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LSG1 is a conserved GTPase involved in ribosome assembly. It is required for the eviction of the nuclear export adapter NMD3 from the pre-60S subunit in the cytoplasm. In human cells, LSG1 has also been shown to interact with vesicle-associated membrane protein-associated proteins (VAPs) that are found primarily on the endoplasmic reticulum. VAPs interact with a large host of proteins which contain FFAT motifs (two phenylalanines (FF) in an acidic tract) and are involved in many cellular functions including membrane traffic and regulation of lipid transport. Here, we show that human LSG1 binds to VAPs via a noncanonical FFAT-like motif. Deletion of this motif specifically disrupts the localization of LSG1 to the ER, without perturbing LSG1-dependent recycling of NMD3 in cells or modulation of LSG1 GTPase activity in vitro. [ABSTRACT FROM AUTHOR]

Carbapenem-resistant Klebsiella pneumoniae (CRKP) infections are a major public health problem, requiring the use of last-resort antibiotics such as colistin. However, there is concern regarding the emergence of isolates resistant to this agent. The report describes two patients with urinary tract infection (UTI) and ventilator-associated pneumonia (VAP) infection caused by CRKP strains. The first case was a 23-year-old male with UTI caused by a strain of ST16 co-harboring blaCTX-M, blaTEM, blaSHV, blaNDM, blaOXA-48-like genes. The second case was a 39-year-old woman with VAP due to hypervirulent ST337-K2 co-harboring blaSHV, blaNDM, blaOXA-48-like,iucA, rmpA2 and rmpA. The patients' general condition improved after combination therapy with colistin (plus meropenem and rifampin, respectively) and both of them recovered and were discharged from the hospital. This study highlights the necessary prevention and control steps to prevent the further spread of CRKP strains should be a priority in our hospital. [ABSTRACT FROM AUTHOR]

Background: Device-associated infections (DAIs) are a significant cause of morbidity following living donor liver transplantation (LDLT). We aimed to assess the impact of bundled care on reducing rates of device-associated infections. Methods: We performed a before-and-after comparative study at a liver transplantation facility over a three-year period, spanning from January 2016 to December 2018. The study included a total of 57 patients who underwent LDLT. We investigated the implementation of a care bundle, which consists of multiple evidence-based procedures that are consistently performed as a unified unit. We divided our study into three phases and implemented a bundled care approach in the second phase. Rates of pneumonia related to ventilators [VAP], bloodstream infections associated with central line [CLABSI], and urinary tract infections associated with catheters [CAUTI] were assessed throughout the study period. Bacterial identification and antibiotic susceptibility testing were performed using the automated Vitek-2 system. The comparison between different phases was assessed using the chi-square test or the Fisher exact test for qualitative values and the Kruskal-Wallis H test for quantitative values with non-normal distribution. Results: In the baseline phase, the VAP rates were 73.5, the CAUTI rates were 47.2, and the CLABSI rates were 7.4 per one thousand device days (PDD). During the bundle care phase, the rates decreased to 33.3, 18.18, and 4.78. In the follow-up phase, the rates further decreased to 35.7%, 16.8%, and 2.7% PDD. The prevalence of Klebsiella pneumonia (37.5%) and Methicillin resistance Staph aureus (37.5%) in VAP were noted. The primary causative agent of CAUTI was Candida albicans, accounting for 33.3% of cases, whereas Coagulase-negative Staph was the predominant organism responsible for CLABSI, with a prevalence of 40%. Conclusion: This study demonstrates the effectiveness of utilizing the care bundle approach to reduce DAI in LDLT, especially in low socioeconomic countries with limited resources. By implementing a comprehensive set of evidence-based interventions, healthcare systems can effectively reduce the burden of DAI, enhance infection prevention strategies and improve patient outcomes in resource-constrained settings. [ABSTRACT FROM AUTHOR]

