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BACKGROUND AND PURPOSE:  The duration of antibiotic coverage in hand tissues during surgery is unknown. We investigated the time the free concentration of cefuroxime was above the minimal inhibitory concentration (fT>MIC) of 4 µg/mL in hand tissues after single and repeated administration. METHODS:  In a prospective, unblinded randomized study 16 patients (13 female, age range 51-80 years) underwent trapeziectomy. Microdialysis catheters were placed in the metacarpal bone (primary effect parameter), synovial sheath, and subcutaneous tissue. Patients were randomized to postoperative administration of either intravenous single administration of cefuroxime (1,500 mg) (Group 1, n = 8) or repeated dosing (2 x 1,500 mg) with a 4 h interval (Group 2, n = 8). Samples were taken over 8 h. RESULTS: The fT>MIC of 4 µg/mL was found to be significantly longer in the metacarpal bone in Group 2 compared with Group 1 with a mean difference of 199 min (95% confidence interval 158-239). The same trend was evident in the remaining compartments. A concentration of 4 µg/mL was reached in all compartments in both groups within a mean time of 6 min (range 0-27 min). In Group 1, the mean concentrations decreased below 4 µg/mL between 3 h 59 min and 5 h 38 min. CONCLUSION:  The fT>MIC was longer after repeated administration compared with single administration in all compartments. A single administration of cefuroxime 1,500 mg provided antimicrobial hand tissue coverage for a minimum of 3 h 59 min. Cefuroxime administration in hand surgeries should be done minimum 27 min prior to incision to achieve sufficient coverage in all individuals. Cefuroxime readministration should be considered in hand surgeries lasting longer than 4 h from time of administration.

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Purpose: Radial head arthroplasty (RHA) reestablishes elbow stability after complex radial head fracture, but complication rates are high, possibly due to inappropriate implant sizing. Knowledge of impact of radial head implant diameter on elbow kinematics is limited and warranted. This study evaluated elbow kinematics of different radial head implant diameters after RHA using dynamic radiostereometric analysis (dRSA). Methods: Eight human donor arms were examined with dRSA during elbow flexion with the forearm in unloaded neutral position, and in supinated- and pronated position without and with 10N either varus or valgus load, respectively. Elbow kinematics were examined before and after RHA with head diameters of anatomical size, -2 mm (undersized), and +2 mm (oversized). The ligaments were kept intact by use of step-cut humerus osteotomy for repeated RHA exchange. Bone models were obtained from CT, and by AutoRSA software bone models were matched with dRSA recordings. The elbow kinematics were described using anatomical coordinate systems. Results: Compared to the native radial head during elbow flexion, the anatomical sized RHA shifted 2.0 mm in ulnar direction during unloaded pronated forearm position. The undersized RHA shifted 1.5 mm in posterior direction and 2.1 mm in ulnar direction during unloaded pronated forearm position and increased the varus angle by 2.4° during supinated loaded forearm position. The oversized RHA shifted 1.6 mm in radial direction during loaded supinated forearm position. Conclusions: The anatomically sized RHA should be preferred as it maintained native elbow kinematics the best. The kinematic changes with oversized and undersized RHA diameters were small, suggesting forgiveness for the RHA diameter size. Level of Evidence: Level III.

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Penicillin is available in both an oral (penicillin V) and intravenous formulation (penicillin G), theoretically allowing for a safe transition between the two. However, the use of oral penicillin remains a topic of debate due to low and variable bioavailability. This study aimed to assess the time for which the free penicillin concentration exceeded targeted minimum inhibitory concentrations for Staphylococcus aureus and Streptococcus species (0.125, 0.25, and 0.5 mg/L) in cancellous bone and subcutaneous tissue after intravenous penicillin and oral penicillin administration. 12 female pigs (68-75 kg) were assigned, according to local standard clinical regimes, to either intravenous penicillin (1.2 g) or oral penicillin (0.8 g) treatment every 6 h over an 18 h period. Microdialysis catheters were placed for sampling in tibial cancellous bone and adjacent subcutaneous tissue. Data was dynamic/continually collected in the first dosing interval (0-6 h), simulating a prophylactic situation, and the third dosing interval (12-18 h), simulating a therapeutic setting. Plasma samples were collected for reference. For all investigated targets, intravenous treatment resulted in a longer mean time above relevant minimum inhibitory concentrations in cancellous bone during the first dosing interval, and in both cancellous bone and subcutaneous tissue during the third dosing interval compared to oral treatment. With clinically relevant dosing, intravenous penicillin provides superior exposure compared to oral penicillin in both a prophylactic and therapeutic setting.

