RESUMEN
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.
Asunto(s)
Cefuroxima , Líquido Sinovial , Animales , Antibacterianos/uso terapéutico , Articulación de la Rodilla , Microdiálisis , Grasa Subcutánea , PorcinosRESUMEN
Treatment of post-traumatic and implant-associated osteomyelitis (IAO) includes surgical debridement, removal of implants and long-term antibiotic therapy. The success of antibiotic therapy relies not only on activity towards the infecting pathogen, but also on sufficient penetration of the target site. The aim of the present study was to characterize the local pathological changes associated with reduced penetration of cefuroxime to infected bone implant cavities. Previously, reduced penetration of systemically administrated cefuroxime was demonstrated in the implant cavity of 10 pigs with Staphylococcus aureus IAO present for 5 days. In the present study, a comprehensive histopathological characterization of the peri-implant bone tissue was performed and correlated with the reduced penetration of cefuroxime. In two pigs, the levels of oxygen, pyruvate and lactate was estimated in the implant cavity. A peri-implant pathological bone area (PIBA) developed with a width of 1.2 up to 3.8 mm. PIBAs included: (1) suppuration, resulting in destruction of the implant cavity contour, and (2) a non-vascular zone of primarily necrotic bone tissue. A strong negative correlation was seen between PIBA width and cefuroxime area under the concentration time curves (AUC[0-last]) and peak concentration of cefuroxime (Cmax). All metabolic measurements demonstrated hypoxia. In conclusion, subacute suppurative bone inflammation with local tissue destruction can result in decreased penetration of antibiotics and insufficient oxygen supply.