Evaluating the efficacy of amikacin in low-clearance unilamellar liposomesin a S-aureus local infection model

Traditional therapies for Staphylococcal infections such as osteomyelitis o r localized abscesses have a difficult time penetrating into tissue sites. To effectively ameliorate these infections, prolonged therapy and/or high d oses of antibiotics are frequently required. Aminoglycosides, such as amika cin, are not routinely utilized for treating local infections due to poor e fficacy associated with ineffective tissue penetration, toxicity, and poor penetration in an acid millieu. We postulated that a formulation of amikaci n in small unilamellar liposomes might readily be engulfed by inflammatory macrophages facilitating drug delivery to the site of infection. This incre ased drug load to the site of bacterial infection may result in enhanced ba ctericidal action compared to conventional aminoglycosides. Tissue drug con centrations were determined for liposomal amikacin (L-AN) and conventional amikacin (AN). Plasma amikacin levels were determined for L-AN. The L-AN wa s very effective at concentrating at the site of infection compared to AN. Following confirmation of adequate tissue drug levels, a rodent subcutaneou s abscess infection using S. aureus as the bacterial challenge agent was ev aluated. Sprague-Dawley rats were intravenously administered L-AN every oth er day due to its prolonged half-life, while the comparator agent. AN, was administered daily. Abscess size, weights, severity, histology, and tissue colony counts were examined. In efficacy studies, L-AN was superior to AN i n reducing colony counts.