Dataset Information

Bone and subcutaneous adipose tissue pharmacokinetics of vancomycin in total knee replacement patients.

ABSTRACT: Background and purpose - The incidence of orthopedic methicillin-resistant Staphylococcus aureus (MRSA) infections is increasing. Vancomycin may therefore play an increasingly important role in orthopedic perioperative antimicrobial prophylaxis. Studies investigating perioperative bone and soft tissue concentrations of vancomycin are sparse and challenged by a lack of appropriate methods. We assessed single-dose plasma, subcutaneous adipose tissue (SCT) and bone concentrations of vancomycin using microdialysis in male patients undergoing total knee replacement. Methods - 1,000?mg of vancomycin was administered postoperatively intravenously over 100?minutes to 10 male patients undergoing primary total knee replacement. Vancomycin concentrations in plasma, SCT, cancellous, and cortical bone were measured over the following 8?hours. Microdialysis was applied for sampling in solid tissues. Results - For all solid tissues, tissue penetration of vancomycin was significantly impaired. The time to a mean clinically relevant minimal inhibitory concentration (MIC) of 2?mg/L was 3, 36, 27, and 110?min for plasma, SCT, cancellous, and cortical bone, respectively. As opposed to the other compartments, a mean MIC of 4?mg/L could not be reached in cortical bone. The area under the concentration-time curve from 0 to the last measured value and peak drug concentrations (Cmax) for SCT, cancellous, and cortical bone was lower than that of free plasma. The time to Cmax was higher for all tissues compared with free plasma. Interpretation - Postoperative penetration of vancomycin to bone and SCT was impaired and delayed in male patients undergoing total knee replacement surgery. Adequate perioperative vancomycin concentrations may not be reached using standard prophylactic dosage.

SUBMITTER: Bue M

PROVIDER: S-EPMC5810840 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature

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Bone and subcutaneous adipose tissue pharmacokinetics of vancomycin in total knee replacement patients.

Bue Mats M Tøttrup Mikkel M Hanberg Pelle P Langhoff Otto O Birke-Sørensen Hanne H Thillemann Theis M TM Andersson Torben L TL Søballe Kjeld K

Acta orthopaedica 20170915 1

Background and purpose - The incidence of orthopedic methicillin-resistant Staphylococcus aureus (MRSA) infections is increasing. Vancomycin may therefore play an increasingly important role in orthopedic perioperative antimicrobial prophylaxis. Studies investigating perioperative bone and soft tissue concentrations of vancomycin are sparse and challenged by a lack of appropriate methods. We assessed single-dose plasma, subcutaneous adipose tissue (SCT) and bone concentrations of vancomycin usin ...[more]

PMID: 28914105

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Project description:Reduced external knee adduction moments in the second half of stance after total hip replacement have been reported in hip osteoarthritis patients. This reduction is thought to shift the load from the medial to the lateral knee compartment and as such increase the risk for knee osteoarthritis. The knee adduction moment is a surrogate for the load distribution between the medial and lateral compartments of the knee and not a valid measure for the tibiofemoral contact forces which are the result of externally applied forces and muscle forces. The purpose of this study was to investigate whether the distribution of the tibiofemoral contact forces over the knee compartments in unilateral hip osteoarthritis patients 1 year after receiving a primary total hip replacement differs from healthy controls. Musculoskeletal modeling on gait was performed in OpenSim using the detailed knee model of Lerner et al. (2015) for 19 patients as well as for 15 healthy controls of similar age. Knee adduction moments were calculated by the inverse dynamics analysis, medial and lateral tibiofemoral contact forces with the joint reaction force analysis. Moments and contact forces of patients and controls were compared using Statistical Parametric Mapping two-sample t-tests. Knee adduction moments and medial tibiofemoral contact forces of both the ipsi- and contralateral leg were not significantly different compared to healthy controls. The contralateral leg showed 14% higher medial tibiofemoral contact forces compared to the ipsilateral (operated) leg during the second half of stance. During the first half of stance, the lateral tibiofemoral contact force of the contralateral leg was 39% lower and the ratio 32% lower compared to healthy controls. In contrast, during the second half of stance the forces were significantly higher (39 and 26%, respectively) compared to healthy controls. The higher ratio indicates a changed distribution whereas the increased lateral tibiofemoral contact forces indicate a higher lateral knee joint loading in the contralateral leg in OA patients after total hip replacement (THR). Musculoskeletal modeling using a detailed knee model can be useful to detect differences in the load distribution between the medial and lateral knee compartment which cannot be verified with the knee adduction moment.

Dataset Information

Bone and subcutaneous adipose tissue pharmacokinetics of vancomycin in total knee replacement patients.

Publications

Bone and subcutaneous adipose tissue pharmacokinetics of vancomycin in total knee replacement patients.

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