This study aimed to assess the efficacy and safety of regional citrate anticoagulation (RCA) and low molecular weight heparin anticoagulation (LMHA) in critically ill patients undergoing continuous renal replacement therapy (CRRT).

The clinical data of patients who underwent CRRT at Inner Mongolia People's Hospital from January 2022 to March 2024 were collected. Patients were divided into the RCA group and the LMHA group. The primary outcomes were filter survival time and 28-day mortality. The secondary outcomes were adverse events of CRRT anticoagulation.

The filter lifespan of the RCA group was significantly extended (33.5 vs. 27.5 h, p ≤ 0.001), and the occurrence of filter coagulation events in the RCA group was markedly reduced (7.0% vs. 21.1%, p = 0.03). There were no statistically significant differences in bleeding and electrolyte disturbances between the two groups. The multivariate COX regression analysis demonstrated that the anticoagulation strategy was the singular factor influencing filter survival time (hazard ratio [HR] = 4.74, 95% CI 1.67-13.50, p = 0.004).

RCA demonstrated significantly prolonged filter lifespan and reduced instances of filter clotting compared to LMHA. RCA represents a safe and effective anticoagulation strategy for CRRT.

Owing to the global increase in carbapenem and colistin resistance, several methods have been actively used for the detection of these antibiotic-resistant bacteria. However, this emerging field still requires development of more efficient and practical diagnostic susceptibility tests for rapid, simple, and economic detection of pathogens. Herein, we prepared phenotypic and colorimetric antibiotic susceptibility tests in liquid and agar forms consisting of a natural and biocompatible pH indicator called "anthocyanins" for colorimetric detection of carbapenem/colistin resistance. The most innovative and original part of this phenotypic test, for the first time, uses plant indicators to detect carbapenem/colistin resistance within 2 h (hrs). Both commercial and clinically isolated bacterial pathogens were colorimetrically detected by a human eye in 2 h. These pathogens release acidic volatile compounds (AVCs) during their growth, resulting in an acidic reaction environment, in which anthocyanin molecules were protonated and then change the color of the susceptibility tests. The color of the susceptibility tests was analyzed by smartphone platform and mobile application to provide quick, clear, and semiquantitative results. We believe that these susceptibility tests will reduce the workload of laboratories with their ease of application and evaluation, contribute to the economy of countries by eliminating economic restrictions, and will be widely used in clinics.

Candidozyma auris (formerly Candida auris; C. auris) raises significant concerns for healthcare facilities due to its ability to cause severe systemic infections, increased resistance to antifungals, and high intra-hospital transmissibility. We conducted a retrospective study on 102 patients diagnosed in 2022 and 2023. Demographic, clinical, and epidemiologic data were collected from the hospital databases. C. auris was identified using MALDI-TOF systems, and antifungal susceptibility was determined with Micronaut. The isolates were sequenced using Illumina next-generation sequencing platforms. Molecular epidemiology analysis was performed with multiple bioinformatics approaches (phylogenetic tools, resistance genes-related predictions, and variant analyses). Most patients (80/102) were admitted to or had been recently transferred from intensive care units at the moment of C. auris detection. Most cases (57/102) were classified as infections; 29 of them were bloodstream infections. All patients had been treated with broad-spectrum antibiotics before C. auris isolation, and 75/102 had received antifungals. All 31 tested isolates showed resistance to fluconazole, 5 were resistant to amphotericin B, and they were all susceptible to echinocandins. Crude mortality for infected patients was 68.18%. The 31 analyzed sequences belonged to clade I and bore multiple resistance markers.IMPORTANCEHighly antifungal-resistant Candidozyma auris keeps spreading in regions previously free of this pathogen, stressing once again the need for active surveillance, flexible control measures, and antimicrobial stewardship. This study is seminal for our understanding of the C. auris outbreak in Romania, providing insights into the evolutionary dynamics and genomic diversity of the pathogen and highlighting clade-specific mutations possibly linked to antifungal resistance. By joining these molecular characteristics with clinical, epidemiological, and microbiology data, such as risk factors for acquiring C. auris and phenotypic antifungal susceptibility, the study can be instrumental for surveillance and infection control strategies that are essential due to the pathogen's high transmissibility and the global health threat that it poses.

Intensive care units (ICUs) are critical environments for the emergence of antibiotic-resistant bacteria, with numerous studies focusing on resistant pathogens in these settings. However, transferable antibiotic resistance plasmids (TARPs)-regardless of their origin from pathogenic or non-pathogenic bacteria-are key drivers of resistance gene dissemination and the emergence of resistant strains. This study investigated TARPs in ICU air. Air samples were directly used to isolate resistant plasmids using Escherichia coli CV601 as the recipient. Plasmid types, antibiotic resistance genes (ARGs), and virulence factors were identified through sequencing, and resistance phenotypes were validated. A total of 30 distinct plasmid types were detected, with IncX3 being the most prevalent. Among 245 ARGs identified, bla NDM-53, bla SHV-12, and BRP(MBL) were dominant. Phylogenetic analysis indicated that these TARPs originated from bacteria commonly colonizing human mucosa. ICU airborne TARPs may significantly contribute to the spread of ARGs and antibiotic resistance transmission.

Ventilator-associated lower respiratory tract infections (VA-LRTIs) cause significant mortality. This study was assigned to explore the association between early microbiological responses defined by quantitative targeted amplicon-based next-generation sequencing (QtNGS) and clinical outcomes in patients with Acinetobacter baumannii-dominant VA-LRTI.

A prospective observational study including 34 participants was conducted to assess the probability of predicting clinical outcomes using sequencing-based early microbiological response. Bronchoalveolar lavage fluids (BALFs) were collected at admission and 3 days post-treatment from these patients for QtNGS to determine the relative quantification ratio (RQR) of A. baumannii. Patients were categorized into survival (n=26) and non-survival (n=8) groups. The RQR was calculated as the quantification of A. baumannii determined by QtNGS after treatment to pretreatment. RQR significantly increased on day 4 in the non-survival group (median 5.285), and decreased in the survival group (median 0.1864). Receiver's operation characteristic curves revealed that an RQR ≥1.41 was predictive of poor outcomes, with an area under the curve of 0.9471 (0.8759-1). The accuracy of the RQR determined by QtNGS was further evaluated by retesting the same specimen using digital droplet PCR, and the linear correlation was confirmed in the RQR calculated by two methods. The 23 patients with RQR<1.41 all survived for 28 days, whereas the survival rate for the 11 patients with RQR ≥1.41 was 27.27%. RQR was significantly and positively correlated with the length of ICU stay in survivors.

The RQR of A. baumannii detected by QtNGS correlates with the prognosis of VA-LRTI patients.

