To describe polymyxin B pharmacokinetics in patients receiving veno-venous extracorporeal membrane oxygenation (ECMO) in comparison with critically ill patients without ECMO support and to explore potential covariates that could affect the pharmacokinetics in this group of patients. In 13 critically ill patients on ECMO and in 21 critically ill patients without ECMO support, 6–8 blood samples were collected during 12 h intervals after reaching steady state. Polymyxin B concentration in serum was determined using a previously developed ELISA. Protein binding was assessed by rapid equilibrium dialysis. In 13 critically ill patients on ECMO who received polymyxin B, the median area under the concentration–time curve over 12 h (AUC_0–12h) was 48.38 mg/h/L for the total drug and 14.08 mg/h/L for the free drug. The unbound fraction was 0.35. Total body clearance was 1.16 L/h. In non-ECMO patients, the median AUC_0–12h was 34.7 mg/h/L and the median CL was 1.76 L/h. The volume of distribution was significantly lower in ECMO patients (19.7 versus 30.4 L, respectively). We found a moderate negative correlation between the ECMO blood flow rate and AUC_0–12h, a strong negative correlation between SOFA score and polymyxin B clearance and a moderate correlation between polymyxin B clearance and renal function in ECMO patients. Currently recommended polymyxin B dosage regimens are sufficient for patients receiving ECMO and no dosage increase is required. In our study, polymyxin B exposure was higher in ECMO patients compared with the control group.

Tigecycline (TGC), a third-generation tetracycline, is characterized by a more potent and broad antibacterial activity, and the ability to overcome different mechanisms of tetracycline resistance. TGC has proven to be of value in treatment of multidrug-resistant infections, but therapy can be complicated by multiple dangerous side effects, including direct drug toxicity. Given that, a TGC immunodetection method has been developed for therapeutic drug monitoring to improve the safety and efficacy of therapy. The developed indirect competitive ELISA utilized TGC selective antibodies and group-specific antibodies interacting with selected coating TGC conjugates. Both assay systems showed high sensitivity (IC50) of 0.23 and 1.59 ng/mL, and LOD of 0.02 and 0.05 ng/mL, respectively. Satisfactory TGC recovery from the spiked blood serum of healthy volunteers was obtained in both assays and laid in the range of 81–102%. TGC concentrations measured in sera from COVID-19 patients with secondary bacterial infections were mutually confirmed by ELISA based on the other antibody–antigen interaction and showed good agreement (R² = 0.966). A TGC pharmacokinetic (PK) study conducted in three critically ill patients proved the suitability of the test to analyze the therapeutic concentrations of TGC. Significant inter-individual PK variability revealed in this limited group supports therapeutic monitoring of TGC in individual patients and application of the test for population pharmacokinetic modelling.

Introduction. Corticosteroids are one of the most promising therapeutic agents for critically ill patients with coronavirus disease 2019 (COVID-19). Despite emerging data, assessed populations and regimens vary, and there are patient subgroups whose response to steroids remains unclear. We aimed to evaluate the outcomes of COVID-19 patients admitted to the intensive care unit (ICU) and treated with a short dexamethasone course to determine which patient categories derive the highest benefit. Methods. A retrospective cohort study was conducted using a prospectively collected single-center ICU database (April 1–October 1, 2020). Adult COVID-19 patients were assigned to dexamethasone (12 mg × 3 days) and usual care groups. Patient, management, and outcome data were extracted. The primary outcome was the 28-day ICU mortality. Subgroup analysis was performed to assess the impact of dexamethasone on mortality in patients with invasive mechanical ventilation (IMV). Results. Of 233 patients, 220 (median age: 65 years, 38% female) were included: 83 patients received dexamethasone and 137 received usual care. Overall, 28 (33.7%) and 54 (39.4%) patients in the dexamethasone and usual care groups, respectively, died within 28 days since ICU admission (rate ratio (RR) 0.86; 95% confidence interval (95% CI): 0.59–1.23; ). In the IMV cohort, dexamethasone did not decrease the 28-day mortality compared with usual care (47.5% vs. 62.0%; RR 0.78; 95% CI: 0.57–1.09; ). A subgroup analysis revealed significantly lower 28-day mortality in IMV patients <65 years receiving dexamethasone vs. usual care (22.6% vs. 48.5%; RR 0.47; 95% CI: 0.22–0.98; ), which was not seen in IMV patients ≥65 years (75.0% vs. 71.1%; RR 1.06; 95% CI: 0.79–1.42; ). Patients ≥65 years experienced hyperglycemia, bacterial infection, and septic shock significantly more often than younger patients who received dexamethasone ( , , and , respectively). Conclusions. A 3-day dexamethasone course is not associated with lower 28-day mortality in critically ill COVID-19 patients, either in the entire ICU cohort or in the IMV. Dexamethasone may significantly reduce the 28-day mortality in IMV patients <65 years, but not in the older IMV subgroup. Dexamethasone administration in patients ≥65 years is associated with a significantly higher rate of adverse events than that in younger patients