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In vitro analyses of the combination of high-dose doxycycline and antifungal agents against Candida albicans biofilms.
- Source :
-
International journal of antimicrobial agents [Int J Antimicrob Agents] 2009 Oct; Vol. 34 (4), pp. 326-32. Date of Electronic Publication: 2009 Jun 09. - Publication Year :
- 2009
-
Abstract
- The potential of antifungal agents used as antimicrobial lock therapy (ALT) for the conservative management of catheter-related candidemia has not been fully defined. We sought to determine the antifungal effect of high-dose doxycycline (DOX), alone or in combination with standard concentrations of amphotericin B (AMB), caspofungin (CAS) or fluconazole (FLC), against biofilms formed by Candida albicans in vitro. DOX alone (at 2048 microg/mL and 1024 microg/mL) demonstrated up to an 85% reduction of the metabolic activity of the C. albicans biofilm. Regardless of the concentration tested, FLC alone showed minimal activity (mean 22.9% reduction) against the C. albicans biofilm. When DOX 2048 microg/mL was used in combination with FLC, antifungal activity also increased up to 85%, suggesting an additive effect. DOX 128 microg/mL in combination with FLC demonstrated synergy (mean 58.3% reduction). The combination of DOX 2048 microg/mL or 512 microg/mL and AMB was superior to AMB alone at low concentrations (0.25-0.03125 microg/mL). However, DOX 128 microg/mL was antagonistic in combination with low concentrations of AMB. Maximal efficacy against the biofilm was observed with CAS at 8-0.25 microg/mL compared with FLC and AMB alone. A paradoxical effect (PE) occurred with CAS at 16 microg/mL, which showed a marked reduction in antifungal activity compared with lower concentrations of CAS. CAS at 16 microg/mL in combination with either DOX 2048 microg/mL or 512 microg/mL resulted in attenuation of the PE. These findings suggest that a high-dose DOX-based ALT strategy in combination with traditional antifungal agents may be useful for the treatment of C. albicans biofilms.
- Subjects :
- Amphotericin B pharmacology
Caspofungin
Dose-Response Relationship, Drug
Doxycycline administration & dosage
Drug Interactions
Drug Therapy, Combination
Echinocandins pharmacology
Fluconazole pharmacology
Humans
Lipopeptides
Microbial Sensitivity Tests
Antifungal Agents pharmacology
Biofilms drug effects
Candida albicans drug effects
Doxycycline pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1872-7913
- Volume :
- 34
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- International journal of antimicrobial agents
- Publication Type :
- Academic Journal
- Accession number :
- 19515537
- Full Text :
- https://doi.org/10.1016/j.ijantimicag.2009.04.011