Implant-associated osteomyelitis is one of the most feared complications following orthopedic surgery. Although the risk is low it is crucial to achieve adequate antibiotic concentrations proximate to the implant for a sufficient amount of time to protect the implant surface and ensure tissue integration. The aim of this study was to assess steady-state piperacillin concentrations in the proximity of an orthopedic implant inserted in cancellous bone. Six female pigs received an intravenous bolus infusion of 4 g/0.5 g piperacillin/tazobactam over 30 min every 6 h. Steady state was assumed achieved in the third dosing interval (12–18 h). Microdialysis catheters were placed in a cannulated screw in the proximal tibial cancellous bone, in cancellous bone next to the screw, and in cancellous bone on the contralateral tibia. Dialysates were collected from time 12 to 18 h and plasma samples were collected as reference.Background and aim
Method
Tourniquet is widely used in extremity surgery. In order to prevent surgical site infection, correct timing of antimicrobial prophylaxis and tourniquet inflation is important. We aimed to evaluate the time for which the free drug concentration of cefuroxime is maintained above the minimal inhibitory concentration (T>MIC) in subcutaneous tissue and calcaneal cancellous bone during three clinically relevant tourniquet application scenarios. Twenty-four female pigs were included. Microdialysis catheters were placed for sampling of cefuroxime concentrations bilaterally in calcaneal cancellous bone and subcutaneous tissue, and a tourniquet cuff was applied on a randomly picked leg of each pig. Subsequently, the pigs were randomized into three groups to receive 1.5 g of cefuroxime by intravenous injection 15 min prior to tourniquet inflation (Group A), 45 min prior to tourniquet inflation (Group B), and at the tourniquet release (Group C). The tourniquet duration was 90 min in all groups. Dialysates and venous blood samples were collected eight-hours postcefuroxime administration.Aim
Method
Flucloxacillin is conventionally administered intravenously for perioperative prophylaxis, while oral administration is typical for bacterial inoculation prophylaxis following smaller traumatic wounds. We aimed to assess the time, for which the free flucloxacillin concentration was maintained above the minimum inhibitory concentration ( 16 pigs were randomly allocated to either intravenous (Group IV) or oral (Group PO) flucloxacillin 1 g every 6 h during 24 h. Microdialysis was used for sampling in cancellous and cortical bone, subcutaneous tissue, and the knee joint. In addition, plasma was sampled. The flucloxacillin Aim
Method
Flucloxacillin is commonly administered intravenously for perioperative antimicrobial prophylaxis, while oral administration is typical for prophylaxis following smaller traumatic wounds. We assessed the time, for which the free flucloxacillin concentration was maintained above the minimum inhibitory concentration ( A total of 16 pigs were randomly allocated to either intravenous (Group IV) or oral (Group PO) flucloxacillin 1 g every six hours during a 24-hour period. Microdialysis was used for sampling in cancellous and cortical bone, subcutaneous tissue, and the knee joint. In addition, plasma was sampled. The flucloxacillin Aims
Methods
Tourniquet is widely used in extremity surgery. In order to prevent surgical site infection, correct timing of antimicrobial prophylaxis and tourniquet inflation is important. We aimed to evaluate the time for which the free drug concentration of cefuroxime is maintained above the minimal inhibitory concentration (T>MIC) in subcutaneous tissue and calcaneal cancellous bone during three clinically relevant tourniquet application scenarios. Twenty-four female pigs were included. Microdialysis catheters were placed for sampling of cefuroxime concentrations bilaterally in calcaneal cancellous bone and subcutaneous tissue, and a tourniquet cuff was applied on a randomly picked leg of each pig. Subsequently, the pigs were randomized into three groups to receive 1.5 g of cefuroxime by intravenous injection 15 min prior to tourniquet inflation (Group A), 45 min prior to tourniquet inflation (Group B), and at the tourniquet release (Group C). The tourniquet duration was 90 min in all groups. Dialysates and venous blood samples were collected eight-hours postcefuroxime administration. Cefuroxime concentrations were maintained above the clinical breakpoint MIC for Staphylococcus aureus (4 μg/mL) in calcaneal cancellous bone and subcutaneous tissue throughout the 90 min tourniquet duration in Group A and B. Cefuroxime administration at tourniquet release (Group C) resulted in concentrations above 4 μg/mL for a minimum of 3.5 hours in the tissues on the tourniquet side. There were no significant differences in the T>MIC (4 μg/mL) in subcutaneous tissue or calcaneal cancellous bone between the three groups. However, Group A tended toward shorter T>MIC in tourniquet calcaneal cancellous bone compared to Group C (p=0.08). We conclude that administration of cefuroxime (1.5 g) in the 15–45 min window prior to tourniquet inflation resulted in sufficient calcaneal cancellous bone and subcutaneous tissue concentrations throughout the 90 min tourniquet application. If the target is to maintain postoperative cefuroxime concentrations above relevant MIC values, our results suggest that a second dose of cefuroxime should be administered at tourniquet release.
In Denmark the most common postoperative pathogen is S. aureus (1), sensitive to dicloxacillin. These bacteria can cause a postoperative infection despite using prophylactic antibiotics. Whether the tissue concentration reached is above the minimal inhibitory concentration (MIC) for the pathogens is unknown, and if lower than expected could result in a postoperative infection. Thus a trial was conducted, measuring the actual tissue concentration of dicloxacillin in human muscle and adipose tissue and compared these to the plasma concentration. MIC for dicloxacillin against S. aureus was determined using the broth macrodilution method. Six healthy male volunteers aging 25 to 27 years (body-mass-index; 20–28), were recruited. A CMA63 (Mdialysis, Stockholm, Sweden) catheter was placed in the subcutaneous tissue of the abdomen and in the rectus muscle of the thigh and the volunteers given 2 g dicloxacillin intravenously over 5 minutes. In 10 min intervals for the following 6 hours, samples from blood and Microdialysis fluid (flowrate 5 ml/min) were collected. Recovery was determined in vitro. Plasma was isolated from blood samples. The unbound dicloxacillin was isolated from plasma using filter plates (AcroPrep 30K Omega, Pall Corporation, US) centrifuged for 30 minutes at 1000 × g and 37°C. All samples were analyzed with High Performance Liquid Chromatography. MIC was determined to be 0.125 µg/ml. Average recovery was 73,7 % Maximum concentrations were reached in muscle tissue after a median of 0.5 hours and adipose tissue after 0.8 hours. The geometric mean ration (GMR) of AUC0-6h for adipose tissue compared to plasma was 0.32 [0.15–0.71]. GMR of AUC0-6h for muscle tissue compared to plasma and adipose tissue compared to muscle showed no statistically significant differences. The tissue concentrations were above MIC for 3.4 hours for adipose tissue and 4.1 hours for muscle tissue. The administration of prophylactic dicloxacillin should be given at least 30 minutes prior to incision to ensure maximum tissue concentrations at the onset of surgery. A second dose should be given after 3.4 hours in case of long surgery time. Since the dicloxacillin concentration reached in the adipose tissue is lower than in plasma, it should be investigated whether this difference is more prominent in adipose patients or patients with impaired peripheral circulation, since these patients are at a greater risk of postoperative infections.
