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.

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

Vancomycin-induced nephrotoxicity is associated with an increased risk of neonatal mortality and prolonged neonatal intensive care unit (NICU) stay. This retrospective cohort study aimed to assess the incidence of vancomycin-associated nephrotoxicity and its risk factors in neonates. The study included neonates admitted to the NICU of the Maternity and Children Hospital (Makkah, Saudi Arabia) from January 2018 to December 2020 who received intravenous vancomycin for more than 48 h. The primary outcome was the incidence of newly developed acute kidney injury (AKI) after the initiation of vancomycin therapy, defined according to the neonatal modified Kidney Disease: Improving Global Outcomes criteria. Analyses included AKI incidence, comparison of clinical parameters between neonates with and without AKI, and multivariable logistic regression to identify predictors of AKI and mortality. Among 362 neonates treated with vancomycin, 11.3% developed AKI. Neonates with AKI had a lower postmenstrual age (31.3 vs. 34.1 weeks, p = 0.01) and higher rates of extreme prematurity (31.7% vs. 14.3%, p = 0.02) and extremely low birth weight (43.9% vs. 18.7%, p = 0.00). Vancomycin trough levels > 15 mg/L were more frequent in the AKI group (26.8%, 11/41) than in others (11.8%, 35/321) (p = 0.00). Only one-third of vancomycin trough measurements were obtained according to guideline-recommended timing. In multivariable analysis, each additional week of postmenstrual age was independently associated with a 10% reduction in the odds of AKI (OR 0.90; p = 0.00). Higher weight was associated with lower mortality (OR = 0.26; p < 0.001), while AKI incidence was associated with increased mortality (OR = 5.88; p < 0.001). Caffeine citrate use was associated with lower odds of mortality, but was not associated with AKI (OR = 0.21; p < 0.001). Lower postmenstrual age independently predicted vancomycin-associated AKI. Lower neonatal weight and AKI were associated with increased mortality, reinforcing the importance of individualized monitoring during vancomycin therapy.

Background: Valproic acid (VPA), an antiepileptic medication, is widely used in pediatric settings. Around 90%–95% of VPA is bound to plasma proteins, predominately albumin. Physiological alterations leading to hypoalbuminemia may increase free VPA concentrations. In such a case, a total VPA may reflect therapeutical total concentration, while the free VPA concentration could be supratherapeutic. Monitoring of total VPA concentrations solely in hypoalbuminemia patients may mislead clinical decisions. The aim of this study is to assess the awareness, knowledge, and attitude levels of pediatric’ physicians and pharmacists regarding monitoring of unbound VPA concentrations in pediatric patients with hypoalbuminemia. Method: A cross‐sectional study was conducted from September to October 2023 in multicenter in Makkah, Saudi Arabia. Sociodemographic information of registered pediatric clinicians and pharmacists were collected. Participants’ knowledge and practice regarding monitoring of VPA were assessed via a reviewed questionnaire. Result: A total of 226 participants completed the survey. Around 62% of respondents ( n = 141) stated knowing how to monitor VPA levels, but only 19.9% ( n = 45) were aware of the association between VPA and albumin plasma concentrations. About half of participants reported availability of total VPA assay in their institutions ( n = 121, 53%), while minor percentage reported the availability of measuring free VPA concentrations in their institutions ( n = 24, 10.6%). Over half of participants do not check albumin levels while monitoring VPA ( n = 132, 58.4%). A statistically significant associations between VPA positive knowledge score were noted with age ( p = 0.019), gender ( p = 0.009), healthcare specialty ( p < 0.001), and years of experience ( p = 0.001). None of these factors were significantly associated with positive practice toward VPA monitoring. Conclusion: The suboptimal practice of monitoring free VPA concentrations in cases of hypoalbuminemia in pediatric settings, mainly due to lack of awareness. Healthcare providers should be educated regarding the importance of monitoring free VPA concentration in the case of hypoalbuminemia.