Nosocomial pneumonia, including hospital-acquired pneumonia and ventilator-associated pneumonia, is the leading cause of death related to hospital-acquired infections among critically ill patients. A growing proportion of these cases are attributed to multi-drug-resistant (MDR-) Gram-negative bacteria (GNB). MDR-GNB pneumonia often leads to delayed appropriate treatment, prolonged hospital stays, and increased morbidity and mortality. This issue is compounded by the increased toxicity profiles of the conventional antibiotics required to treat MDR-GNB infections. In recent years, several novel antibiotics have been licensed for the treatment of GNB nosocomial pneumonia. These novel antibiotics are promising therapeutic options for treatment of nosocomial pneumonia by MDR pathogens with certain mechanisms of resistance. Still, antibiotic resistance remains an evolving global crisis, and resistance to novel antibiotics has started emerging, making their judicious use crucial to prolong their shelf-life. This article presents an up-to-date review of these novel antibiotics and their current role in the antimicrobial armamentarium. We critically present data for the pharmacokinetics/pharmacodynamics, the in vitro spectrum of antimicrobial activity and resistance, and in vivo data for their clinical and microbiological efficacy in trials. Where possible, available data are summarized specifically in patients with nosocomial pneumonia, as this cohort may exhibit \'critical illness\' physiology that affects drug efficacy.

UNASSIGNED: Serum anion gap (AG) can potentially be applied to the diagnosis of various metabolic acidosis, and a recent study has reported the association of AG with the mortality of patients with coronavirus disease 2019 (COVID-19). However, the relationship of AG with the short-term mortality of patients with ventilator-associated pneumonia (VAP) is still unclear. Herein, we aimed to investigate the association between AG and the 30-day mortality of VAP patients, and construct and assess a multivariate predictive model for the 30-day mortality risk of VAP.
UNASSIGNED: This retrospective cohort study extracted data of 477 patients with VAP from the Medical Information Mart for Intensive Care III (MIMIC-III) database. Data of patients were divided into a training set and a testing set with a ratio of 7:3. In the training set, variables significantly associated with the 30-day mortality of VAP patients were included in the multivariate predictive model through univariate Cox regression and stepwise regression analyses. Then, the predictive performance of the multivariate predictive model was assessed in both training set and testing set, and compared with the single AG and other scoring systems including the Sequential Organ Failure Assessment (SOFA) score, the confusion, urea, respiratory rate (RR), blood pressure, and age (≥65 years old) (CURB-65) score, and the blood urea nitrogen (BUN), altered mental status, pulse, and age (>65 years old) (BAP-65) score. In addition, the association of AG with the 30-day mortality of VAP patients was explored in subgroups of gender, age, and infection status. The evaluation indexes were hazard ratios (HRs), C-index, and 95% confidence intervals (CIs).
UNASSIGNED: A total of 70 patients died within 30 days. The multivariate predictive model consisted of AG (HR =1.052, 95% CI: 1.008-1.098), age (HR =1.037, 95% CI: 1.019-1.055), duration of mechanical ventilation (HR =0.998, 95% CI: 0.996-0.999), and vasopressors use (HR =1.795, 95% CI: 1.066-3.023). In both training set (C-index =0.725, 95% CI: 0.670-0.780) and testing set (C-index =0.717, 95% CI: 0.637-0.797), the multivariate model had a relatively superior predictive performance to the single AG value. Moreover, the association of AG with the 30-day mortality was also found in patients who were male (HR =1.088, 95% CI: 1.029-1.150), and whatever the pathogens they infected (bacterial infection: HR =1.059, 95% CI: 1.011-1.109; fungal infection: HR =1.057, 95% CI: 1.002-1.115).
UNASSIGNED: The AG-related multivariate model had a potential predictive value for the 30-day mortality of patients with VAP. These findings may provide some references for further exploration on simple and robust predictors of the short-term mortality risk of VAP, which may further help clinicians to identify patients with high risk of mortality in an early stage in the intensive care units (ICUs).

Ventilator-associated pneumonia (VAP) is common in Pediatric Intensive Care Units. Although early detection is crucial, current diagnostic methods are not definitive. This study aimed to identify lung ultrasound (LUS) findings and procalcitonin (PCT) values in pediatric patients with VAP to create a new early diagnosis score combined with the Clinical Pulmonary Infection Score (CPIS), the CPIS-PLUS score. Prospective longitudinal and interventional study. Pediatric patients with suspected VAP were included and classified into VAP or non-VAP groups, based on Centers of Disease Control (CDC) criteria for the final diagnosis. A chest-X-ray (CXR), LUS, and blood test were performed within the first 12 h of admission. CPIS score was calculated. A total of 108 patients with VAP suspicion were included, and VAP was finally diagnosed in 51 (47%) patients. CPIS-PLUS showed high accuracy in VAP diagnosis with a sensitivity (Sn) of 80% (95% CI 65-89%) and specificity (Sp) of 73% (95% CI 54-86%). The area under the curve (AUC) resulted in 0.86 for CPIS-PLUS vs. 0.61 for CPIS. In conclusion, this pilot study showed that CPIS-PLUS could be a potential and reliable tool for VAP early diagnosis in pediatric patients. Internal and external validations are needed to confirm the potential value of this score to facilitate VAP diagnosis in pediatric patients.

