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Novel Synergistic Antibiofilm Combinations for Salvage of Infected Catheters

¹ Baylor College of Medicine;

² MD Anderson Cancer Center

³ E-mail: mohanv{at}bcm.edu

Received January 21, 2009
Accepted March 20, 2009

Biofilms on catheters are responsible for catheter-related bloodstream infections (CRBSI) that cause significant mortality and morbidity. Antimicrobial catheter-lock solutions may salvage precious catheters by eradicating biofilms. S. epidermidis and C. albicans are frequently isolated organisms in CRBSIs. We evaluated N-acetyl cysteine (NAC), ethylene diamine tetra-acetic acid (EDTA), ethanol and talactoferrin (TLF) individually and in combination with antibiotics against biofilms of S. epidermidis and C. albicans to identify effective catheter-lock solutions. Minimum biofilm-eradication concentrations of EDTA, NAC, ethanol and TLF at 50% inhibition (MBEC50) were determined against biofilms of S. epidermidis and C. albicans formed on 96-well microtiter plates. Biomass, mean thickness and viability of S. epidermidis and C. albicans biofilms were evaluated after exposure to MBEC50 concentrations of EDTA, NAC, ethanol and TLF. Antimicrobial combinations of EDTA, NAC, ethanol and TLF with nafcillin, vancomycin, fluconazole and amphotericin were evaluated systematically for synergy using combination indices (CI). EDTA, NAC, ethanol and TLF significantly reduced biofilm biomass and mean thickness (p< 0.05, one way ANOVA) of monomicrobial and polymicrobial biofilms as evaluated by confocal microscopy. Combination indices evaluated at equipotency ratios and 50, 75 and 90% effects showed that EDTA, NAC, ethanol and TLF were synergistic (CI <1) with antibiotics (with few exceptions) against biofilms of S. epidermidis and C. albicans. EDTA, NAC, ethanol and TLF inhibit monomicrobial and polymicrobial biofilms of neonatal strains of S. epidermidis and C. albicans and are synergistic with antibiotics. Catheter-lock solutions of EDTA, NAC, and ethanol alone or in combination with antibiotics may be used to salvage infected catheters, which will directly impact patient morbidity and health care costs.