In vitro interactions between fluconazole and minocycline against mixed cultures of Candida albicans and Staphylococcus aureus

J Microbiol Immunol Infect. 2015 Dec;48(6):655-61. doi: 10.1016/j.jmii.2014.03.010. Epub 2014 May 22.

Abstract

Background/purpose: It is difficult to manage coinfections in critically ill patients, especially in the presence of mixed-species biofilms. The aim of this study was to seek an effective drug combination for managing the dual-species biofilm of Candida albicans and Staphylococcus aureus.

Methods: The interaction between fluconazole and minocycline against polymicrobial planktonic cells and polymicrobial biofilms formed over four different time intervals (4 hours, 8 hours, 12 hours, and 24 hours) was investigated using a microdilution checkerboard method. To explore whether the combined effects against the polymicrobial cultures involved calcium regulation, the effects of benidipine and ethylene glycol tetraacetic acid were characterized using a plate streaking method and a liquid-based quantitative method.

Results: Fluconazole combined with minocycline exerted strong effects against polymicrobial planktonic cells and polymicrobial biofilms formed over 4 hours, 8 hours, and 12 hours. The addition of benidipine and ethylene glycol tetraacetic acid enhanced the activity of the drug combination, suggesting that the combined effects may involve the perturbation of calcium homeostasis.

Conclusion: Fluconazole in combination with minocycline is a potential approach for counteracting C. albicans-S. aureus dual-species biofilms.

Keywords: Antimicrobial resistance; Calcium regulation; Candida albicans; Drug combination; Polymicrobial biofilms.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / pharmacology*
  • Antifungal Agents / pharmacology*
  • Biofilms / drug effects
  • Calcium / metabolism
  • Candida albicans / drug effects*
  • Candida albicans / growth & development
  • Candidiasis / drug therapy
  • Coinfection / drug therapy
  • Coinfection / microbiology
  • Drug Interactions
  • Drug Synergism
  • Fluconazole / pharmacology*
  • Humans
  • Microbial Sensitivity Tests
  • Minocycline / pharmacology*
  • Staphylococcal Infections / drug therapy
  • Staphylococcus aureus / drug effects*
  • Staphylococcus aureus / growth & development

Substances

  • Anti-Bacterial Agents
  • Antifungal Agents
  • Fluconazole
  • Minocycline
  • Calcium