Endotracheal cuff-pressure monitoring is a critical component of patient care in the intensive care unit, ensuring the safety and efficacy of mechanical ventilation. Despite its importance, there remains a lack of standardized protocols regarding optimal pressure targets and documentation practices. This editorial examines the significance of endotracheal intracuff-pressure monitoring in enhancing patient outcomes, highlighting the challenges and potential solutions in clinical practice.

In response to the urgent requirement for rapid, precise, and cost-effective detection in intensive care units (ICUs) for ventilated patients, as well as the need to overcome the limitations of traditional detection methods, researchers have turned their attention towards advancing novel technologies. Among these, biosensors have emerged as a reliable platform for achieving accurate and early diagnoses. In this study, we explore the possibility of using Pyocyanin analysis for early detection of pathogens in ventilator-associated pneumonia (VAP) and lower respiratory tract infections in ventilated patients. To achieve this, we developed an electrochemical sensor utilizing a graphene oxide-copper oxide-doped MgO (GO - Cu - Mgo) (GCM) catalyst for Pyocyanin detection. Pyocyanin is a virulence factor in the phenazine group that is produced by Pseudomonas aeruginosa strains, leading to infections such as pneumonia, urinary tract infections, and cystic fibrosis. We additionally investigated the use of DNA aptamers for detecting Pyocyanin as a biomarker of Pseudomonas aeruginosa, a common causative agent of VAP. The results of this study indicated that electrochemical detection of Pyocyanin using a GCM catalyst shows promising potential for various applications, including clinical diagnostics and drug discovery.

Introduction Patients admitted to intensive care units (ICU), especially those with devices used to support their condition, are at a higher risk of getting healthcare-associated infections (HAIs). The aim of the present study was to analyze the surveillance data and assess the device-associated infection (DAI) rates such as central line-associated blood-stream infection (CLABSI), catheter-associated urinary tract infection (CAUTI), ventilator-associated pneumonia (VAP) and ventilator-associated event (VAE) in ICUs of the Ministry of Health (MoH) hospitals in Al-Ahsa region. Methodology The study was conducted retrospectively using the surveillance data of governmental hospitals\' intensive care units in the Al-Ahsa region. The surveillance data was collected from 10 ICUs at six MoH hospitals in the Al-Ahsa region during the year 2022. The data from the participating hospitals was entered into the Health Electronic Surveillance Network (HESN) plus program by trained infection prevention control practitioners of the respective hospitals. Results An overall CLABSI rate of 4.29 per 1000 central line days was reported during the study period. The CAUTI rate was 0.55 with a range from 0 to 1.29 cases per 1000 urinary catheter days. VAP rate ranged from 0.33 to 2.21 cases per 1000 ventilator days (average of 1.17). The study reported VAE only for the adult medical-surgical ICU (3.36 per 1000 ventilator days). Conclusion The present study revealed that the most common DAIs in the Al-Ahsa region are CLABSI and CAUTI. DAI rates generated from this study may be used as benchmarks for regional hospitals. An educational program regarding the prevention and control of DAIs targeting all healthcare workers, especially ICU staff, has to be done in the Al-Ahsa region.

In critical patients, generally, microorganisms originating from nasal cause Ventilator-Associated Pneumonia (VAP). This systematic review was aimed to identify the toothbrush U shape model usage, in potentially decrease the prevalence of ventilator-associated pneumonia among patients in intensive care units. Search strategy identified 15 potentially eligible articles, were 7 RCTs, 4 Meta-analysis, and 4 Observational studies. A total of 15 studies demonstrated the use of toothbrushing and chlorhexidine in mechanically ventilator patients in preventing VAP. Ten studies found positive association between toothbrushing and the use of chlorhexidine in preventing VAP. However, there were 5 studies that did not reveal an additional decrease of VAP incidence either of CHX and only toothbrushing or combination thereof. We cautiously assumed that toothbrushing and chlorhexidine might reduce VAP but the implementation of brushing should be taken into reconsideration in the terms of maintaining it.

