RESUMO
This study evaluated target tissue concentrations of double dose cefuroxime administered intravenously as either one 15â¯min infusion of 3000â¯mg (Group 1) or two single 15â¯min infusions of 1500â¯mg administered 4â¯h apart (Group 2). Sixteen pigs were randomised into two groups of eight. Cortical and cancellous bone, synovial fluid of the knee joint and subcutaneous adipose tissue concentrations were measured based on sampling via microdialysis. Plasma samples were collected as a reference. Comparison of the groups was based on time with concentrations above relevant minimal inhibitory concentrations (fT>MIC) of 4⯵g/mL. The mean time fT>MIC (4⯵g/mL) across compartments was longer for Group 2 (280-394â¯min) than for Group 1 (207-253â¯min) (p<0.01). Cortical bone showed a tendency towards longer fT>MIC (4⯵g/mL) in Group 2 (280â¯min) than in Group 1 (207â¯min) (pâ¯=â¯0.053). Within 50â¯min after administration, the mean concentration of 4⯵g/mL was reached in all compartments for both groups. The mean concentrations decreased below 4⯵g/mL after approximately 4â¯h (Group 1) and 3â¯h (Group 2) from initiation of administration (time zero). During an 8â¯h interval, double-dose cefuroxime administered as 2â¯×â¯1500â¯mg with a 4â¯h interval provides longer time above MIC breakpoint for Staphylococcus aureus (4⯵g/mL) than a single bolus of 3000â¯mg cefuroxime. To maintain sufficient tissue concentrations during longer surgeries, re-administration of cefuroxime (1500â¯mg) should be considered 3â¯h after the first administration.