Efficacious antibiotic treatment is crucial for managing and preventing orthopedic infections due to their complexity and associated risk of treatment failure. Previous reviews on antibiotic target tissue concentrations have primarily focused on static measurements, which may not accurately reflect the dynamic pharmacokinetic/pharmacodynamic (PK/PD) changes encountered in clinical settings. This review aimed to summarize the current literature on antibiotic distribution in orthopedically relevant tissues and settings using dynamic sampling methods. In accordance with PRISMA guidelines, a literature search was conducted with a scientific librarian's assistance. PubMed and Embase databases were systematically searched using relevant MeSH terms, entries, and keywords. English-published studies between 2004 and 2023 involving systemic antibiotic administration and dynamic measurements were included. 4467 titles were identified. After title and abstract screening, 77 eligible studies remained.Aim
Method
Antibiotic prophylaxis is central in preventing postoperative spine infections, yet knowledge of clinical spine tissue antibiotic concentrations remains limited. Pooled postoperative spine infection rates are constant (approximately 3%), resulting in severe patient morbidity, mortality, and prolonged hospitalization. Current antibiotic dosing regimens often involve fixed doses based on empirical knowledge, surrogate measures (plasma samples), non-clinical evidence (experimental models), and inferior methodology (tissue specimens). Therefore, personalized antibiotic dosing may be the future of antibiotic prophylaxis to prevent postoperative infections, especially implant infections. The aim was to continuously evaluate intra- and postoperative cefuroxime target spine tissue concentrations in long-lasting spine surgery after personalized dosing by repeated weight-dosed intravenous administrations. Twenty patients (15 female, 5 male) scheduled for long-lasting spine deformity surgery with hypotensive anaesthesia were included; median age (range): 17.5 years (12-74), mean BMI (range): 22.2 (16.2-37.7), and mean surgery time (range): 4h 49min (3h 57min-6h 9min). Weight-dosed cefuroxime (20 mg/kg) was administered intravenously to all patients on average 25 min before incision and repeated after 4 hours. Microdialysis catheters were placed for sampling of cefuroxime concentrations in vertebral bone (only intraoperative sampling), paravertebral muscle, and subcutaneous tissue as soon as possible after surgery start. Upon wound closure, two additional catheters were placed in the profound and superficial part of the wound. Microdialysis and plasma samples were obtained continuously intra- and postoperative for up to 12 hours. The primary endpoint was (based on cefuroxime time-dependent efficacy) the time with cefuroxime concentrations above the clinical breakpoint minimal inhibitory concentration for patients’ individual surgery time, first dosing interval (0-4 hours), second dosing interval (4-12 hours).Aim
Method
The β-lactam penicillin is often used in the treatment of soft tissue infections and osteomyelitis caused by penicillin susceptible 12 female pigs (75kg) were assigned to standard clinical regimens of either three doses of IV penicillin G (1.2g) or oral penicillin V (0.8g) every 6h over 18h. Microdialysis catheters were placed for sampling in tibial cancellous bone and adjacent subcutaneous tissue. Data was collected in the first dosing interval (0–6h; prophylactic situation) and the third dosing interval (12–18h; assumed steady state). Plasma samples were collected for reference. MIC targets of 0.125μg/mL (Aim
Method
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
This study investigated if co-administration of rifampicin with moxifloxacin led to a decrease in moxifloxacin concentrations in relevant tissues in a porcine model of implant-associated osteomyelitis caused 15 female pigs received a stainless-steel implant in the right proximal tibia and were randomized into two groups. Infection was introduced by inoculating the implant with Aim
Method
Surgical site infection following spine surgery is associated with increased morbidity, mortality and increased cost for the health care system. The reported pooled incidence is 3%. Perioperative antibiotic prophylaxis is a key factor in lowering the risk of acquiring an infection. Previous studies have assessed perioperative cefuroxime concentrations in the anterior column of the cervical spine with an anterior surgical approach. However, the majority of surgeries are performed in the posterior column and often involve the lumbar spine. Accordingly, the objective was to compare the perioperative tissue concentrations of cefuroxime in the anterior and posterior column of the same lumbar vertebra using microdialysis in an experimental porcine model. The lumbar vertebral column was exposed in 8 female pigs. Microdialysis catheters were placed for sampling in the anterior column (vertebral body) and posterior column (posterior arch) within the same vertebra (L5). Cefuroxime (1.5 g) was administered intravenously over 10 min. Microdialysates and plasma samples were continuously obtained over 8 hours. Cefuroxime concentrations were quantified by Ultra High Performance Liquid Chromatography Tandem Mass Spectrometry. Microdialysis is a catheter-based pharmacokinetic tool, that allows dynamic sampling of unbound and pharmacologic active fraction of drugs e.g., cefuroxime. The primary endpoint was the time with cefuroxime above the clinical breakpoint minimal inhibitory concentration (T>MIC) for Background
Method