Sepsis and septic shock are common in critically ill patients and, as recommended by the Surviving Sepsis Campaign (SSC), early empiric antimicrobial therapy, specifically within the first hour, is crucial for the successful management of these conditions. To be effective, the antimicrobial therapy must also be appropriately administered: the drugs should cover the most probable pathogens and achieve effective concentrations at the site of infection. However, pharmacokinetics are frequently altered in critically ill patients and continuously change since the clinical conditions of these patients quickly and markedly change over time, either improving or deteriorating. Accordingly, optimizing antimicrobial drug dosing is fundamental in intensive care units (ICUs). This Special Issue of Microorganisms examines the epidemiology, diagnostic innovations, and strategies applied in the context of infections in critically ill patients with MDR infections.

Ambient air pollutants can be hazardous to human health, especially for vulnerable children. The impact of ambient air pollutant exposure before and during intensive care unit (ICU) stays on the development of ventilator-associated pneumonia (VAP) in critically ill children has not been established. We aimed to determine the correlations between short-term exposures to ambient fine particulate matter (PM2.5) and VAP in pediatric cardiac surgery patients in the ICU, and explore the effect of delayed exposure.
The medical record of 1755 child patients requiring artificial ventilation in the ICU between December 2013 to December 2020, were analyzed. The daily average concentrations of particulate matters (PM2.5 and PM10), sulfur dioxide (SO2), and ozone (O3) were calculated from public data. Interactions between these pollutants and VAP were simulated with the distributed lag non-linear model.
Three hundred forty-eight cases (19.829%) of VAP were identified in this study, while the average concentrations of PM2.5, PM10, O3 and SO2 were 58, 118, 98 and 26 μg/m3, respectively. Exposure to increased levels of PM2.5 two days prior (lag 2-day) to VAP diagnosis is significantly correlated with an enhanced risk for VAP development. Even a slight increase of 10 μg/m3 in PM2.5 can translate to a 5.4% increase in VAP incidence (95% CI: 1.4%-9.5%) while the VAP incidence increased to 11.1% (95%CI: 4.5-19.5%) when PM2.5 concentration is well below the National Ambient Air Quality standard (NAAQS) of 50 μg/m3. The association was more pronounced in those aged below 3-months, with low body mass index or suffered from pulmonary arterial hypertension.
Short-term PM2.5 exposure is a significant risk for development of VAP in pediatric patients. This risk is present even with PM2.5 levels below the NAAQS. Ambient PM2.5 may represent a previously unrecognized risk factor for pneumonia and the current environmental pollution standards need to be reevaluated to consider susceptible populations.
The trial was registered with the National Clinical Trial Center: The correlation between ambient air pollution and the complications in ICU underwent cardiac surgery.
ChiCTR2000030507. Date of registration: March 5, 2020. URL of trial registry record: http://www.chictr.org.cn/index.aspx .

UNASSIGNED: Basic studies show that selective 5-hydroxytryptamine type 3 (5-HT3) serotonin-receptor antagonists can protect organs from inflammatory injury and have shown lung protection. Whether 5-HT3 receptor antagonists ondansetron benefits patients with mechanical ventilation is unclear in the intensive care unit (ICU).
UNASSIGNED: The Medical Information Mart for Intensive Care-IV (MIMIC-IV) database was reviewed to identify patients on mechanical ventilation (aged >16 years) in the ICU, which was divided into two groups according to whether ondansetron is used. Demographic characteristics, medical history data, clinical parameters, diagnosis and treatment measures were included as covariates. Ondansetron use was defined as any kind of ondansetron administration regardless of the dose before the induction of mechanical ventilation. The primary outcome was in-hospital death. Hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated by multivariable Cox regression. Propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) were performed to further adjust for confounding factors. Kaplan-Meier (KM) curves with log-rank test were also performed.
UNASSIGNED: A total of 18,566 patients on mechanical ventilation were included (5,735 with ondansetron use). The overall in-hospital mortality rate of patients on mechanical ventilation was 18.9% (3,512/18,566). Approximately 13.0% (746/5,735) and 21.6% (2,766/12,831) in-hospital mortality rates occurred in the ondansetron and non-ondansetron use groups, respectively. Multivariable regression indicated that ondansetron usage was associated with a 33% and 32% lower risk of in-hospital and 60-day death (HR =0.77, 95% CI: 0.70-0.85, P<0.001; HR =0.68, 95% CI: 0.62-0.75, P<0.001) in the whole sample. Multivariable regression post-PSM indicated that ondansetron usage was associated with a 38% and 31% lower risk of in-hospital and 60-day death (HR =0.62, 95% CI: 0.56-0.68, P<0.001; HR =0.69, 95% CI: 0.62-0.77, P<0.001). Log-rank test for the KM curve of ondansetron and 60-day death was statistically significant (P<0.001). The duration of ventilator use pre- and post-PSM was statistically different (P<0.001 and P=0.007) in the two groups.
UNASSIGNED: Ondansetron usage was significantly associated with a lower mortality risk of ventilated patients in the ICU. The 5-HT3 receptor antagonist use is may be new potential adjunctive therapeutic strategy for patients on mechanical ventilation in the ICU.