Evaluation of prophylactic cefuroxime dose in obese pregnant women undergoing caesarean section

Alrammaal, Hanadi Hassan A. ORCID: 0000-0002-8294-1861 (2022). Evaluation of prophylactic cefuroxime dose in obese pregnant women undergoing caesarean section. University of Birmingham. Ph.D.

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Abstract

Cefuroxime and cefazolin are used intravenously pre–caesarean section (CS) to prophylactically prevent or decrease post–surgical infections. Cefazolin pharmacokinetics (PK) has been evaluated in obese–pregnant women; while cefuroxime posology, appropriateness of doses, has not been assessed in this population. The aim of the current project was to investigate the appropriateness of cefuroxime dose given to obese–pregnant women at time of CS. Available cefazolin PK data in an obese-pregnant population was utilised to guide investigation of cefuroxime PK in an obese–pregnant population. This project comprised of four work packages: (1) Systematic review to identify information regarding cefazolin PK and rate of infection when cefazolin was given pre–CS in obese–pregnant women, and a systematic review to identify information on cefuroxime PK and rate of infection when cefuroxime is administrated to lean– or obese–pregnant at CS; (2) A research study was developed to clinically measure cefuroxime concentrations in plasma and adipose tissue in lean– and obese–pregnant (this study was approved by ethical authorities, and currently is suspended due to COVID-19 pandemic); (3) A partial validation of an analytical method to measure cefuroxime concentrations in plasma and adipose tissue samples using High Performance Liquid Chromatography; and (4) A physiologically based pharmacokinetic (PBPK) obese–pregnant model was utilised to predict cefazolin and cefuroxime disposition in such population.
At around 1–1.5 hours post cefuroxime 1500 mg dose, reported clinical cefuroxime plasma concentrations ranged within 8.7–57 mg/L in lean–pregnant women (4 articles, n=108 women); while a dose of 750 mg attained a mean plasma concentration of 14.9 mg/L at around 1 hour. There is no publicly available information of cefuroxime adipose tissue concentration in a lean–pregnant population. To the best of our knowledge, there is no clinical information regarding cefuroxime plasma or adipose concentrations in obese–pregnant women. Information from both cefuroxime PK systematic review in lean–pregnant and PBPK modelling proposed the following: (1) A dose of 1500 mg cefuroxime appears therapeutically more appropriate than 750 mg dose for obese–pregnant women undergoing CS, if a minimum inhibitory concentration of 8 mg/L is required for up to 2 hours post dose; and (2) giving cefuroxime 15–30 minutes before skin incision is superior to current guidelines (15–60 minutes before skin incision). A clinical study is required to measure cefuroxime concentrations in plasma and site of incision to assess the appropriateness of cefuroxime dose in obese-pregnant population and to use these data to optimise the obese–pregnant PBPK model.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

Supervisor(s):

Supervisor(s)	Email	ORCID
Hodgetts Morton, Victoria	UNSPECIFIED	orcid.org/0000-0001-9817-4313
Marriott, John	UNSPECIFIED	orcid.org/0000-0001-5267-2018
Morris, Katie	UNSPECIFIED	orcid.org/0000-0003-1247-429X
Batchelor, Hannah	UNSPECIFIED	orcid.org/0000-0002-8729-9951
Chong, Hsu	UNSPECIFIED	UNSPECIFIED