Sepsis is a life-threatening condition that occurs when the body is unable to effectively combat infection, leading to systemic inflammation and multi-organ failure. Interestingly, females exhibit lower sepsis incidence and improved clinical outcomes compared to males. However, the mechanisms underlying these sex-specific differences remain poorly understood. While sex hormones have been a primary focus, emerging evidence suggests that non-hormonal factors also play contributory roles. Despite sex differences in sepsis, clinical management is the same for both males and females, with treatment focused on combating infection using antibiotics and hemodynamic support through fluid therapy. However, even with these interventions, mortality remains high, highlighting the need for more effective and targeted therapeutic strategies. Sepsis-induced cardiomyopathy (SIC) is a key contributor to multi-organ failure and is characterized by left ventricular dilation and impaired cardiac contractility. In this review, we explore sex-specific differences in sepsis and SIC, with a particular focus on mitochondrial metabolism. Mitochondria generate the ATP required for cardiac function through fatty acid and glucose oxidation, and recent studies have revealed distinct metabolic profiles between males and females, which can further differ in the context of sepsis and SIC. Targeting these metabolic pathways could provide new avenues for sepsis treatment.

To compare the efficacy of continuous renal replacement therapy (CRRT) using either oXiris or conventional hemopurification filters in the treatment of intra-abdominal sepsis.

We conducted a retrospective analysis of septic patients with severe intra-abdominal infections admitted to our hospital from October 2019 to August 2023. Patients who meet the criteria for intra-abdominal sepsis based on medical history, symptoms, physical examination, and laboratory/imaging findings were included.

pregnancy, terminal malignancy, prior CRRT before intensive care unit admission, pre-existing liver or renal failure. Heart rate (HR), mean arterial pressure, oxygenation index, lactic acid level (Lac), platelet count (PLT), neutrophil percentage, serum levels of procalcitonin, C-reactive protein, interleukin (IL)-6, norepinephrine dosage, acute physiology and chronic health evaluation II (APACHE II), and sequential organ failure assessment (SOFA) scores before and after 24 h and 72 h of treatment, as well as ventilator use time, hemopurification treatment time, intensive care unit and hospital lengths of stay, and 14-day and 28-day mortality were compared between patients receiving CRRT using either oXiris or conventional hemofiltration. Statistical analysis was performed using SPSS Statistics 26.0 software, including the construction of predictive models via logistic regression equations and repeated measures ANOVA.

Baseline values including time to antibiotic administration, time to source control, and time to initiation of CRRT were similar between the 2 groups (all p>0.05). Patients receiving conventional CRRT exhibited significant changes in HR but of none of the other indexes at the 24 h and 72 h time points (p=0.041, p=0.026, respectively). The oXiris group showed significant improvements in HR, Lac, IL-6, and APACHE II score 24 h after treatment (p<0.05); after 72 h, all indexes were improved except PLT (all p<0.05). Intergroup comparison disclosed significant differences in HR, Lac, norepinephrine dose, APACHE II, SOFA, neutrophil percentage, and IL-6 after 24 h of treatment (p<0.05). Mean arterial pressure, serum levels of procalcitonin, C-reactive protein, SOFA score, and norepinephrine dosage were similar between the 2 groups at 24h (p>0.05). Except for HR, oxygenation index, and PLT, post-treatment change rates of △ (%) were significantly greater in the oXiris group (p < 0.05). Duration of ventilator use, CRRT time, and intensive care unit and hospital lengths of stay were similar between the 2 groups (p>0.05). The 14-day mortality rates of the 2 groups were similar (p=0.091). After excluding patients whose CRRT was interrupted, 28-day mortality was significantly lower in the oXiris than in the conventional group (25.0% vs. 54.2%; p=0.050). The 28-day mortality rate increased by 9.6% for each additional hour required for source control and by 21.3% for each 1-point increase in APACHE II score.

In severe abdominal infections, the oXiris filter may have advantages over conventional CRRT, which may provide an alternative to clinical treatment. Meanwhile, early active infection source control may reduce the case mortality rate of patients with severe abdominal infections.

Procalcitonin (PCT) is a biomarker for bacterial infections, with controversial utility in diagnosing hospital-acquired pneumonia (HAP) in neurosurgical intensive care unit (NICU) patients. Establishing an optimal PCT cutoff value could enhance diagnostic accuracy. This retrospective single-center study included NICU patients hospitalized between January 1, 2021, and December 31, 2022, who underwent routine serum PCT measurement. HAP was diagnosed based on clinical, biochemical, microbiological, and radiological data. The optimal PCT cutoff value was identified using the Youden Index. Associations between PCT levels, radiological findings, sputum cultures, and confirmed HAP were analyzed using chi-square tests. A multivariate logistic regression was performed to identify independent predictors of elevated PCT. Among 2363 patients, 193 met inclusion criteria, and 148 were diagnosed with HAP. The optimal PCT cutoff value was 0.095 ng/mL, yielding a sensitivity of 89.2% and specificity of 93.3% (p < 0.001). This cutoff resulted in a positive likelihood ratio of 13.3 and a negative likelihood ratio of 0.116. Radiological signs of pneumonia and positive sputum cultures were observed in 48.4% and 78.4% of HAP cases, respectively, but neither showed a significant association with HAP (p = 0.135 and p = 0.056). Leukocytosis was significantly associated with HAP but had low specificity, while CRP showed a non-significant trend. In multivariate analysis, only confirmed HAP independently predicted PCT elevation. PCT, with a cutoff value of 0.095 ng/mL, shows high diagnostic accuracy for HAP in NICU patients and could enhance early identification and treatment. Our findings suggest that elevated PCT is primarily driven by HAP rather than non-infectious inflammatory triggers such as trauma or recent surgery. Further prospective studies are warranted to validate these findings.

Sepsis, a severe systemic inflammatory condition triggered by infection, is associated with high morbidity and mortality worldwide. While medical diagnosis and treatment have advanced in recent years, a specific therapy remains unavailable. Recently, significant progress has been made in studying the epigenetic RNA modification N6-methyladenosine (m6A) and its core methyltransferase METTL3. The role of m6A in sepsis has also been increasingly elucidated. This review aims to explore the pathological mechanisms of sepsis and its relationship with m6A, focusing on the role of the key m6A writer, METTL3, in sepsis.

To provide evidence of the cost savings of a quality improvement (QI) initiative preventing healthcare-associated infections (HAIs) in critical care settings.

A micro-costing study focused on financial data related to a nationwide multicentric project preventing central line-associated bloodstream infection (CLABSI), ventilator-associated pneumonia (VAP) and catheter-associated urinary tract infection (CAUTI).

