Weight‐based cefuroxime dosing provides comparable orthopedic target tissue concentrations between weight groups – a microdialysis porcine study

Tøstesen, Sara Kousgaard; Hanberg, Pelle; Bue, Mats; Thillemann, Theis Muncholm; Falstie-Jensen, Thomas; Tøttrup, Mikkel; Knudsen, Martin B.; Schmedes, Anne; Stilling, Maiken

doi:10.1111/apm.13198

Cited by 6 publications

(4 citation statements)

References 38 publications

(44 reference statements)

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“…The intermediate precision for the internal controls at four levels, determined over 43 runs, for cefuroxime was 14.2% (target 0.010 μg·ml −1 ), 9.6% (target 0.050 μg·ml −1 ), 2.6% (target 5.00 μg·ml −1 ), and 3.9% (target 10.00 μg·ml −1 ), whereas it was 16.6% (target 0.050 μg·ml −1 ), 3.9% (target 5.00 μg ml −1 ), and 5.6% (target 10.00 μg·ml −1 ) for meropenem at three levels, determined over 36 runs. The chemical analysis has previously been applied in studies examining cefuroxime concentrations (Hvistendahl, Bue, et al, 2022; Tøstesen et al, 2022).…”

Section: Methodsmentioning

confidence: 99%

Evaluation of cefuroxime concentration in the intrathecal and extrathecal compartments of the lumbar spine—an experimental study in pigs

Kaspersen

Hanberg

Hvistendahl

et al. 2023

British J Pharmacology

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Background and Purpose Optimal antibiotic prophylaxis is crucial to prevent postoperative infection in spinal surgery. Sufficient time above the minimal inhibitory concentration (fT > MIC) for relevant bacteria in target tissues is required for cefuroxime. We assessed cefuroxime concentrations and fT > MIC of 4 μg·ml−1 for Staphylococcus aureus in the intrathecal (spinal cord and cerebrospinal fluid, CSF) and extrathecal (epidural space) compartments of the lumbar spine. Experimental Approach Eight female pigs were anaesthetized and laminectomized at L3–L4. Microdialysis catheters were placed for sampling in the spinal cord, CSF, and epidural space. A single dose of 1500 mg cefuroxime was administered intravenously over 10 min. Microdialysates and plasma were obtained continuously during 8 h. Cefuroxime concentrations were determined by ultra‐high‐performance liquid chromatography. Key Results Mean fT > MIC (4 μg·ml−1) was 58 min in the spinal cord, 0 min in the CSF, 115 min in the epidural space, and 123 min in plasma. Tissue penetration was 32% in the spinal cord, 7% in the CSF, and 63% in the epidural space. Conclusion and Implications fT > MIC (4 μg·ml−1) and tissue penetration for cefuroxime were lower in the intrathecal compartments (spinal cord and CSF) than in the extrathecal compartment (epidural space) and plasma, suggesting a significant effect of the blood–brain barrier. In terms of fT > MIC, a single dose of 1500 mg cefuroxime seems inadequate to prevent intrathecal infections related to spinal surgery for bacteria presenting with a MIC target of 4 μg· ml−1 or above.

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Section: Methodsmentioning

confidence: 99%

Evaluation of cefuroxime concentration in the intrathecal and extrathecal compartments of the lumbar spine—an experimental study in pigs

Kaspersen

Hanberg

Hvistendahl

et al. 2023

British J Pharmacology

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“…Laboratory analyses were utilised at the Department of Clinical Biochemistry, Lillebaelt Hospital Vejle, Denmark. Adhering to recommendations of Replacement, Reduction or Refinement in animal studies [ 36 ], the same 18 pigs were included in a study investigating the effect of weight-based cefuroxime dosing on orthopaedic relevant target tissue concentrations in the first dosing interval [ 37 ].…”

Section: Methodsmentioning

confidence: 99%

“…The free unbound concentrations of cefuroxime in plasma and dialysates and meropenem in dialysates were quantified using a validated LC-MS/MS assay [ 37 ]. For cefuroxime the inter-run imprecisions were 14.2% at 0.01 µg/mL, 9.6% at 0.05 µg/mL, 2.6% at 5.00 µg/mL and 3.9% at 10.00 µg/mL.…”

