LIPOSOME ENCAPSULATION - A METHOD FOR ENHANCING THE EFFECTIVENESS OF LOCAL ANTIBIOTICS

Background. Treatment of contaminated surgical wounds is often complic ated by the failure of local or systemic antibiotic treatment and prop hylaxis. Locally administered liposome-encapsulated antimicrobials may offer advantages over free antibiotics, including an increase in effi cacy, ease of administration, and safety. The therapeutic advantages, as well as the absorption and distribution of locally administered lip osome-encapsulated antibiotics, were compared with those of locally ap plied unencapsulated antibiotics in a contaminated wound model. Method s. Anesthetized rats had a 1 cm incision over the midback that was ino culated 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 sal ine solution (untreated; n = 30), 5.5 mg tobramycin in 0.3 ml saline s olution (free tobramycin; n = 30), or 0.3 ml liposome-encapsulated tob ramycin (LET; n = 42). Animals were killed 24, 48, and 72 hours after operation; serum and tissue tobramycin concentrations and tissue quant itative 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 dos e of antibiotic. LET reduced tissue bacterial counts to a greater exte nt 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 effe ctively than locally applied free drug. Animals treated with LET had c onsistently less than the 10(5) organisms per gm tissue considered cri tical for invasive infection, suggesting that liposomal antibiotics ma y be clinically useful in surgical wound prophylaxis.