Daiana Toma

Cefiderocol is among the few agents reliably active against carbapenem-resistant Gram-negative pathogens, and its value depends on durability. Resistance emerging during therapy is documented across pathogens and settings, yet reported incidences span 1% to 40%. The question was last synthesised in 2022; the reviews published since address baseline non-susceptibility, clinical outcomes, testing methodology and resistance development across the novel agents as a class, and none revisits incidence. This review finds that spread is produced by definition, denominator, population, testing method and epidemiological setting rather than by biology: one dataset yields 7%, or between 1% and 2% according to the criterion applied, and the highest figures come from outbreak units where clonal transmission was counted as within-patient evolution. The frequently cited figure of under 2% is what methods of limited sensitivity detect, applied without a standard definition and usually without paired isolates; the true incidence remains unknown. Heteroresistance, present in about half of carbapenem-resistant Acinetobacter baumannii isolates, has not been shown to predict emergence or outcome. Supported measures include reference broth microdilution, storage of the baseline isolate, and repeat testing on triggers during therapy rather than afterwards. A consensus definition is the precondition for everything else.

Metallo-β-lactamase (MBL)-producing Enterobacterales represent a major antimicrobial-resistance threat because MBLs hydrolyse most clinically used β-lactams and are not inhibited by currently approved serine β-lactamase inhibitors. Aztreonam–avibactam (ATM-AVI; Emblaveo^®) addresses this therapeutic gap by combining aztreonam, a monobactam that is stable to MBL-mediated hydrolysis, with avibactam, which inhibits many co-produced class A, class C, and selected class D serine β-lactamases. This narrative review synthesizes evidence on ATM-AVI pharmacology, microbiological activity, pharmacokinetics/pharmacodynamics, clinical efficacy, safety, resistance, and regulatory positioning. Large surveillance datasets show high in vitro activity against most MBL-producing Enterobacterales, including many co-producing β-lactamases from multiple Ambler classes. Population pharmacokinetic modelling supports a renal-function-adjusted fixed 3:1 dosing ratio and more reliable joint target attainment than separately administered ceftazidime–avibactam plus aztreonam. In the phase 3 REVISIT trial, clinical cure with ATM-AVI was comparable to meropenem in the overall population; however, few participants had confirmed MBL-positive infections. Direct clinical evidence therefore remains limited, supported by convergent microbiological, pharmacokinetic, and observational data. Regulatory indications differ substantially between the European Union and the United States. ATM-AVI is an important advance for selected MBL-producing and multi-class-co-producing Gram-negative infections, but its long-term value will depend on targeted use, reliable susceptibility testing, continued surveillance, and further trials in the intended target population.

Hemorrhagic shock is a leading cause of preventable death following multiple trauma, driven by a cascade of interacting cellular and molecular disturbances that extend well beyond simple volume loss. Acute blood loss initiates tissue hypoperfusion and cellular hypoxia, setting in motion the lethal triad of hypothermia, acidosis, and coagulopathy through several converging pathways: complement activation with excessive C3a and C5a production; neutrophil-mediated tissue injury; NADPH-oxidase-driven reactive oxygen species (ROS) overproduction that overwhelms superoxide dismutase defenses; mitochondrial respiratory chain impairment; dysregulation of the pro-inflammatory cytokine network; and endothelial apoptosis with degradation of the endothelial glycocalyx and disruption of interendothelial junctions, with consequent vascular hyperpermeability. These mechanisms provide the biological rationale for the resuscitation strategy. Each class of fluid acts on these pathways in a distinct way: crystalloids modulate acid–base homeostasis, chloride-mediated renal vasoconstriction, and coagulation factor activity; colloids influence oncotic pressure, endothelial integrity, and microvascular perfusion; and blood products, particularly plasma and whole blood, actively modulate mitochondrial metabolism, endothelial permeability, and pro-apoptotic signaling beyond their volume-expanding role. Translating this biology to the bedside requires a multimodal monitoring framework that converts molecular endpoints into real-time therapeutic targets, integrating lactate and base excess as markers of cellular oxygen debt, dynamic preload indices such as pulse pressure and stroke volume variation, advanced hemodynamic platforms, point-of-care ultrasonography, viscoelastic coagulation testing, and near-infrared spectroscopy of tissue oxygenation. This review synthesizes the biological basis of hemorrhagic shock and its translation into an individualized, goal-directed resuscitation strategy for the critically ill polytrauma patient.

