Concentrations of co-administered vancomycin and meropenem in the internal dead space of a cannulated screw and in cancellous bone adjacent to the screw – Evaluated by microdialysis in a porcine model

Vittrup, Sofus; Stilling, Maiken; Hanberg, Pelle; Tøstesen, Sara Kousgaard; Knudsen, Martin B.; Kipp, Josephine Olsen; Bue, Mats

doi:10.1016/j.injury.2022.06.008

Cited by 4 publications

(6 citation statements)

References 32 publications

(22 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, in a mechanical deadspace, as in the hollow center of a cannulated screw, a complex situation may arise since the immune system cannot be expected to assist the antibiotic effect as in normally blood perfused tissue. A deadspace is presumably a poorly vascularized void with low oxygen tension and pH, which may favour bacterial proliferation and biofilm formation [ 25 ]. A recent microdialysis study has demonstrated the same tendencies of longer elimination of cefuroxime from a physiological hematoma deadspace, indicating longer diffusion distance and lower antibiotic turn-over in a deadspace [ 26 ].…”

Section: Discussionmentioning

confidence: 99%

“…Interestingly, the comparable mean f T>MIC piperacillin between the cancellous bone next to the screw and the contralateral tibia, did unexpectedly indicate that f T>MIC piperacillin is not affected by the screw-induced stress in the cancellous bone. In contrast to this, a recent study with a comparable setup, investigating co-administered vancomycin and meropenem concentrations in relation to a cannulated screw, suggested that the presence of the screw lowered the concentrations next to the screw in comparison to the contralateral cancellous bone, especially for vancomycin [ 25 ]. The investigated drugs differ in molecular sizes, chemical structure and protein binding, but the key difference between the two study setups is the timing of the sampling interval: first dosing interval versus third dosing interval (steady state) in the present study.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Steady-State Piperacillin Concentrations in the Proximity of an Orthopedic Implant: A Microdialysis Porcine Study

et al. 2023

Self Cite

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Steady-State Piperacillin Concentrations in the Proximity of an Orthopedic Implant: A Microdialysis Porcine Study

et al. 2023

Self Cite

View full text Add to dashboard Cite

show abstract

“…Whether the cefuroxime concentrations measured in the opposite non-instrumented vertebral pedicle of the same lumbar vertebra could serve as a proxy for the outer surface protection of the cannulated pedicle screw needs further investigation. A recent porcine study has demonstrated that the presence of a cannulated screw impaired the penetration of meropenem and vancomycin into cancellous bone (tibial metaphysis) adjacent to the screw (average distance from screw 3 mm) ( 21 ). This supports further analytical discussion as regards the extent to which the mechanical stress (following screw insertion) affects the local environment and thus antibiotic protection of the screw.…”

Section: Discussionmentioning

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

View full text Add to dashboard Cite

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.

show abstract

“…2017/15-0201-01184). To meet the three Rs by reducing the number of animals used, the same pigs have provided data to other studies with different purposes [ 29 , 30 ]. All chemical analyses were performed at the Department of Forensic Medicine, Aarhus University Hospital and at the Department Clinical Biochemistry, Aarhus University Hospital.…”

Section: Methodsmentioning

confidence: 99%

“…Collected plasma samples were stored at 5 °C for a maximum of 6 h before being centrifuged at 3000× g for 10 min. Dialysates and plasma samples were frozen at −80 °C until analysis [ 30 ].…”

Section: Methodsmentioning

confidence: 99%

Comparison of Intravenous Microdialysis and Standard Plasma Sampling for Monitoring of Vancomycin and Meropenem Plasma Concentrations—An Experimental Porcine Study

et al. 2023

Self Cite

View full text Add to dashboard Cite

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.

show abstract

Concentrations of co-administered vancomycin and meropenem in the internal dead space of a cannulated screw and in cancellous bone adjacent to the screw – Evaluated by microdialysis in a porcine model

Cited by 4 publications

References 32 publications

Steady-State Piperacillin Concentrations in the Proximity of an Orthopedic Implant: A Microdialysis Porcine Study

Steady-State Piperacillin Concentrations in the Proximity of an Orthopedic Implant: A Microdialysis Porcine Study

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

Comparison of Intravenous Microdialysis and Standard Plasma Sampling for Monitoring of Vancomycin and Meropenem Plasma Concentrations—An Experimental Porcine Study

Contact Info

Product

Resources

About