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BACKGROUND: Penicillin may be administered enterally or intravenously for the treatment of bacterial infections within the oropharynx and the frontal sinuses. We aimed to assess and compare penicillin concentrations in oropharyngeal and frontal sinus tissues following enteral and intravenous administration in a porcine model. METHOD: Twelve pigs were randomized to receive either enteral (0.8 g Penicillin V) or intravenous (1.2 g Penicillin G) penicillin. Microdialysis was used for sampling in oropharyngeal and frontal sinus tissues during a six-hour dosing interval. In addition, plasma samples were collected. The primary endpoints were time with drug concentration above the minimal inhibitory concentration (T>MIC) for two MIC targets: 0.125 (low target) and 0.5 (high target) µg/mL (covering Group A Streptococci, Fusobactarium necrophorum, Streptococcus pneumoniae and Hemophilus influenza) and attainment of these treatment targets for ≥50 % T>MIC. RESULTS: For both the low and high MIC targets, intravenous administration resulted in higher T>MIC in oropharyngeal and frontal sinus tissues compared to enteral administration. In oropharyngeal tissue, the treatment target (≥50 % T>MIC) was achieved for both the low target (96 %) and high target (68 %) when penicillin was administrated intravenously. In frontal sinus tissue, the treatment target was reached for the low target (70 %), but not the high target (35 %) when administered intravenously. None of the two tissues reached the treatment targets when penicillin was administered enterally. CONCLUSION: Intravenous administrated penicillin in standard dosage is superior to enteral administration of penicillin in standard dosage in achieving clinically important T>MIC as the majority of targets were achieved following intravenously administration, while none of the targets were achieved following enteral administration. These results support the general notion of higher tissue concentrations following intravenous compared to enteral administration.

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Opening remarks: These guidelines are the result of discussions within a diverse group of RSA researchers. They were approved in December 2023 by the board and selected members of the International Radiostereometry Society to update the guidelines by Valstar et al. [1]. By adhering to these guidelines, RSA studies will become more transparent and consistent in execution, presentation, reporting, and interpretation. Both authors and reviewers of scientific papers using RSA may use these guidelines, summarized in the Checklist, as a reference. Deviations from these guidelines should have the underlying rationale stated.

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The dysplastic hip is characterized by incomplete coverage of the femoral head, resulting in increased risk of early osteoarthritis. The morphological variation of the hip joint is diverse and clear differences exist between females and males. The aim of this observational study was therefore to investigate the relationship between the morphology of the hip, sex, and hip dysplasia using a three-dimensional model. Statistical shape models of the combined femur and pelvic bones were created from bilateral hips of 75 patients. Using manual angle measurements and regression analysis, the characteristic shape differences associated with sex and hip dysplasia were determined. The model showed clear differences associated with sex and hip dysplasia. We found that the acetabular anteversion in females was significantly higher (p < 0.0001) than in males while no significant difference in acetabular anteversion was found between normal and dysplastic hips (p = 0.11). The model showed that decreased acetabular anteversion resulted in the appearance of the cross-over sign and the prominent ischial spine sign commonly associated with retroversion. Sex could be predicted with an area under the curve of 0.99 and hip dysplasia could be predicted with an area under the curve of ≥0.73. Our findings suggest that retroversion is a result of decreased anteversion of the acetabulum and is primarily associated with sex. This finding should be taken into account during the reorientation of the acetabulum in the surgical treatment of hip dysplasia.

