title: Integrated pharmacokinetic-pharmacodynamic modelling to evaluate antimicrobial prophylaxis in abdominal surgery.
abstract: To use Monte Carlo simulation with an integrated pharmacokinetic-pharmacodynamic (PK-PD) model to evaluate guideline-recommended antimicrobial prophylaxis (AP) regimens with anaerobic coverage in abdominal surgery.
  
  
  
  AP regimens were tested in simulated subjects undergoing elective abdominal surgery using relevant PK models and pathogen distributions in surgical site infections (SSIs). Predicted cumulative target attainment was the percentage of simulated subjects with free (unbound) antimicrobial plasma concentrations above the MICs for potential SSI pathogens.
  
  
  
  Cefazolin plus metronidazole covered SSI aerobes in 70% and the Bacteroides fragilis group in 99% of subjects, whereas cefoxitin only covered aerobes and anaerobes in 63% and 27% of cases, respectively. The broad-spectrum ceftriaxone plus metronidazole covered aerobes in 82% and anaerobes in 99% of simulations, while ertapenem covered aerobes in 88% and anaerobes in 90% of cases. Clindamycin covered the B. fragilis group in only 11% of cases. For cefazolin, 2 g doses maintained target attainment in simulated subjects from 80 to 120 kg, whereas 1 g doses were associated with lower target attainment against potential Gram-negative pathogens even in those <80 kg. For gentamicin, 3 mg/kg doses were comparable to the suggested 5 mg/kg, but superior to the traditional 1.5 mg/kg.
  
  
  
  This study demonstrates the use of PK-PD to inform decisions regarding AP in abdominal surgery. In this case, the findings support avoiding cefoxitin, avoiding clindamycin for anaerobic coverage, selecting 2 g doses of cefazolin even in patients <80 kg and using 3 mg/kg doses of gentamicin.
authors.affiliation: College of Pharmacy, Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada Department of Pharmacy, St. Boniface Hospital, Winnipeg, Manitoba, Canada zelenits@umanitoba.ca.
authors.forename: S A
authors.initials: SA
authors.lastname: Zelenitsky
authors.affiliation: College of Pharmacy, Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada.
authors.forename: C
authors.initials: C
authors.lastname: Lawson
authors.affiliation: College of Pharmacy, Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada.
authors.forename: D
authors.initials: D
authors.lastname: Calic
authors.affiliation: College of Pharmacy, Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada Department of Pharmacy, St. Boniface Hospital, Winnipeg, Manitoba, Canada.
authors.forename: R E
authors.initials: RE
authors.lastname: Ariano
authors.affiliation: Burns Trauma and Critical Care Research Centre, The University of Queensland, Brisbane, Queensland, Australia School of Pharmacy, The University of Queensland, Brisbane, Queensland, Australia Australia Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia.
authors.forename: J A
authors.initials: JA
authors.lastname: Roberts
authors.affiliation: Burns Trauma and Critical Care Research Centre, The University of Queensland, Brisbane, Queensland, Australia Australia Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia Faculty of Health, Queensland University of Technology, Brisbane, Queensland, Australia The University of Witwatersrand, Johannesburg, South Africa.
authors.forename: J
authors.initials: J
authors.lastname: Lipman
authors.affiliation: Department of Medical Microbiology and Infectious Diseases, College of Medicine, Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada.
authors.forename: G G
authors.initials: GG
authors.lastname: Zhanel
mesh_terms: D000005:Abdomen / Q000382:microbiology / Q000601:surgery*; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D000890:Anti-Infective Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D019072:Antibiotic Prophylaxis; D001421:Bacteria, Anaerobic / Q000187:drug effects; D001441:Bacteroides fragilis / Q000187:drug effects; D002440:Cefoxitin / Q000008:administration & dosage; D002981:Clindamycin / Q000008:administration & dosage; D003198:Computer Simulation; D054796:Drug Dosage Calculations; D000077727:Ertapenem; D005260:Female; D005839:Gentamicins / Q000008:administration & dosage; D006801:Humans; D008297:Male; D008795:Metronidazole / Q000008:administration & dosage; D008826:Microbial Sensitivity Tests; D009010:Monte Carlo Method; D013530:Surgical Wound Infection / Q000382:microbiology* / Q000517:prevention & control*; D047090:beta-Lactams / Q000008:administration & dosage
chemical_list: D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents; D005839:Gentamicins; D047090:beta-Lactams; D008795:Metronidazole; D002981:Clindamycin; D002440:Cefoxitin; D000077727:Ertapenem