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.

Background and Objectives: Romania reported the highest measles incidence in the European Union during the 2023–2024 epidemic, largely driven by declining vaccination coverage. We aimed to characterize the epidemiological, clinical, and laboratory profile of hospitalized measles patients and to identify age-related differences, with particular emphasis on systemic and hepatic involvement. Materials and Methods: We conducted a retrospective observational study including 360 consecutive patients with laboratory-confirmed measles admitted to a tertiary infectious disease hospital in northeastern Romania between 1 January and 31 December 2024. Demographic, clinical, laboratory, therapeutic, and outcome data were collected. Pediatric (<15 years) and adult patients were compared using appropriate statistical tests. Results: Children accounted for 71.4% of cases, including 16.1% infants under one year. Over 90% of patients were unvaccinated or incompletely vaccinated. Household transmission represented the most frequent identifiable source. Adults presented significantly higher inflammatory markers and more pronounced hepatic involvement than children. ALT elevation occurred in 63.1% of adults versus 34.2% of children (p < 0.001), with moderate-to-severe cytolysis predominantly observed in adults (34.9% vs. 1.9%, p < 0.001). Pulmonary complications were documented in 28% of cases, mainly viral interstitial pneumonia. Thrombocytopenia was significantly more frequent in adults (p < 0.001). Overall mortality was 0.27%, occurring in an unvaccinated infant with secondary bacterial pneumonia. Conclusions: The 2024 measles epidemic in our area was characterized by sustained transmission among unvaccinated individuals and frequent systemic involvement. Hepatic dysfunction emerged as a prominent feature in adults, suggesting a shifting clinical phenotype in contemporary outbreaks. Strengthening vaccination coverage and early recognition of systemic complications remain critical to reducing measles-related morbidity and mortality.

Background: Infective endocarditis is a severe, life-threatening condition which affects the endocardial lining of the heart. Right-sided IE typically affects the tricuspid valve and, less commonly, the pulmonary valve, often in association with intravenous drug use and intracardiac devices. Enterococcus faecalis, a significant pathogen in healthcare settings, is frequently resistant to several antibiotics, complicating treatment. Results: We present the case of a 69-year-old man diagnosed with isolated pulmonary valve endocarditis, with no identifiable risk factors, good oral hygiene, and no recent dental procedures. In our case, the E. faecalis strain, initially susceptible to ampicillin, acquired resistance during high-dose ampicillin and gentamicin therapy, leading to cardiac surgery and prolonged antibiotic treatment. Conclusions: IPE is rare, emphasizing the need for heightened clinical awareness and thorough diagnostic evaluation, especially in patients with endocarditis symptoms and known risk factors. Although ampicillin resistance in E. faecalis is uncommon, its emergence during treatment presents a challenge, necessitating careful antibiotic stewardship to improve outcomes.

Aim: Chronic fatigue syndrome is a long-term neurological manifestation that significantly affects the quality of life of patients. Its etiology is incompletely known, although it can occur after various infections including COVID-19, and the associated risk factors are not fully defined. The aim of the current study was to evaluate neurological manifestations in long-COVID and to identify potential risk factors for these complications. Materials and methods: We performed retro - prospective study on patients with history of COVID-19 infections. Patients were assessed up to 3 years after infection. Clinical and neurological investigations, brain imaging, analysis of inflammatory markers, levels of vitamin B12, folic acid and vitamin D were carried out. Neurocognitive status was assessed using a validated semiquantitative scale. Results: In 132 eligible patients, 41.67% of cases developed chronic fatigability. Other neurological manifestations associated with Long-COVID were dizziness (29.17% cases), and memory impairment (25% cases). The deterioration of the neurocognitive status 1 year after infection was significantly correlated with the patient’s age (p<0,0001), serum vitamin D ​​(p=0.015), as well as vitamin B12 (p=0.006). Conclusions: Chronic fatigability is a common neurological complication of COVID-19 infection. Older people, those with low vitamin D and vitamin B12 levels, have higher risk of developing this syndrome. The COVID-19 infected patients need multiple investigations and a multidisciplinary approach to prevent these long-term complications.

Background and Objectives: Viral meningitis presents significant diagnostic challenges. The aim of this study was to identify predictive factors for meningitis etiology and clinical outcomes. Methods: This prospective, single center, comparative study enrolled patients meeting clinical, biological, and microbiological criteria for bacterial (BM) or viral (VM) meningitis. Serum inflammatory markers, namely the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and systemic immune-inflammation index (SII), were quantified. In addition, the concentrations of oxidative stress biomarkers, glutathione peroxidase 3 (GPx3) and copper/zinc superoxide dismutase (Cu/Zn SOD), were also determined. Spearman correlation and logistic regression were used to evaluate associations between biomarkers and etiology, while receiver operating characteristic (ROC) curves assessed outcome correlations. Results: VM patients showed a significantly lower NLR (p = 0.007), PLR (p = 0.010), and SII (p = 0.016), with higher GPx3 (p < 0.0001) levels compared with BM patients. Cu/Zn SOD showed no significant difference (p = 0.442) between groups. Multivariate logistic regression identified the SII (OR = 1.015; 95% CI = 1.004–1.026) and GPx3 (OR = 0.847; 95% CI = 0.740–0.970) as etiology predictors. The SII was the strongest predictor of mortality in VM (AUC = 0.833). Conclusions: Serum markers of inflammation, including the systemic immune–inflammation index, along with antioxidant indicators such as GPx3, may serve as valuable additional tools for predicting meningitis etiology and forecasting patient outcomes.

Background and Objectives: Neurological complications of SARS-CoV-2 infection frequently impair patients’ long-term quality of life. This study aimed to identify clinical and laboratory risk factors—including inflammatory markers and micronutrients—for the occurrence or worsening of neurocognitive disorders in long COVID patients. Materials and Methods: In this prospective observational study, patients presenting with long COVID neurological manifestations were stratified by baseline MoCA score into two groups (≥23 and <23). Clinical, laboratory (inflammatory markers, 25-hydroxy vitamin D, vitamin B12, folic acid), and neuroimaging assessments (global cortical atrophy scale, Fazekas score) were performed over 24 months. Propensity score matching (PSM) for age, gender, and neurological comorbidities yielded 54 patients per group. Results: In the MoCA ≥ 23 group, significant predictors of cognitive decline included severe COVID-19 (OR = 2.211, 95% CI = 1.819–5.973, p = 0.012), autoimmune comorbidities (OR = 1.676, 95% CI = 1.191–2.390, p = 0.043), and elevated neutrophil-to-lymphocyte ratio (NLR; OR = 1.586, 95% CI = 1.431–2.122, p = 0.011). In the MoCA < 23 group, independent predictors were diabetes mellitus (OR = 3.021, 95% CI = 2.65–14.004, p = 0.016), autoimmune comorbidities (OR = 4.987, 95% CI = 1.412–6.033, p = 0.021), and NLR (OR = 5.944, 95% CI = 2.353–19.321, p = 0.015). Serum vitamin D levels were significantly associated with MoCA scores in both groups. Conclusions: COVID-19 severity, autoimmune comorbidities, NLR, and serum vitamin D represent key risk factors for neurocognitive decline in long COVID, highlighting potential targets for early intervention.