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Aims: Micromotion of the polyethylene (PE) inlay may contribute to backside PE wear in addition to articulate wear of total knee arthroplasty (TKA). Using radiostereometric analysis (RSA) with tantalum beads in the PE inlay, we evaluated PE micromotion and its relationship to PE wear. Methods: A total of 23 patients with a mean age of 83 years (77 to 91), were available from a RSA study on cemented TKA with Maxim tibial components (Zimmer Biomet). PE inlay migration, PE wear, tibial component migration, and the anatomical knee axis were evaluated on weightbearing stereoradiographs. PE inlay wear was measured as the deepest penetration of the femoral component into the PE inlay. Results: At mean six years' follow-up, the PE wear rate was 0.08 mm/year (95% confidence interval 0.06 to 0.09 mm/year). PE inlay external rotation was below the precision limit and did not influence PE wear. Varus knee alignment did not influence PE wear (p = 0.874), but increased tibial component total translation (p = 0.041). Conclusion: The PE inlay was well fixed and there was no relationship between PE stability and PE wear. The PE wear rate was low and similar in the medial and lateral compartments. Varus knee alignment did not influence PE wear.

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PURPOSE: The pivot-shift test is used to clinically assess knee instability in patients with anterior cruciate ligament (ACL) lesions; however, it has low interobserver reliability. Dynamic radiostereometry (dRSA) is a highly precise and noninvasive method for the objective evaluation of joint kinematics. The purpose of this study was to quantify precise knee kinematics during a pivot-shift test using dRSA imaging. METHOD: Eight human donor legs, including hemipelvises, were evaluated. Arthroscopic intervention was performed inducing ligament lesions in the ACL, and anterolateral ligament (ALL) section was performed as a capsular incision. The pivot-shift test was recorded with dRSA on knees with intact ligaments, ACL-deficient and ACL + ALL-deficient knees. RESULTS: A pivot-shift pattern was identifiable after ligament lesion, as a change in tibial posterior drawer velocity from 7.8 mm/s (95% CI: 3.7; 11.9) in ligament intact knees to 30.4 mm/s (95% CI 23.0; 38.8) after ACL lesion to 35.1 mm/s (95% CI 23.4; 46.7) after combined ACL-ALL lesion. The anterior-posterior drawer excursion increased from 2.8 mm (95% CI 2.1; 3.4) in ligament intact knees to 7.2 mm (95% CI 5.5; 8.9) after ACL lesion to 7.6 mm (95% CI 5.5; 9.8) after combined lesion. A statistically significant increase in tibial external rotation towards the end of the pivot-shift motion was observed when progressing from intact to ACL + ALL-deficient knees (p < 0.023). CONCLUSION: This experimental study demonstrates the feasibility of dRSA to objectively quantify the kinematic laxity patterns of the knee during the pivot-shift test. The dynamic parameters obtained through dRSA revealed the kinematic changes from ACL to combined ACL-ALL ligament lesion. LEVEL OF EVIDENCE: Not applicable.

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PURPOSE: Doxorubicin is a widely used chemotherapeutic drug that can be administered intravenously as both a bolus infusion and a continuous infusion. The latter is believed to lower the risk of cardiotoxicity, which is a critical long-term complication of doxorubicin treatment. The local tissue concentrations of doxorubicin will be reflected in both treatment efficacy and toxicity, but very limited information is available. The aim of this study was to measure the concentration of doxorubicin after continuous and bolus infusion in tissue compartments around a typical location of a bone tumour. METHODS: Sixteen pigs (female, Danish Landrace, mean weight 77 kg) were randomized into two groups of eight. Both groups received an intravenous infusion of 150 mg doxorubicin; Group 1 received a bolus infusion (10-15 min) and Group 2 received a continuous infusion (6 h). Before infusion, microdialysis catheters were placed intravenously and in four bone tumour-relevant tissue compartments (cancellous bone, subcutaneous tissue, synovial fluid of the knee joint and muscle tissue). Sampling was done (n = 15) over 24 h, and venous blood samples were collected as a reference. RESULTS: Area under the concentration-time curve (AUC0-24 h) for plasma (total concentration) was significantly different between the two groups, while peak drug concentration (Cmax) was significantly higher in two compartments (plasma and synovial fluid of the knee joint) in Group 1 compared to Group 2. Overall, the unbound tissue concentrations were extremely low with values below 0.20 µg/mL. CONCLUSION: The pharmacokinetic profile for doxorubicin in the investigated tissues is very similar when comparing bolus and 6 h continuous infusion.