Introduction: Early antibiotic discontinuation in clinically suspected ventilator-associated pneumonia (VAP) may lead to infection relapse/recurrence and increase mortality. This study aimed to evaluate the incidence and potential predictors of treatment failure with this approach. Methodology: A retrospective observational study was conducted between September 2014 and November 2016 in a mixed intensive care unit. We included clinically suspected VAP patients whose quantitative sputum cultures from endotracheal aspirate were negative, allowing antibiotic discontinuation within 24 hours. Patients were monitored for signs and symptoms of recurrent VAP. Incidence and risk factors for treatment failure, defined as pneumonia recurrence, were determined using univariate logistic regression analysis and receiver operating characteristic (ROC) curves. Results: Forty-three patients met the inclusion criteria. The incidence of treatment failure among culture-negative VAP following early antibiotic discontinuation was 27.9% (12 patients). There were no significant differences in procalcitonin levels, leukocyte counts or body temperature between the two groups, except for the modified clinical pulmonary infection score (mCPIS) (5.42 ± 2.19 versus 3.9 ± 1.54, p = 0.014). Procalcitonin levels at VAP diagnosis and antibiotic cessation both showed low predictive capacity for treatment failure (AUC 0.56, CI 95% 0.36--0.76 and AUC 0.57, CI 95% 0.37--0.76, respectively). However, combining mCPIS with procalcitonin improved the predictive value for treatment failure (AUC 0.765, CI 95% 0.56--0.96). Conclusions: Early antibiotic discontinuation may lead to a high incidence of treatment failure among culture-negative VAP patients. Procalcitonin alone should not guide antibiotic discontinuation decisions while combining mCPIS and procalcitonin enhances predictive accuracy for treatment failure. [ABSTRACT FROM AUTHOR]

Background: Ventilator‑associated pneumonia (VAP) is the commonest healthcare‑associated infection (HAI) in intensive care units (ICU), especially in trauma patients. VAP imposes a significant cost burden on the healthcare ecosystem. However, there are few data from the developing world. Methodology: We conducted this study in the trauma ICU (TICU) of PGIMER, Chandigarh, from October 2021 to December 2022. The incidence, incidence density, and average length of stay (ALOS) of both VAP and non‑VAP patients were established. The health system cost was assessed using a mixed (top‑down and bottom‑up) micro‑costing approach. We collected data for all the resources (direct and indirect costs) utilized during service delivery and estimated the health system cost per bed per day. Results: In this study, 494 patients were admitted to TICU, of which 484 received Mechanical Ventilation (MV) and 47 developed VAP. We included 41 and 44 patients with and without VAP. The VAP incidence rate was 9.7% and the VAP incidence density was 10.79/1000 MV days. The ALOS for VAP patients was 21 days, and for non‑ VAP patients was 8.2 days. Our study estimated a total health system cost of INR 25,927 per bed per day. The health system cost of treating a VAP patient was INR 544,467 compared to INR 207,416 for a non‑VAP patient. Conclusion: Treatment of VAP poses substantial costs for the health system and patients. There is a need to focus on preventing VAP, which would eventually reduce the length of stay and the resultant financial impact on the health system and the patient. [ABSTRACT FROM AUTHOR]

Hospital-acquired pneumonia (HAP) and ventilation-associated pneumonia (VAP) are challenging clinical conditions due to the challenging tissue penetrability of the lung. This study aims to evaluate the potential role of fosfomycin (FOS) associated with ceftazidime/avibactam (CZA) in improving the outcome in this setting. We performed a retrospective study including people with HAP or VAP treated with CZA or CZA+FOS for at least 72 h. Clinical data were collected from the SUSANA study, a multicentric cohort to monitor the efficacy and safety of the newer antimicrobial agents. A total of 75 nosocomial pneumonia episodes were included in the analysis. Of these, 34 received CZA alone and 41 in combination with FOS (CZA+FOS). People treated with CZA alone were older, more frequently male, received a prolonged infusion more frequently, and were less frequently affected by carbapenem-resistant infections (p = 0.01, p = 0.06, p < 0.001, p = 0.03, respectively). No difference was found in terms of survival at 28 days from treatment start between CZA and CZA+FOS at the multivariate analysis (HR = 0.32; 95% CI = 0.07–1.39; p = 0.128), while prolonged infusion showed a lower mortality rate at 28 days (HR = 0.34; 95% CI = 0.14–0.96; p = 0.04). Regarding safety, three adverse events (one acute kidney failure, one multiorgan failure, and one urticaria) were reported. Our study found no significant association between combination therapy and mortality. Further investigations, with larger and more homogeneous samples, are needed to evaluate the role of combination therapy in this setting. [ABSTRACT FROM AUTHOR]

Abstract Carbapenem-resistant Klebsiella pneumoniae (CRKP) infections are a major public health problem, requiring the use of last-resort antibiotics such as colistin. However, there is concern regarding the emergence of isolates resistant to this agent. The report describes two patients with urinary tract infection (UTI) and ventilator-associated pneumonia (VAP) infection caused by CRKP strains. The first case was a 23-year-old male with UTI caused by a strain of ST16 co-harboring bla CTX-M, bla TEM, bla SHV, bla NDM, bla OXA-48-like genes. The second case was a 39-year-old woman with VAP due to hypervirulent ST337-K2 co-harboring bla SHV, bla NDM, bla OXA-48-like, iucA, rmpA2 and rmpA . The patients’ general condition improved after combination therapy with colistin (plus meropenem and rifampin, respectively) and both of them recovered and were discharged from the hospital. This study highlights the necessary prevention and control steps to prevent the further spread of CRKP strains should be a priority in our hospital.

