Microdialysis as a tool to determine the local tissue concentration of dicloxacillin in man

Kristian Kraft Hansen, F Nielsen, T B Stage, U Jørgensen, O Skov, L E Rasmussen

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Abstract

Aims: The most common pathogen to cause postoperative infections in Denmark is Staphylococcus aureus. Despite using prophylactic antibiotics, infections are still seen. Whether the tissue concentration is above the minimal inhibitory concentration (MIC) for the pathogen is unknown. Thus, the concentration of dicloxacillin in muscle and adipose tissue was measured after intravenous administration, in healthy men. Methods: MIC for dicloxacillin against S. aureus was determined using the broth macrodilution method. A microdialysis (MD) catheter was placed in the subcutaneous tissue of the abdomen and in the lateral vastus muscle of the thigh of six healthy male volunteers. They were given 2 g dicloxacillin intravenously. Samples from blood and MD fluid were collected. The unbound dicloxacillin was isolated from plasma. Samples were analysed with high performance liquid chromatography (HPLC). Results: The maximum concentration was reached in muscle tissue after 0.5 h and in adipose tissue after 0.8 h. AUC 0–6h for the dicloxacillin concentration in adipose tissue was significantly lower when compared to the unbound dicloxacillin concentration in plasma. The dicloxacillin concentration was above the MIC for sensitive S. aureus for a minimum of 2.3 h and a median of 4.1 h in muscle tissue and a minimum of 1.8 h and a median of 3.2 h in adipose tissue. Conclusions: The unbound dicloxacillin concentration in adipose and muscle tissue remained above the MIC for sensitive S. aureus, for a period sufficient for many orthopaedic procedures. Whether this is true in patients with compromised circulation remains to be investigated.

Original languageEnglish
JournalBritish Journal of Clinical Pharmacology
Volume84
Issue number3
Pages (from-to)533–541
ISSN0306-5251
DOIs
Publication statusPublished - Mar 2018

Fingerprint

Dicloxacillin
Microdialysis
Adipose Tissue
Muscles
Subcutaneous Tissue
Denmark
Area Under Curve
Catheters
High Pressure Liquid Chromatography

Keywords

  • Journal Article
  • prophylactic antibiotics
  • dicloxacillin
  • microdialysis
  • tissue pharmacokinetics
  • Dicloxacillin/administration & dosage
  • Anti-Bacterial Agents/administration & dosage
  • Area Under Curve
  • Humans
  • Male
  • Muscle, Skeletal/metabolism
  • Chromatography, High Pressure Liquid
  • Microbial Sensitivity Tests
  • Tissue Distribution
  • Microdialysis/methods
  • Administration, Intravenous
  • Adipose Tissue/metabolism
  • Staphylococcus aureus/drug effects
  • Adult

Cite this

Kraft Hansen, Kristian ; Nielsen, F ; Stage, T B ; Jørgensen, U ; Skov, O ; Rasmussen, L E. / Microdialysis as a tool to determine the local tissue concentration of dicloxacillin in man. In: British Journal of Clinical Pharmacology. 2018 ; Vol. 84, No. 3. pp. 533–541.
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title = "Microdialysis as a tool to determine the local tissue concentration of dicloxacillin in man",
abstract = "Aims: The most common pathogen to cause postoperative infections in Denmark is Staphylococcus aureus. Despite using prophylactic antibiotics, infections are still seen. Whether the tissue concentration is above the minimal inhibitory concentration (MIC) for the pathogen is unknown. Thus, the concentration of dicloxacillin in muscle and adipose tissue was measured after intravenous administration, in healthy men. Methods: MIC for dicloxacillin against S. aureus was determined using the broth macrodilution method. A microdialysis (MD) catheter was placed in the subcutaneous tissue of the abdomen and in the lateral vastus muscle of the thigh of six healthy male volunteers. They were given 2 g dicloxacillin intravenously. Samples from blood and MD fluid were collected. The unbound dicloxacillin was isolated from plasma. Samples were analysed with high performance liquid chromatography (HPLC). Results: The maximum concentration was reached in muscle tissue after 0.5 h and in adipose tissue after 0.8 h. AUC 0–6h for the dicloxacillin concentration in adipose tissue was significantly lower when compared to the unbound dicloxacillin concentration in plasma. The dicloxacillin concentration was above the MIC for sensitive S. aureus for a minimum of 2.3 h and a median of 4.1 h in muscle tissue and a minimum of 1.8 h and a median of 3.2 h in adipose tissue. Conclusions: The unbound dicloxacillin concentration in adipose and muscle tissue remained above the MIC for sensitive S. aureus, for a period sufficient for many orthopaedic procedures. Whether this is true in patients with compromised circulation remains to be investigated.",
keywords = "Journal Article, prophylactic antibiotics, dicloxacillin, microdialysis, tissue pharmacokinetics, Dicloxacillin/administration & dosage, Anti-Bacterial Agents/administration & dosage, Area Under Curve, Humans, Male, Muscle, Skeletal/metabolism, Chromatography, High Pressure Liquid, Microbial Sensitivity Tests, Tissue Distribution, Microdialysis/methods, Administration, Intravenous, Adipose Tissue/metabolism, Staphylococcus aureus/drug effects, Adult",
author = "{Kraft Hansen}, Kristian and F Nielsen and Stage, {T B} and U J{\o}rgensen and O Skov and Rasmussen, {L E}",
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Microdialysis as a tool to determine the local tissue concentration of dicloxacillin in man. / Kraft Hansen, Kristian; Nielsen, F; Stage, T B; Jørgensen, U; Skov, O; Rasmussen, L E.

