While several meropenem population pharmacokinetic (popPK) models have been developed, few have undergone external validation, a crucial step to confirm their robustness and applicability in real-world settings. This study aimed to conduct an external evaluation of published meropenem popPK models to assess their predictive performance and determine their suitability for implementing Model-Informed Precision Dosing strategies in the Intensive Care Unit (ICU) setting. The external validation dataset consisted of data retrospectively collected from a tertiary university hospital. Eight published popPK models were selected from the literature and bias and inaccuracy was calculated. Predictive performance was assessed in two subpopulations: CRRT and non-CRRT patients, with further stratification by BMI. Eight popPK models were evaluated with an independent dataset of 30 ICU patients and 48 samples. The Ulldemolins et al. model exhibited the lowest bias for population-level predictions in the overall CRRT cohort. In the overall non-CRRT cohort, the models by Chung et al. and Lan et al. demonstrated excellent population and individual prediction performance. Within the obese subpopulation, the Shekar et al. model showed the lowest bias and inaccuracy in the CRRT cohort, while the models by Li et al., Lan et al., and Chung et al. performed best in the non-CRRT cohort. Published meropenem popPK models exhibit considerable variability in predictive performance when validated in an external dataset of ICU patients failing to generalize across broader patient populations. These findings underscore the need for external validation with independent datasets to ensure reliable performance across diverse populations.

Toxic epidermal necrolysis (TEN) is a rare life-threatening mucocutaneous reaction characterized by epidermal detachment. Treatment success relies on early diagnosis, rapid withdrawal of the causative drug and supportive care. However, clinical evidence for therapeutic management and specific treatment is insufficient and controversial. We describe the successful management of a TEN case secondary to sulfadoxine managed in our intensive care unit. The patient presented a generalized exanthema with mucocutaneous detachment affecting 45% of the body surface area, positive Nikolsky sign, perianal enanthema and conjunctival hyperemia. Treatment with intravenous immunoglobulins and corticosteroids was prescribed, as well as calcium folinate to prevent myelotoxicity of the causative drug. In this case, hemodialysis was dismissed due to the low efficiency of this technique in removing the triggering drug. Our case report confirms the efficacy of corticosteroids, IGIV, topical treatment on mucocutaneous lesions and supportive care for the management of TEN secondary to sulfadoxine.

Background: Isavuconazole, a broad-spectrum triazole antifungal, exhibits high lipophilicity and extensive plasma protein binding, properties that may predispose it to sequestration within extracorporeal membrane oxygenation (ECMO) circuits. This study aimed to characterize the pharmacokinetics (PK) of isavuconazole and to evaluate drug sequestration within the ECMO circuit in critically ill patients receiving ECMO support. Methods: We conducted a prospective, exploratory, single-center observational study including critically ill patients receiving ECMO (veno-venous (VV) or veno-arterial (VA)) and treated with intravenous isavuconazole. Serial blood samples were collected simultaneously from the patient’s arterial line and from pre- and post-membrane oxygenator sampling sites. Non-compartmental analysis was performed on arterial line samples to estimate PK measures, and concentration differences across sampling sites were analyzed to estimate circuit-related drug loss. PK/pharmacodynamic (PD) target attainment was assessed using established efficacy thresholds (AUC_0–24/MIC ≥ 25 and Cmin > 2 mg/L). Results: A total of 41 plasma samples from 3 critically ill patients (2 VV-ECMO, 1 VA-ECMO) were included in the analysis. Limited, component-specific isavuconazole loss was observed in tubing and connectors (6.62% ± 20.8%, p = 0.294) and across the entire ECMO circuit (7.74% ± 20.2%, p = 0.211). Likewise, no relevant concentration difference was detected across the membrane oxygenator (0.849% ± 6.15%, p = 0.642). Interindividual variability was observed across PK parameters, particularly in measures of elimination and distribution. All patients achieved predefined PK/PD efficacy targets, with mean Cmin and AUC_0–24/MIC of 3.07 ± 0.261 mg/L and 85.3 ± 4.03, respectively, and none exceeded the established toxicity threshold. Conclusions: Preliminary results showed variable concentration differences across ECMO sampling sites, with no consistent pattern of isavuconazole loss across the ECMO circuit under the conditions evaluated. All patients achieved predefined PK/PD efficacy targets using currently recommended dosing regimens; however, interindividual PK variability was observed, supporting the potential value of therapeutic drug monitoring (TDM) to guide individualized dosing decisions in this population. Larger population PK studies are warranted to further characterize determinants of isavuconazole exposure during ECMO support and refine evidence-based dosing strategies.

Spanish pharmacovigilance alerts have highlighted vitamin D overdosing. We retrospectively analysed adult serum 25(OH)D results from a Barcelona tertiary hospital (2020-2025), measured using a VDSCP-certified immunoassay. For results >100 ng/mL (250 nmol/L), concomitant calcium, phosphorus, albumin, alkaline phosphatase and parathyroid hormone were retrieved. Hypercalcemia was defined as albumin-corrected calcium >10.5 mg/dL. Among 185 604 results, annual testing increased by 54.1% and median 25(OH)D rose from 25.3 to 28.6 ng/mL. Very high results more than doubled (31 [0.14%] to 108 [0.31%]; n = 393). Calcium was available in 324/393 results, and hypercalcemia occurred in 14/324 (4.3%). Calcifediol was documented in 183/201 (91.0%) hypervitaminosis D patients with available supplementation data and in 12/14 (85.7%) hypercalcemic cases, often in short-interval dosing regimens. Rapid test growth paralleled a rightward shift and expanding high-concentration tail, supporting evidence-based requesting, clearer intermittent-dosing and supplementation instructions, and selective serum calcium surveillance when 25(OH)D is greatly elevated.