Brazilian public healthcare system.

Adult, paediatric and neonatal intensive care units (ICUs) participating in the QI initiative.

This collaborative QI project implemented a multifaceted strategy to enhance infection-control measures. Participating ICUs reported the number of patients with and without HAIs and information on each HAI's aggregate average cost (AC), which was analysed following the Brazilian Ministry of Health's micro-costing guidelines. The 1-year preintervention period evidenced an aggregated AC in adult, paediatric and neonatal ICUs, respectively, of Intl$21 763.5 (95% CI 20 683.6 to 22 843.0), Intl$34 062.4 (95% CI 25 819.6 to 42 304.9) and Intl$32 903.2 (95% CI 29 203.6 to 36 602.4) for CLABSI; Intl$25 202.5 (95% CI 24 276.6 to 26 127.8), Intl$44 753.6 and Intl$17 238.4 for VAP and Intl$19 166.3 (95% CI 17 676.2 to 20 656.1) and Intl$55 873.3 (95% CI 43 563.1 to 68 183.1) for CAUTI (not included neonatal ICUs).

The cost savings were estimated using the HAIs prevented-expenses avoided-during the QI intervention period from September 2021 to December 2023. The HAIs prevented were estimated using the difference between observed and predicted infections based on the aggregated preintervention baseline.

Of the 188 participating ICUs, 31 voluntarily completed and provided the requested financial data with 100% accuracy. Considering the prevented 7342 HAIs for adult, paediatric and neonatal ICUs, respectively: 1647, 86 and 205 CLABSI; 3775, 114 and 118 VAP; and 1377 and 20 CAUTI, we estimated a saving of Intl$175.3 million (95% CI 153.2 to 180.9 million) to the Brazilian unified health system and a resultant estimated return on investment (ROI) of 890%.

This QI collaborative is a value-based initiative preventing HAIs in adult, paediatric and neonatal ICUs in South American settings. The substantial cost savings and a remarkable ROI underscore the economic viability of investing in comprehensive QI infection prevention strategies.

No data exist regarding the potential impact of a blue light system on environmental colonization and perioperative infections in neurosurgery. Main objective of this work was to analyze the clinical efficacy of a novel blue light system on the rate of environmental colonization and perioperative infections in a neurosurgical department.

In this observational prospective cohort study, we prospectively enrolled all head/spine neurosurgical patients (January-December 2023) at a third-level referral center in Italy. Patients were followed after surgery in two separate neurosurgical wards, following normal institutional protocol. One ward was previously equipped with the INTEGRALIS® (Artemide®) blue light (405 nm) as the primary light source and the other with common neon lights. We longitudinally assessed both wards for environmental colonization (contact plates, contact swabs, and air samplings) and for the rate of clinically manifest perioperative infections (primary end points). A dedicated questionnaire evaluated patient and health professional satisfaction with the new luminous system (secondary end point).

Nine hundred seventy-seven patients (5765 days of hospitalization, DoH) and 1252 patients (6332 DoH) were followed, respectively, in blue light and neon wards. From an environmental perspective, a higher incidence of plates with a CFU level below 25 CFU/plate threshold was found in blue light ward compared with the neon ward at 1 month (46.2% vs 33.3%, P = .26) and, significantly, at 5 months (68.3% vs 42.3%, P = .001). No difference was observed considering cultures executed at 1 year (P = .17). On a clinical perspective, the overall number of infections/10000 DoH was lower in blue light ward (79.0 vs 45.1, P = .02, CI 95% 1.1-2.9), with a significantly reduced rate of wound infections in respect to neon ward (10.4 vs 41.1, P = .001, CI 95% 1.6-11.7).

Blue light systems may in a surgical setting may help in lowering bacterial colonization and clinically manifest infections.

Sepsis is a severe and often life-threatening condition which can lead to widespread organ dysfunction, septic shock, and even death. Antimicrobials are critical in improving outcomes for patients with sepsis. This chapter details the general principles of antimicrobial therapy, appropriate selection and de-escalation of antimicrobials, and challenges in antimicrobial stewardship.

Introduction: Infections due to carbapenem-resistant Enterobacteriaceae (CRE) in intensive care units (ICUs) pose a significant threat. Colonization with CRE is a prerequisite for bacterial translocation/infections. This work aimed to determine risk factors for CRE colonization in ICU patients. Methods: To find relevant works, PubMed, EMBASE, and references of eligible studies were systematically searched using appropriate keywords up to September 2023. Odds ratios (ORs) and 95% confidence intervals were used to compare risk factor between CRE colonized cases and CRE noncolonized controls. Results: Twelve studies were included. Previous hospitalization (OR: 2.26), previous ICU stay (OR: 10.33), higher acute physiology and chronic health evaluation (APACHE) II score (mean difference [MD]: 4.38), central venous catheter (OR: 4.07), long-term gastric tube (OR: 3.01), hemodialysis catheter (OR: 3.38), urinary catheter (OR: 2.59), mechanical ventilation (OR: 3.41), endoscopy (OR: 3.37), tracheostomy (OR: 3.46), and exposure to antibiotics such as glycopeptide (OR: 10.68), aminoglycosides (OR: 6.53), tigecycline (OR: 6.87), vancomycin (OR: 5.32), carbapenems (OR: 5.23), cephalosporins (OR: 4.96), metronidazole (OR: 4.82), penicillin (OR: 4.41), and β-lactams/β-lactamase inhibitor (OR: 4.28) are highly associated with CRE colonization. Conclusions: ICU-admitted patients with prior hospitalization, ICU stay, previous antibiotic use, and invasive devices/procedures exposures should be prioritized in the screening strategy for CRE colonization to prevent nosocomial infections.

We aim to describe a large, multicenter cohort of patients with bloodstream infection (BSI) acquired during extracorporeal membrane oxygenation (ECMO) support.

We conducted a retrospective observational study in 12 Europeans ICUs. Only patients who developed a BSI of unknown source during ECMO support were included in the present analysis. Primary aim was to describe BSI epidemiology in patients with ECMO support. Secondary objectives were to describe antimicrobial susceptibility of incriminated micro-organisms.

One hundred and eighty-two patients were included. Main reason for ECMO support was ARDS, followed by cardiogenic shock and post-cardiotomy. Half of the patients (51.9%) received early antimicrobial therapy. Main incriminated microorganisms were Enterococcus sp. (37.4%), Enterobacterales (26.9%), coagulase negative Staphylococci (15.9%) and Gram negative bacilli (11.5%). Multi drug resistant organisms (MDRO) were incriminated in 26 (14.3%) BSI and were mainly extended spectrum producing-Enterobacterales (17/26). Antimicrobial therapy was considered as appropriate in 130 patients (71.4%). Patients who received inappropriate antimicrobial therapy were more frequently infected with MDRO. Only 59 (32.4%) of cases were susceptible to 3rd generation cephalosporin while association of piperacillin/tazobactam with vancomycin was considered appropriate in 155 cases (85.2%) as compared with 168 cases (92.3%) for carbapenems combined with vancomycin.

