Combination Prophylactic Therapy with Rifampin Increases Efficacy against an Experimental Staphylococcus epidermidis Subcutaneous Implant-Related Infection

Abstract

eThe incidence of infections related to cardiac devices (such as permanent pacemakers) has been increasing out of proportion to implantation rates. As management of device infections typically requires explantation of the device, optimal prophylactic strategies are needed. Cefazolin and vancomycin are widely used as single agents for surgical prophylaxis against cardiac device-related infections. However, combination antibiotic prophylaxis may further reduce infectious complications. To model a localized subcutaneous implant-related infection, a bioluminescent strain of Staphylococcus epidermidis was inoculated onto a medical-procedure-grade titanium disc, which was placed into a subcutaneous pocket in the backs of mice. In vivo bioluminescence imaging, quantification of ex vivo CFU from the capsules and implants, variable-pressure scanning electron microscopy (VP-SEM), and neutrophil enhanced green fluorescent protein (EGFP) fluorescence in LysEGFP mice were employed to monitor the infection. This model was used to evaluate the efficacies of low-and high-dose cefazolin (50 and 200 mg/kg of body weight) and vancomycin (10 and 110 mg/kg) intravenous prophylaxis with or without rifampin (25 mg/kg). High-dose cefazolin and high-dose vancomycin treatment resulted in almost complete bacterial clearance, whereas both low-dose cefazolin and low-dose vancomycin reduced the in vivo and ex vivo bacterial burden only moderately. The addition of rifampin to low-dose cefazolin and vancomycin was highly effective in further reducing the CFU harvested from the implants. However, vancomycin-rifampin was more effective than cefazolin-rifampin in further reducing the CFU harvested from the surrounding tissue capsules. Future studies in humans will be required to determine whether the addition of rifampin has improved efficacy in preventing devicerelated infections in clinical practice.

Direct Microscopic Observation of Human Neutrophil-Staphylococcus aureus Interaction In Vitro Suggests a Potential Mechanism for Initiation of Biofilm Infection on an Implanted Medical Device

“…Data from The time scale for neutrophil recruitment to an implanted abiotic surface is also uncertain. Animal studies of neutrophil dynamics at sites of infection indicate that the time scale for neutrophil recruitment may range from an hour to a day (46)(47)(48).…”

Is the prognosis the same for periprosthetic joint infections due to Staphylococcus aureus versus coagulase-negative staphylococci? A retrospective study of 101 patients with 2-year minimum follow-up

“…This is the first published study to compare the result of revisions for PJI due to different Staphylococcus species. Various studies have analysed the healing rate based on the type of procedure (single-or two-phase revision), antibiotic therapy, type of surgical procedure (conservative or revision), and resistant or susceptible nature of the microorganism [1,9,18,[23][24][25][26][27][28][29][30][31]. Vielpeau et al [32] [33] also evaluated the healing rate after conservative surgical treatment (lavage, debridement) of THA and TKA infections; they found no differences between the two microorganisms.…”

Combinatory antibiotic therapy increases rate of bacterial kill but not final outcome in a novel mouse model of Staphylococcus aureus spinal implant infection

“…To obtain noninvasive measurement of bacterial burden, mice were anesthetized with inhalation isoflurane (2%), the dorsal region of the mouse was shaved, and in vivo bioluminescence imaging was performed using the Xenogen IVIS Lumina II (PerkinElmer, Hopkinton, MA) on post-operative days (POD) 0, 1, 3, 5, 7, 10, 14, 17, 21, 25, 28, 32, and 35 as previously described. [ 26 , 37 – 39 ] The Xen36 bioluminescent signals were obtained with a 5-minute acquisition time, a 13 cm field of view (FOV), and medium binning settings. Data are presented on a color scale overlaid on a grayscale photograph of mice and quantified as total flux (photons per second (s) per cm 2 per steradian (sr) [photons/s/cm 2 /sr]) within a circular region of interest (1X10 3 pixels) using Living Image software (PerkinElmer, Hopkinton, MA).…”