Background/Objectives: Carbapenem-resistant Gram-negative (CR-GN) infections are associated with high mortality in intensive care units (ICUs), with limited therapeutic options. We aimed to evaluate microbiological and clinical outcomes associated with cefiderocol in critically ill patients with multidrug-resistant (MDR) Gram-negative infections. Methods: This retrospective, single-center case series included 25 critically ill patients with carbapenem-resistant or multidrug-resistant Gram-negative infections treated with cefiderocol between May 2024 and October 2025 in a mixed ICU of a tertiary hospital in Romania. Microbiological cure was defined as eradication of the designated target pathogen at the end of therapy. Clinical evolution was assessed using the Acute Physiology and Chronic Health Evaluation II (APACHE II) and Sequential Organ Failure Assessment (SOFA) scores, as well as inflammatory biomarkers including white blood cell count (WBC), C-reactive protein (CRP), and procalcitonin (PCT). Results: Klebsiella pneumoniae was the predominant pathogen, identified in 23 of 25 patients (92%), followed by Acinetobacter baumannii (11/25, 44%) and Pseudomonas aeruginosa (6/25, 24%). As multiple pathogens were co-isolated in 16 patients (64%), percentages exceed 100% and are reported as proportions of patients rather than of total isolates. Microbiological cure was achieved in 68% of patients. Mortality was markedly higher in patients without microbiological eradication (88% vs. 35%). Higher baseline APACHE II (HR 1.18, 95% CI 1.02–1.37) and SOFA scores (HR 1.33, 95% CI 1.07–1.65) were associated with increased mortality. Early initiation of cefiderocol (≤10 days from ICU admission) was associated with improved microbiological and clinical outcomes compared to delayed treatment. Reductions in severity scores and inflammatory markers, including C-reactive protein (CRP) and procalcitonin (PCT), were observed during therapy. Pathogen type and combination therapy were not clearly associated with outcomes in this cohort. Conclusions: Cefiderocol was observed in association with clinically relevant rates of microbiological eradication and improvements in clinical parameters in critically ill patients with MDR Gram-negative infections. Outcomes appeared to be primarily determined by baseline disease severity, while earlier initiation of therapy was associated with more favourable microbiological and clinical outcomes, although causality cannot be established given the observational design and absence of a comparator group. These findings are hypothesis-generating and supportive of a potential role for cefiderocol as a salvage option in high-risk ICU populations, pending validation in larger, prospective, controlled studies.

Background: Multidrug-resistant Gram-negative infections remain a major challenge in critically ill patients, particularly when caused by carbapenem-resistant pathogens with limited therapeutic options. Although eravacycline has emerged as a potential salvage agent, real-world data in high-acuity intensive care populations remain scarce. Methods: We conducted a retrospective cohort study including adult ICU patients who received eravacycline as salvage therapy for multidrug-resistant Gram-negative infections between February 2024 and September 2025 in a tertiary-care center. Demographic, clinical, microbiological, and treatment-related variables were extracted from electronic records. Infection complexity was classified as monomicrobial single-site, monomicrobial multi-site, or polymicrobial. The primary outcome was in-hospital mortality; secondary outcomes included clinical response, microbiological eradication, and safety. Results: Forty critically ill patients were included (median age 58 years, IQR 47–69; mean APACHE II 16.4 ± 6.9; mean SOFA 5.5 ± 3.3). Pulmonary (62.5%) and intra-abdominal (55.0%) infections were most frequent. Klebsiella pneumoniae predominated (75.0%), followed by Acinetobacter baumannii (35.0%) and Pseudomonas aeruginosa (22.5%). Most patients received combination antimicrobial therapy. Microbiological eradication or presumed eradication was documented in 24 patients (60.0%), yet overall in-hospital mortality remained high (75.0%). Baseline disease severity and persistent inflammatory response were more strongly associated with unfavorable outcomes than treatment timing or duration. Conclusions: In this real-world ICU cohort, eravacycline-based salvage therapy was associated with moderate microbiological response but very high mortality, reflecting the severity of underlying critical illness. The dissociation between microbiological eradication and survival suggests that outcomes are more closely related to host factors and unresolved systemic inflammation than to pathogen clearance alone. Eravacycline remains one of the few agents active against MDR Gram-negative pathogens (with no activity against Pseudomonas aeruginosa), frequently used off-label; larger controlled studies are needed to establish efficacy beyond complicated intra-abdominal infections.

