Effect of caspofungin and micafungin in combination with farnesol against Candida parapsilosis biofilms

Renátó Kovács, Aliz Bozó, R. Gesztelyi, Marianna Domán, G. Kardos, Fruzsina Nagy, Zoltán Tóth, László Majoros

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

The in vitro activities of caspofungin and micafungin were determined with and without farnesol against Candida parapsilosis biofilms. Drug interactions were examined using the XTT colorimetric assay-based broth microdilution chequerboard method. Drug-drug interactions were assessed utilising the FICI, Bliss independence models and time-kill experiments. Median sessile MICs of five C. parapsilosis clinical isolates ranged between 32-256. mg/L, 16-512. mg/L and >300. μM for caspofungin, micafungin and farnesol, respectively. Median MICs for caspofungin and micafungin in combination with farnesol showed 8-64- and 4-64-fold decreases, respectively. Paradoxical growth noticed with both echinocandins was eliminated by farnesol. Based on FICIs for sessile clinical isolates, synergism was observed for caspofungin (range of median FICIs, 0.155-0.5) and micafungin (range of median FICIs, 0.093-0.5). Concordantly, MacSynergy analysis and global fitting of non-linear regression based on a Bliss independence models also showed synergism for caspofungin and micafungin. In line with FICI findings and the Bliss independence model, synergistic interactions were confirmed by time-kill experiments. The metabolic activity of fungal cells was significantly inhibited by caspofungin + farnesol at all three tested combinations (4. mg/L + 75. μM, 8. mg/L + 75. μM and 16. mg/L + 75. μM) between 3 and 24. h compared with the control (P

Original languageEnglish
JournalInternational Journal of Antimicrobial Agents
DOIs
Publication statusAccepted/In press - Jul 14 2015

Keywords

  • Drug interaction
  • Echinocandin
  • FICI
  • Fractional inhibitory concentration index
  • Non-linear regression
  • Time-kill experiment

ASJC Scopus subject areas

  • Microbiology (medical)
  • Infectious Diseases
  • Pharmacology (medical)

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