TY - JOUR
T1 - Intermittent Short-Term Infusion vs. Continuous Infusion of Piperacillin
T2 - Steady State Concentrations in Porcine Cervical Spine Tissue Evaluated by Microdialysis
AU - Petersen, Elisabeth Krogsgaard
AU - Hanberg, Pelle
AU - Knudsen, Martin
AU - Tøstesen, Sara Kousgaard
AU - Jørgensen, Andrea René
AU - Öbrink-Hansen, Kristina
AU - Søballe, Kjeld
AU - Stilling, Maiken
AU - Bue, Mats
PY - 2022/7
Y1 - 2022/7
N2 - Background: Piperacillin is a central drug in the treatment of Pseudomonas aeruginosa spondylodiscitis. Intermittent short-term infusion (STI) remains standard treatment in most centres, although the application of continuous infusion (CI) has shown promising results in other clinical settings. We aimed to evaluate time above the minimal inhibitory concentration (f T > MIC) of the free fraction of piperacillin in steady state conditions in porcine cervical spine tissue following CI and STI using microdialysis with MIC targets of 4, 8, and 16 µg/mL. Methods: 16 female pigs were randomized to receive piperacillin/tazobactam as STI (4/0.5 g every 6 h) or CI (4/0.5 g as a bolus followed by 12/1.5 g) for 18 h. Microdialysis catheters were placed for sampling of piperacillin concentrations from the intervertebral disc, vertebral cancellous bone, paravertebral muscle, and adjacent subcutaneous tissue during the third dosing interval (12–18 h). Blood samples were collected as reference. Results: CI resulted in f T > MIC > 82% across all compartments and targets, except for intervertebral disc (37%) and vertebral cancellous bone (28%) at MIC = 16 µg/mL. In Group STI, >72% f T >MIC was reached for MIC = 4 µg/mL in all investigated compartments, while for MIC = 16 µg/mL only subcutaneous tissue exhibited f T > MIC > 50%. Conclusion: CI of piperacillin resulted in higher f T > MIC compared to STI infusion across the investigated tissues and targets. CI should therefore be considered in spondylodiscitis cases requiring piperacillin treatment.
AB - Background: Piperacillin is a central drug in the treatment of Pseudomonas aeruginosa spondylodiscitis. Intermittent short-term infusion (STI) remains standard treatment in most centres, although the application of continuous infusion (CI) has shown promising results in other clinical settings. We aimed to evaluate time above the minimal inhibitory concentration (f T > MIC) of the free fraction of piperacillin in steady state conditions in porcine cervical spine tissue following CI and STI using microdialysis with MIC targets of 4, 8, and 16 µg/mL. Methods: 16 female pigs were randomized to receive piperacillin/tazobactam as STI (4/0.5 g every 6 h) or CI (4/0.5 g as a bolus followed by 12/1.5 g) for 18 h. Microdialysis catheters were placed for sampling of piperacillin concentrations from the intervertebral disc, vertebral cancellous bone, paravertebral muscle, and adjacent subcutaneous tissue during the third dosing interval (12–18 h). Blood samples were collected as reference. Results: CI resulted in f T > MIC > 82% across all compartments and targets, except for intervertebral disc (37%) and vertebral cancellous bone (28%) at MIC = 16 µg/mL. In Group STI, >72% f T >MIC was reached for MIC = 4 µg/mL in all investigated compartments, while for MIC = 16 µg/mL only subcutaneous tissue exhibited f T > MIC > 50%. Conclusion: CI of piperacillin resulted in higher f T > MIC compared to STI infusion across the investigated tissues and targets. CI should therefore be considered in spondylodiscitis cases requiring piperacillin treatment.
KW - microdialysis
KW - pharmacokinetics
KW - piperacillin
KW - Pseudomonas aeruginosa
KW - spondylodiscitis
UR - http://www.scopus.com/inward/record.url?scp=85133794502&partnerID=8YFLogxK
U2 - 10.3390/antibiotics11070910
DO - 10.3390/antibiotics11070910
M3 - Journal article
C2 - 35884164
AN - SCOPUS:85133794502
SN - 2079-6382
VL - 11
JO - Antibiotics
JF - Antibiotics
IS - 7
M1 - 910
ER -