Bone penetration of intravenous flucloxacillin and gentamicin as antibiotic prophylaxis during total hip and knee arthroplasty

Bone Joint J. 2017 Mar;99-B(3):358-364. doi: 10.1302/0301-620X.99B3.BJJ-2016-0328.R1.

Abstract

Aims: To investigate the bone penetration of intravenous antibiotic prophylaxis with flucloxacillin and gentamicin during hip and knee arthroplasty, and their efficacy against Staphylococcus (S.) aureus and S. epidermidis.

Patients and methods: Bone samples from the femoral head, neck and acetabulum were collected from 18 patients undergoing total hip arthroplasty (THA) and from the femur and tibia in 21 patients during total knee arthroplasty (TKA). The concentration of both antibiotics in the samples was analysed using high performance liquid chromatography. Penetration was expressed as a percentage of venous blood concentration. The efficacy against common infecting organisms was measured against both the minimum inhibitory concentration 50, and the more stringent epidemiological cutoff value for resistance (ECOFF).

Results: The bone penetration of gentamicin was higher than flucloxacillin. Relative to ECOFF, flucloxacillin concentrations were effective against S. aureus and S. epidermidis in all THAs and 20 (95%) TKAs. Gentamicin concentrations were effective against S. epidermidis in all bone samples. Gentamicin was effective against S. aureus in 11 (61.1%) femoral neck samples in THA. Effective concentrations of gentamicin against S. aureus were only achieved in four (19%) femoral and six (29%) tibial samples in TKA.

Conclusion: Flucloxacillin and gentamicin were found to penetrate bone during THA and TKA. Gentamicin was effective against S. epidermidis in both THA and TKA, while levels were subtherapeutic against S. aureus in most TKAs. Bone penetration of both antibiotics was less in TKA than THA, and may relate to the use of a tourniquet. Using this antibiotic combination, effective cover against the two common infective organisms was achieved in all THAs and all but one TKA. Cite this article: Bone Joint J 2017;99-B:358-64.

Keywords: Antibiotic; Arthroplasty; Flucloxacillin; Gentamicin; Prophylaxis.

MeSH terms

  • Acetabulum / metabolism
  • Adult
  • Aged
  • Aged, 80 and over
  • Anti-Bacterial Agents / administration & dosage
  • Anti-Bacterial Agents / pharmacokinetics*
  • Antibiotic Prophylaxis / methods
  • Arthroplasty, Replacement, Hip
  • Arthroplasty, Replacement, Knee
  • Chromatography, High Pressure Liquid / methods
  • Female
  • Femur / metabolism
  • Floxacillin / administration & dosage
  • Floxacillin / pharmacokinetics*
  • Gentamicins / administration & dosage
  • Gentamicins / pharmacokinetics*
  • Hip Prosthesis / adverse effects*
  • Humans
  • Knee Prosthesis / adverse effects*
  • Male
  • Microbial Sensitivity Tests
  • Middle Aged
  • Prosthesis-Related Infections / prevention & control*
  • Staphylococcal Infections / prevention & control
  • Staphylococcus aureus
  • Staphylococcus epidermidis / drug effects
  • Tibia / metabolism

Substances

  • Anti-Bacterial Agents
  • Gentamicins
  • Floxacillin