Abstract Background Device-associated infections (DAIs) are a significant cause of morbidity following living donor liver transplantation (LDLT). We aimed to assess the impact of bundled care on reducing rates of device-associated infections. Methods We performed a before-and-after comparative study at a liver transplantation facility over a three-year period, spanning from January 2016 to December 2018. The study included a total of 57 patients who underwent LDLT. We investigated the implementation of a care bundle, which consists of multiple evidence-based procedures that are consistently performed as a unified unit. We divided our study into three phases and implemented a bundled care approach in the second phase. Rates of pneumonia related to ventilators [VAP], bloodstream infections associated with central line [CLABSI], and urinary tract infections associated with catheters [CAUTI] were assessed throughout the study period. Bacterial identification and antibiotic susceptibility testing were performed using the automated Vitek-2 system. The comparison between different phases was assessed using the chi-square test or the Fisher exact test for qualitative values and the Kruskal-Wallis H test for quantitative values with non-normal distribution. Results In the baseline phase, the VAP rates were 73.5, the CAUTI rates were 47.2, and the CLABSI rates were 7.4 per one thousand device days (PDD). During the bundle care phase, the rates decreased to 33.3, 18.18, and 4.78. In the follow-up phase, the rates further decreased to 35.7%, 16.8%, and 2.7% PDD. The prevalence of Klebsiella pneumonia (37.5%) and Methicillin resistance Staph aureus (37.5%) in VAP were noted. The primary causative agent of CAUTI was Candida albicans, accounting for 33.3% of cases, whereas Coagulase-negative Staph was the predominant organism responsible for CLABSI, with a prevalence of 40%. Conclusion This study demonstrates the effectiveness of utilizing the care bundle approach to reduce DAI in LDLT, especially in low socioeconomic countries with limited resources. By implementing a comprehensive set of evidence-based interventions, healthcare systems can effectively reduce the burden of DAI, enhance infection prevention strategies and improve patient outcomes in resource-constrained settings.

Background Ventilator-associated pneumonia (VAP) is the commonest healthcare-associated infection (HAI) in intensive care units (ICU), especially in trauma patients. VAP imposes a significant cost burden on the healthcare ecosystem. However, there are few data from the developing world. Methodology We conducted this study in the trauma ICU (TICU) of PGIMER, Chandigarh, from October 2021 to December 2022. The incidence, incidence density, and average length of stay (ALOS) of both VAP and non-VAP patients were established. The health system cost was assessed using a mixed (top-down and bottom-up) micro-costing approach. We collected data for all the resources (direct and indirect costs) utilized during service delivery and estimated the health system cost per bed per day. Results In this study, 494 patients were admitted to TICU, of which 484 received Mechanical Ventilation (MV) and 47 developed VAP. We included 41 and 44 patients with and without VAP. The VAP incidence rate was 9.7% and the VAP incidence density was 10.79/1000 MV days. The ALOS for VAP patients was 21 days, and for non- VAP patients was 8.2 days. Our study estimated a total health system cost of INR 25,927 per bed per day. The health system cost of treating a VAP patient was INR 544,467 compared to INR 207,416 for a non-VAP patient. Conclusion Treatment of VAP poses substantial costs for the health system and patients. There is a need to focus on preventing VAP, which would eventually reduce the length of stay and the resultant financial impact on the health system and the patient.

Introduction: Invasive device-associated nosocomial infections commonly occur in intensive care units (ICUs). These infections include intravascular catheter-related bloodstream infection (CRBSI), ventilator-associated pneumonia (VAP), and catheter-associated urinary tract infection (CAUTI). This study aimed to evaluate the factors associated with invasive device-associated nosocomial infections based on the underlying diseases of the patients and antibiotic resistance profiles of the pathogens causing the infections detected in the ICU in our hospital over a five-year period. Methodology: Invasive device-associated infections (CRBSI, VAP, and CAUTI) were detected retrospectively by the laboratory- and clinicbased active surveillance system according to the criteria of the US Centers for Disease Control and Prevention (CDC) in patients hospitalized in the ICU of the tertiary hospital between 1 January 2018 and 30 June 2023. Results: A total of 425 invasive device-associated nosocomial infections and 441 culture results were detected (179 CRBSI, 176 VAP, 70 CAUTI). Out of them, 57 (13.4%) patients had hematological malignancy, 145 (34.1%) had solid organ malignancy, and 223 (52.5%) had no histopathologic diagnosis of any malignancy. An increase in extended-spectrum beta lactamase (ESBL) and carbapenem resistance in pathogens was detected during the study period. Conclusions: Antibiotic resistance of the Gram-negative bacteria associated with invasive device-associated infections increased during the study period. Antimicrobial stewardship will reduce rates of nosocomial infections, reduce mortality, and shorten hospital stay. Long-term catheterization and unnecessary antibiotic use should be avoided. [ABSTRACT FROM AUTHOR]

