Effects of renal function on the pharmacokinetics and pharmacodynamics of prophylactic cefazolin in cardiothoracic surgery

Abstract

The purpose of this investigation was to study the effects of renal function on the pharmacokinetics and pharmacodynamics (PK-PD) of free cefazolin administered prophylactically in cardiothoracic surgery. Patients received an initial 2-g dose of cefazolin, followed by 1-g doses 6, 12, 18 and 24 h after the first dose. In patients who underwent cardiopulmonary bypass, 1 g was added to the priming solution. In 35 patients with a normal estimated creatinine clearance (CLcr) ≥50 ml/min, a free cefazolin concentration <4 μg/ml was observed in 11.4, 5.7 and 54.3% of patients before the second dose, at the end and 24 h after operation, respectively. In contrast, only 7.4% of 27 patients with CLcr <49 ml/min had a free cefazolin concentration <4 μg/ml 24 h after the operation. There was a high negative correlation between CLcr and time above the target minimal inhibitory concentration (MIC) when the CLcr was <50 ml/min (r(2) = 0.807), and no correlation when the CLcr was ≥50 ml/min. Renal function has a significant impact on the PK-PD of prophylactic cefazolin in cardiothoracic surgery. The postoperative drug dosing intervals should be <6 h in order to achieve a 100% time above the MIC in patients with CLcr ≥ 50 ml/min.

Antimicrobial Prophylaxis for Patients Undergoing Cardiac Surgery: Intraoperative Cefazolin Concentrations and Sternal Wound Infections

“…The importance of AP pharmacodynamics during cardiac surgery was first suggested by Goldmann et al, who found that patients with longer procedures and lower cephalothin concentrations during valve replacement surgery were more likely to develop wound infection (15). In a more recent study of cefazolin prophylaxis, Kosaka et al noted a higher incidence of SSI in patients with better renal function, a potential surrogate for lower cefazolin concentrations during surgery (16). Our study provides the first direct evidence of a relationship between intraoperative antimicrobial concentrations during cardiac surgery and postoperative wound infection.…”

Pharmacokinetic characteristics and microbiologic appropriateness of cefazolin for perioperative antibiotic prophylaxis in elective cardiac surgery

“…Our analysis identifies factors influencing the perioperative kinetics of cefazolin in cardiac surgery with use of CPB. Only few studies so far have performed pharmacokinetic calculations in this setting, 11,16,18,19 typically mere drug levels are reported without further insight into details. 9,10,12,13,15,17,21 We are not aware of population pharmacokinetic studies of cefazolin in cardiac surgery, attempting to identify influential factors for the building of a predictive model.…”

“…A number of publications report serum levels of cefazolin achieved with various dosing regimens in cardiac surgery patients. [10][11][12][13][14][15][16][17] Besides drug levels, little information is available with regard to factors influencing the pharmacokinetic parameters of cefazolin. An issue of uncertainty is the definition of adequacy of cefazolin levels.…”

Are children undergoing cardiac surgery receiving antibiotics at subtherapeutic levels?

“…At least in adults, we know that CPB alters cefuroxime hemodynamics [23, 24]. The altered protein-binding and/or the decreased metabolism may explain the long cefuroxime half-life reported by Knoderer et al [12] that is nearly twice the half-life reported in all other pediatric studies.…”