Susceptibility of Candida albicans biofilms to azithromycin, tigecycline and vancomycin and the interaction between tigecycline and antifungals

• Published in: International journal of antimicrobial agents Vol. 36; no. 5; pp. 441 - 446
• Main Authors: Ku, Tsun Sheng N, Palanisamy, Suresh K.A, Lee, Samuel A
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 01-11-2010; Elsevier
• Subjects: Amphotericin; Anti-Infective Agents - pharmacology; Antibiotics. Antiinfectious agents. Antiparasitic agents; Azithromycin - pharmacology; Biofilms; Biofilms - drug effects; Biofilms - growth & development; Biological and medical sciences; Candida albicans; Candida albicans - drug effects; Candida albicans - growth & development; Candida albicans - physiology; Caspofungin; Drug Interactions; Fluconazole; Humans; Infectious Disease; Inhibitory Concentration 50; Medical sciences; Minocycline - analogs & derivatives; Minocycline - pharmacology; Pharmacology. Drug treatments; Tigecycline; Vancomycin - pharmacology; Candida albicans; Biofilms; Fluconazole; Tigecycline; Amphotericin; Caspofungin; Glycylcycline derivatives; Yeast; Peptides; Azole derivatives; Azithromycin; Vancomycin; Echinocandine derivatives; Fungi; Antiprotozoal agent; Antifungal agent; Glycopeptide; Fungi Imperfecti; Protein synthesis inhibitor; Interaction; Macrolide; Antibiotic; Sensitivity; Amphotericin B; Polyenic compound; Polypeptide; Triazole derivatives; Biofilm; Parasiticide; Antibacterial agent
• ISSN: 0924-8579; 1872-7913
• DOI: 10.1016/j.ijantimicag.2010.06.034

Abstract Despite growing data on antimicrobial lock therapy (ALT) in treating bacterial catheter-related bloodstream infections (CR-BSIs), ALT has not been established as a treatment option for CR-BSI caused by Candida albicans . Based on our finding that high-dose doxycycline exhibited antifungal activity against mature C. albicans biofilms, we evaluated additional antibacterial agents with Gram-positive activity [azithromycin, tigecycline (TIG) and vancomycin]. After screening these antibiotics, it was found that TIG had substantial antifungal activity against mature C. albicans biofilms. Therefore, TIG was assayed alone and in combination with fluconazole (FLC), amphotericin B (AmB) or caspofungin (CAS). TIG at 2048 μg/mL resulted in a >50% reduction in the growth of planktonic C. albicans cells. TIG inhibited the formation of biofilms from 128 μg/mL. Against mature biofilms, 2048 μg/mL TIG reduced metabolic activity by 84.2%. Furthermore, addition of 512 μg/mL TIG to FLC at all concentrations tested provided additional reduction in the metabolic activity of mature biofilms. However, this was not superior to 512 μg/mL TIG alone. TIG at 512 μg/mL increased the antifungal effect of lower concentrations of AmB (0.03125–0.25 μg/mL), but at 0.03125 μg/mL and 0.0625 μg/mL this effect was not superior to 512 μg/mL TIG alone. TIG inhibited the antifungal effect of higher concentrations of AmB (≥2 μg/mL). TIG at 512 μg/mL inhibited the antifungal activity of CAS at lower concentrations (0.25–8 μg/mL). These data indicate that high-dose TIG is highly active in vitro against planktonic cells, forming biofilms and mature biofilms of C. albicans.