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

Johanne Gade Lilleøre; Andrea René Jørgensen; Martin Bruun Knudsen; Pelle Hanberg; Kristina Öbrink-Hansen; Sara Kousgaard Tøstesen; Kjeld Søballe; Maiken Stilling; Mats Bue

doi:10.3390/antibiotics12030615

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

Johanne Gade Lilleøre^*, Andrea René Jørgensen, Martin Bruun Knudsen, Pelle Hanberg, Kristina Öbrink-Hansen, Sara Kousgaard Tøstesen, Kjeld Søballe, Maiken Stilling, Mats Bue

^*Corresponding author for this work

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

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Abstract

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.

Original language	English
Article number	615
Journal	Antibiotics
Volume	12
Issue	3
ISSN	2079-6382
DOIs	https://doi.org/10.3390/antibiotics12030615
Publication status	Published - Mar 2023

Keywords

implants
microdialysis
osteomyelitis
piperacillin
steady state
tazobactam

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10.3390/antibiotics12030615Licence: CC BY

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@article{c127f7e46cf044c48c24531b4ae23c3b,

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

abstract = "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.",

keywords = "implants, microdialysis, osteomyelitis, piperacillin, steady state, tazobactam",

author = "Lille{\o}re, {Johanne Gade} and J{\o}rgensen, {Andrea Ren{\'e}} and Knudsen, {Martin Bruun} and Pelle Hanberg and Kristina {\"O}brink-Hansen and T{\o}stesen, {Sara Kousgaard} and Kjeld S{\o}balle and Maiken Stilling and Mats Bue",

note = "Publisher Copyright: {\textcopyright} 2023 by the authors.",

year = "2023",

month = mar,

doi = "10.3390/antibiotics12030615",

language = "English",

volume = "12",

journal = "Antibiotics",

issn = "2079-6382",

publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",

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Steady-State Piperacillin Concentrations in the Proximity of an Orthopedic Implant: A Microdialysis Porcine Study. / Lilleøre, Johanne Gade ; Jørgensen, Andrea René; Knudsen, Martin Bruun et al.
In: Antibiotics, Vol. 12, No. 3, 615, 03.2023.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

TY - JOUR

T1 - Steady-State Piperacillin Concentrations in the Proximity of an Orthopedic Implant

T2 - A Microdialysis Porcine Study

AU - Lilleøre, Johanne Gade

AU - Jørgensen, Andrea René

AU - Knudsen, Martin Bruun

AU - Hanberg, Pelle

AU - Öbrink-Hansen, Kristina

AU - Tøstesen, Sara Kousgaard

AU - Søballe, Kjeld

AU - Stilling, Maiken

AU - Bue, Mats

PY - 2023/3

Y1 - 2023/3

N2 - 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.

AB - 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.

KW - implants

KW - microdialysis

KW - osteomyelitis

KW - piperacillin

KW - steady state

KW - tazobactam

U2 - 10.3390/antibiotics12030615

DO - 10.3390/antibiotics12030615

M3 - Journal article

C2 - 36978481

AN - SCOPUS:85151700242

SN - 2079-6382

VL - 12

JO - Antibiotics

JF - Antibiotics

IS - 3

M1 - 615

ER -

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

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Keywords

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