title: Susceptibility of Candida albicans biofilms to azithromycin, tigecycline and vancomycin and the interaction between tigecycline and antifungals.
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.
authors.affiliation: Section of Infectious Diseases, New Mexico Veterans Healthcare System, Albuquerque, NM 87108, USA.
authors.forename: Tsun Sheng N
authors.initials: TS
authors.lastname: Ku
authors.forename: Suresh K A
authors.initials: SK
authors.lastname: Palanisamy
authors.forename: Samuel A
authors.initials: SA
authors.lastname: Lee
mesh_terms: D000890:Anti-Infective Agents / Q000494:pharmacology*; D017963:Azithromycin / Q000494:pharmacology*; D018441:Biofilms / Q000187:drug effects* / Q000254:growth & development; D002176:Candida albicans / Q000187:drug effects* / Q000254:growth & development / Q000502:physiology; D004347:Drug Interactions; D006801:Humans; D020128:Inhibitory Concentration 50; D008911:Minocycline / Q000031:analogs & derivatives* / Q000494:pharmacology; D000078304:Tigecycline; D014640:Vancomycin / Q000494:pharmacology*
chemical_list: D000890:Anti-Infective Agents; D014640:Vancomycin; D000078304:Tigecycline; D017963:Azithromycin; D008911:Minocycline