High-dose vancomycin spacers provided early recovery without nephrotoxicity compared with standard-dose in MRSA-induced periprosthetic joint infection model of rats

Abstract

BackgroundPeriprosthetic joint infections (PJIs) are commonly treated with two-stage revision surgery utilising antibiotic-loaded spacers; however, antibiotic release from spacers is limited and usually drops below effective levels a few days after placement. This study compared high-dose and standard-dose vancomycin-loaded spacers in terms of efficacy, safety, and overall treatment duration in a rat periprosthetic joint infection model. MethodsThirty male Wistar albino rats (8–10 weeks old, 300–320 g) were housed individually at standard conditions. A periprosthetic infection model was established in the right knee of the rats using methicillin-resistant Staphylococcus aureus (MRSA) −contaminated Kirschner wires. Two weeks later, the infection was verified, and the Kirschner wires were removed. Rats were randomly divided into three groups (n = 10): standard-dose (SVanc) and high-dose (HVanc) vancomycin groups had 2.5 and 7.5% vancomycin in their spacers, respectively, while the control group had no spacers. All groups received intramuscular (IM) vancomycin and gentamicin for 4 weeks after spacer implantation. Microbiological counts and vancomycin levels in the blood and joint flush samples were measured, and histopathological assessments were conducted on the femur and kidneys. ResultsAfter spacer implantation, MRSA was eliminated in the HVanc group with 4 weeks of treatment, while the SVanc group required 6 weeks of treatment (P < 0.001). Histopathological findings of the femoral medulla and cortical samples were better in the HVanc group compared with other groups (P = 0.007). Vancomycin levels in serum remained within safe limits in all groups, and kidney damage was not observed. ConclusionThe use of high-dose vancomycin spacers might accelerate the transition period, which in turn reduces the duration of systemic antibiotic use and mitigates the risk of nephrotoxicity. Thus, this method may decrease the medical costs associated with PJI treatment.