APPLICATION OF A RAT OSTEOMYELITIS MODEL TO COMPARE IN-VIVO AND IN-VITRO THE ANTIBIOTIC EFFICACY AGAINST BACTERIA WITH HIGH-CAPACITY TO FORM BIOFILMS

A rat experimental osteomyelitis model was eased to study the efficien cy of antibiotics on biofilm bacteria adhered to implants in relation to the efficiency obtained in vitro. Tn the osteomyelitis model, 10(4) bacteria of the strain variant used for the in vitro studies (a slime -producing variant of Staphylococcus aureus) were inoculated into the rat tibia at surgery, after implanting a stainless steel canula precol onized for 12 h with this strain. After 5 weeks, a 21-day antibiotic t reatment was applied (using cefuroxime, vancomycin, or tobramycin). Su bsequently, implant and tibia were studied far presence of bacteria. T n this osteomyelitis model, cefuroxime inhibited bone colonization and reduced the number of bacteria in metal and bone at a higher degree ( P < 0.05) than vancomycin and trobramycin (the latter antibiotic did n ot have this reduction effect), The in vitro assay was applied using t hree concentrations of each antibiotic (8, 100, and 500 mu g/ml) and 6 -, 24-, and 48-h biofilms. Bacterial viability was evaluated by ATP-bi oluminescence after 24 h of antibiotic treatment. Tn this in vitro ass ay, cefuroxime significantly (P < 0.05) reduced in all cases the numbe r of viable bacteria in biofilms, tobramycin did not affect viability, and vancomycin affected viability except at the lowest concentration used (8 mu g/ml, i.e., 8x the minimal bactericidal concentration of th is antibiotic) when facing the oldest (48 h) biofilm, These results de monstrate the usefulness of the osteomyelitis model applied in providi ng evidence for a close correlation between the in vitro and in vivo f indings on the effect of three antibiotics under study. (C) 1998 Acade mic Press.