Background: MDRO colonization at ICU admission may identify patients at increased risk for hospital-acquired infection (HAI), but its independent predictive value remains incompletely defined. Methods: We conducted a retrospective observational study of 560 consecutive ICU admissions (July–October 2024). Admission screening assessed colonization with extended-spectrum beta-lactamase (ESBL)-producing Enterobacterales, carbapenem-resistant Enterobacterales (CRE), and vancomycin-resistant enterococci (VRE). The primary outcome was microbiologically confirmed HAI; the secondary outcome was in-hospital mortality. Associations were evaluated using multivariable logistic regression, ROC/AUC analysis, mediation analysis, and a sensitivity analysis restricted to first admissions. Results: Of 560 admissions, 223 were screen-positive and 283 screen-negative. HAI occurred in 49 patients (8.8%). Positive screening was associated with increased HAI odds, narrowly missing significance in the primary adjusted analysis (OR 1.81, 95% CI 0.96–3.41, p = 0.065) but reaching significance in the first-admission sensitivity analysis (OR 2.09, p = 0.034). CRE showed the strongest adjusted association with HAI (OR 2.33, 95% CI 1.21–4.51, p = 0.012). Screening alone showed poor discrimination (AUC 0.574); combined with clinical variables, discrimination improved substantially (AUC 0.788). Conclusions: MDRO admission screening was associated with increased HAI odds, particularly for CRE, though screening alone has limited predictive performance. Larger prospective studies are needed to confirm these findings.

Background/Objectives: Inpatient clinical deterioration is a major contributor to adverse hospital outcomes, such as unplanned intensive care unit (ICU) admissions and death. Rapid response systems aim to address this challenge by enabling early identification and intervention in at-risk patients. This study evaluated the impact of implementing a mobile intensive care team on clinical outcomes in surgical patients. Methods: A retrospective observational cohort study was conducted in a tertiary care hospital, comparing two consecutive periods: a pre-intervention phase (PRETIM) and a post-intervention phase (TIM). The study included 17,156 adult surgical patients. The TIM consisted of a proactive outreach team composed of one attending intensivist and two resident physicians, focusing on post-ICU monitoring and early identification of clinical deterioration on surgical wards. The primary outcome was in-hospital mortality. Secondary outcomes included ICU readmission and length of stay. Multivariable logistic regression adjusted for age, sex and surgical section was performed, along with subgroup and sensitivity analyses excluding early non-modifiable deaths. Results: Baseline characteristics were comparable between groups. In-hospital mortality decreased significantly following implementation of the TIM (8.0% vs. 5.3%; p < 0.001), corresponding to an absolute risk reduction of 2.7% and a number needed to treat of 37. ICU readmission rates did not differ significantly between groups. Sensitivity analysis excluding early deaths confirmed the mortality reduction. Subgroup analysis demonstrated consistent effects across surgical specialties, with the largest reductions observed in neurosurgery and general surgery. Conclusions: The implementation of a mobile intensive care team was associated with a significant and clinically meaningful reduction in in-hospital mortality among surgical patients. The findings support the role of proactive post-ICU monitoring and early intervention strategies in improving patient outcomes in high-risk hospital populations.

Background/Objectives: Digitalization of intensive care units (ICUs) aims to enhance patient safety and efficiency through standardized documentation, real-time data integration, and clinical decision support. This study evaluated whether the implementation of a patient data management system (PDMS) was associated with improvements in quality of care, infection prevention, and patient outcomes in a trauma ICU. Methods: We conducted a single-center, retrospective, before–after cohort study comparing a pre-digitalization period (2021–2022) with a post-digitalization period (2025). Consecutive adult trauma ICU admissions were analyzed. The exposure was unit-wide adoption of a PDMS implemented in 2024. The primary outcome was ICU length of stay (LOS); secondary outcomes included ICU mortality, nosocomial infection rates (episodes per 1000 ICU-days), ventilation- and antibiotic-days, device utilization, and infection epidemiology. Prespecified sensitivity analyses were performed. Results: A total of 108 patients were included (43 pre- and 65 post-digitalization). Baseline characteristics were comparable between groups. Median ICU LOS decreased from 13.0 to 6.0 days (p = 0.02). Mortality declined from 18.6% to 6.2% (p = 0.06), and crude infection rates decreased from 42.2 to 30.8 per 1000 ICU-days (rate ratio 0.73; p = 0.28). Adjusted analyses showed no statistically significant differences for mortality (aOR 0.40; p = 0.45), infection rates (aIRR 0.88; p = 0.68), LOS (aRR 1.04; p = 0.87), ventilation-days (aRR 0.86; p = 0.65), or antibiotic-days (aRR 0.70; p = 0.30). Per-patient rates of ventilator-associated pneumonia and bloodstream infection were significantly lower after digitalization (both p = 0.04), and Acinetobacter spp. infections decreased markedly (7 to 0 cases; p = 0.001). Findings were consistent after exclusion of ICU stays < 24 h. Conclusions: ICU digitalization was associated with shorter unadjusted ICU stays and favorable trends in infection and mortality outcomes, though adjusted analyses were neutral. Larger multicenter studies incorporating device-day denominators and time-to-event analyses are needed to confirm the causal impact of digital transformation on ICU quality of care.

