JAC Advance Access originally published online on December 24, 2008
Journal of Antimicrobial Chemotherapy 2009 63(2):343-348; doi:10.1093/jac/dkn473
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Original research |
Comparative pharmacodynamic interaction analysis between ciprofloxacin, moxifloxacin and levofloxacin and antifungal agents against Candida albicans and Aspergillus fumigatus
1 Immunocompromised Host Section, Pediatric Oncology Branch, Clinical Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA 2 3rd Pediatric Department, Aristotle University, Hippokration Hospital, Thessaloniki, Greece 3 Laboratory of Clinical Microbiology, Attiko University Hospital, University of Athens, Athens, Greece 4 SAIC-Frederick, Inc., A subsidiary of Science Applications International Corporation, Frederick, MD 21702-12, USA 5 Department of Pharmacology, Medical Faculty, Aristotle University, Thessaloniki, Greece
Received 28 July 2008; returned 25 August 2008; revised 19 October 2008; accepted 20 October 2008
* Correspondence address. 10 Center Drive, Bldg 10/Rm 1-5750, National Cancer Institute, Paediatric Oncology Branch, Bethesda, MD 20892, USA. Tel: +1-301-402-0023; Fax: +1-301-480-2308; E-mail: walsht{at}mail.nih.gov
Objectives: Patients suffering from invasive mycoses often receive concomitant antifungal therapy and antibacterial agents. Ciprofloxacin, a carboxyfluoroquinolone, was previously observed to demonstrate the pharmacodynamic interactions with antifungal agents by altering their growth inhibitory activity against Candida albicans and Aspergillus fumigatus. However, little is known about the interaction between other extended-spectrum fluoroquinolones, such as levofloxacin and moxifloxacin, and antifungal agents against C. albicans and A. fumigatus.
Methods: Using a microdilution chequerboard technique, we employed isobolographic analysis adapted to incorporate a non-active agent in order to analyse the potential in vitro interaction between ciprofloxacin, levofloxacin or moxifloxacin and the following representative antifungal agents: amphotericin B, fluconazole or voriconazole and caspofungin.
Results: Synergistic interactions [interaction indices (Iis) 0.69–0.83, P < 0.05] were observed between amphotericin B (0.07–0.31 mg/L) and either ciprofloxacin (0.19–7.65 mg/L) or levofloxacin (0.41–32.88 mg/L) against C. albicans and A. fumigatus. Synergy (Iis 0.56–0.87, P < 0.05) also was found between voriconazole (0.09–0.14 mg/L) and ciprofloxacin (0.22–11.41 mg/L) as well as between caspofungin (8.94–22.07 mg/L) and levofloxacin (0.14–5.17 mg/L) against A. fumigatus. Some antagonistic (Iis 1.16–1.29, P < 0.05) interactions were observed between fluoroquinolones and fluconazole against C. albicans. In general, ciprofloxacin enhanced the activity of antifungal agents more than moxifloxacin and levofloxacin against both C. albicans and A. fumigatus.
Conclusions: The knowledge of the pharmacodynamic interactions between fluoroquinolones and antifungal agents may guide selection and potentially improve the outcome of immunosuppressed patients with concurrent bacterial and fungal infections.
Keywords: C. albicans , A. fumigatus , fluoroquinolones