Combination Bacteriophage and Antibiotic Treatment for In Vitro Enterococcal Biofilms on Left Ventricular Assist Device Drivelines

Abstract

Background. Left ventricular assist devices (LVADs) have revolutionized the treatment of advanced heart failure and their use is expanding. However, LVAD driveline infections affect up to 30% of patients with LVADs per year. Due to biofilm formation, these infections often persist despite optimal antibiotic therapy and can result in longterm antibiotic suppression and, eventually, death. While staphylococci are the most frequent cause of driveline infections, enterococci are especially challenging to treat due to their intrinsic antibiotic resistance. We have previously shown that frequently used antibiotics have little effect on enterococcal biofilms grown on LVAD drivelines in vitro. Here, we investigate the ability of a lytic enterococcal bacteriophage to eradicate driveline biofilms alone and in combination with ampicillin. Methods. Sections of LVAD drivelines, composed of silicone coated in Dacron velour, were pre-treated in human serum and then submerged in growth medium with a laboratory strain of Enterococcus faecalis for 24 hours to allow for biofilm establishment. Ampicillin and a lytic bacteriophage were then added alone and in combination for an additional 24 hours. Planktonic cells were sampled from the growth medium and quantified. Biofilm bacteria were then removed from the driveline by sonication and quantified. Treatments were compared using ANOVA. Results. The combination of ampicillin and bacteriophage completely eradicated the planktonic cells and was more effective than either bacteriophage or ampicillin alone (0 versus 1.6 x 108 cfu/ml and 0 versus 3.2 x 107 cfu/mL respectively, p < 0.001 for both comparisons). For biofilm cells, combination treatment did not completely eradicate the biofilm but was more effective than either bacteriophage or ampicillin alone (3.2 x 104 versus 3.2 x 107 cfu/cm of driveline and 3.2 x 104 versus 1.3 x 108 cfu/cm of driveline respectively, p < 0.01 for both comparisons). Conclusion. Bacteriophage therapy may prove to be an important novel therapy for LVAD driveline infections and other device-related infections, especially when combined with traditional antibiotic therapies. Combination therapy may be especially useful in treating infections caused by bacteria with high levels of intrinsic antibiotic resistance, such as enterococci.