Enterococcus sp. was incriminated in about a third of BSI among patients with ECMO support. High appropriateness would only be obtained with piperacilline/tazobactam or carbapenems in association with vancomycin while 3rd generation cephalosporin would have failed in the majority of BSI cases.

Not applicable.

Antimicrobial stewardship (AMS) for ventilator-associated pneumonia (VAP) in carriers of extended-spectrum β-lactamase-producing Enterobacterales (ESBL-E) presents significant challenges. The abundance of ESBL-E rectal carriage has emerged as a potentially valuable tool for predicting ESBL-E-related VAP.

This single-center, retrospective study was conducted between October 2019 and April 2023 in the medical ICU of a university hospital. The relative abundance of ESBL-E rectal carriage (RAC) was calculated as the ratio of ESBL-E counts to the total number of aerotolerant bacteria. The aim was to evaluate the predictive value of RAC for diagnosing ESBL-E-related VAP in patients with confirmed VAP who were ESBL-E carriers.

During the study period, 478 patients with ESBL-E carriage were admitted to the ICU, of whom 231 (48%) required mechanical ventilation. Eighty-three patients (17%) developed a total of 131 confirmed VAP episodes, of which 62 episodes (47%) were ESBL-E-related VAP. The median interval between the last rectal screening and VAP occurrence was 4 [3-7] days. RAC was not associated with ESBL-E-related VAP in the entire cohort (p = 0.39). Similar findings were observed in several sensitivity analyses, including the following subsets: recent and high-quality screening (interval between screening and VAP ≤ 7 days and bacterial load on rectal swab > 104 CFU/mL, p = 0.21); first VAP episodes only (p = 0.41); cases involving Escherichia coli exclusively (p = 0.08) or other ESBL-E strains (p = 0.29); and VAP associated with Gram-negative bacteria (p = 0.26) or Enterobacterales (p = 0.34). However, in a multivariable model, rectal colonization with non-Escherichia coli ESBL strains was independently associated with ESBL-E-related VAP (adjusted odds ratio [aOR] 1.213 [95% CI 1.005-1.463], p = 0.045).

RAC was not associated with confirmed VAP in ESBL-E carriers. Further studies are needed to explore effective strategies for improving AMS in ESBL-E carriers with suspected VAP.

Critically ill patients are susceptible to serious infections due to their compromised conditions and extensive use of medical devices, often requiring empiric broad-spectrum antimicrobial therapy. Failure of antimicrobial therapy in this vulnerable population has a direct impact on the patient's survival; hence, selecting the optimal dosage is critical. This population, however, exhibits complex and diverse disease-related physiological changes that can markedly alter antimicrobial disposition. Inflammatory cytokines overexpressed in the systemic inflammatory response syndrome increase vascular permeability, leading to higher volume of distribution for hydrophilic antimicrobials. These cytokines also downregulate metabolic enzyme activities, reducing the clearance of their substrates. Hypoalbuminemia can increase the volume of distribution and clearance of highly protein-bound antimicrobials. Acute kidney injury decreases, while augmented renal clearance increases the clearance of antimicrobials primarily excreted by the kidneys. Furthermore, continuous renal replacement therapy and extracorporeal membrane oxygenation used in critical illness substantially affect antimicrobial pharmacokinetics. The complex interplay of multiple factors observed in critically ill patients poses a significant challenge in predicting the pharmacokinetics of antimicrobials. Therapeutic drug monitoring is the most effective tool to address this issue, and is proactively recommended for vancomycin, teicoplanin, aminoglycosides, voriconazole, β-lactams, and linezolid in critically ill patients. To streamline this process, model-informed precision dosing is expected to promote personalized medicine for this population.

Autophagy-lysosome pathways play a crucial role in the intracellular killing of pathogenic microorganisms. This study aimed to explore the mechanism by which acute lung injury (ALI) of Pseudomonas aeruginosa affects the autophagy-lysosome pathway.

ALI mouse models were induced by lipopolysaccharide and P. aeruginosa strain K (PAK). Lung tissue sections were stained with hematoxylin-eosin for observation. Flow cytometry was used to analyze bacteria and inflammatory cell infiltration. ELISA was performed to measure inflammatory factor levels. Transmission electron microscopy evaluated autolysosome quantity. Western blot detected levels of related proteins. Immunofluorescence evaluated LC3 expression, and the localization of TFEB in cells was observed. Co-immunoprecipitation and pull-down experiments confirmed the interaction between CAPN1 and TFEB. qRT-PCR measured capn1 and tfeb expression.

Mouse experiments revealed that PAK infection led to the suppression of autolysosomes in mouse lung tissue, along with increased CAPN1 expression and decreased TFEB in the lung tissue of PAK-induced pneumonia mice. CAPN1-deficient mice could reverse the impact of PAK infection on autolysosomes in mouse lung tissue. These findings were further verified by cell experiments. At a mechanistic level, CAPN1 can interact with TFEB after PAK infection and prevent its entry into the nucleus, thereby inhibiting the autophagolysosomal pathway.

CAPN1 promotes PAK-induced ALI by inhibiting the autophagy-lysosome pathway by targeting TFEB.

Autophagy-lysosome pathways play a crucial role in the intracellular killing of pathogenic microorganisms. This study aimed to explore the mechanism by which acute lung injury (ALI) of Pseudomonas aeruginosa affects the autophagy-lysosome pathway.

ALI mouse models were induced by lipopolysaccharide and P. aeruginosa strain K (PAK). Lung tissue sections were stained with hematoxylin-eosin for observation. Flow cytometry was used to analyze bacteria and inflammatory cell infiltration. ELISA was performed to measure inflammatory factor levels. Transmission electron microscopy evaluated autolysosome quantity. Western blot detected levels of related proteins. Immunofluorescence evaluated LC3 expression, and the localization of TFEB in cells was observed. Co-immunoprecipitation and pull-down experiments confirmed the interaction between CAPN1 and TFEB. qRT-PCR measured capn1 and tfeb expression.

Mouse experiments revealed that PAK infection led to the suppression of autolysosomes in mouse lung tissue, along with increased CAPN1 expression and decreased TFEB in the lung tissue of PAK-induced pneumonia mice. CAPN1-deficient mice could reverse the impact of PAK infection on autolysosomes in mouse lung tissue. These findings were further verified by cell experiments. At a mechanistic level, CAPN1 can interact with TFEB after PAK infection and prevent its entry into the nucleus, thereby inhibiting the autophagolysosomal pathway.