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BACKGROUND AND PURPOSE: Cementless arthroplasty fixation relies on early bone ingrowth and may be poor in patients with low proximal tibial bone density or abnormal bone turnover. We aimed first to describe the baseline bone properties in patients undergoing medial unicompartmental knee replacement (UKR), and second to investigate its association with cemented and cementless tibial component migration until 2 years. METHODS: A subset investigation of 2 patient groups from a 3-armed randomized controlled trial was conducted. There were 26 cemented and 25 cementless medial UKRs with twin-pegged femoral components. Volumetric bone mineral density (vBMD) and microstructure of the excised medial tibial plateau were ascertained with µCT. Bone turnover was estimated using dynamic histomorphometry (eroded surface/bone surface = ES/BS, osteoid surface/bone surface = OS/BS, mineralizing surface/bone surface = MS/BS). Tibial component migration in 4 feature points was followed for 2 years with radiostereometry. RESULTS: At the 2-year follow-up, the cementless tibial components migrated 0.38 mm (95% confidence interval [CI] 0.14-0.62) total translation more than the cemented components at the posterior feature point. The greatest migration in the cementless group was subsidence at the posterior feature point of 0.66 mm (CI 0.48-0.84) until 6 weeks, and from 3 months the components were stable. Cemented tibial components subsided very little. Between 1- and 2-year follow-ups, no cementless but 4 cemented tibial components revealed continuous migration. OS/BS was half of the ES/BS. No µCT or histomorphometric parameters showed any clinically relevant correlation with tibial component migration at the posterior feature point for either cemented or cementless UKR at 6 weeks' or 2 years' follow-up after adjustment for age, BMI, and sex. CONCLUSION: Preoperative vBMD, bone turnover, and microstructure were not associated with postoperative tibial component migration of cemented and cementless medial UKR.

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Doxorubicin is a chemotherapeutic agent used for more than fifty years to treat a great variety of cancers in both children and adults. Despite hereof, pharmacokinetic knowledge is almost solely based on systemic plasma concentrations. Microdialysis is a catheter-based pharmacokinetic sampling tool enabling simultaneous target site sampling of unbound molecules of interest. The aim of this study was to thoroughly evaluate the feasibility of applying microdialysis for sampling of Doxorubicin in both in vitro experiments and an in vivo setting. Doxorubicin relative recovery by gain and by loss was tested for different catheter types, perfusion fluids, concentrations and collection vials. Adsorption tests revealed polystyrene/santoprene vials to be the biggest contributor of unwanted adsorption between Doxorubicin and the microdialysis equipment, and confirmed LoBind Eppendorf tubes to be a suitable alternative. The methodological combination of polyamide membranes, saline as perfusion fluid and LoBind Eppendorf sampling tubes demonstrated no statistically significant differences for relative recovery by gain and by loss, and the relative recovery was also found to be concentration independent. We conclude, that a proper microdialysis set-up can be used to collect samples containing concentrations of the chemotherapeutic drug Doxorubicin in vitro and in vivo, which encourage future pharmacokinetic studies to evaluate current treatment regimens to find the most effective and least toxic anti-neoplastic treatment for the patients.

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We aimed to evaluate moxifloxacin steady-state concentrations in infected bone and soft tissue and to explore the additive microbiological and pathological treatment effect of rifampicin to standard moxifloxacin treatment of implant-associated osteomyelitis (IAO). 16 pigs were included. On Day 0, IAO was induced in the proximal tibia using a susceptible Staphylococcus aureus strain. On Day 7, the pigs underwent one-stage exchange surgery of the IAO lesions and were randomized to receive seven days of intravenous antibiotic treatment of either rifampicin combined with moxifloxacin or moxifloxacin monotherapy. On Day 14, microdialysis was applied for continuous sampling (8 h) of moxifloxacin concentrations. Microbiological, macroscopical pathology, and histopathological analyses were performed postmortem. Steady-state moxifloxacin area under the concentration-time curve was lower in the combination therapy group in plasma (total) and subcutaneous tissue compartments (infected and noninfected) (p < 0.04), while no differences were found in bone compartments. No additional treatment effect of rifampicin to moxifloxacin treatment was found (p = 0.57). Conclusive, additive rifampicin treatment does not reduce moxifloxacin concentrations at the infection site. Rifampicin treatment may not be necessary in a one-stage exchange treatment of IAO. However, our sample size and treatment period may have been too small and short to reveal true clinical differences.

