ANTIBIOTIC-IMPREGNATED HEART-VALVE SEWING RINGS FOR TREATMENT AND PROPHYLAXIS OF BACTERIAL-ENDOCARDITIS

Prosthetic heart valve sewing rings were impregnated with gentamicin c robefat (EMD 46217), a poorly soluble gentamicin salt, gentamicin sulf ate, and clindamycin palmitate to prevent early prosthetic endocarditi s, MICs and MBCs of gentamicin and/or clindamycin were tested against several pathogens of early prosthetic endocarditis. The combination of gentamicin and clindamycin was found to be effective against most rel evant bacterial pathogens. With an in vitro pharmacokinetic model, the antibacterial activity of gentamicin and clindamycin was tested again st Staphylococcus aureus and Escherichia coli. High gentamicin levels over the first 24 h were required for a strong reduction of bacterial counts of both strains, Equal amounts of gentamicin and clindamycin su stained the antibacterial effect and prevented regrowth. The most effe ctive release curves of gentamicin and clindamycin found with an in vi tro model were used for monitoring release profiles of these antibioti cs from impregnated sewing rings by investigating combinations of gent amicin sulfate, gentamicin crobefat, and clindamycin palmitate. Sewing rings impregnated with 4 mg of gentamicin sulfate, 14 mg of gentamici n crobefat, and 20 mg of clindamycin palmitate gave an initial gentami cin burst and afterwards yielded a lower sustained release of gentamic in and clindamycin palmitate, These in vitro release kinetics were con firmed in vivo by pharmacokinetic analysis after intramuscular Implant ation of impregnated sewing ring segments. Gentamicin and active clind amycin palmitate metabolites were obtained at the implantation site fo r at least 2 weeks in concentrations of 3 and 5 mu g per g of muscle, respectively. The investigated method of impregnation holds promise fo r revision implants after prosthetic valve endocarditis, It may also s erve as a prophylactic tool for routine use against this disease.