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In vitro and in vivo effects of rifampin on Staphylococcus epidermidis graft infections
J R Garrison1, P K Henke, K R Smith
1Department of Surgery, University of Louisville School of Medicine, KY 40292, USA.
Abstract:
Rifampin, bound in high concentrations to prosthetic grafts, has been proposed for the treatment of vascular graft infections. The optimum antibiotic concentration and duration of treatment for infected grafts is not known. This study compared the in vitro and in vivo efficacy of varying concentrations of rifampin against three different strains of slime producing Staphylococcus epidermidis (RP62A, KC2, and KB1) bound to the knitted Dacron at high and low concentrations at 10(4) and 10(7) CFU/cm2 of prosthetic. Time kill experiments were performed at 4, 18, and 42 hr, in which each Dacron bound bacterial strain was exposed in vitro to 4X, 64X, 100X, and 1,000X minimum inhibitory concentration (MIC) of rifampin. In vitro, the Dacron bound laboratory strain RP62A was implanted subcutaneously in the backs of male Swiss-Webster mice and exposed to 4X, 100X, and 1,000X the MIC of rifampin for similar time periods. In addition, systemic vancomycin (10 mg/kg) was assessed for synergy and prevention of rifampin resistance. In vitro, all concentrations of rifampin showed near total killing (< 1 log) of all bacterial strains at low initial concentrations (10(4) CFU/cm2) but not high (10(7) CFU/cm2) to 42 hr. Importantly, resistance was shown to develop in all three strains of S. epidermidis with high initial bacterial biofilm concentrations. In vivo, rifampin concentrations between 4X MIC and 100X MIC achieved a balance between optimal killing and prevention of resistance. Systemic vancomycin slightly improved bacterial clearance but did not alter the development of rifampin resistance at high local concentrations. Caution is advised with the use of antibiotic bonded grafts because resistance may develop even with the addition of systemic antibiotics.
Insights
Rifampin-bound grafts show limited efficacy against high bacterial loads, risking resistance. Optimal concentrations balance killing and resistance prevention, even with vancomycin.
Area of Science:
- Infectious Diseases
- Biomaterials Science
- Pharmacology
Background:
- Vascular graft infections pose significant clinical challenges.
- Rifampin-bound prosthetic grafts are a proposed treatment, but optimal parameters are unknown.
Purpose of the Study:
- To evaluate the in vitro and in vivo efficacy of varying rifampin concentrations against Staphylococcus epidermidis on Dacron grafts.
- To assess the impact of initial bacterial load and systemic vancomycin on rifampin efficacy and resistance development.
Main Methods:
- In vitro time-kill experiments exposed Dacron-bound S. epidermidis strains (RP62A, KC2, KB1) to different rifampin concentrations (4X-1000X MIC) at low (10^4 CFU/cm2) and high (10^7 CFU/cm2) bacterial loads.
- In vivo studies implanted infected Dacron grafts in mice, treated with varying rifampin concentrations and systemic vancomycin.
- Resistance development was monitored under different conditions.
Main Results:
- In vitro, rifampin achieved significant killing at low bacterial loads but was less effective at high loads, with resistance emerging in all strains.
- In vivo, rifampin concentrations between 4X and 100X MIC balanced bacterial killing and resistance prevention.
- Systemic vancomycin showed minimal impact on bacterial clearance and did not prevent rifampin resistance at high local concentrations.
Conclusions:
- Antibiotic-bonded grafts require careful concentration and duration selection to avoid resistance.
- High bacterial loads on grafts can lead to rifampin resistance, even with systemic vancomycin co-administration.
- Further research is needed to optimize antibiotic-bonded graft strategies for vascular infections.