Evaluating the efficacy of amikacin in low-clearance unilamellar liposomes in a s. Aureus local infection model.
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.
Garrison
A E
AE
Gilead Sciences, Inc., 2860 Wilderness Place, Boulder, CO, 80301, U.S.A.
Bendele
R
R
Knauer
S
S
Wolf
J
J
Moon-McDermott
L
L
Gill
S
S
Colagiovanni
D B
DB