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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.

El-Azizi M, Farag N, Khardori N - Ann. Clin. Microbiol. Antimicrob. (2015)

Bottom Line: Amphotericin B significantly reduced the dispersion of C. albicans cells from the biofilm.Voriconazole showed no significant effect on the viability of C. albicans within the biofilm.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.

View Article: PubMed Central - PubMed

Affiliation: German University in Cairo, GUC, Faculty of Pharmacy and Biotechnology, Department of Microbiology, Immunology and Biotechnology, Al-Tagmoa Al-Khamis, New Cairo City, Egypt. mohamed.el-azizi@guc.edu.eg.

ABSTRACT

Background: Candida 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.

Methods: RPMI medium containing 1-5 X 10(6) 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.

Results: The 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.

Conclusion: Both 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.

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A novelin vitrobiofilm device integrated in a pharmacokinetic biofilm model system. The device was configured to simulate the in vivo condition in which the biofilms of C. albican on IV vascular catheter are under continuously perfusion with fresh medium and exposed to exponentially decreasing concentrations of antifungal agents.
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Fig1: A novelin vitrobiofilm device integrated in a pharmacokinetic biofilm model system. The device was configured to simulate the in vivo condition in which the biofilms of C. albican on IV vascular catheter are under continuously perfusion with fresh medium and exposed to exponentially decreasing concentrations of antifungal agents.

Mentions: A novel in vitro biofilm device was developed (Figure 1). The device comprises a tubular body defining a test chamber. The size of the test chamber is of 10 cm height and 0.80 cm diameter with a volume of 5 ml. The body has upper and lower ends provided with closures. Each of the ends has one port which can be used as an outlet or inlet based on the study conditions. The body has a built in side port and all the three ports can be connected to a tubing system or blocked by the removable closures. The ports in the upper and lower ends of the device are designed to mount the tested materials (catheters or tubes). The design allows the fluid to be pumped through the inner lumen of the implant tube before filling the inner chamber to allow biofilm formation on the inner and outer surfaces of the catheters.Figure 1


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.

El-Azizi M, Farag N, Khardori N - Ann. Clin. Microbiol. Antimicrob. (2015)

A novelin vitrobiofilm device integrated in a pharmacokinetic biofilm model system. The device was configured to simulate the in vivo condition in which the biofilms of C. albican on IV vascular catheter are under continuously perfusion with fresh medium and exposed to exponentially decreasing concentrations of antifungal agents.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4389768&req=5

Fig1: A novelin vitrobiofilm device integrated in a pharmacokinetic biofilm model system. The device was configured to simulate the in vivo condition in which the biofilms of C. albican on IV vascular catheter are under continuously perfusion with fresh medium and exposed to exponentially decreasing concentrations of antifungal agents.
Mentions: A novel in vitro biofilm device was developed (Figure 1). The device comprises a tubular body defining a test chamber. The size of the test chamber is of 10 cm height and 0.80 cm diameter with a volume of 5 ml. The body has upper and lower ends provided with closures. Each of the ends has one port which can be used as an outlet or inlet based on the study conditions. The body has a built in side port and all the three ports can be connected to a tubing system or blocked by the removable closures. The ports in the upper and lower ends of the device are designed to mount the tested materials (catheters or tubes). The design allows the fluid to be pumped through the inner lumen of the implant tube before filling the inner chamber to allow biofilm formation on the inner and outer surfaces of the catheters.Figure 1

Bottom Line: Amphotericin B significantly reduced the dispersion of C. albicans cells from the biofilm.Voriconazole showed no significant effect on the viability of C. albicans within the biofilm.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.

View Article: PubMed Central - PubMed

Affiliation: German University in Cairo, GUC, Faculty of Pharmacy and Biotechnology, Department of Microbiology, Immunology and Biotechnology, Al-Tagmoa Al-Khamis, New Cairo City, Egypt. mohamed.el-azizi@guc.edu.eg.

ABSTRACT

Background: Candida 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.

Methods: RPMI medium containing 1-5 X 10(6) 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.

Results: The 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.

Conclusion: Both 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.

Show MeSH
Related in: MedlinePlus