Antifungal activity of amphotericin B and voriconazole against the biofilms and biofilm-dispersed cells of Candida albicans employing a newly developed in vitro pharmacokinetic model

Annals of Clinical Microbiology and Antimicrobials

Research

Nancy Khardori¹  Noha Farag²  Mohamed El-Azizi² 

[1] East Virginia Medical School, Virginia, USA;German University in Cairo, GUC, Faculty of Pharmacy and Biotechnology, Department of Microbiology, Immunology and Biotechnology, Al-Tagmoa Al-Khamis, New Cairo City, Egypt;

关键词: Candida albicans;    Biofilm;    Amphotericin B;    Voriconazole;    Pharmacokinetic biofilm model;   

DOI  :  10.1186/s12941-015-0083-3

 received in 2014-11-07, accepted in 2015-03-23,  发布年份 2015

来源: Springer

【 摘 要 】

BackgroundCandida albicans is a common cause of a variety of superficial and invasive disseminated infections the majority of which are associated with biofilm growth on implanted devices. The aim of the study is to evaluate the activity of amphotericin B and voriconazole against the biofilm and the biofilm-dispersed cells of Candida albicans using a newly developed in vitro pharmacokinetic model which simulates the clinical situation when the antifungal agents are administered intermittently.MethodsRPMI medium containing 1–5 X 106 CFU/ml of C. albicans was continuously delivered to the device at 30 ml/h for 2 hours. The planktonic cells were removed and biofilms on the catheter were kept under continuous flow of RPMI medium at 10 ml/h. Five doses of amphotericin B or voriconazole were delivered to 2, 5 and 10 day-old biofilms at initial concentrations (2 and 3 μg/ml respectively) that were exponentially diluted. Dispersed cells in effluents from the device were counted and the adherent cells on the catheter were evaluated after 48 h of the last dose.ResultsThe minimum inhibitory concentration of voriconazole and amphotericin B against the tested isolate was 0.0325 and 0.25 μg/ml respectively. Amphotericin B significantly reduced the dispersion of C. albicans cells from the biofilm. The log10 reduction in the dispersed cells was 2.54-3.54, 2.30-3.55, and 1.94-2.50 following addition of 5 doses of amphotericin B to 2-, 5- and 10-day old biofilms respectively. The number of the viable cells within the biofilm was reduced by 18 (±7.63), 5 and 4% following addition of the 5 doses of amphotericin B to the biofilms respectively. Voriconazole showed no significant effect on the viability of C. albicans within the biofilm.ConclusionBoth antifungal agents failed to eradicate C. albicans biofilm or stop cell dispersion from them and the resistance progressed with maturation of the biofilm. These findings go along with the need for removal of devices in spite of antifungal therapy in patients with device-related infection. This is the first study which investigates the effects of antifungal agents on the biofilm and biofilm-dispersion of C. albicans in an in vitro pharmacokinetic biofilm model.

【 授权许可】

CC BY   
© El-Azizi et al.; licensee BioMed Central. 2015