CAPN1 promotes PAK-induced ALI by inhibiting the autophagy-lysosome pathway by targeting TFEB.

Background and Objective: Irrational use and overuse of antibiotics is considered a major cause of antimicrobial resistance (AMR) among patients admitted to hospitals, especially in intensive care units (ICUs). ICUs are the most critical wards in healthcare settings, where the use of antibiotics is much higher compared to other wards. Therefore, the appropriate administration and monitoring of antibiotic usage in these units is a matter of concern. Materials and Methods: This retrospective study evaluated the types, utilization patterns, sensitivity, and resistance of various antibiotics used among patients admitted to the ICUs of different hospitals after the third wave of the coronavirus disease in 2019 (COVID-19) in Pakistan. Results: It was observed that more than 40% of the patients were given two antibiotics and 54.3% were given at least one antibiotic each day. A total of 768 antibiotics from different groups, based on the World Health Organization (WHO) Access, Watch, and Reserve (AWaRe) classification, were prescribed to 313 patients admitted to ICUs between April and August 2021. Among the types of antibiotics, amoxicillin/clavulanic acid was the most frequently used antibiotic (75 prescriptions). It was also observed that the majority of the bacterial isolates were more sensitive to carbapenems than the other antibiotics. The current study showed that antibiotic usage according to the AWaRe classifications was 31.8% in the Access category, 59.5% in the Watch category, and 8.7% in the Reserve category in ICUs of the studied hospitals after the third wave of COVID-19. Conclusions: The findings of the study also highlight the importance and continuous need for the implementation of antibiotic stewardship programs to optimize the appropriate utilization of antibiotics in the ICUs of the studied hospitals.

Pharmacokinetics (PK)/pharmacodynamics (PD) modeling and simulation is crucial for optimizing antimicrobial dosing. This study assessed covariate impact on PK variability and identified scenarios where fixing the covariate with median value proves effective PK/PD simulations for antibiotics with population PK (popPK) model including only one covariate effect. Three published popPK models were employed, with creatinine clearance (CRCL) identified as a covariate on clearance (CL) for meropenem and tobramycin, and total body weight (WT) associated with the volume of distributions for daptomycin. Given a fixed dose for Meropenem (1000 mg), and a WT based dose for tobramycin (7 mg/kg) and daptomycin (6 mg/kg), PK/PD simulation outcomes (e.g., percentage of PK/PD target attainment (PTA) and toxicity risk) were compared between fixed covariate-based and covariate distribution-based approaches. Covariate impact on PK was assessed through deterministic simulation using outer bounds of covariate versus simulation using median covariate value, with an overlap ratio calculated the percentage of overlapped area under concentration-time curve (AUC) between these two simulation approaches. Meropenem and tobramycin simulations showed a broader PK profiles and distinct PTA distribution with sampled covariate distribution, while daptomycin simulations exhibited consistency in PK/PD characteristics. CRCL had a relative strong impact on meropenem and tobramycin PK, while a weak impact of WT on daptomycin PK was observed from extensive overlap in simulated PK curves, with an overlap ratio of 99.5%. Regarding a weak covariate impact on PK with high overlap ratio, sampling from covariate distribution may not significantly enhance simulation performance, fixing covariate with median value could be efficient for antibiotic PK/PD simulations.

Background: Prompt administration of optimal antibiotic therapy is essential in the management of bacteraemia to reduce morbidity and mortality and to facilitate antibiotic stewardship. To identify the most effective therapy, rapid and accurate antimicrobial susceptibility testing (AST) is essential. ASTar is an automated AST system that delivers minimum inhibitory concentrations (MICs) for 23 antimicrobials and is designed for testing Gram-negative bacteria directly from positive blood cultures, with results available after 6 h. Methods: The ASTar system was evaluated with 64 positive blood cultures from patients with bacteraemia and 56 simulated blood cultures inoculated with a range of antibiotic-resistant isolates. The ASTar results for 12 antibiotics commonly used in our hospitals were compared with the results derived from three different methods of disc susceptibility testing and MICs determined by broth microdilution (BMD). Results: For 121 isolates of Gram-negative bacteria, ASTar showed an average essential agreement of 87.2% and an average categorical agreement of 94%, when compared with BMD. Very major errors (false susceptibility) and major errors (false resistance) were associated with 0.9% and 3.4% of results, respectively. The results were at least as accurate as those obtained from EUCAST disc susceptibility methods (both rapid and overnight methods). Conclusions: The ASTar system is an effective method for delivering accurate and rapid (6 h) AST results for Gram-negative bacteria by the direct testing of positive blood cultures.

Acinetobacter baumannii (A. baumannii) is an opportunistic, Gram-negative human pathogen, which is predominantly found in hospital patients. Its antimicrobial resistance is escalating, leading to less efficient treatments, and an increasing interest in identifying new therapeutic drugs. Metals as antimicrobials are vital in healthcare and agriculture, and copper-containing surfaces are known to reduce microbial counts, also in clinical settings. Indeed, copper (Cu) is an essential element required for survival in all organisms from bacteria to humans, but nevertheless elevated levels are highly toxic for cells. Through different regulatory mechanisms, cells maintain Cu homeostasis, and ion channels and transporters are critical in this process. Precise understanding of such ion transport requires insight into the protein structures of the involved proteins, which will also provide information important for applied sciences. Considering the medical significance of A. baumannii and the possibility to exploit Cu to handle such infections, channels and transporters represent appealing targets. Here we approached the putative outer membrane CopB (Copper resistance protein B) from A. baumannii that is postulated to conduct Cu, with characterization of its structure and function as well as to enable rational drug-design. To this end, we demonstrate in this work procedures to produce purified sample and to recover diffracting protein crystals of CopB. The protein was overproduced in E. coli and membrane extracted in a range of detergents. The solubilized protein was subjected to crystallization, which yielded hits that scatter X-rays to low resolution. Our findings have the potential to pave the way for subsequent drug discovery.