Hospital-acquired pneumonia (HAP) represents a significant cause of mortality among critically ill patients admitted to Intensive Care Units (ICUs). Timely and precise diagnosis is imperative to enhance therapeutic efficacy and patient outcomes. However, the diagnostic process is challenged by test limitations and a wide-ranging list of differential diagnoses, particularly in patients exhibiting escalating oxygen requirements, leukocytosis, and increased secretions. This narrative review aims to update diagnostic modalities, facilitating the prompt identification of nosocomial pneumonia while guiding, developing, and assessing therapeutic interventions. A comprehensive literature review was conducted utilizing the MEDLINE/PubMed database from 2013 to April 2024. An integrated approach that integrates clinical, microbiological, and imaging tools is paramount. Progress in diagnostic techniques, including novel molecular methods, the expanding utilization and accuracy of bedside ultrasound, and the emergence of Artificial Intelligence, coupled with an improved comprehension of lung microbiota and host-pathogen interactions, continues to enhance our capability to accurately and swiftly identify HAP and its causative agents. This advancement enables the refinement of treatment strategies and facilitates the implementation of precision medicine approaches. [ABSTRACT FROM AUTHOR]

Background and Aims: Ventilator-associated pneumonia (VAP) is a nosocomial infection associated with high morbidity and mortality. This study was undertaken to monitor the trend of the demographical details, comorbid conditions, bacterial etiological agents, and their antibiogram causing VAP in adults in the year 2008, 2013 and 2018. Material and Methods: A retrospective study conducted at the Department of Microbiology, Hospital Infection control and Quality Control at a tertiary care teaching hospital. All the adult patients with more than 48 h of the mechanical ventilator with endotracheal intubation with Clinical Pulmonary infection Score >6 with suspicion of VAP were included in the study at a difference of 5 years, i.e., 2008, 2013, and 2018. Results: A total of 338 patients were included in the study, of which males accounted for more than two-third of the patients studied. Nearly 45% of the patients belonged to geriatric (>60 years) age group. The most common comorbid conditions were chronic obstructive pulmonary disease, hypertension and diabetes mellitus. Among the gram-negative isolates, Klebsiella pneumoniae, Acinetobacter species, and Pseudomonas aeruginosa were the most common. There is an emergence of resistance to most commonly administered antimicrobial agents like aminoglycosides, levofloxacin, piperacillin/tazobactum, and carbapenems during the study period. Conclusion: This is a ten-year study on the antibiotic resistance pattern of organisms causing VAP. As far as the authors are aware, this is the first study addressing the pattern of change in drug resistance in the organisms causing VAP over a decade. The emergence of multi-drug resistant (MDR) MDR pathogens, especially in intensive care unit (ICU), is a great concern for the intensivist and infection control physicians. Preventive measures need to be undertaken to control the spread of these pathogens to the patients in the ICU. [ABSTRACT FROM AUTHOR]