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PURPOSE: The most used cup designs for trapeziometacarpal (TMC) arthroplasty are of hemispherical and conical geometrical shape. Using a validated pig bone model, we compared the bone fixation using radiostereometry (RSA). METHODS: Twenty saddle-shaped pig forefoot bones were prepared with insertion of bone markers and reaming. Hemispherical Type T cups (Beznoska, Kladno, Czech Republic) (N = 10) and conical Moovis cups (Stryker, Pusignan, France) (N = 10) of 9-mm diameter were inserted press-fit. The bones were fixed in cement blocks for stability, and the cups were loaded in a motorized test stand. First, a low-pressure cyclic load test (0-150N) with 130 compression cycles was performed. Next, a push-in test of progressive loads with 50N increments (range: 150-900N) was applied until a visual change in cup position appeared. Cup migration was evaluated with RSA after every new load application. Cup failure was defined as total translation > 0.5 mm between two load applications. RESULTS: Both cup types tolerated a compression load of 450 N without failure. Beyond this load level, the total translation cup migration of mean 0.20 mm (95% CI 0.11; 0.30) for the Type T group was higher than mean 0.10 mm (95% CI 0.06; 0.15) of the Moovis group (p = 0.046). The Hazard ratio for failure was 0.52 (95% CI 0.12; 2.17) (p = 0.37), indicating that the risk of failure was two-fold higher in the Type T group. CONCLUSION: We conclude that conical TMC cups have superior fixation as compared to hemispherical cups above a loading level of 450 N, which correspond to a 3.8 kg tip-pinch. In a clinical perspective, based on the fixation strength of both cup types, it seems safe to allow light-load activities of daily living such as buttoning a shirt and using a key shortly after surgery and until sufficient osseointegration is achieved.

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INTRODUCTION: Cut-out is the most frequently reported mechanical failure of internal fixation of pertrochanteric fractures. The purpose of this study was to examine if hydroxyapatite-coated screw thread on a sliding hip screw (SHS) could reduce screw migration within the femoral head in patients with stable pertrochanteric fractures. MATERIALS AND METHODS: In a double-blinded randomized controlled study, 37 patients at mean age 78 (range 56-96), with pertrochanteric fracture (Evans I, II, IV) received surgery with a SHS with a hydroxyapatite-coated or a non-coated lag screw thread. Radiostereometry and standard radiographs were obtained 1 day, 6 weeks, 3- and 6 months post-operatively to evaluate screw and fracture migration and fracture reposition. The two groups were combined to describe fracture migration. RESULTS: There was similar and small screw migration in the femoral head between the two groups at 6 weeks, 3- and 6 months (p > 0.12). Fracture migration occurred predominantly in the first 6 weeks, where fracture impaction was 5.95 mm (CI 95% 2.87 to 9.04) and anterior rotation of the femoral head was -2.94° (CI 95% - 5.22 to - 0.66). Migration of the fracture (total translation) correlated to the post-operative fracture reposition (p = 0.002), but not significantly to screw migration (p = 0.09). Neither screw total translation (rho 0.06, p = 0.79) nor fracture total translation (rho 0.04, p = 0.77) correlated with bone mineral density. CONCLUSION: There was no clinical benefit of hydroxyapatite coating on lag screw migration in this patient cohort. Migration of the pertrochanteric fractures was higher with poor fracture reposition but fractures generally stabilized after 6 weeks follow-up. The study was registered at ClinicalTrials.gov (NCT05677061). LEVEL OF EVIDENCE II: Patient-blinded prospective randomized study. Trial registration number The study was registered at ClinicalTrials.gov (NCT05677061).

