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

Surgical site infection (SSI) is one of the most frequent healthcare associatedinfections in Scotland and has a significant clinical and financial burden to hospitalsand society. Colorectal surgery is associated with the highest SSI rate amongelective operations and from the various measures to prevent SSIs, antimicrobialprophylaxis is one of the most effective. It is important to maintain free antibioticconcentrations in serum and tissue above the minimum inhibitory concentration(MIC) breakpoints of microorganisms commonly associated with SSIs until skinclosure.This thesis demonstrates the value of using population pharmacokinetic (PopPK)modelling to assess an antibiotic prophylaxis regimen in colorectal surgery with theaim of identifying optimal dosing regimens.PopPK models were developed for amoxicillin, metronidazole, and gentamicin usingNONMEM® in order to determine the probability of maintaining free drugconcentrations above the MIC breakpoints of the following microorganisms:methicillin-sensitive Staphylococcus aureus, Escherichia coli, Bacteroides fragilisgroup, enterococci, and Streptococcus anginosus group.Pharmacokinetics for all three antibiotics were best described by a onecompartment model. Elimination and distribution of amoxicillin and metronidazolewere affected by body weight. Elimination of gentamicin was influenced bycreatinine 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 mgmetronidazole, a re-dosing interval of 8 hours would be acceptable for patients withnormal weight (BMI <25 kg/m2), whereas for patients with a BMI ³25 kg/m2 theresults suggest that an additional dose of 500 mg should be given 4 hours after theinitial dose. Finally, gentamicin doses that are based on 5 mg/kg ideal body weightand banded according to height are recommended to be re-dosed at 5 hours.

Name dc:type.qualificationname

mphil

Level dc:type.qualificationlevel

masters-pg

Grantor dc:publisher.institution

University of Strathclyde

Year dc:date.issued

2020

Author dc:creator

• Da Silva Neto, Michael

Advisors dc:contributor.advisor

• Watson, David
• Thomson, Alison

DOI

10.48730/z3bb-vg88

Identifier

T15501

Author Identifier

201482583

OAI identifier oai:identifier

oai:strathclyde:7m01bk68h