Summary: Background: Ventilator-associated pneumonia (VAP) is a major cause of morbidity and mortality in patients receiving mechanical ventilation in India. Surveillance of VAP is essential to implement data-based preventive measures. Implementation of ventilator-associated events (VAE) criteria for surveillance has major constraints for low resource settings, which can lead to significant underreporting. Surveillance of VAP using common protocols in a large network of hospitals would give meaningful estimates of the burden of VAP in low resource settings. This study leverages a previously established healthcare-associated infections (HAI) surveillance network to develop and test a modified VAP definition adjusted for Indian settings. Methods: In this observational pilot study, thirteen hospitals from the existing HAI surveillance network were selected for developing and testing a modified VAP definition between February 2021 and April 2023. The criteria used for diagnosing VAP were adapted from the CDC’s Pediatric VAP definition and modified to cater to the needs of Indian hospitals. Designated nurses recorded each VAP event in a case report form (CRF) and also collected denominator data. The data was entered into an indigenously developed database for validation and analysis. At the time of data analysis, a questionnaire was sent to sites to get feedback on the performance of the modified VAP definitions. Findings: Out of 133,445 patient days and 40,533 ventilator days, 261 VAP events were recorded, with an overall VAP rate of 6.4 per 1000 ventilator days and a device utilization ratio (DUR) of 0.3. A total of 344 organisms were reported from the VAP events. Of these, Acinetobacter spp (29.6%, 102) was the most frequent, followed by Klebsiella spp (26.7%, 92). Isolates of Acinetobacter spp (98%) and Enterobacterales (85.5%) showed very high resistance against Carbapenem. Colistin resistance was observed in 6% of Enterobacterales and 3.2% of Acinetobacter spp. Interpretation: Data from this pilot study needs to validated in the larger Indian HAI surveillance network so that it can help in wider implementation of this protocol in order to assess its applicability p VAP across India. Funding: This work was supported by a grant received from the Indian Council of Medical Research (code I-1203).

Karyne Rangel,1,2 Salvatore Giovanni De-Simone1– 4 1Center for Technological Development in Health (CDTS)/National Institute of Science and Technology for Innovation in Neglected Population Diseases (INCT-IDPN), Oswaldo Cruz Foundation (FIOCRUZ), Rio de Janeiro, RJ, 21040-900, Brazil; 2Epidemiology and Molecular Systematics Laboratory (LEMS), Oswaldo Cruz Institute, Oswaldo Cruz Foundation (FIOCRUZ), Rio de Janeiro, RJ, 21040-900, Brazil; 3Program of Post-Graduation on Science and Biotechnology, Department of Molecular and Cellular Biology, Biology Institute, Federal Fluminense University, Niterói, RJ, 22040-036, Brazil; 4Program of Post-Graduation on Parasitic Biology, Oswaldo Cruz Institute, Oswaldo Cruz Foundation (FIOCRUZ), Rio de Janeiro, RJ, 21040-900, BrazilCorrespondence: Salvatore Giovanni De-Simone, Center for Technological Development in Health (CDTS)/National Institute of Science and Technology for Innovation in Neglected Population Diseases (INCT-IDPN), Oswaldo Cruz Foundation (FIOCRUZ), Av. Brasil, 4365 - Manguinhos, Rio de Janeiro, 21040-900, Tel +55 2138658181, Email salvatore.simone@fiocruz.brAbstract: Acinetobacter pneumonia is a significant healthcare-associated infection that poses a considerable challenge to clinicians due to its multidrug-resistant nature. Recent world events, such as the COVID-19 pandemic, have highlighted the need for effective treatment and management strategies for Acinetobacter pneumonia. In this review, we discuss lessons learned from recent world events, particularly the COVID-19 pandemic, in the context of the treatment and management of Acinetobacter pneumonia. We performed an extensive literature review to uncover studies and information pertinent to the topic. The COVID-19 pandemic underscored the importance of infection control measures in healthcare settings, including proper hand hygiene, isolation protocols, and personal protective equipment use, to prevent the spread of multidrug-resistant pathogens like Acinetobacter. Additionally, the pandemic highlighted the crucial role of antimicrobial stewardship programs in optimizing antibiotic use and curbing the emergence of resistance. Advances in diagnostic techniques, such as rapid molecular testing, have also proven valuable in identifying Acinetobacter infections promptly. Furthermore, due to the limited availability of antibiotics for treating infections caused A. baumannii, alternative strategies are needed like the use of antimicrobial peptides, bacteriophages and their enzymes, nanoparticles, photodynamic and chelate therapy. Recent world events, particularly the COVID-19 pandemic, have provided valuable insights into the treatment and management of Acinetobacter pneumonia. These lessons emphasize the significance of infection control, antimicrobial stewardship, and early diagnostics in combating this challenging infection.Keywords: Acinetobacter baumannii, ventilator-associated pneumonia, VAP, hospital-acquired pneumonia, HAP, carbapenem-resistant A. baumannii, CRAB, pneumonia, COVID-19

