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Optimizing the entire therapeutic regimen in septic critically ill patients should be based not only on improving antibiotic use but also on optimizing the entire therapeutic regimen by considering possible drug-drug or drug-nutrient interactions. The aim of this narrative review is to provide a comprehensive overview on recent advances to optimize the therapeutic regimen in septic critically ill patients based on a pharmacokinetics and pharmacodynamic approach. Studies on recent advances on TDM-guided drug therapy optimization based on PK and/or PD results were included. Studies on patients <18 years old or with classical TDM-guided therapy were excluded. New approaches in TDM-guided therapy in septic critically ill patients based on PK and/or PD parameters are presented for cefiderocol, carbapenems, combinations beta-lactams/beta-lactamase inhibitors (piperacillin/tazobactam, ceftolozane/tazobactam, ceftazidime/avibactam), plazomicin, oxazolidinones and polymyxins. Increased midazolam toxicity in combination with fluconazole, nephrotoxic synergism between furosemide and aminoglycosides, life-threatening hypoglycemia after fluoroquinolone and insulin, prolonged muscle weakness and/or paralysis after neuromuscular blocking agents and high-dose corticosteroids combinations are of interest in critically ill patients. In the real-world practice, the use of probiotics with antibiotics is common; even data about the risk and benefits of probiotics are currently spares and inconclusive. According to current legislation, probiotic use does not require safety monitoring, but there are reports of endocarditis, meningitis, peritonitis, or pneumonia associated with probiotics in critically ill patients. In addition, probiotics are associated with risk of the spread of antimicrobial resistance. The TDM-guided method ensures a true optimization of antibiotic therapy, and particular efforts should be applied globally. In addition, multidrug and drug-nutrient interactions in critically ill patients may increase the likelihood of adverse events and risk of death; therefore, the PK and PD particularities of the critically ill patient require a multidisciplinary approach in which knowledge of clinical pharmacology is essential.

(1) Background: There are limited clinical data in patients from the Eastern European regions hospitalized for a severe form of Coronavirus disease 2019 (COVID-19). This study aims to identify risk factors associated with intra-hospital mortality in patients with COVID-19 severe pneumonia admitted to a tertiary center in Iasi, Romania. (2) Methods: The study is of a unicentric retrospective observational type and includes 150 patients with severe COVID-19 pneumonia divided into two subgroups, survivors and non-survivors. Demographic and clinical parameters, as well as comorbidities, laboratory and imaging investigations upon admission, treatments, and evolution during hospitalization were recorded. First, we sought to identify the risk factors associated with intra-hospital mortality using logistic regression. Secondly, we assessed the correlations between D-Dimer and C-reactive protein and predictors of poor prognosis. (3) Results: The predictors of in-hospital mortality identified in the study are D-dimers >0.5 mg/L ( p = 0.002), C-reactive protein >5 mg/L ( p = 0.001), and heart rate above 100 beats per minute ( p = 0.001). The biomarkers were also significantly correlated the need for mechanical ventilation, admission to intensive care unit, or multiple organ dysfunction syndrome. By area under the curve (AUC) analysis, we noticed that both D-Dimer (AUC 0.741) and C-reactive protein (AUC 0.707) exhibit adequate performance in predicting a poor prognosis in patients with severe viral infection. (4) Conclusions: COVID-19's outcome is significantly influenced by several laboratory and clinical factors. As mortality induced by severe COVID-19 pneumonia is considerable, the identification of risk factors associated with negative outcome coupled with an early therapeutic approach are of paramount importance, as they may significantly improve the outcome and survival rates.