Single‐stage revision of MRSA orthopedic device‐related infection in sheep with an antibiotic‐loaded hydrogel

Abstract

Local antimicrobial therapy is an integral aspect of treating orthopedic devicerelated infection (ODRI), which is conventionally administered via polymethylmethacrylate (PMMA) bone cement. PMMA, however, is limited by a suboptimal antibiotic release profile and a lack of biodegradability. In this study, we compare the efficacy of PMMA versus an antibiotic-loaded hydrogel in a single-stage revision for chronic methicillin-resistant Staphylococcus aureus (MRSA) ODRI in sheep. Antibiofilm activity of the antibiotic combination (gentamicin and vancomycin) was determined in vitro. Swiss alpine sheep underwent a single-stage revision of a tibial intramedullary nail with MRSA infection. Local gentamicin and vancomycin therapy was delivered via hydrogel or PMMA (n = 5 per group), in conjunction with systemic antibiotic therapy. In vivo observations included: local antibiotic tissue concentration, renal and liver function tests, and quantitative microbiology on tissues and hardware post-mortem. There was a nonsignificant reduction in biofilm with an increasing antibiotic concentration in vitro (p = 0.12), confirming the antibiotic tolerance of the MRSA biofilm. In the in vivo study, four out of five sheep from each treatment group were culture-negative. Antibiotic delivery via hydrogel resulted in 10-100 times greater local concentrations for the first 2-3 days compared with PMMA and were comparable thereafter. Systemic concentrations of gentamicin were minimal or undetectable in both groups, while renal and liver function tests were within normal limits. This study shows that a single-stage revision with hydrogel or PMMA is equally effective, although the hydrogel offers certain practical benefits over PMMA, which make it an attractive proposition for clinical use.

Biodegradable Antimicrobial Agent/Analgesic/Bone Morphogenetic Protein-Loaded Nanofibrous Fixators for Bone Fracture Repair

“…Moreover, previous studies revealed that a locally applied antibiotic-loaded carrier (biodegradable or non-biodegradable) would not increase the systemic concentration of the drugs. 31 , 42 In our study, the concentration of the applied antimicrobial agents remained above the MIC90, yet localized, without systemic spreading. Compared with other delivery agents, the tunable porosity and pore size of nanofibers permit them to mimic the extracellular matrix (ECM) to enhance cell proliferation.…”

Infections @ Trauma/Orthopedic Implants: Recent Advances on Materials, Methods, and Microbes—A Mini-Review

“…A group of the AO Research Institute, Davos, Switzerland, published two laborious studies using sheep infection models to test the efficacy of a gentamicin and vancomycin-loaded hydrogel. One study described the effect of a single-stage revision [ 28 ], while in the other study, a two-stage model was used [ 29 ]. Both studies used poly(N-isopropylacrylamide)-grafted thermoresponsive hyaluronic acid hydrogel loaded with gentamicin and vancomycin and systemic antibiotic treatment.…”

Polymyxin B‐Triggered Assembly of Peptide Hydrogels for Localized and Sustained Release of Combined Antimicrobial Therapy

“…For example, when treating fracture or implantrelated bone infections, a higher stiffness is typically desired to provide mechanical stability. [30] Therefore, the possibility to regulate the mechanical properties of the PMB-triggered PA hydrogels was exploited here to expand their potential applications. Even though tunable stiffness of the PMB-triggered PA hydrogel could be obtained by adjusting the concentration of TPA, the variation range is narrow with the highest G′ obtained under 10 kPa (Figure 4b).…”