Cefuroxime plasma and tissue concentrations in patients undergoing elective cardiac surgery: Continuous vs bolus application. A pilot study

Br J Clin Pharmacol. 2019 Apr;85(4):818-826. doi: 10.1111/bcp.13865. Epub 2019 Feb 13.

Abstract

Aims: Surgical site infections contribute to morbidity and mortality after surgery. The authors hypothesized that higher antibiotic tissue concentrations can be reached for a prolonged time span by continuous administration of prophylactic cefuroxime compared to bolus administration.

Methods: Twelve patients undergoing elective cardiac surgery were investigated. Group A received 1.5 g cefuroxime as bolus infusions before surgery, and 12 and 24 hours thereafter. In group B, a continuous infusion of 3.0 g cefuroxime was started after a bolus of 1.5 g. Cefuroxim levels were determined in blood and tissue (microdialysis). T-test, Wilcoxon signed rank test and χ2 test were used for statistical analysis.

Results: The area under the curve (AUC) of plasma cefuroxime concentrations was greater in group B (399 [333-518]) as compared to group A (257 [177-297] h mg L-1 , [median and interquartile range], P = .026). Furthermore, a significantly longer percentage of time > minimal inhibitory concentrations of 2 mg L-1 (100% vs 50%), 4 mg L-1 (100% vs 42%), 8 mg L-1 (100% vs 17%) and 16 mg L-1 (83% vs 8%) was found for free plasma cefuroxime in group B. In group B, area under the curve in subcutaneous tissue (78 [61-113] h mg L-1 ) and median peak concentration (33 [26-38] mg L-1 ) were markedly higher compared to group A (P = 0.041 and P = .026, respectively).

Conclusions: Higher cefuroxime concentrations were measured in plasma and subcutaneously over a prolonged period of time when cefuroxime was administered continuously. The clinical implication of this finding still has to be elucidated.

Keywords: antibiotic prophylaxis; cardiac surgery; microdialysis; surgical site infection; tissue cefuroxime concentration.

Publication types

  • Comparative Study

MeSH terms

  • Aged
  • Aged, 80 and over
  • Anti-Bacterial Agents / administration & dosage*
  • Anti-Bacterial Agents / analysis
  • Anti-Bacterial Agents / pharmacokinetics
  • Antibiotic Prophylaxis / methods*
  • Area Under Curve
  • Cardiac Surgical Procedures / adverse effects
  • Cefuroxime / administration & dosage*
  • Cefuroxime / analysis
  • Cefuroxime / pharmacokinetics
  • Drug Administration Schedule
  • Elective Surgical Procedures / adverse effects
  • Female
  • Humans
  • Male
  • Middle Aged
  • Pilot Projects
  • Plasma / chemistry
  • Subcutaneous Fat / chemistry
  • Surgical Wound Infection / etiology
  • Surgical Wound Infection / prevention & control*
  • Tissue Distribution

Substances

  • Anti-Bacterial Agents
  • Cefuroxime