C I Price1, J W Horton, C R Baxter. 1. Department of Surgery, University of Texas Southwestern Medical Center at Dallas 75235-9031.
Abstract
BACKGROUND: Treatment of contaminated surgical wounds is often complicated by the failure of local or systemic antibiotic treatment and prophylaxis. Locally administered liposome-encapsulated antimicrobials may offer advantages over free antibiotics, including an increase in efficacy, ease of administration, and safety. The therapeutic advantages, as well as the absorption and distribution of locally administered liposome-encapsulated antibiotics, were compared with those of locally applied unencapsulated antibiotics in a contaminated wound model. METHODS: Anesthetized rats had a 1 cm incision over the midback that was inoculated with 10(8) colony-forming units Pseudomonas aeruginosa (group 1; n = 102) or left uninfected (group 2; n = 35). Before wound closure, infected animals were treated with a local application of 0.3 ml saline solution (untreated; n = 30), 5.5 mg tobramycin in 0.3 ml saline solution (free tobramycin; n = 30), or 0.3 ml liposome-encapsulated tobramycin (LET; n = 42). Animals were killed 24, 48, and 72 hours after operation; serum and tissue tobramycin concentrations and tissue quantitative cultures were studied. Liposomes were radiolabeled to examine organ distribution. RESULTS: The data show that LET produced sustained local concentrations of antibiotic compared with free drug; sustained concentration prolonged the antimicrobial effect despite a single dose of antibiotic. LET reduced tissue bacterial counts to a greater extent and for a longer period of time than free tobramycin. The presence of infection further reduced clearance of LET from the infected site. CONCLUSIONS: The liposomal delivery of local antibiotics in this model of surgical wound infection reduced the number of organisms more effectively than locally applied free drug. Animals treated with LET had consistently less than the 10(5) organisms per gm tissue considered critical for invasive infection, suggesting that liposomal antibiotics may be clinically useful in surgical wound prophylaxis.
BACKGROUND: Treatment of contaminated surgical wounds is often complicated by the failure of local or systemic antibiotic treatment and prophylaxis. Locally administered liposome-encapsulated antimicrobials may offer advantages over free antibiotics, including an increase in efficacy, ease of administration, and safety. The therapeutic advantages, as well as the absorption and distribution of locally administered liposome-encapsulated antibiotics, were compared with those of locally applied unencapsulated antibiotics in a contaminated wound model. METHODS: Anesthetized rats had a 1 cm incision over the midback that was inoculated with 10(8) colony-forming units Pseudomonas aeruginosa (group 1; n = 102) or left uninfected (group 2; n = 35). Before wound closure, infected animals were treated with a local application of 0.3 ml saline solution (untreated; n = 30), 5.5 mg tobramycin in 0.3 ml saline solution (free tobramycin; n = 30), or 0.3 ml liposome-encapsulated tobramycin (LET; n = 42). Animals were killed 24, 48, and 72 hours after operation; serum and tissue tobramycin concentrations and tissue quantitative cultures were studied. Liposomes were radiolabeled to examine organ distribution. RESULTS: The data show that LET produced sustained local concentrations of antibiotic compared with free drug; sustained concentration prolonged the antimicrobial effect despite a single dose of antibiotic. LET reduced tissue bacterial counts to a greater extent and for a longer period of time than free tobramycin. The presence of infection further reduced clearance of LET from the infected site. CONCLUSIONS: The liposomal delivery of local antibiotics in this model of surgical wound infection reduced the number of organisms more effectively than locally applied free drug. Animals treated with LET had consistently less than the 10(5) organisms per gm tissue considered critical for invasive infection, suggesting that liposomal antibiotics may be clinically useful in surgical wound prophylaxis.