Background/Objectives: Multidrug-resistant (MDR) nosocomial infections remain a major challenge in intensive care units (ICUs), where delays in diagnosis and suboptimal antimicrobial therapy significantly impact outcomes. This narrative review synthesizes international literature and local epidemiological data from Western Romania to examine the role of rapid molecular diagnostics in the management of MDR infections and their integration with prevention and antimicrobial stewardship (AMS) strategies. Methods: Evidence was collected through a narrative literature review using PubMed, WHO, and ECDC sources published between 2010 and 2025. Key terms included “rapid molecular diagnostics,” “sepsis,” “ICU,” “UNYVERO,” “GeneXpert,” “BioFire,” and “carbapenem resistance.” Studies were selected based on clinical relevance to rapid diagnostics and MDR pathogens; no PRISMA-based systematic methodology was applied. Results: Diagnostic performance varies by platform and clinical syndrome. UNYVERO Hospitalized Pneumonia panel demonstrates a sensitivity range of 88.8–91.4% and specificity of 94.9–99.5% in respiratory infections, with a turnaround time of approximately 4–5 h. The GeneXpert Carba-R assay identifies major carbapenemases within 45–60 min with reported sensitivity 96–100% and specificity of 93–99%. BioFire^® Pneumonia and Blood Culture Identification panels similarly provide rapid syndromic results within 1 h, enabling earlier optimization of antimicrobial therapy. Local ICU data from Western Romania identified a substantial burden of carbapenem-resistant Acinetobacter baumannii, underscoring the need for rapid resistance detection to guide therapy. Conclusions: Rapid molecular diagnostics, when integrated with prevention bundles and AMS programs, facilitate earlier targeted therapy, support responsible antimicrobial use, and improve clinical decision-making in MDR infections. Their value is amplified in settings with high resistance prevalence. Wider implementation, combined with surveillance and access to novel antimicrobials, is essential to improve outcomes in critically ill patients.

Background: Healthcare-associated infections (HAIs) remain a significant challenge in intensive care units (ICUs), especially in trauma settings where invasive interventions are frequent. This study aimed to assess the impact of a structured quality improvement project (QIP) on nosocomial infection rates and patient outcomes in a polytrauma ICU. Methods: We conducted a retrospective observational study at the “Pius Brînzeu” County Emergency Clinical Hospital, Timișoara. A total of 78 ICU trauma patients were included: 35 in the Pre-QIP group and 43 in the Post-QIP group. The QIP integrated evidence-based interventions, including hand hygiene reinforcement, individualized protective equipment, improved nurse staffing, and antimicrobial stewardship. Outcomes analyzed included nosocomial infection rate, ICU length of stay, antibiotic use, mechanical ventilation days, and mortality. Multivariable logistic, linear, and Poisson regression models were applied to control for confounding variables. Results: The Post-QIP group showed a significantly lower number of infections per patient (0.60 ± 0.95 vs. 1.41 ± 1.97, p = 0.03) and a trend toward lower mortality (0.19 vs. 0.34, p = 0.18). While ICU stay, antibiotic use, and ventilation days decreased post-QIP, these changes were not statistically significant. ISS and Charlson scores were consistent predictors of worse outcomes. Conclusions: Implementation of a targeted, multidisciplinary QIP was associated with improved infection control and patient outcomes. These results support the feasibility and value of structured infection prevention strategies in resource-constrained ICU settings.