RESUMEN
Intravenous (IV) cefuroxime and cefazolin are used prophylactically in caesarean sections (CS). Currently, there are concerns regarding sub-optimal dosing in obese pregnant women compared to lean pregnant women prior to CS. The current study used a physiologically based pharmacokinetic (PBPK) approach to predict cefazolin and cefuroxime pharmacokinetics in obese pregnant women at the time of CS as well as the duration that these drug concentrations remain above a target concentration (2, 4 or 8 µg/mL or µg/g) in plasma or adipose tissue. Cefazolin and cefuroxime PBPK models were first built using clinical data in lean and in obese non-pregnant populations. Models were then used to predict cefazolin and cefuroxime pharmacokinetics data in lean and obese pregnant populations. Both cefazolin and cefuroxime models sufficiently described their total and free levels in the plasma and in the adipose interstitial fluid (ISF) in non-pregnant and pregnant populations. The obese pregnant cefazolin model predicted adipose exposure adequately at different reference time points and indicated that an IV dose of 2000 mg can maintain unbound plasma and adipose ISF concentration above 8 µg/mL for 3.5 h post dose. Predictions indicated that an IV 1500 mg cefuroxime dose can achieve unbound plasma and unbound ISF cefuroxime concentration of ≥8 µg/mL up to 2 h post dose in obese pregnant women. Re-dosing should be considered if CS was not completed within 2 h post cefuroxime administration for both lean or obese pregnant if cefuroxime concentrations of ≥8 µg/mL is required. A clinical study to measure cefuroxime adipose concentration in pregnant and obese pregnant women is warranted.
RESUMEN
BACKGROUND: The aim of the C-LACE study is to measure cefuroxime concentration in plasma and adipose tissue of non-obese and obese pregnant women undergoing caesarean section. METHODS: This study plans to compare maternal cefuroxime concentrations (plasma and adipose tissue), at the time of skin incision and time of skin closure during a caesarean section from non-obese (body mass index BMI < 30 kg/m2) and obese (BMI ≥ 30 kg/m2) pregnant women. The incidence of post-surgical site infection will also be measured. At least 15 participants are required for each arm (non-obese vs obese) with a total of 30 participants. The study participants will be followed up between 30 and 40 days post-caesarean section to record details of any post-caesarean surgical infection to explore correlations between BMI, measured cefuroxime concentrations and post-caesarean infection rates. DISCUSSION: This pilot study will allow the development of a model testing the inter-patient variability in plasma and adipose tissue concentrations of cefuroxime. The results will facilitate the development of a larger study to determine whether differences in cefuroxime plasma and tissue concentration in obese and non-obese women can support the development of a physiologically based pharmacokinetic model. This model can then be used to propose dosing adjustments that can be used in a further trial to optimise cefuroxime dosing for women undergoing caesarean section. TRIAL REGISTRATION: ISRCTN Registry , ISRCTN17527512 . Registered on 26 October 2020.
RESUMEN
Intravenous (IV) Cefuroxime (CFX) is widely used in Caesarean Section (CS) as a prophylactic antibiotic. The objective of this systematic review to compare CFX concentration in maternal blood and adipose tissue with the incidence of surgical site infection (SSI) following IV CFX in non-obese and obese women undergoing CS. A search in Medline, EMBASE, Cochrane, Web of Science, CINHAL Plus, Scopus and Google Scholar was conducted without language or date restrictions. Published articles or abstracts reporting CFX concentration or rates of SSI following CFX IV administration in adult women requiring CS were included. Studies were screened by title and abstract. Quality of studies was assessed via the ClinPK Statement checklist (Pharmacokinetics studies), or Joanna Briggs Institute Critical Appraisal Tools (SSI studies). The Cochrane Effective Practice and Organisation of Care checklist evaluated the risk of bias (SSI studies). There were no studies evaluating CFX concentrations in obese women undergoing CS. For non-obese women, CFX plasma concentrations ranged from 9.85 to 95.25â¯mg/L within 30-60â¯min of administration (1500â¯mg dose; 4 articles, nâ¯=â¯108 women). Plasma CFX concentrations were above the minimum inhibitory concentration (8â¯mg/L) for up to 3â¯h post-dose. No studies reported on CFX concentration in adipose tissue. Reported rates of SSI were 4.7% and 6.8% after administration of a single 1500â¯mg dose of CFX administrated after cord clamping (nâ¯=â¯144 women). There is limited data on pharmacokinetics of CFX for CS. There were no studies that reported CFX concentrations or SSI in obese women.