Intestinal perforations lead to a high risk of sepsis-associated morbidity and multi-organ dysfunctions. A perforation allows intestinal contents (IC) to enter the peritoneal cavity, causing abdominal infections. Right- and left-sided perforations have different prognoses in humans, but the mechanisms associated with different cecum and colon perforations remain unclear. This study investigates how gut flora influences outcomes from perforations at different sites in mice. Using fecal-induced peritonitis mouse model, isolated IC from the cecum or colon was injected peritoneally at 2 mg/kg. Bacterial burden was quantified with quantitative PCR, and microbial communities were analyzed using 16S rRNA gene sequencing. Survival rates were monitored, and blood biochemical indices, histological changes, cytokines expression, immunological signaling and multiple-organ damage were assessed at 16 h post-injections. The results showed cecum IC developed more severe sepsis than colon IC, with shorter median survival time and greater multi-organ damage. Mice treated with cecum IC displayed elevated tissue damage markers in the liver, heart, and kidneys, contributing to worsened pathology. This was likely driven by systematic inflammatory cytokines production and lung inflammation. Mechanistically, cecum IC triggered stronger cGAS-STING and TBK1-NF-κB signaling, promoting systemic inflammation compared to the colon IC. Moreover, bacterial analysis demonstrated that cecum IC carry a higher bacterial burden than colon IC and exhibit a different microbial community. A detailed microbiome comparison revealed an increased abundance of potentially pathogenic bacteria in the cecum IC. These findings suggest that the site of intestinal perforation influences sepsis severity, with the cecum being associated with a higher bacterial burden and a relatively increased abundance of potentially pathogenic bacteria compared to the colon. Our findings first compared the lethality associated with the microbial composition of the cecum and colon, indicating the perforation site could help providers predict the severity of sepsis, thereby introducing a novel perspective to microbiology and sepsis research.

Antimicrobial resistance is a rising global health threat, leading to ineffective treatments, increased mortality and rising healthcare costs. In ICUs, inappropriate empiric antibiotic therapy is often given due to treatment urgency, causing poor outcomes. This study developed a machine learning model to predict the appropriateness of empiric antibiotics for ICU-acquired bloodstream infections, using data from the MIMIC-III database. To address missing values and dataset imbalances, novel computational methods were introduced. The model achieved an AUROC of 77.3% and AUPRC of 40.4% on validation, with similar results on external datasets from MIMIC-IV and Rambam Hospital. The model also predicted mortality risk, identifying a 30% mortality rate in high-risk patients versus 16.8% in low-risk groups. External validation on the eICU database showed a comparable gap, with mortality rates at 24% for high-risk and 7.7% for low-risk groups. Our study demonstrates the potential of machine learning models to predict inappropriate empiric antibiotic treatment.

Pathogen identification is essential in sepsis and septic shock. Metagenomic next-generation sequencing (mNGS) is a novel pathogen detection method with several advantages over traditional tests. However, the consistency between mNGS and traditional pathogen tests requires further investigation.

We aimed to assess the consistency between mNGS and traditional pathogen tests and to identify the factors influencing this consistency.

This systematic review and meta-analysis involved a comprehensive search of mNGS and traditional pathogen tests in PubMed, Embase, Scopus, Web of Science, and the Cochrane Library. Data from included studies were extracted, and kappa consistency between mNGS and traditional tests was calculated. Study quality was evaluated using the QUADAS-2 tool.

The search identified 415 studies, of which 27 were included in the analysis, involving 4112 individuals. Meta-analysis showed a pooled consistency of 0.319 ± 0.013 (p < 0.001), indicating a moderate relationship. In terms of sample type, cerebrospinal fluid showed the highest pooled kappa consistency at 0.500 ± 0.029 (p < 0.001). Immunocompromised patients had a lower pooled kappa consistency of 0.294 ± 0.014 (p < 0.001) compared to 0.321 ± 0.028 (p < 0.001) in immunocompetent patients. Positive percent agreement of mNGS was 83.63% over traditional microbiological test, and negative percent agreement was 54.59%.

This review demonstrates a moderate relationship between mNGS and traditional pathogen tests, indicating a complex relationship between these two methods. Sterile samples show higher consistency than non-sterile samples. Immune function deficiency may reduce the consistency between mNGS and traditional tests. Further research is needed on the use of mNGS in sepsis and septic shock.

Despite the widespread use of voriconazole in antifungal treatment, its high pharmacokinetic and pharmacodynamic variability may lead to suboptimal efficacy, especially in intensive care unit (ICU) patients. Machine learning (ML), an artificial intelligence modeling approach, is increasingly being applied to personalized medicine. The effectiveness of ML models for predicting voriconazole blood concentrations in ICU patients, compared to traditional population pharmacokinetics (popPK) models, has been uncertain until now. This study aims to identify the most effective modeling strategy for voriconazole.

We developed six ML models using 244 concentrations from 62 patients in our previous popPK dataset. Another additional dataset, consisting of 282 trough concentrations from 177 patients, was used to externally evaluate both ML models and five other published popPK models, utilizing prediction-based diagnostics, simulation-based diagnostics, and Bayesian forecasting.

The XGBoost model exhibited superior predictive performance among the six ML models, achieving an R2 of 0.73. Its performance metrics (RMSE%: 127.21 %, median absolute prediction error: 29.65 %, median prediction error: 9.82 %, F20: 34.04 %, F30: 50.71 %) outperformed those of the best popPK model (RMSE%: 152.41 %, median absolute prediction error: 44.75 %, median prediction error: -0.99 %, F20: 23.40 %, F30: 36.88 %), suggesting greater accuracy and precision in predicting pharmacokinetics.

Both ML and popPK models can be utilized for individualized voriconazole therapy. Our comparative study provides insights into the most effective methods for modeling and predicting voriconazole concentrations.

Background: Antimicrobial resistance represents a continuing threat to the health of patients with intra-abdominal infections (IAIs). This study aimed to provide clinicians with guidance to optimize antibiotic therapy. Methods: The clinical data and antibiotic susceptibility results of pathogens from patients with IAIs from 2017 to 2022 were retrospectively collected. The 6-year period was segmented into two stages, namely, the early (2017-2020) and recent stages (2021-2022). The distribution and antibiotic resistance of pathogens were compared between the stages. Results: In total, 5,795 pathogens were isolated from 2,283 patients diagnosed with IAIs. Gram-negative bacteria, Gram-positive bacteria, and fungi accounted for 71.0%, 21.4%, and 7.5% of the isolates, respectively. Klebsiella pneumoniae (1,037, 17.9%) was the primary isolate. The proportion of extended-spectrum β-lactamase-producing Enterobacteriaceae was 89.8% (2,028/2,259), with extended-spectrum β-lactamase-producing Escherichia coli and K. pneumoniae accounting for 27.4% and 43.2%, respectively, of all such isolates. The carbapenem resistance rates of E. coli and K. pneumoniae were 17.1% and 75.9%, respectively. Compared with that in the early stage, the imipenem resistance rate of E. coli was significantly higher in the recent stage (13.8% vs. 25.1%, p < 0.001). Among Gram-positive bacteria, 88 strains of vancomycin-resistant Enterococcus were detected, giving a resistance rate of 10.3%, and the detection rate of methicillin-resistant Staphylococcus aureus was 65.7%. Conclusions: Enterobacteriales and non-fermentative bacteria from IAIs remain highly resistant to carbapenems. The epidemiological characteristics and antibiotic resistance profiles of pathogens in various regions should be closely monitored to mitigate the appearance of drug-resistant bacteria in clinical settings.

