Discrepancies Between Bayesian Vancomycin Models Can Affect Clinical Decisions in the Critically Ill.

Purpose: To assess the agreement in 24-hour area under the curve (AUC24) value estimates between commonly used vancomycin population pharmacokinetic models in the critically ill. Materials and Methods: Adults admitted to intensive care who received intravenous vancomycin and had a serum vancomycin concentration available were included. AUC24 values were determined using Tucuxi (revision cd7bd7a8) for dosing intervals with a vancomycin concentration using three models (Goti 2018, Colin 2019, and Thomson 2009) previously evaluated in the critically ill. AUC24 values were categorized as subtherapeutic (<400 mg·h/L), therapeutic (400-600 mg·h/L), or toxic (>600 mg·h/L), assuming a minimum inhibitory concentration of 1 mg/L. AUC24 value categorization was compared across the three models and reported as percent agreement. Results: Overall, 466 AUC24 values were estimated in 188 patients. Overall, 52%, 42%, and 47% of the AUC24 values were therapeutic for the Goti, Colin, and Thomson models, respectively. The agreement of AUC24 values between all three models was 48% (223/466), Goti-Colin 59% (193/466), Goti-Thomson 68% (318/466), and Colin-Thomson 67% (314/466). Conclusion: In critically ill patients, vancomycin AUC24 values obtained from different pharmacokinetic models are often discordant, potentially contributing to differences in dosing decisions. This highlights the importance of selecting the optimal model.

Posaconazole trough concentrations are not influenced by inflammation: A prospective study.

During inflammation, several cytochrome P450 enzymes are downregulated. Recently it was shown that voriconazole metabolism is reduced during inflammation. Posaconazole, another triazole with broad-spectrum antifungal activity, is metabolised only to a limited extent by cytochrome P450 enzymes and to a wider extent by phase 2 enzyme systems. The aim of this study was to investigate posaconazole concentrations during inflammation. Patients aged ≥18 years receiving posaconazole prophylaxis or treatment for fungal infections were enrolled in a prospective observational study. Samples for posaconazole and C-reactive protein (CRP) concentrations were collected routinely for each patient. Longitudinal data analysis was performed to analyse the correlation between posaconazole serum trough concentrations and CRP values, corrected for potential factors that could influence the posaconazole concentration. Between August 2015 and June 2017, 64 patients were recruited to this study. Data for 55 patients (511 posaconazole samples) were included in the final analysis. The overall median posaconazole concentration was 1.8 mg/L [interquartile range (IQR) 1-2.9 mg/L, range 0.1-7.94 mg/L] and the overall median CRP concentration was 23.5 mg/L (IQR 5-75 mg/L, range 0-457 mg/L). Longitudinal data analysis showed that only the posaconazole daily dose (in mg/kg body weight) had a significant influence on posaconazole concentration after correction for other factors (P < 0.0001). Posaconazole concentrations were not influenced by CRP concentrations (P = 0.77). Posaconazole concentrations are not influenced by inflammation, reflected by CRP concentration. Therefore, more frequent therapeutic drug monitoring of posaconazole during inflammation or after an infection subsides is not necessary.