Background: Ventilator-associated pneumonia (VAP) causes heavy losses in terms of finances, hospitalization, and death for elderly patients in the intensive care unit (ICU); however, the risk is difficult to evaluate due to a lack of reliable assessment tools. We aimed to create and validate a nomogram to estimate VAP risk to provide early intervention for high-risk patients. Methods: Between January 2016 and March 2021, 293 patients from a tertiary hospital in China were retrospectively reviewed as a training set. Another 84 patients were enrolled for model validation from April 2021 to February 2022. Least absolute shrinkage and selection operator (LASSO) regression and multivariable logistic regression analysis were employed to select predictors, and a nomogram model was constructed. The calibration, discrimination, and clinical utility of the nomogram were verified. Finally, a web-based online scoring system was created to make the model more practical. Results: The predictors were hypoproteinemia, long-term combined antibiotic use, intubation time, length of mechanical ventilation, and tracheotomy/intubation. The area under the curve (AUC) was 0.937 and 0.925 in the training and validation dataset, respectively, suggesting the model exhibited effective discrimination. The calibration curve demonstrated high consistency with the observed result and the estimated values. Decision curve analysis (DCA) demonstrated that the nomogram was clinically applicable. Conclusions: We have created a novel nomogram model that can be utilized to anticipate VAP risk in elderly ICU patients, which is helpful for healthcare professionals to detect patients at high risk early and adopt protective interventions.

Introduction: Ventilator‐associated pneumonia (VAP) is a hospital‐acquired infection with high mortality, and remains a challenge for clinical treatment. Red blood cell distribution width (RDW) was associated with worse outcomes in several diseases. The purpose of this study was to investigate the relationship between mean RDW values, changes in RDW (delta RDW), and in‐hospital mortality among patients with VAP. Methods: In the present study, we enrolled 1266 VAP patients from the Medical Information Mart for Intensive Care IV (MIMIC‐IV) database. All patients were categorized into low group, medium group, and high group according to tertiles of mean RDW values. The primary outcome was all‐cause in‐hospital mortality. Univariate logistic regression analysis, multivariate logistic regression analysis, and restricted cubic spline (RCS) curve were performed to determine the association between mean RDW values and in‐hospital mortality in VAP. Moreover, RCS curve was plotted to explore the dose–response relationship between delta RDW and in‐hospital mortality in VAP. Results: Among the VAP patients included in the study, the in‐hospital mortality was 20.85% with 264 non‐survivors and 1002 survivors. The non‐survivors exhibited significantly higher mean RDW values and delta RDW values compared to survivors. Multivariate logistic regression analysis indicated that mean RDW values were positively associated with in‐hospital mortality in VAP after adjusting for relevant covariates. The RCS curve demonstrated a dose–response relationship between mean RDW and the mortality in VAP. Moreover, a linear relationship was observed between delta RDW and in‐hospital mortality in VAP. Conclusion: Higher mean RDW values were significantly associated with an increased risk of in‐hospital mortality in VAP. Additionally, a linear relationship was found between delta RDW values and in‐hospital mortality. These findings suggest that RDW can be used to identify high‐risk patients with poorer outcomes in VAP. [ABSTRACT FROM AUTHOR]

Sepsis stands as a formidable global health challenge, with persistently elevated mortality rates in recent decades. Each year, sepsis not only contributes to heightened morbidity but also imposes substantial healthcare costs on survivors. This narrative review aims to highlight the targeted measures that can be instituted to alleviate the incidence and impact of sepsis in intensive care. Here we discuss measures to reduce nosocomial infections and the prevention of equipment and patient colonisation by resilient pathogens. The overarching global crisis of bacterial resistance to newly developed antimicrobial agents intensifies the imperative for antimicrobial stewardship and de-escalation. This urgency has been accentuated in recent years, notably during the COVID-19 pandemic, as high-dose steroids and opportunistic infections presented escalating challenges. Ongoing research into airway colonisation's role in influencing disease outcomes among critically ill patients underscores the importance of tailoring treatments to disease endotypes within heterogeneous populations, which are important lessons for intensivists in training. Looking ahead, the significance of novel antimicrobial delivery systems and drug monitoring is poised to increase. This narrative review delves into the multifaceted barriers and facilitators inherent in effectively treating critically ill patients vulnerable to nosocomial infections. The future trajectory of intensive care medicine hinges on the meticulous implementation of vigilant stewardship programs, robust infection control measures, and the continued exploration of innovative and efficient technological solutions within this demanding healthcare landscape. [ABSTRACT FROM AUTHOR]