Patients undergoing extracorporeal membrane oxygenation (ECMO) are susceptible to fungal infections, also from rare or emerging pathogens. We present a case of a 3-year-old male patient hospitalized for respiratory failure and subjected to open-chest ECMO support, with a fungal infection from a pathogen not identifiable by standard methods.

Although T2Candida panel (T2 Biosystems) resulted negative, blood cultures resulted positive for fungi after 4 days, confirmed by Gram staining. The fungus underwent typing using Bruker matrix-assisted laser desorption ionization-time of flight mass spectrometry system and Autobio Autof ms1000, which could not precisely identify the microorganism. Ultimately, whole genome sequencing (WGS) was performed directly on blood culture.

WGS analysis revealed in 5 days the presence of a fungus belonging to the Ustilago genus, a group of fungi commonly found in the environment but rarely causing human diseases.

To the best of our knowledge, we presented the first case of an Ustilago spp infection in a pediatric patient undergoing ECMO, not identified by standard techniques but only by WGS performed directly on a blood sample in 5 days. Despite the paucity of literature on Ustilago spp infections treatment, therapy adjustments led to the eradication of the pathogen, underscoring the importance of advanced molecular techniques for the correct and timely identification of these microorganisms.

Dahuang Mudan decoction (DMD) is a traditional Chinese prescription from Zhang Zhongjing's Synopsis of the Golden Chamber. In clinical practice, it is often used in the treatment of infectious diseases.

To assess the therapeutic effect of DMD and its disassembled prescriptions on septic mice, and explore its potential mechanism.

Cecal ligation and puncture (CLP) sepsis and endotoxemia mice models were established. The effects of DMD, its disassembled prescriptions and active compounds were studied. Xuebijing injection (XBJ) was used as positive drug. Mice 7-day survival rates, blood biochemical markers, hematoxylin and eosin (HE) staining and immune cell infiltration were used to evaluate the overall protective effect of the drugs on mice. Inflammatory cytokines and coagulation activation indicators were detected by enzyme-linked immunosorbent assay (ELISA).

DMD, its Huoxue prescription, constituent drugs Mudanpi (MDP) and Taoren (TR) significantly protected mice with sepsis, improved the survival rate, reduced the degree of organ damage, and reduced the infiltration of immune cells in the lung tissues. The protective effect is comparable to that of XBJ. MDP and TR inhibited the levels of inflammatory factors and coagulation activation in septic mice. Paeonol and paeoniflorin in MDP showed significant protective effects on septic mice, and inhibited inflammatory cytokines level and coagulation activation.

These results confirm that DMD and its disassembled prescriptions have good therapeutic effect on septic mice, and the mechanism may be related to inhibition of the inflammatory response and coagulation activation.

Background: Nosocomial lower respiratory tract infections (nLRTIs) are associated with unfavorable clinical outcomes and significant healthcare costs. nLRTIs include hospital-acquired pneumonia (HAP), ventilator-associated pneumonia (VAP), and other ICU-acquired pneumonia phenotypes. While risk factors for mortality in these infections are critical to guide preventive strategies, it remains unclear whether they vary based on their requirement of invasive mechanical ventilation (IMV) at any point during the hospitalization. Objectives: This study aims to identify risk factors associated with short- and long-term mortality in patients with nLRTIs, considering differences between those requiring IMV and those who do not. Methods: This multinational prospective cohort study included ICU-admitted patients diagnosed with nLRTI from 28 hospitals across 13 countries in Europe and South America between May 2016 and August 2019. Patients were selected based on predefined inclusion and exclusion criteria, and clinical data were collected from medical records. A random forest classifier determined the most optimal clustering strategy when comparing pneumonia site acquisition [ward or intensive care unit (ICU)] versus intensive mechanical ventilation (IMV) necessity at any point during hospitalization to enhance the accuracy and generalizability of the regression models. Results: A total of 1060 patients were included. The random forest classifier identified that the most efficient clustering strategy was based on ventilation necessity. In total, 76.4% of patients [810/1060] received IMV at some point during the hospitalization. Diabetes mellitus was identified to be associated with 28-day mortality in the non-IMV group (OR [IQR]: 2.96 [1.28-6.80], p = 0.01). The 90-day mortality-associated factor was MDRP infection (1.98 [1.13-3.44], p = 0.01). For ventilated patients, chronic liver disease was associated with 28-day mortality (2.38 [1.06-5.31] p = 0.03), with no variable showing statistical and clinical significance at 90 days. Conclusions: The risk factors associated with 28-day mortality differ from those linked to 90-day mortality. Additionally, these factors vary between patients receiving invasive mechanical ventilation and those in the non-invasive ventilation group. This underscores the necessity of tailoring therapeutic objectives and preventive strategies with a personalized approach.

Therapeutic and prophylactic use of antifungals is rising continuously. However, inadequate awareness of diagnostic and treatment guidelines and limited laboratory modalities lead to inappropriate use. This study assessed the impact of an institutional antifungal stewardship program on antifungal use practices and patient outcomes. In the pre-intervention phase, data was collected regarding antifungal therapy among patients with invasive fungal infections. Appropriateness of antifungal prescription was assessed. In the intervention phase, simple algorithms for diagnosis and management of fungal infections were prepared from international guidelines and incorporated into a booklet for distribution. Monthly training sessions were conducted. New serological and molecular tests and therapeutic drug monitoring were introduced. In the post-intervention phase, an antifungal stewardship team was constituted for clinical advisory on demand and ongoing training. Data regarding antifungal therapy was collected and compared with pre-intervention data. Untreated patients decreased from 25% to 18.9% post-intervention (P = .28). Appropriate antifungal use increased from 72.6% to 77.9% (P = .4) among patients with a single fungal infection, and from 57.1% to 88.5% (P = .04) for at least one infection among those with dual fungal infections. 49 incidents of inappropriate use in various categories were seen among 75 patients receiving antifungals pre-intervention, decreasing to 42 incidents among 94 patients post-intervention (P = .06), particularly evident among patients with dual infections (P = .002). Mortality increased from 51% to 75.86% post-intervention (P = .0001). Overall, the small improvement noticed in antifungal usage pattern can still be considered significant, given the limited study period.

