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Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_19 | Pages 50 - 50
22 Nov 2024
Hvistendahl MA Bue M Hanberg P Tøstesen S Vittrup S Stilling M Høy K
Full Access

Aim

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.

Method

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 Staphylococcus aureus of 4 µg/mL in percentage (%fT>MIC4) of

patients’ individual surgery time,

first dosing interval (0-4 hours),

second dosing interval (4-12 hours).


Orthopaedic Proceedings
Vol. 105-B, Issue SUPP_17 | Pages 43 - 43
24 Nov 2023
Rasmussen HC Stilling M Lilleøre JG Petersen E Jørgensen AR Hvistendahl MA Hanberg P Bue M
Full Access

Aim

The β-lactam penicillin is often used in the treatment of soft tissue infections and osteomyelitis caused by penicillin susceptible Staphylococcus aureus. Oral antibiotic treatment has been shown to be non-inferior to intravenous (IV) therapy when used during the first 6 weeks in complex orthopedic infections (OVIVA trial). However, the use of oral β-lactams in osteomyelitis treatment remains a topic of debate due to low and variable bioavailability. The aim was to assess the time for which the unbound penicillin concentration exceeded targeted minimum inhibitory concentrations (fT>MIC) in cancellous bone and subcutaneous tissue after IV (penicillin G) and oral (penicillin V) treatment in a porcine microdialysis model.

Method

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 (Staph. aureus breakpoint), 0.25μg/mL (Strep. Group A, B, C and G breakpoint) and 0.5μg/mL (4xMIC) were applied.


Orthopaedic Proceedings
Vol. 104-B, Issue SUPP_10 | Pages 27 - 27
1 Oct 2022
Vittrup S Jensen LK Hanberg P Slater J Hvistendahl MA Stilling M Jørgensen N Bue M
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Aim

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 S. aureus. Pharmacokinetics were measured using microdialysis and treatment effect was measured by quantifying bacterial load from implant and periprosthetic bone following a 1-stage revision and antibiotics.

Method

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 Staphylococcus aureus as previously described1. On day 7 post surgery, all pigs were revised with implant removal, debridement of implant cavity and insertion of a sterile implant. 7 days of treatment was then initiated with either moxifloxacin 400 mg iv q.d. (M) or moxifloxacin and rifampicin 450 mg iv b.i.d. (RM). At day 14, animals were sedated and microdialysis was applied for continuous sampling of moxifloxacin concentrations during 8 h in five compartments: the implant cavity, cancellous bone in both the infected and non-infected proximal tibia, and adjacent subcutaneous tissue on both the infected and non-infected side using a previously described setup2. Venous blood samples were collected. Implant and adjacent bone were removed for analysis.


Orthopaedic Proceedings
Vol. 104-B, Issue SUPP_10 | Pages 81 - 81
1 Oct 2022
Hvistendahl MA Bue M Hanberg P Kaspersen AE Schmedes AV Stilling M Høy K
Full Access

Background

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.

Method

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 Staphylococcus aureus of 4 µg/mL as this has been suggested as the best predictor of efficacy for cefuroxime. The secondary endpoint was tissue penetration (AUCtissue/AUCplasma).