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BACKGROUND: The component design and fixation method of joint arthroplasty may affect component migration and survival. The aim of this study was to compare fixation of cementless twin-peg (CLTP), cemented twin-peg (CTP) and cemented single-peg (CSP) femoral components of medial unicompartmental knee replacement (UKR). METHODS: Eighty patients (mean age = 63 years, 48 males) with medial knee osteoarthritis were randomized in three ways to CLTP (n = 25), CTP (n = 26) or CSP (n = 29) femoral UKR components. The patients were followed 5 years postoperatively with RSA, bone mineral density (BMD), PROMs and radiological evaluation of radiolucent lines (RLL), femoral component flexion angle and complications. RESULTS: At the 5-year follow-up, femoral component total translation was comparable between the three groups (p = 0.60). Femoral component internal rotation was 0.50° (95% CI 0.3; 0.69) for the CLTP group, 0.58° (95% CI 0.38; 0.77) for the CTP group and 0.25° (95% CI 0.07; 0.43) for the CSP group (p = 0.01). BMD decreased peri-prosthetically (range - 11.5%; - 14.0%) until 6-month follow-up and increased toward the 5-year follow-up (range - 3.6%; - 5.8%). BMD change did not correlate with component migration. Lower flexion angle was correlated with higher 5-year subsidence, total translation, varus rotation and maximum total point motion (p = 0.01). Two patients (1 CLTP, 1 CTP) had RLL in the posterior zone. There were two revisions. CONCLUSION: At 5-year follow-up, fixation of UKA femoral components with twin-peg was not superior to the single-peg design. Cementless and cemented twin-peg femoral components had similar fixation. A lower flexion angle was correlated with higher component migration.

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Aims: The Exeter short stem was designed for patients with Dorr type A femora and short-term results are promising. The aim of this study was to evaluate the minimum five-year stem migration pattern of Exeter short stems in comparison with Exeter standard stems. Methods: In this case-control study, 25 patients (22 female) at mean age of 78 years (70 to 89) received cemented Exeter short stem (case group). Cases were selected based on Dorr type A femora and matched first by Dorr type A and then age to a control cohort of 21 patients (11 female) at mean age of 74 years (70 to 89) who received with cemented Exeter standard stems (control group). Preoperatively, all patients had primary hip osteoarthritis and no osteoporosis as confirmed by dual X-ray absorptiometry scanning. Patients were followed with radiostereometry for evaluation of stem migration (primary endpoint), evaluation of cement quality, and Oxford Hip Score. Measurements were taken preoperatively, and at three, 12, and 24 months and a minimum five-year follow-up. Results: At three months, subsidence of the short stem -0.87 mm (95% confidence interval (CI) -1.07 to -0.67) was lower compared to the standard stem -1.59 mm (95% CI -1.82 to -1.36; p < 0.001). Both stems continued a similar pattern of subsidence until five-year follow-up. At five-year follow-up, the short stem had subsided mean -1.67 mm (95% CI -1.98 to -1.36) compared to mean -2.67 mm (95% CI -3.03 to -2.32) for the standard stem (p < 0.001). Subsidence was not influenced by preoperative bone quality (osteopenia vs normal) or cement mantle thickness. Conclusion: The standard Exeter stem had more early subsidence compared with the short Exeter stem in patients with Dorr type A femora, but thereafter a similar migration pattern of subsidence until minimum five years follow-up. Both the standard and the short Exeter stems subside. The standard stem subsides more compared to the short stem in Dorr type A femurs. Subsidence of the Exeter stems was not affected by cement mantle thickness.