Aim/Purpose of the study: Acute lung injury (ALI) is a severe respiratory disease with high mortality, mainly due to overactivated oxidative stress and subsequent pyroptosis. Mesencephalic astrocyte-derived neurotrophic factor (MANF), an inducible secretory endoplasmic reticulum (ER) stress protein, inhibits lipopolysaccharide (LPS)-induced acute lung injury (ALI). However, the exact molecular mechanism remains unclear. Peroxiredoxin 6 (PRDX6), a peroxidase with a dual enzymatic function, is essential in regulating oxidative stress, which is closely associated with ALI. Furthermore, PRDX6 is an interacting protein of MANF. Therefore, this study aims to investigate the role of PRDX6 in the protective effect of MANF on ALI.

Materials and Methods: In this study, we used LPS to establish the LPS-induced ALI model. Recombinant human MANF was administrated to wide-type (WT) and PRDX6 knockout (PRDX6-/-) rats.

Results: In WT rats, MANF reversed the increases of PRDX6, ROS overgeneration, and pyroptosis-related protein-Gasdermin D (GSDMD) induced by LPS challenge. In PRDX6-/- rats, ROS generation, the protein level of GSDMD-N, and lung injury were not significantly decreased after human recombinant MANF administration in LPS-induced ALI.

Conclusions: PRDX6 is involved in the protective role of MANF on ALI. It is a key target molecule for MANF to exert ALI inhibitory effects.

Invasive infections with Aspergillus fumigatus in ICU patients are linked to high morbidity and mortality. Diagnosing invasive pulmonary aspergillosis (IPA) in non-immunosuppressed patients is difficult, as Aspergillus antigen (galactomannan [GM]) may have other causes. This retrospective study analyzed 160 ICU surgical patients with positive GM in broncho-alveolar lavage fluid (BALF), classifying them based on AspICU criteria for suspected IPA (pIPA) or aspiration. Patients with pIPA had higher disease severity than those with aspiration, including higher dialysis rates, organ transplantation, corticosteroid use, and Sequential Organ Failure Assessment (SOFA) score. Aspergillus culture was positive in 47.0% of pIPA cases but only 2.6% of aspiration cases (p < 0.001). SOFA score at first positive GM in BALF independently predicted 28-day mortality. In surgical patients with a positive GM in BALF, aspiration is more likely if there's no corticosteroid therapy, negative Aspergillus culture, and a history of aspiration events. Diagnosis of pIPA requires Aspergillus culture or prior corticosteroid therapy in this cohort of critically ill patients.

Pathogenic bioaerosols are critical for outbreaks of airborne disease; however, rapidly and accurately identifying pathogens directly from complex air environments remains highly challenging. We present an advanced method that combines open-set deep learning (OSDL) with single-cell Raman spectroscopy to identify pathogens in real-world air containing diverse unknown indigenous bacteria that cannot be fully included in training sets. To test and further enhance identification, we constructed the Raman datasets of aerosolized bacteria. Through optimizing OSDL algorithms and training strategies, Raman-OSDL achieves 93% accuracy for five target airborne pathogens, 84% accuracy for untrained air bacteria, and 36% reduction in false positive rates compared to conventional close-set algorithms. It offers a high detection sensitivity down to 1:1000. When applied to real air containing >4600 bacterial species, our method accurately identifies single or multiple pathogens simultaneously within an hour. This single-cell tool advances rapidly surveilling pathogens in complex environments to prevent infection transmission.

We evaluated the cost-effectiveness of a bundled intervention including an antimicrobial stewardship program (ASP), procalcitonin (PCT) testing, and rapid blood culture identification (BCID), compared with pre-implementation standard care in critically ill adult patients with sepsis.

We conducted a decision tree model-based cost-effectiveness analysis alongside a previously published pre- and post-implementation quality improvement study. We adopted a public Canadian healthcare payer's perspective. Two intensive care units in Alberta with 727 adult critically ill patients were included. Our bundled intervention was compared with pre-implementation standard care. We collected healthcare resource use and estimated unit costs in 2022 Canadian dollars (CAD) over a time horizon from study entry to hospital discharge or death. We calculated the incremental net monetary benefit (iNMB) of the intervention group compared with the pre-intervention group. The primary outcome was cost per sepsis case. Secondary outcomes included readmission rates, Clostridioides difficile infections, mortality, and lengths of stay. Uncertainty was investigated using cost-effectiveness acceptability curves, cost-effectiveness plane scatterplots, and sensitivity analyses.

Mean (standard deviation [SD]) cost per index hospital admission was CAD $83,251 ($107,926) for patients in the intervention group and CAD $87,044 ($104,406) for the pre-intervention group, though the difference ($3,793 [$7,897]) was not statistically significant. Costs were higher in the pre-intervention group for antibiotics, readmissions, and C. difficile infections. The intervention group had a lower mean expected cost; $110,580 ($108,917) compared with pre-intervention ($125,745 [$113,210]), with a difference of $15,165 ($8278). There were no statistically significant differences in quality adjusted life years (QALYs) between groups. The iNMB of the intervention group compared with pre-intervention was greater than $15,000 for willingness-to-pay (WTP) per QALY values of between $0 and $100,000. In our sensitivity analysis, the intervention was most likely to be cost-effective in roughly 56% of simulations at all WTP thresholds.

Our bundled intervention of ASP, PCT, and BCID among adult critically ill patients with sepsis was potentially cost-effective, but with substantial decision uncertainty.

The survival of paediatric oncology patients has improved substantially in the past decades due to advances in the field of oncology. Modern cancer treatments often come with life-threatening complications, of which infection is one of the most common causes in this patient population. This study aims to investigate the prevalence and outcomes of common infections in haemato-oncology patients during their stay in paediatric intensive care unit (PICU) and to identify any factors associated with these infections.

A retrospective observational study was conducted on all children with a haemato-oncology diagnosis or who underwent haematopoietic stem cell transplantation (HSCT) and who were admitted to the Hong Kong Children's Hospital PICU over a one-year period. Infection characteristics and patient outcomes were evaluated and compared between different sub-groups. Univariable and multi-variable analyses were employed to identify risk factors associated with the development of active infection.

Forty-five (36.3%) of 124 critically ill haemato-oncology admissions to PICU were associated with infections, of which 31 (25%) admissions involved bacterial infections, 26 (20.9%) involved viral infections and 6 (4.8%) involved fungal infections. Bloodstream infection was the most common type of infection. More than half (61.3%) of the bacterial infections were due to an antibiotic-resistant strain. After adjusting for confounding variables, post-HSCT status and neutropenia were significantly associated with active infections.

Infections in critically-ill haemato-oncological patients are associated with post haematopoietic stem cell transplant status and neutropenia. Further study is warranted to review effective strategies that may mitigate the likelihood of infection in this patient population.