In vitro activity of antibiotic monotherapy and combination therapy with bacteriophages against Staphylococcus aureus LVAD-driveline infections

Abstract

Left-ventricular assist devices (LVADs) are increasingly used as a bridge to heart transplantation and destination therapy. These devices, especially the driveline, are susceptible to difficult-to-treat infections, associated with high morbidity and mortality rates. Staphylococcus aureus (S. aureus) is a major causative pathogen of LVAD infections. Antibiotic resistance and biofilm formation can complicate the treatment of these infections. A novel in vitro assay was developed to study the antibiotic susceptibility of S. aureus biofilm grown on LVAD drivelines. Besides antibiotic monotherapy, the effect of various antibiotics combined with rifampicin was studied. Additionally, we explored the efficacy of four individual phages and phage-antibiotic combinations as potential treatment strategies. Our data showed a decrease of susceptibility of the S. aureus biofilms to antibiotic monotherapy compared to planktonic S. aureus. With only rifampicin and erythromycin monotherapy resulting in full bacterial clearance. Combining antibiotics with rifampicin showed similar antimicrobial efficacy against S. aureus biofilms as rifampicin monotherapy. While both individual phages and a phage cocktail were effective against planktonic bacteria, phage efficacy was limited against S. aureus in biofilm. Combining phages with antibiotics did not clearly improve treatment efficacy, compared to antibiotic monotherapy. Contrarily, it even increased bacterial growth when phage administration preceded antibiotic treatment. Here, both antibiotic- and phage monotherapy showed reduced efficacy on LVAD-driveline biofilms. Additionally, phages did not show an additive value to antibiotic treatment of LVAD driveline infections. Further studies are needed to elucidate optimal treatment strategies for LVAD-driveline infections.