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PMID: 12019089 Published · ppublish English Comparative Study Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Antifungal susceptibility of Candida biofilms: unique efficacy of amphotericin B lipid formulations and echinocandins.

Antimicrobial agents and chemotherapy ·Vol. 46 ·No. 6 ·2002-06-00 ·Pages 1773-80

Kuhn DM, George T, Chandra J, Mukherjee PK, Ghannoum MA

Abstract

Biofilms, likely the predominant mode of device-related microbial infection, exhibit resistance to antimicrobial agents. Evidence suggests that Candida biofilms have dramatically reduced susceptibility to antifungal drugs. We examined antifungal susceptibilities of Candida albicans and Candida parapsilosis biofilms grown on a bioprosthetic model. In addition to conventional agents, we determined if new antifungal agents (triazoles, amphotericin B lipid formulations, and echinocandins) have activities against Candida biofilms. We also explored effects of preincubation of C. albicans cells with subinhibitory concentrations (sub-MICs) of drugs to see if they could modify subsequent biofilm formation. Finally, we used confocal scanning laser microscopy (CSLM) to image planktonic- and biofilm-exposed blastospores to examine drug effects on cell structure. Candida biofilms were formed on silicone elastomer and quantified by tetrazolium and dry weight (DW) assays. Susceptibility testing of fluconazole, nystatin, chlorhexidine, terbenafine, amphotericin B (AMB), and the triazoles voriconazole (VRC) and ravuconazole revealed resistance in all Candida isolates examined when grown as biofilms, compared to planktonic forms. In contrast, lipid formulations of AMB (liposomal AMB and AMB lipid complex [ABLC]) and echinocandins (caspofungin [Casp] and micafungin) showed activity against Candida biofilms. Preincubation of C. albicans cells with sub-MIC levels of antifungals decreased the ability of cells to subsequently form biofilm (measured by DW; P < 0.0005). CSLM analysis of planktonic and biofilm-associated blastospores showed treatment with VRC, Casp, and ABLC resulted in morphological alterations, which differed with each agent. In conclusion, our data show that Candida biofilms show unique susceptibilities to echinocandins and AMB lipid formulations.

MeSH Terms
Amphotericin B/administration & dosage,pharmacology Anti-Bacterial Agents/pharmacology Antifungal Agents/administration & dosage,pharmacology Biofilms/drug effects Candida/drug effects,ultrastructure Culture Media Drug Resistance, Microbial Echinocandins Fungal Proteins Liposomes Microbial Sensitivity Tests Microscopy, Confocal Peptides Peptides, Cyclic Polyenes/pharmacology Prosthesis-Related Infections/microbiology Triazoles/pharmacology
Chemicals
Anti-Bacterial Agents Antifungal Agents Culture Media Echinocandins Fungal Proteins Liposomes Peptides Peptides, Cyclic Polyenes Triazoles Amphotericin B echinocandin B
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Kuhn D M
Division of Infectious Diseases, Department of Medicine, University Hospitals of Cleveland and Case Western Reserve University, Cleveland, Ohio 44106, USA.
George T
Chandra J
Mukherjee P K
Ghannoum M A
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Article Info
Journal
Antimicrobial agents and chemotherapy
Abbr.
Antimicrob Agents Chemother
ISSN
0066-4804
DOI
10.1128/AAC.46.6.1773-1780.2002
Published
2002-06-00
Pages
1773-80
Language
English
Region
United States
NLM ID
0315061
PMCID
PMC127206
Subset
IM
Grants
NIAID NIH HHS · R01 AI035097 · United States
NCI NIH HHS · P30 CA043703 · United States
NIAID NIH HHS · AI07024 · United States
NIAID NIH HHS · T32 AI007024 · United States
NIAID NIH HHS · AI-36219 · United States
NIAID NIH HHS · AI35097-03 · United States
NIAID NIH HHS · P30 AI036219 · United States
NCI NIH HHS · P30 CA43703-12 · United States
External Links
PubMed source DOI: 10.1128/AAC.46.6.1773-1780.2002 PMC Full Text View journal details
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