Section: Methodsmentioning

confidence: 99%

High Cefuroxime Concentrations and Long Elimination in an Orthopaedic Surgical Deadspace—A Microdialysis Porcine Study

et al. 2022

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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 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 (fT > MIC (4 μg/mL)). During the two dosing intervals, mean fT > MIC (4 μg/mL) was significantly longer in deadspace (605 min) compared with plasma (284 min) and bone (334 min). For deadspace, the mean time to reach 4 μg/mL was prolonged from the first dosing interval (8 min) to the second dosing interval (21 min), while the peak drug concentration was lower and half-life was longer in the second dosing interval. In conclusion, weight-adjusted cefuroxime fT > MIC (4 μg/mL) and elimination from the deadspace was longer in comparison to plasma and bone. Our results suggest a deadspace consolidation and a longer diffusions distance, resulting in a low cefuroxime turn-over. Based on theoretical targets, cefuroxime appears to be an appropriate prophylactic drug for the prevention of PJI.

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“…Cefuroxime, a second-generation cephalosporin with few side effects, is widely used for perioperative antibiotic prophylaxis in spine surgery, as its antimicrobial spectrum covers the most frequent bacteria causing infection after spine surgery ( 7 , 8 ). The pharmacokinetic tool, microdialysis, allows for dynamic real-time perioperative sampling of the unbound fraction of cefuroxime and has the potential to estimate perioperative proximate implant concentrations ( 9 , 10 ). We compared the perioperative concentrations of cefuroxime inside a cannulated pedicle screw with the opposite non-instrumented vertebral pedicle using microdialysis, following a single-dose intravenous cefuroxime administration of 1.5 g. We hypothesized that introduction of a commonly applied cannulated pedicle screw induces subtherapeutic perioperative proximate internal implant concentrations.…”

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confidence: 99%

Subtherapeutic levels of cefuroxime inside a cannulated pedicle screw used in spine surgery: results from a porcine microdialysis study

Hvistendahl

Hanberg

Stilling

et al. 2022

ActaO

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Background and purpose: Minimally invasive spine surgery has continuously evolved for specific surgical procedures and patient populations to lower morbidity and the risk of postoperative bacterial infection. Perioperative antibiotic prophylaxis is an important preventive measure and local tissue concentrations can be quantified with microdialysis. Insertion of spinal implants induces tissue trauma and inflammation, which may affect antibiotic proximate implant concentrations. We compared perioperative cefuroxime concentrations inside a cannulated pedicle screw used in minimally invasive spine surgery with the opposite non-instrumented vertebral pedicle.Materials and methods: Microdialysis catheters were placed inside a cannulated pedicle screw and in the opposite non-instrumented vertebral pedicle of the same vertebra (L1) in 8 female pigs through a posterior lumbar surgical approach. Following a single-dose intravenous cefuroxime administration (1.5 g), dialysates and plasma were dynamically sampled over 8 hours. The primary endpoint was time above the cefuroxime clinical breakpoint minimal inhibitory concentration for Staphylococcus aureus of 4 μg/mL (T>MIC4).Results: Median T>MIC4 was 0 h (range 0–0) inside the cannulated pedicle screw, 1.6 h (range 1.1–2.4) in non-instrumented vertebral pedicle, and 1.9 h (range 1.9–2.9) in plasma.Conclusion: A single-dose intravenous cefuroxime administration provided low and subtherapeutic concentrations for prevention of infection inside a cannulated pedicle screw in the lumbar spine. Therapeutic concentrations were achieved in the opposite non-instrumented vertebral pedicle up to 1.5–2 h. Therefore, additional prophylactic strategies may be considered in cannulated instrumented spine surgery, especially in high-risk patients. Alternative dosing regimens seem relevant in lumbar spine surgery lasting longer than 1.5 h.

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Weight‐based cefuroxime dosing provides comparable orthopedic target tissue concentrations between weight groups – a microdialysis porcine study

Cited by 6 publications

References 38 publications

Evaluation of cefuroxime concentration in the intrathecal and extrathecal compartments of the lumbar spine—an experimental study in pigs

Evaluation of cefuroxime concentration in the intrathecal and extrathecal compartments of the lumbar spine—an experimental study in pigs

High Cefuroxime Concentrations and Long Elimination in an Orthopaedic Surgical Deadspace—A Microdialysis Porcine Study

Subtherapeutic levels of cefuroxime inside a cannulated pedicle screw used in spine surgery: results from a porcine microdialysis study

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