1) and PIP/TAZ (FICI=0.3) was determined. The fungal burden in antifungal treated mice was decreased compared with controls in a time dependent manner. In comparison to group 1, there was 1.3 log10 reduction of fungal burden in group 2 (p=0.002). There was no significant difference in group 3. Both in vitro and in vivo tests showed that VRC plus antibiotics had no greater efficacy compared to VRC alone. Although TNF-α and INF-γ levels did not change significantly in all treatment groups, an increase in IL-23/17 levels were observed third day of treatment only with CAS plus antibiotics. Conclusion: These results showed that there was a synergistic interaction between CAS and CPZ/SAM or PIP/TAZ but not with VRC but the reason of this interaction remained unclear.
Full conference title:
53rd Interscience Conference on Antimicrobial Agents and Chemotherapy
- ICAAC, 53rd (2013)