Christian Lanckohr1, Dagmar Horn2, Swantje Voeller3, Georg Hempel3, Manfred Fobker4, Henryk Welp5, Robin Koeck6, Bjoern Ellger7. 1. Department of Anesthesiology, Intensive Care Medicine and Pain Therapy, University of Muenster, Muenster, Germany. Electronic address: lanckohr@anit.uni-muenster.de. 2. Department of Pharmacy, University of Muenster, Muenster, Germany. 3. Department of Pharmaceutical and Medical Chemistry - Clinical Pharmacy, Westfaelische Wilhelm-University Muenster, Muenster, Germany. 4. Department of Laboratory Medicine, University of Muenster, Muenster, Germany. 5. Department of Cardiac Surgery, University of Muenster, Muenster, Germany. 6. Institute of Medical Microbiology, University of Muenster, Muenster, Germany. 7. Department of Anesthesiology, Intensive Care Medicine and Pain Therapy, University of Muenster, Muenster, Germany.
Abstract
OBJECTIVE: Adequate levels of perioperative antibiotic prophylaxis are essential for prevention of surgical site infections. We examined pharmacokinetic details of 2 g cefazolin administered during induction of anesthesia with repeat dosing shortly after initiation of cardiopulmonary bypass (CPB) in cardiac surgery. METHODS: To identify the microbiologic flora targeted with prophylaxis, pre-, and postoperative swabs were taken from sternal skin. Blood samples for measurement of cefazolin were obtained in 24 patients. Drug levels were used for population pharmacokinetic modeling using Nonmem software (Icon Development Solutions, San Antonio, Tex). RESULTS: More than 90% of bacteria on sternal skin were sensitive to cefazolin, indicating minimal inhibitory concentrations <8 mg/L. All serum levels of cefazolin were above 8 mg/L and might thus effectively prevent infection. Pharmacokinetic modeling in a 1-compartment model predicted a population mean clearance (CL) of 5.23 L/h and a volume of distribution (Vd) of 15.8 L. CPB increased Vd from 14.4 L to 22.1 L with a consecutive reduction to 18 L after the end of extracorporeal circulation. The final model implemented interindividual variability on CL and Vd, incorporating the covariates CPB and albumin on Vd and creatinine clearance on CL. Goodness-of-fit calculations showed that this model adequately describes the data derived from our clinical cohort. CONCLUSIONS: Two grams of cefazolin at induction of anesthesia with a repeat dose after initiation of CPB ensures adequate drug levels to target a majority of pathogens of surgical site infections. Pharmacokinetic modeling demonstrated a significant influence of CPB on the volume of distribution and elimination of cefazolin. Other influences on pharmacokinetic parameters were albumin, protein, and creatinine clearance.
OBJECTIVE: Adequate levels of perioperative antibiotic prophylaxis are essential for prevention of surgical site infections. We examined pharmacokinetic details of 2 g cefazolin administered during induction of anesthesia with repeat dosing shortly after initiation of cardiopulmonary bypass (CPB) in cardiac surgery. METHODS: To identify the microbiologic flora targeted with prophylaxis, pre-, and postoperative swabs were taken from sternal skin. Blood samples for measurement of cefazolin were obtained in 24 patients. Drug levels were used for population pharmacokinetic modeling using Nonmem software (Icon Development Solutions, San Antonio, Tex). RESULTS: More than 90% of bacteria on sternal skin were sensitive to cefazolin, indicating minimal inhibitory concentrations <8 mg/L. All serum levels of cefazolin were above 8 mg/L and might thus effectively prevent infection. Pharmacokinetic modeling in a 1-compartment model predicted a population mean clearance (CL) of 5.23 L/h and a volume of distribution (Vd) of 15.8 L. CPB increased Vd from 14.4 L to 22.1 L with a consecutive reduction to 18 L after the end of extracorporeal circulation. The final model implemented interindividual variability on CL and Vd, incorporating the covariates CPB and albumin on Vd and creatinine clearance on CL. Goodness-of-fit calculations showed that this model adequately describes the data derived from our clinical cohort. CONCLUSIONS: Two grams of cefazolin at induction of anesthesia with a repeat dose after initiation of CPB ensures adequate drug levels to target a majority of pathogens of surgical site infections. Pharmacokinetic modeling demonstrated a significant influence of CPB on the volume of distribution and elimination of cefazolin. Other influences on pharmacokinetic parameters were albumin, protein, and creatinine clearance.
Authors: Isabelle S Byers; Nicholas A Turner; Nicole L Levine; Alexander L Lazarides; Daniel R Evans; Ivan Spasojevic; Ping Fan; Sin-Ho Jung; Junheng Gao; Julia D Visgauss; Brian E Brigman; William C Eward Journal: Antimicrob Agents Chemother Date: 2022-09-27 Impact factor: 5.938
Authors: M Edlinger-Stanger; V Al Jalali; M Andreas; W Jäger; M Böhmdorfer; M Zeitlinger; D Hutschala Journal: Antimicrob Agents Chemother Date: 2021-07-19 Impact factor: 5.191