Velvet antler polypeptide (VAP) is the active compounds of velvet antler, an animal derived traditional Chinese medicine. In this work, the myocardial ischemia-reperfusion injury (MIRI) model was established to investigate the protective mechanism of VAP on MIRI in rats. Total 90 male Sprague Dawley (SD) rats were divided into the control, model (MIRI), positive (Diltiazem, DLZ, 20 mg/kg), VAP high, medium, low dose (VAP 300, 200, and 100 mg/kg) groups. After 21 days of intragastric administration, the electrocardiogram (ECG) changes in each group were detected. The activities of lactate dehydrogenase (LDH) and creatine kinase-MB (CK-MB) isoenzymes in serum, and superoxide dismutase (SOD), malondialdehyde (MDA), glutathione peroxidase (GSH-Px) and catalase (CAT) in myocardial tissue were detected by ELISA. Hematoxylin and eosin (HandE) staining was used to detect the histological changes of rat myocardium. Western blotting (WB) was used to detect the protein expression levels of nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), and NADH quinone oxidoreductase 1 (NQO1) in rat myocardial tissue. In the results, ECG showed that the MIRI model was successfully established; VAP can significantly reduce the activities of LDH, CK-MB in serum of rats, increase the activities of SOD, GSH-Px, CAT in myocardial tissue, reduce the activity of MDA in myocardial tissue, reduce interstitial edema and inflammatory infiltration, and improve the structural damage of rat myocardial tissue. The expression levels of HO-1, NQO1 and Nrf2 protein in rat myocardial tissue were up-regulated. In conclusion, VAP can improve the structural damage of rat myocardial tissue, improve the antioxidant activity of myocardial, and reduce oxidative stress injury. The relevant mechanism may be related to the regulation of Nrf2/ARE signaling pathway in rat myocardial tissue by VAP. [ABSTRACT FROM AUTHOR]

Background: Small intestinal bacterial overgrowth (SIBO), although associated with potentially serious complications, has not been adequately studied in critically ill patients. The primary objective of this study was to assess the prevalence of SIBO in critically ill patients. Secondary outcomes included the assessment of its effect on ventilator-associated pneumonia (VAP), intensive care unit (ICU) length of stay (LOS), and all-cause in-hospital mortality rate. Methods: This prospective observational study was conducted in a mixed medical-surgical ICU. In 52 consecutive ICU patients, a noninvasive modified hydrogen breath test (HBT) with lactulose was employed for SIBO diagnosis. The HBT was conducted at predetermined time intervals (first day of admission; third, fifth, and seventh day of ICU stay). Patients with an abnormal HBT suggesting SIBO on the day of ICU admission were excluded from the study. Participants were classified as either positive or negative based on their HBT on the third, fifth, and/or seventh day. A comparative assessment of demographic data, APACHE II score, incidence of VAP, duration of ICU stay, and all-cause in-hospital mortality was conducted. Multivariate logistic regression analysis was performed to identify the predictive factors for SIBO. Results: The groups were homogeneous in terms of their baseline characteristics. The prevalence of SIBO was 36.5%. The all-cause in-hospital mortality was 34.6%. The presence of SIBO was associated with an increased incidence of VAP (P <.001) and a prolonged ICU length of stay (P <.033). All-cause in-hospital mortality was similar between the groups. Regarding the results of the multivariate logistic regression model, only age was identified as a statistically significant independent predictor of SIBO (OR 1.08, P =.018). Conclusions: The prevalence of SIBO in ICU patients appears to be increased. Both early diagnosis and effective treatment are of utmost importance, especially for critically ill patients since it appears to be associated with VAP and prolonged hospitalization. [ABSTRACT FROM AUTHOR]

Background: Mechanical ventilation (MV) is an important part of the neonatal intensive care unit (NICU). MV, nevertheless, is linked to higher risks of ventilator associated pneumonia (VAP). The 2nd most frequent hospital acquired infection is VAP, which develops in mechanically ventilated cases after 2 days of MV. Aim: The aim of this study was to determine the incidence of VAP and to assess risk factors of VAP in neonatal intensive care unit in Al-Ahrar teaching hospital. Methods: This study was a prospective observational study which conducted at the neonatal intensive care unit in Al-Ahrar teaching hospital on 84 neonates on MV during six months from January 2019 to June 2019. All patients were subjected to full history taking. Full clinical examination and laboratory investigations were done and included complete blood count (CBC), C-reactive protein (CRP), liver function tests, kidney function tests, serum albumin level and blood culture. Chest radiograph was done on admission and repeated as required. Results: The percentage of VAP was (54.8 %). There was a statistically significant decrease in gestational age, weight, and serum albumin among VAP than non-VAP cases. Conclusion: The high prevalence of VAP in the intubated neonates poses a serious risk. Diagnosis, risk factor identification, precautions, and empirical treatments are all important strategies for VAP. VAP was found in a high percentage of mechanically ventilated newborns. [ABSTRACT FROM AUTHOR]

