Predicting the Area under the Plasma Concentration-Time Curve (AUC) for First Dose Vancomycin Using First-Order Pharmacokinetic Equations.

To treat critically ill patients, early achievement of the target area under the plasma concentration-time curve/minimum inhibitory concentration (AUC/MIC) in the first 24 h is recommended. However, accurately calculating the AUC before steady state is an obstacle to this goal. A first-order pharmacokinetic equation to calculate vancomycin AUC after a first dose of vancomycin has never been studied. We sought to estimate AUC using two first-order pharmacokinetic equations, with different paired concentration time points, and to compare these to the actual first dose vancomycin AUC calculated by the linear-log trapezoid rule as a reference. The equations were validated using two independent intensive first dose vancomycin concentration time data sets, one from 10 adults and another from 14 children with severe infection. The equation with compensation for the alpha distribution phase using a first vancomycin serum concentration from 60 to 90 min and the second concentration from 240 to 300 min after the completed infusion showed good agreement and low bias of calculated AUC, with mean differences <5% and Lin's correlation coefficient >0.96. Moreover, it gave an excellent correlation with Pearson's r > 0.96. Estimating the first dose vancomycin AUC calculated using this first-order pharmacokinetic equation is both reliable and reproducible in clinical practice settings.

Multisystem inflammatory syndrome in children (MIS-C) showing disseminated aspergillosis, cytomegalovirus reactivation and persistent SARS-COV-2: Case report with autopsy review.

Multisystem inflammatory syndrome in children (MIS-C) is an emerging phenomenon associated with SARS-COV-2 infection (COVID-19) occurring in < 1 % of infected children. MIS-C is characterized by a hyperinflammatory state with excessive cytokine release ('storm') leading to hemodynamic compromise and multiorgan failure, with a death rate of ∼2 %. Autopsy examination can play a particularly important role in helping to understand the pathogenesis of MIS-C. Yet, only five autopsy studies have been reported to date. We report a fatal case of MIS-C involving a previously healthy, 5-year-old Thai boy admitted with MIS-C, one month after exposure to SARS-COV-2. While in intensive care, he was found to have a hypertrophic cardiomyopathy, and despite immunosuppressive treatment for MIS-C, developed shock and died. Multiorgan inflammation was not found at autopsy, implying that the MIS-C had responded to treatment. However, there was disseminated aspergillosis and cytomegalovirus reactivation, attributed to the immunosuppression. SARS-COV-2 virus was also found in multiple organs. To the best of our knowledge, this is the first reported autopsy of an MIS-C patient from Asia, and the first report of aspergillosis in MIS-C. This case underscores that the risks of immunosuppression are also a concern in MIS-C. Although MIS-C is generally considered to be a post-infectious hyperimmune reaction, persistence of SARS-COV-2 is a feature in all autopsies of MIS-C patients reported to date, suggesting a possible role in the pathogenesis, at least in fatal cases.