In: British Journal of Clinical Pharmacology, Vol. 84, No. 3, 03.2018, p. 533–541.

Research output: Contribution to journalJournal articleResearchpeer-review

TY - JOUR

T1 - Microdialysis as a tool to determine the local tissue concentration of dicloxacillin in man

AU - Kraft Hansen, Kristian

AU - Nielsen, F

AU - Stage, T B

AU - Jørgensen, U

AU - Skov, O

AU - Rasmussen, L E

N1 - This article is protected by copyright. All rights reserved.

PY - 2018/3

Y1 - 2018/3

N2 - Aims: The most common pathogen to cause postoperative infections in Denmark is Staphylococcus aureus. Despite using prophylactic antibiotics, infections are still seen. Whether the tissue concentration is above the minimal inhibitory concentration (MIC) for the pathogen is unknown. Thus, the concentration of dicloxacillin in muscle and adipose tissue was measured after intravenous administration, in healthy men. Methods: MIC for dicloxacillin against S. aureus was determined using the broth macrodilution method. A microdialysis (MD) catheter was placed in the subcutaneous tissue of the abdomen and in the lateral vastus muscle of the thigh of six healthy male volunteers. They were given 2 g dicloxacillin intravenously. Samples from blood and MD fluid were collected. The unbound dicloxacillin was isolated from plasma. Samples were analysed with high performance liquid chromatography (HPLC). Results: The maximum concentration was reached in muscle tissue after 0.5 h and in adipose tissue after 0.8 h. AUC 0–6h for the dicloxacillin concentration in adipose tissue was significantly lower when compared to the unbound dicloxacillin concentration in plasma. The dicloxacillin concentration was above the MIC for sensitive S. aureus for a minimum of 2.3 h and a median of 4.1 h in muscle tissue and a minimum of 1.8 h and a median of 3.2 h in adipose tissue. Conclusions: The unbound dicloxacillin concentration in adipose and muscle tissue remained above the MIC for sensitive S. aureus, for a period sufficient for many orthopaedic procedures. Whether this is true in patients with compromised circulation remains to be investigated.

AB - Aims: The most common pathogen to cause postoperative infections in Denmark is Staphylococcus aureus. Despite using prophylactic antibiotics, infections are still seen. Whether the tissue concentration is above the minimal inhibitory concentration (MIC) for the pathogen is unknown. Thus, the concentration of dicloxacillin in muscle and adipose tissue was measured after intravenous administration, in healthy men. Methods: MIC for dicloxacillin against S. aureus was determined using the broth macrodilution method. A microdialysis (MD) catheter was placed in the subcutaneous tissue of the abdomen and in the lateral vastus muscle of the thigh of six healthy male volunteers. They were given 2 g dicloxacillin intravenously. Samples from blood and MD fluid were collected. The unbound dicloxacillin was isolated from plasma. Samples were analysed with high performance liquid chromatography (HPLC). Results: The maximum concentration was reached in muscle tissue after 0.5 h and in adipose tissue after 0.8 h. AUC 0–6h for the dicloxacillin concentration in adipose tissue was significantly lower when compared to the unbound dicloxacillin concentration in plasma. The dicloxacillin concentration was above the MIC for sensitive S. aureus for a minimum of 2.3 h and a median of 4.1 h in muscle tissue and a minimum of 1.8 h and a median of 3.2 h in adipose tissue. Conclusions: The unbound dicloxacillin concentration in adipose and muscle tissue remained above the MIC for sensitive S. aureus, for a period sufficient for many orthopaedic procedures. Whether this is true in patients with compromised circulation remains to be investigated.

KW - Journal Article

KW - prophylactic antibiotics

KW - dicloxacillin

KW - microdialysis

KW - tissue pharmacokinetics

KW - Dicloxacillin/administration & dosage

KW - Anti-Bacterial Agents/administration & dosage

KW - Area Under Curve

KW - Humans

KW - Male

KW - Muscle, Skeletal/metabolism

KW - Chromatography, High Pressure Liquid

KW - Microbial Sensitivity Tests

KW - Tissue Distribution

KW - Microdialysis/methods

KW - Administration, Intravenous

KW - Adipose Tissue/metabolism

KW - Staphylococcus aureus/drug effects

KW - Adult

U2 - 10.1111/bcp.13468

DO - 10.1111/bcp.13468

M3 - Journal article

C2 - 29105799

VL - 84

SP - 533

EP - 541

JO - British Journal of Clinical Pharmacology

JF - British Journal of Clinical Pharmacology

SN - 0306-5251

IS - 3

ER -