title: In vitro interactions between fluconazole and minocycline against mixed cultures of Candida albicans and Staphylococcus aureus.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  Fluconazole in combination with minocycline is a potential approach for counteracting C. albicans-S. aureus dual-species biofilms.
authors.affiliation: School of Pharmaceutical Sciences, Shandong University, Jinan 250012, Shandong Province, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Respiratory Medicine, Qianfoshan Hospital Affiliated to Shandong University, Jinan 250014, Shandong Province, China.
authors.forename: Caiqing
authors.initials: C
authors.lastname: Zhang
authors.affiliation: School of Pharmaceutical Sciences, Shandong University, Jinan 250012, Shandong Province, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Liu
authors.affiliation: Department of Pharmacy, Qianfoshan Hospital Affiliated to Shandong University, Jinan 250014, Shandong Province, China.
authors.forename: Weiguo
authors.initials: W
authors.lastname: Liu
authors.affiliation: School of Pharmaceutical Sciences, Shandong University, Jinan 250012, Shandong Province, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Gao
authors.affiliation: Department of Pharmacy, Qianfoshan Hospital Affiliated to Shandong University, Jinan 250014, Shandong Province, China. Electronic address: sunshujuan888@163.com.
authors.forename: Shujuan
authors.initials: S
authors.lastname: Sun
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D000935:Antifungal Agents / Q000494:pharmacology*; D018441:Biofilms / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D002176:Candida albicans / Q000187:drug effects* / Q000254:growth & development; D002177:Candidiasis / Q000188:drug therapy; D060085:Coinfection / Q000188:drug therapy / Q000382:microbiology; D004347:Drug Interactions; D004357:Drug Synergism; D015725:Fluconazole / Q000494:pharmacology*; D006801:Humans; D008826:Microbial Sensitivity Tests; D008911:Minocycline / Q000494:pharmacology*; D013203:Staphylococcal Infections / Q000188:drug therapy; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000254:growth & development
chemical_list: D000900:Anti-Bacterial Agents; D000935:Antifungal Agents; D015725:Fluconazole; D008911:Minocycline; D002118:Calcium
keywords: Antimicrobial resistance; Calcium regulation; Candida albicans; Drug combination; Polymicrobial biofilms