EFFECTS OF HOST IMMUNITY ON ANTIBIOTIC TREATMENT OF STAPHYLOCOCCUS AUREUS BIOFILM INFECTIONS

Purpose: Staphylococcus aureus is a pathogen often seen in the hospital setting and the cause of various infections in humans. Multiple antibiotic resistant S. aureus strains (MRSA) have been clinically isolated, which becomes problematic when S. aureus forms biofilms or slime layers on synthetic materials like catheters. Biofilm infections are difficult to treat, and if a patient has compromised immunity due to underlying medical conditions, the infection can be life threatening. To understand the impact of host immunity on the treatment of S. aureus biofilm infections, we subcutaneously (SC) implanted S. aureus infected catheter pieces in mice that have severe combined immunodeficiency (SCID), treated them for 7 days with rifampin, and measured the number of rifampin-resistant and rifampin-sensitive cells associated with the catheter pieces. Methods: Using broth media supplemented with glucose and sodium chloride, 1 cm Teflon catheters were inoculated with a non-resistant strain of S. aureus for one hour. Infected catheters were surgically placed subcutaneously in four mouse strains, BALB/c, BALB/c-SCID, C57BL/6J and C57BL/6J-SCID. Seven days after implantation, an antibiotic regimen was started using either rifampicin or vehicle, 2 times a day for 7 days. The catheters were aseptically removed within 20 hours of the final dose. The catheters were processed and plated on non-antibiotic agar media and media containing 1 mg/mL of rifampin. Results: Catheter-associated CFU stabilized at 6.3 log CFU in C57BL/6J mice and 7.4 log CFU in BALB/c mice 14 days after implantation. Rifampin 7-day treatment at 25mg/kg yielded mean log CFU reductions of 1.8 and 2.6 in BALB/c wild-type and SCID mice, respectively. The same treatment resulted in mean log CFU reductions of 2.3 and 2.7 in C57BL/6J wild-type and SCID mice, respectively. Rifampin resistant isolates (1mg/mL) were recovered at a mean log CFU of 3.8 and 2.6 in C57BL/6J wild-type and SCID mice, respectively. Conclusions: SCID mice are lymphocyte deficient and have an impaired adaptive immune response. Our data shows that the reduced immunity enhances rifampin's ability to treat the S. aureus biofilm infection, while reducing the frequency of rifampin-resistance in the model. Therefore, our data suggests that the host's immune response can influence an antibiotic's ability to treat S. aureus biofilm infections.