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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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Related in: MedlinePlus

The antifungal activity of amphotericin B and voriconazole against mature biofilms ofC. albianson IV vascular catheter following addition of 5 doses of the antifungal agents. The viable cells within the biofilm were determined after 48 hours of the last dose and calculated as colony forming unit (CFU) per 1 cm of the catheter segment.
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Fig4: The antifungal activity of amphotericin B and voriconazole against mature biofilms ofC. albianson IV vascular catheter following addition of 5 doses of the antifungal agents. The viable cells within the biofilm were determined after 48 hours of the last dose and calculated as colony forming unit (CFU) per 1 cm of the catheter segment.

Mentions: The antifungal agents were tested against 2-, 5-, and 10- day old biofilms of C. albicans in the pharmacokinetic biofilm model (Figure 4). Adherent cells were evaluated by viable count of the released cells following sonication of the biofilms. The biofilms of C. albicans were resistant to the antifungal drugs. Amp-B was more active against the 2-day old biofilms compared to the effect on 5- and 10-day old biofilms. Following addition of 5 doses to 2-day old biofilms, Amp-B reduced the number of the viable cells within the biofilm by 18% (±7.63) compared to untreated biofilms (drug-free controls), while the reduction was 5 and 4% following addition of the antifungal agent to 5- and 10-day old biofilms. VCZ, on the other hand, showed no significant effect on the viability of C. albicans within the tested biofilms after addition of 5 doses of the drug compared to drug-free controls.Figure 4


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)

The antifungal activity of amphotericin B and voriconazole against mature biofilms ofC. albianson IV vascular catheter following addition of 5 doses of the antifungal agents. The viable cells within the biofilm were determined after 48 hours of the last dose and calculated as colony forming unit (CFU) per 1 cm of the catheter segment.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Fig4: The antifungal activity of amphotericin B and voriconazole against mature biofilms ofC. albianson IV vascular catheter following addition of 5 doses of the antifungal agents. The viable cells within the biofilm were determined after 48 hours of the last dose and calculated as colony forming unit (CFU) per 1 cm of the catheter segment.
Mentions: The antifungal agents were tested against 2-, 5-, and 10- day old biofilms of C. albicans in the pharmacokinetic biofilm model (Figure 4). Adherent cells were evaluated by viable count of the released cells following sonication of the biofilms. The biofilms of C. albicans were resistant to the antifungal drugs. Amp-B was more active against the 2-day old biofilms compared to the effect on 5- and 10-day old biofilms. Following addition of 5 doses to 2-day old biofilms, Amp-B reduced the number of the viable cells within the biofilm by 18% (±7.63) compared to untreated biofilms (drug-free controls), while the reduction was 5 and 4% following addition of the antifungal agent to 5- and 10-day old biofilms. VCZ, on the other hand, showed no significant effect on the viability of C. albicans within the tested biofilms after addition of 5 doses of the drug compared to drug-free controls.Figure 4

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