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
| Date of Award | 20 Feb 2020 |
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| Original language | English |
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| Awarding Institution | - University Of Strathclyde
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| Supervisor | Alison Thomson (Supervisor) & David Watson (Supervisor) |
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