Traditional
therapies for
Staphylococcal infections such as
osteomyelitis or localized
abscesses have a difficult time penetrating into tissue sites. To effectively ameliorate these
infections, prolonged
therapy and/or high doses of
antibiotics are frequently required.
Aminoglycosides, such as
amikacin, are not routinely utilized for treating local
infections due to poor efficacy associated with ineffective tissue penetration, toxicity, and poor penetration in an
acid millieu. We postulated that a formulation of
amikacin in small
unilamellar liposomes might readily be engulfed by inflammatory macrophages facilitating
drug delivery to the site of
infection. This increased
drug load to the site of
bacterial infection may result in enhanced bactericidal action compared to conventional
aminoglycosides. Tissue
drug concentrations were determined for liposomal
amikacin (L-AN) and conventional
amikacin (AN). Plasma
amikacin levels were determined for L-AN. The L-AN was very effective at concentrating at the site of
infection compared to AN. Following confirmation of adequate tissue
drug levels, a rodent subcutaneous
abscess infection using S. aureus as the bacterial challenge agent was evaluated. Sprague-Dawley rats were intravenously administered L-AN every other 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 in reducing colony counts.