Interaction between caspofungin or voriconazole and cefoperazone-sulbactam or piperacillin-tazobactam byin vitroandin vivomethods

Abstract

Immunosuppressive patients are at risk of fungal and bacterial infections. Therefore, these patients receive prophylactic, preemptive, empirical or target antifungal and concomitant antibiotic therapy. To this end, caspofungin (CAS) or voriconazole (VRC) antifungals and cefoperazone-sulbactam (CPZ/SAM) or piperacillin-tazobactam (PIP/TAZ) antibiotics may be used. Here, we aimed to investigate the interaction between these antifungals and antibiotics by in vitro and in vivo methods. The interaction was tested by chequerboard analysis and fractional inhibitory concentration index (FICI). It was also tested in a neutropenic mice-invasive candidiasis model and evaluated by fungal burden in kidney tissue of infected animals from the first day to the fifth day of treatment with 24 h intervals. A synergism was detected between CAS and CPZ/SAM (FICI = 0.1) and PIP/TAZ (FICI = 0.3). Fungal burden in tissues of drug-treated mice was reduced compared with controls in a time-dependent manner. In comparison with CAS-alone treated group, there were 1.32 log10 reductions of fungal burden in CAS + CPZ/SAM (p = 0.002) and in CAS + PIP/TAZ group (p = 0.14). The same interactions were not found with VRC and antibiotics. CPZ/SAM had stronger synergistic interaction with CAS than PIP/TAZ. The mechanism of synergism is not well understood. This is most likely due to an increase in the anticandidal effect of CAS plus antibiotics.

Synergistic Activity of the Plant Defensin HsAFP1 and Caspofungin against Candida albicans Biofilms and Planktonic Cultures

“…albicans . In that study, CPZ/SAM is suggested to have more affinity for the same efflux pump as caspofungin, leading to an increase in intracellular levels of caspofungin and hence, synergy between caspofungin and CPZ/SAM [ 70 ]. In another report, Chen and colleagues demonstrated that posaconazole exhibits synergistic antifungal activity with caspofungin in vitro and in vivo against C .…”

Drug repurposing strategies in the development of potential antifungal agents

“…Many animal models have also been used to verify the antifungal activity of antibacterial agents. In the murine model of candidiasis, a combination of cefoperazone–sulbactam, colistin, or meropenem with caspofungin has been found to result in lower fungal burden in the kidneys, than that after treatment with caspofungin alone (Ozcan et al 2006 ; Zeidler et al 2013 ; Keçeli et al 2014 ). Histopathological results indicated that the degree of inflammation was 25 % less in the group treated with caspofungin and meropenem than caspofungin monotherapy (Ozcan et al 2006 ).…”

In Vitro Synergism Observed with Azithromycin, Clarithromycin, Minocycline, or Tigecycline in Association with Antifungal Agents against Pythium insidiosum

“…The different methods of interpreting the in vitro interactions between drugs (26) and the contradictory results observed in in vitro and in vivo correlations (27)(28)(29) may contribute to the divergent results, indicating the need for standardization of the methods used to evaluate the drug interactions.…”