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Antimicrobial Agents and Chemotherapy, June 2008, p. 2196-2204, Vol. 52, No. 6
0066-4804/08/$08.00+0     doi:10.1128/AAC.00735-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Isobolographic Analysis of Pharmacodynamic Interactions between Antifungal Agents and Ciprofloxacin against Candida albicans and Aspergillus fumigatus{triangledown}

Theodouli Stergiopoulou,1,3 Joseph Meletiadis,1 Tin Sein,1,2 Paraskevi Papaioannidou,3 Ioannis Tsiouris,4 Emmanuel Roilides,1,4 and Thomas J. Walsh1*

Immunocompromised Host Section, Pediatric Oncology Branch, Clinical Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland,1 SAIC—Frederick, Inc., Frederick, Maryland 21702,2 Department of Pharmacology, Medical Faculty, Aristotle University,3 3rd Pediatric Department, Aristotle University, Hippokration Hospital, Thessaloniki, Greece4

Received 6 June 2007/ Returned for modification 18 November 2007/ Accepted 17 February 2008

Patients suffering from invasive mycoses often receive concomitant antifungal therapy and antibacterial agents. Assessment of pharmacodynamic interactions between antifungal and antibacterial agents is complicated by the absence of a common antifungal end point for both agents. Ciprofloxacin has no intrinsic antifungal activity but may interact with antifungal agents, since it inhibits DNA gyrase (topoisomerase II), which is abundant in fungi. We therefore employed isobolographic analysis adapted to incorporate a nonactive agent in order to analyze the potential in vitro interaction between the fluoroquinolone ciprofloxacin and several representative antifungal agents against Candida albicans and Aspergillus fumigatus strains by using a microdilution checkerboard technique. In agreement with earlier in vitro studies, conventional fractional inhibitory concentration index analysis was unable to detect interactions between ciprofloxacin and antifungal agents. However, isobolographic analysis revealed significant pharmacodynamic interactions between antifungal agents and ciprofloxacin against C. albicans and A. fumigatus strains. Amphotericin B demonstrated concentration-dependent interactions for both species, with synergy (interaction indices, 0.14 to 0.81) observed at ciprofloxacin concentrations of <10.64 µg/ml. Synergy (interaction indices, 0.10 to 0.86) was also found for voriconazole and caspofungin against A. fumigatus. Isobolographic analysis may help to elucidate the pharmacodynamic interactions between antifungal and non-antifungal agents and to develop better management strategies against invasive candidiasis and aspergillosis.

* Corresponding author. Mailing address: 10 Center Dr., Bldg. 10, Rm. 1-5888, Pediatric Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892. Phone: (301) 402-0023. Fax: (301) 480-2308. E-mail: walsht{at}mail.nih.gov

{triangledown} Published ahead of print on 25 February 2008.

Antimicrobial Agents and Chemotherapy, June 2008, p. 2196-2204, Vol. 52, No. 6
0066-4804/08/$08.00+0     doi:10.1128/AAC.00735-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Stergiopoulou, T., Meletiadis, J., Sein, T., Papaioannidou, P., Tsiouris, I., Roilides, E., Walsh, T. J. (2009). Comparative pharmacodynamic interaction analysis between ciprofloxacin, moxifloxacin and levofloxacin and antifungal agents against Candida albicans and Aspergillus fumigatus. J Antimicrob Chemother 63: 343-348 [Abstract] [Full Text]  


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