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

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.

Model antibiotic use to improve outcomes

“…Whilst routine bolus dosing appeared sufficient for prophylaxis, continuous infusion of cefuroxime was demonstrated to provide a higher percentage of ƒT > bacterial MIC 7 . Similar findings were reported by Skhirtladze‐Dworschak et al, who showed that higher cefuroxime concentrations were achieved in plasma—and importantly, subcutaneously—over a prolonged period of time when cefuroxime was administered to adult patients undergoing elective cardiac surgery via infusion rather than standard bolus dosing 8 . Finally, Rimmler et al used a physiologically based pharmacokinetic model (PK‐Sim ®/MoBi ®) to investigate unbound plasma concentrations of cefuroxime following pre‐operative administration in the context of thoracic surgery.…”

Population pharmacokinetic evaluation of cefuroxime in perioperative antibiotic prophylaxis during and after cardiopulmonary bypass

“…Our pharmacokinetic/pharmacodynamic study of cefuroxime as PAP in cardiac surgery differs from several previous investigations, 27,29–32 some of which were merely descriptively without the development of a pharmacokinetic model 33–35 …”

“…In this study of cefuroxime in cardiac surgery, we used plasma concentrations taken Our PK/PD-study of cefuroxime as PAP in cardiac surgery differs from several previous investigations [27,[29][30][31][32], some of which were merely descriptively without the development of a pharmacokinetic model [33][34][35].…”

“…Target attainment was approximately 50% at a concentration of 16 mg/L, showing a necessity of refinement. An identical dosing scheme of continuous cefuroxime was recently studied by Skhirdladze‐Dworschak et al ., 34 who compared this to a bolus regimen. Continuous infusion was found to be superior in reaching target concentration in plasma and interstitial fluid.…”

What’s New in Infection on Surgical Site and Antibioticoprophylaxis in Surgery?

“…Skhirtladze-Dworschaket al 28 compared antibiotic prophylaxis with cefuroxime in intermittent bolus and continuous infusion assessing their serum and subcutaneous tissue concentrations; observed higher concentrations of cefuroxime and for a longer period of time in the plasma and subcutaneous tissue, when cefuroxime was administered continuously, and concluded that its concentration measurements were higher in patients who received the antibiotic in continuous infusion.…”