Evaluation of amoxicillin, metronidazole and gentamicin dosage regimens for use in antibiotic prophylaxis in colorectal surgery

Rights statement
Awarding institution
  • University of Strathclyde
Date of award
  • 2020
Thesis identifier
  • T15501
Person Identifier (Local)
  • 201482583
Qualification Level
Qualification Name
Department, School or Faculty
  • Surgical site infection (SSI) is one of the most frequent healthcare associated infections in Scotland and has a significant clinical and financial burden to hospitals and society. Colorectal surgery is associated with the highest SSI rate among elective operations and from the various measures to prevent SSIs, antimicrobial prophylaxis is one of the most effective. It is important to maintain free antibiotic concentrations in serum and tissue above the minimum inhibitory concentration (MIC) breakpoints of microorganisms commonly associated with SSIs until skin closure. This thesis demonstrates the value of using population pharmacokinetic (PopPK) modelling to assess an antibiotic prophylaxis regimen in colorectal surgery with the aim of identifying optimal dosing regimens. PopPK models were developed for amoxicillin, metronidazole, and gentamicin using NONMEM® in order to determine the probability of maintaining free drug concentrations above the MIC breakpoints of the following microorganisms: methicillin-sensitive Staphylococcus aureus, Escherichia coli, Bacteroides fragilis group, enterococci, and Streptococcus anginosus group. Pharmacokinetics for all three antibiotics were best described by a onecompartment model. Elimination and distribution of amoxicillin and metronidazole were affected by body weight. Elimination of gentamicin was influenced by creatinine clearance and height. Distribution was affected by height. The findings of this study support 1000 mg of amoxicillin being re-dosed intraoperatively every 4 hours, however, in patients at high risk of infective endocarditis, additional doses are required every 2 hours. Following a dose of 500 mg metronidazole, a re-dosing interval of 8 hours would be acceptable for patients with normal weight (BMI <25 kg/m2 ), whereas for patients with a BMI ³25 kg/m2 the results suggest that an additional dose of 500 mg should be given 4 hours after the initial dose. Finally, gentamicin doses that are based on 5 mg/kg ideal body weight and banded according to height are recommended to be re-dosed at 5 hours.
Advisor / supervisor
  • Watson, David
  • Thomson, Alison
Resource Type
  • Previously held under moratorium from 2 April 2020 until 6 May 2022
Former identifier
  • 9912791093102996