Deadspace is the tissue and bony defect in a surgical wound after closure. This space is presumably poorly perfused favouring bacterial proliferation and biofilm formation. In arthroplasty surgery, an obligate deadspace surrounding the prosthesis is introduced and deadspace management, in combination with obtaining therapeutic prophylactic antibiotic concentrations, is important for limiting the risk of acquiring a periprosthetic joint infection (PJI). This study aimed to investigate cefuroxime distribution to an orthopaedic surgical deadspace in comparison with plasma and bone concentrations during two dosing intervals (8 h × 2). In a setup imitating shoulder arthroplasty surgery, but without insertion of a prosthesis, microdialysis catheters were placed for cefuroxime sampling in a deadspace in the glenohumeral joint and in cancellous bone of the scapular neck in eighteen pigs. Blood samples were collected from a central venous catheter as a reference. Cefuroxime was administered according to weight (20 mg/kg). The primary endpoint was time above the cefuroxime minimal inhibitory concentration of the free fraction of cefuroxime for Staphylococcus aureus (Aim
Method
Prompt and sufficient broad spectrum empirical antibiotic treatment is key to prevent infection following open tibial fractures. Succeeding co-administration, we dynamically assessed the time for which vancomycin and meropenem concentrations were above relevant epidemiological cut-off minimal inhibitory concentrations (T>MIC) in tibial compartments for the bacteria most frequently encountered in open fractures. Low and high MIC-targets were applied: 1 and 4 µg/mL for vancomycin and 0.125 and 2 µg/mL for meropenem. 8 pigs received a single dose of 1000 mg vancomycin and 1000 mg meropenem simultaneously over 100 min and 10 min, respectively. Microdialysis catheters were placed for sampling over 8 h in tibial cancellous bone, cortical bone, and adjacent subcutaneous adipose tissue. Venous blood samples were collected as references.Aim
Materials and methods
This study evaluated target tissue concentrations of double dose cefuroxime administered intravenously as either one 15 min infusion of 3,000 mg (Group 1) or two single 15 min infusions of 1,500 mg administered 4 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 (Aim
Method
Systemically administered vancomycin may provide insufficient target-site concentrations. Intraosseous vancomycin administration has the potential to overcome this concern by providing high target-site concentrations. To evaluate the local bone and tissue concentrations following tibial intraosseous vancomycin administration in a porcine model.Background
Aim
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
Pyogenic spondylodiscitis remains a therapeutic challenge, as demonstrated by divergent treatment guidelines. The combination of moxifloxacin and rifampicin may be an attractive treatment option for cases caused by staphylococci; however, previous studies have reported a reduction in plasma concentrations of moxifloxacin when co-administered with rifampicin. The magnitude of this reduction in spinal tissues is not known. We aimed to investigate the interaction of rifampicin on moxifloxacin tissue concentrations in vertebral cancellous bone, intervertebral disc and subcutaneous adipose tissue in steady-state conditions using microdialysis in a porcine model. Twenty female pigs were randomized into two groups of ten pigs: Group A received moxifloxacin 400 mg orally once daily for three days preoperatively. Group B received moxifloxacin 400 mg orally for three days preoperatively combined with rifampicin 450 mg twice daily for seven days preoperatively. Measurements were obtained from plasma, vertebral cancellous bone, intervertebral disc and subcutaneous adipose tissue for 24 h. Microdialysis was applied for sampling in solid tissues.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
Cefuroxime is a time-dependent antibiotic widely used as intravenous perioperative prophylaxis in spine surgery. A previous study has indicated that a single dose of cefuroxime provided insufficient spine tissue concentrations for spine procedures lasting more than 2–3 hours. Due to the fact that postoperative pyogenic spondylodiscitis is associated with prolonged antimicrobial therapy and high relapse rates, we aimed to evaluate if a twofold increase of standard dosage of 1.5g cefuroxime given as one double dose or two single doses with 4-hours intervals will lead to sufficient cefuroxime spine tissue concentrations throughout the dosing interval. This is preliminary data for 8 out of 16 female pigs. Data from all 16 pigs will be included for the conference. Eight pigs were randomized into two groups: Group A received one double dose of cefuroxime (3g) as a bolus, and Group B received two single doses of cefuroxime (2×1.5g) with 4-hours intervals. Measurements were obtained from plasma, subcutaneous tissue (SCT), vertebral cancellous bone and the intervertebral disc (IVD) for 8-hours thereafter. Microdialysis was applied for sampling in solid tissues. The cefuroxime concentrations were determined using ultra-high performance liquid chromatography.Aim
Method
Local treatment with gentamicin may be an important tool in the prevention and treatment of surgical site infections in high-risk procedures and patients. The aim of this study was to evaluate the pharmacokinetic profile of gentamicin in bone and surrounding tissue, released from a controlled application of a GentaColl sponge in a porcine model. In 8 female pigs, a GentaColl sponge of 10×10 cm (1.3 mg gentamicin/cm2) was placed in a cancellous bone cavity in the proximal tibia. Microdialysis was used for sampling of gentamicin concentrations over 48 hours from the cavity with the implanted GentaColl sponge, cancellous bone parallel to the cavity over and under the epiphyseal plate, cortical bone, the intramedullary canal, subcutaneous tissue, and the joint cavity of the knee. Venous blood samples were obtained as reference.Aim
Method
