LIPID-BASED SLOW-RELEASE FORMULATION OF AMIKACIN SULFATE REDUCES FOREIGN BODY-ASSOCIATED INFECTION IN MICE

Treatment and prophylaxis of uncomplicated infections with standard sy stemic antibiotics are usually successful, However, standard systemic antibiotic therapy alone is frequently unsatisfactory in certain circu mstances, such as the presence of a foreign body (FB), necrotic tissue , overwhelming bacterial inoculum, or poor vascular supply to the invo lved tissues. We have developed a lipid-based sustained release formul ation of amikacin sulfate (DepoFoam encapsulated amikacin sulfate [DEA S]) as a biodegradable, locally injectable antibiotic for such circums tances, The encapsulated drug is released over 7 to 10 days. We tested the efficacy of this formulation in an PB infection model in which Te flon tubes (length, 1 cm; outside diameter, 1.6 mm) were implanted int o the subcutaneous tissue in mice and the local site was inoculated wi th 0.87 x 10(7) CFU of Staphylococcus aureus 3 days later, Inoculation was followed by either no treatment or a local injection of DEAS, fre e amikacin sulfate, non-drug-containing DepoFoam, or systemic free-ami kacin sulfate. All drug applications contained 1 mg of amikacin, One g roup was implanted with the FB and left unchallenged with bacteria and untreated as a sterile control group, All animals were sacrificed 10 days following FB implantation. PBs were retrieved from tissues by an aseptic technique and incubated in liquid culture media for 7 days. Lo cal wound tissue was excised and processed to determine the number of CFU per gram of tissue, Treatment with local or systemic free amikacin had no effect on the number of infected PBs or on the log CFU in woun d tissue compared with the untreated or non-drug-containing DepoFoam g roup, Compared with local free amikacin therapy, the number of infecte d FBs was reduced from 86 to 25% (P = 0.02) following treatment with D EAS, and log CFU per gram of tissue was significantly decreased from 3 .8 +/- 0.9 to 1.3 +/- 0.6 (P < 0.0005). DEAS may have clinical utility as locally injected antibiotic in certain infections.