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Co-administration of meropenem and vancomycin has been suggested as a systemic empirical antibiotic treatment of pyogenic spondylodiscitis. The aim of this study was, in an experimental porcine model, to evaluate the percentage of an 8-h dosing interval of co-administered meropenem and vancomycin concentrations above the relevant minimal inhibitory concentrations (MICs) (%T>MIC) in spinal tissues using microdialysis. Eight female pigs (Danish Landrace breed, weight 78-82 kg) received a single-dose bolus infusion of 1000 mg of meropenem and 1000 mg vancomycin simultaneously before microdialysis sampling. Microdialysis catheters were applied in the third cervical (C3) vertebral cancellous bone, the C3-C4 intervertebral disc, paravertebral muscle, and adjacent subcutaneous tissue. Plasma samples were obtained for reference. The main finding was that for both drugs, the %T>MICs were highly reliant on the applied MIC target, but were heterogeneous across all targeted tissues, ranging from 25-90% for meropenem, and 10-100% for vancomycin. For both MIC targets, the highest %T>MIC was demonstrated in plasma, and the lowest %T>MIC was demonstrated in the vertebral cancellous bone for meropenem, and in the intervertebral disc for vancomycin. When indicated, our findings may suggest a more aggressive dosing approach of both meropenem and vancomycin to increase the spinal tissue concentrations to treat the full spectrum of potentially encountered bacteria in a spondylodiscitis treatment setting.

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Microdialysis is a catheter-based method suitable for dynamic sampling of unbound antibiotic concentrations. Intravenous antibiotic concentration sampling by microdialysis has several advantages and may be a superior alternative to standard plasma sampling. We aimed to compare concentrations obtained by continuous intravenous microdialysis sampling and by standard plasma sampling of both vancomycin and meropenem in a porcine model. Eight female pigs received 1 g of both vancomycin and meropenem, simultaneously over 100 and 10 min, respectively. Prior to drug infusion, an intravenous microdialysis catheter was placed in the subclavian vein. Microdialysates were collected for 8 h. From a central venous catheter, plasma samples were collected in the middle of every dialysate sampling interval. A higher area under the concentration/time curve and peak drug concentration were found in standard plasma samples compared to intravenous microdialysis samples, for both vancomycin and meropenem. Both vancomycin and meropenem concentrations obtained with intravenous microdialysis were generally lower than from standard plasma sampling. The differences in key pharmacokinetic parameters between the two sampling techniques underline the importance of further investigations to find the most suitable and reliable method for continuous intravenous antibiotic concentration sampling.

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(1) Introduction: Piperacillin is a common antibiotic choice in the treatment of periprosthetic joint infections (PJI) caused by Pseudomonas aeruginosa. The aim of this study was to assess and compare the time with free piperacillin concentration above the minimum inhibitory concentration (fT > MIC) at steady state in target tissues relevant for PJI treatment following continuous and intermittent short-term infusion. (2) Methods: 16 pigs were randomized to receive either continuous or intermittent short-term infusion of piperacillin. Steady state piperacillin concentrations were assessed using microdialysis in tibial cortical bone, tibial cancellous bone, synovial fluid of the knee joint, and subcutaneous tissue. MIC-targets of 4, 8, 16, and 64 mg/L were applied. Plasma samples were obtained as reference. (3) Results: Continuous infusion resulted in longer fT > MIC for MIC targets of 4 mg/L and 8 mg/L compared to intermittent short-term infusion in all compartments with the exception of tibial cortical bone. For the MIC-target of 16 mg/L, continuous infusion resulted in a longer fT > MIC in all compartments except for the bone compartments. No differences between groups were seen when applying a MIC-target of 64 mg/L. (4) Conclusions: An aggressive dosing strategy may be necessary to obtain sufficient piperacillin concentrations in all bone compartments, particularly if more aggressive targets are applied. Based on the present study, continuous infusion should be considered in the treatment of PJI.

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Implant-associated osteomyelitis is one of the most feared complications following orthopedic surgery. Although the risk is low, sufficient antibiotic protection of the implant surface is important. The aim of this study was to assess steady-state piperacillin concentrations in the proximity of an orthopedic implant. Time above the minimal inhibitory concentration (fT>MIC) was evaluated for MIC of 8 (low target) and 16 µg/mL (high target). 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. For the low piperacillin target (8 µg/mL), comparable mean fT>MIC across all the investigated compartments (mean range: 54-74%) was found. For the high target (16 µg/mL), fT>MIC was shorter inside the cannulated screw (mean: 16%) than in the cancellous bone next to the screw and plasma (mean range: 49-54%), and similar between the two cancellous bone compartments. To reach more aggressive piperacillin fT>MIC targets in relation to the implant, alternative dosing regimens such as continuous infusion may be considered.