Local antimicrobial delivery from temperature-responsive hydrogels reduces incidence of intra-abdominal infection in rats.

The objective of this study was to evaluate local antimicrobial delivery from temperature-responsive hydrogels for preventing infection in a rat model of intra-abdominal infection (IAI), and to determine whether delivery of tobramycin and vancomycin in combination is effective against IAI pathogens. Rats received intraperitoneal inoculation of E. coli, rat cecal contents, or cecal contents supplemented with E. coli, and received either no treatment, subcutaneous cefoxitin, or local delivery from hydrogels containing vancomycin, tobramycin, or both antimicrobials. Only the hydrogel with tobramycin and vancomycin significantly increased the infection free-rate compared to no treatment for all inocula (E. coli: 13/17, p < 0.0001; cecal contents: 11/17, p = 0.0013; cecal contents + E. coli: 15/19, p < 0.0001). Additionally, tobramycin and vancomycin displayed no synergy or antagonism against clinical isolates in vitro. Local delivery of tobramycin and vancomycin from temperature-responsive hydrogels provides broad coverage and high antimicrobial concentrations for several hours that may be effective for preventing IAIs.