EFFICACY AND PHARMACOKINETICS OF SITE-SPECIFIC CEFAZOLIN DELIVERY USING BIODEGRADABLE IMPLANTS IN THE PREVENTION OF POSTOPERATIVE WOUND INFECTIONS

Purpose. The study objective was to evaluate the efficacy and pharmaco kinetics of cefazolin delivered locally as a glyceryl monostearate (GM S) based biocompatible implant for prevention of post-operative wound infection in Sprague Dawley rats subcutaneously inoculated with Staphy lococcus aureus. Methods. For the efficacy and pharmacokinetic studies , 18 rats were subcutaneously inoculated with 4.5 x 10(7) CFU of S. au reus on the dorsum (6 per rat), and randomly assigned into three group of 6 rats each: (I)the control group, in which rats did not receive a ntibiotics, (2) the intermittent IM treatment group, in which rats rec eived IM injections of 10 mg/kg cefazolin every 4 hr (total of 180 mg/ kg in 3 days), and (3) the implant treatment group, in which rats were implanted subcutaneously with four Cefazolin-GMS implants in the vici nity of the inoculations. The implants were designed to deliver 180 mg /kg cefazolin over a 3 day period. For efficacy evaluation, the rats w ere euthanized one week post-inoculation and abscess count, weight and size were determined. Results. Rats in the control group had develope d 21 abscesses out of the 36 inoculations, indicating validity of the infection model. The local delivery of cefazolin resulted in complete eradication of the infection, since no abscesses formed in the rats in the implant group. In the IM treatment group, only one abscess was fo rmed and no significant difference in efficacy between the two treatme nt groups was observed. The GMS implants sustained the release of cefa zolin for a period of three days with only 3-fold fluctuations in plas ma concentration (5.5-17.5 mu g/ml). However, plasma concentrations af ter the intermittent IM administration of cefazolin fluctuated 110-fol d between 44-0.4 mu g/ml every 4 hr. The release rate of cefazolin fro m the implants was nearly zero order for the entire duration. Bioerosi on of the implants was determined by examining the condition of the im plants six weeks post-implantation. Two of the 12 implants had complet ely disappeared and the remaining implants were in a pasty form and ha d lost 20-80% of their weight. Absence of irritation or inflammation a round the implants indicated biocompatibility of the GMS implants. Con clusions. Implantable system that provided a prolonged delivery of cef azolin was found to be effective against S. aureus infection, and demo nstrated suitable pharmacokinetics and biocompatibility with significa nt bioerosion.