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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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Activity of voriconazole on the dispersion of cells from mature biofilms ofC. ablicansfollowing addition of 5 doses of the antifungal agent. The doses were added at 12 hours intervals. The effluent samples, 1 milliliter portions, were collected after 12 hours of addition of each dose.
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Fig3: Activity of voriconazole on the dispersion of cells from mature biofilms ofC. ablicansfollowing addition of 5 doses of the antifungal agent. The doses were added at 12 hours intervals. The effluent samples, 1 milliliter portions, were collected after 12 hours of addition of each dose.

Mentions: The dispersed cells from the biofilm were quantified before adding each dose of the antifungal agents. Amp-B significantly (p < 0.05) reduced the number of dispersed cells of C. albicans from the biofilm (Figures 2 and 3). It was noted that with exponentially decreasing exposure of the biofilms to Amp-B or VCZ, the older the biofilm, the less was the reduction in the number of dispersed cells from it. The maximum log10 reduction in the number of eluted cells from the biofilms occurred after the second dose of the antifungal agents, and the reduction values not significantly changed after exposure to the remaining three doses (p > 0.05). When 5 doses of Amp-B were added to 2-day old biofilm, the dispersed cells were reduced by 2.54-3.54 logs. The log10 reduction was 2.30-3.55, and 1.94-2.50 following addition of Amp-B to 5- and 10-day old biofilms. On the other hand, VCZ did not show such activity against the dispersed cells. The log10 reduction was 0.43-1.22, 0.50-1.11 and 0.16-1.02 when 5 doses of VCZ were added to 2-, 5- and 10-day old biofilms respectively.Figure 2


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)

Activity of voriconazole on the dispersion of cells from mature biofilms ofC. ablicansfollowing addition of 5 doses of the antifungal agent. The doses were added at 12 hours intervals. The effluent samples, 1 milliliter portions, were collected after 12 hours of addition of each dose.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Fig3: Activity of voriconazole on the dispersion of cells from mature biofilms ofC. ablicansfollowing addition of 5 doses of the antifungal agent. The doses were added at 12 hours intervals. The effluent samples, 1 milliliter portions, were collected after 12 hours of addition of each dose.
Mentions: The dispersed cells from the biofilm were quantified before adding each dose of the antifungal agents. Amp-B significantly (p < 0.05) reduced the number of dispersed cells of C. albicans from the biofilm (Figures 2 and 3). It was noted that with exponentially decreasing exposure of the biofilms to Amp-B or VCZ, the older the biofilm, the less was the reduction in the number of dispersed cells from it. The maximum log10 reduction in the number of eluted cells from the biofilms occurred after the second dose of the antifungal agents, and the reduction values not significantly changed after exposure to the remaining three doses (p > 0.05). When 5 doses of Amp-B were added to 2-day old biofilm, the dispersed cells were reduced by 2.54-3.54 logs. The log10 reduction was 2.30-3.55, and 1.94-2.50 following addition of Amp-B to 5- and 10-day old biofilms. On the other hand, VCZ did not show such activity against the dispersed cells. The log10 reduction was 0.43-1.22, 0.50-1.11 and 0.16-1.02 when 5 doses of VCZ were added to 2-, 5- and 10-day old biofilms respectively.Figure 2

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