Efficacy of Caspofungin or Voriconazole with Cefoperazone-Sulbactam or Piperacillin-Tazobactam in Neutropenic Murine Invasive Candidiasis Model and Its Relation to Cytokine Levels

Ref ID: 19265

Author:

A. Willke, S. A. Keçeli, G. S. Tamer, O. B. Boral, N. Sonmez, P. Cagatay

Author address:

Kocaeli Univ. Med. Faculty, Kocaeli, TURKEY; 304;stanbul Univ. Med. Faculty, 304;stanbul, TURKEY; 304;stanbul Univ. Med. Faculty, Kocaeli, TURKEY

Full conference title:

53rd Interscience Conference on Antimicrobial Agents and Chemotherapy

Date: 10 September 2014

Abstract:

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.

Abstract Number: NULL

Conference Year: 2013

Link to conference website: NULL

New link: NULL

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