Introduction: Ventilator-associated pneumonias (VAPs) are a complication of mechanical ventilation in the intensive care unit (ICU) that increase length of stay, morbidity, and mortality. While identifying and treating infections early is paramount to improving patient outcomes, more and more data demonstrate limited courses of antibiotics improve outcomes. Prolonged (10–14 day) courses of antibiotics have remained the standard of care for pneumonia due to gram-negative bacilli (GNR). We aimed to review our GNR VAPs to assess risk factors for recurrent GNR infections. Methods: We reviewed trauma patients who developed VAP from 02/2019 through 05/2022. Demographics, injury characteristics, and outcomes were reviewed with a focus on pneumonia details including the cultured pathogen(s), antibiotic(s) used, treatment duration, and presence of recurrent infections. We then compared single episode VAPs to multiple episode VAPs among patients infected by GNRs. Results: Eleven of the fifty trauma patients admitted to the ICU suffered a VAP caused by a GNR. Of these eleven patients, six experienced a recurrent infection, four of which were caused by Pseudomonas aeruginosa and two of which were caused by Enterobacter aerogenes. Among the patients who received ten days of antibiotic treatment, half suffered a recurrence. Although, there was no difference in the microbiology or antibiotic duration between the recurrences and single episodes. Conclusion: Despite prolonged use of antibiotics, we found that the risk of recurrent or persistent infections was high among patients with VAP due to GNB. Further study is needed to determine optimal treatment to minimize the risk of these recurrences. Key message: Ventilator-associated pneumonia due to gram-negative bacilli is a rare but high morbidity complication in intensive care units. Despite prolonged duration of therapy, these infections still appear to account for many recurrent infections and further study into optimal therapy is warranted.

Abstract Background Epidemiological studies have demonstrated an association between red blood cell distribution width (RDW) and the prognosis of pneumonia-associated diseases. However, prognostic value of RDW in patients with ventilator-associated pneumonia (VAP) has yet to be investigated. This study aimed to explore the association between RDW and in-hospital mortality in VAP patients and explore predictive value of RDW for VAP patients. Methods This retrospective cohort study included 1,543 VAP patients from the Medical Information Mart for Intensive Care IV database 2008-2019. The primary outcome was considered to 30-day in-hospital mortality of VAP patients in this study. Non-high RDW level group was defined as

Hospital-acquired pneumonia (HAP) and ventilation-associated pneumonia (VAP) are challenging clinical conditions due to the challenging tissue penetrability of the lung. This study aims to evaluate the potential role of fosfomycin (FOS) associated with ceftazidime/avibactam (CZA) in improving the outcome in this setting. We performed a retrospective study including people with HAP or VAP treated with CZA or CZA+FOS for at least 72 h. Clinical data were collected from the SUSANA study, a multicentric cohort to monitor the efficacy and safety of the newer antimicrobial agents. A total of 75 nosocomial pneumonia episodes were included in the analysis. Of these, 34 received CZA alone and 41 in combination with FOS (CZA+FOS). People treated with CZA alone were older, more frequently male, received a prolonged infusion more frequently, and were less frequently affected by carbapenem-resistant infections (p = 0.01, p = 0.06, p < 0.001, p = 0.03, respectively). No difference was found in terms of survival at 28 days from treatment start between CZA and CZA+FOS at the multivariate analysis (HR = 0.32; 95% CI = 0.07–1.39; p = 0.128), while prolonged infusion showed a lower mortality rate at 28 days (HR = 0.34; 95% CI = 0.14–0.96; p = 0.04). Regarding safety, three adverse events (one acute kidney failure, one multiorgan failure, and one urticaria) were reported. Our study found no significant association between combination therapy and mortality. Further investigations, with larger and more homogeneous samples, are needed to evaluate the role of combination therapy in this setting.

Background: Epidemiological studies have demonstrated an association between red blood cell distribution width (RDW) and the prognosis of pneumonia-associated diseases. However, prognostic value of RDW in patients with ventilator-associated pneumonia (VAP) has yet to be investigated. This study aimed to explore the association between RDW and in-hospital mortality in VAP patients and explore predictive value of RDW for VAP patients. Methods: This retrospective cohort study included 1,543 VAP patients from the Medical Information Mart for Intensive Care IV database 2008-2019. The primary outcome was considered to 30-day in-hospital mortality of VAP patients in this study. Non-high RDW level group was defined as <15 %, and high RDW level group as ≥15%. The possible confounding factors were screened by least absolute shrinkage and selection operator regression. Univariate and multivariate COX regression analyses were used for the assessment on the association of RDW and 30-day in-hospital mortality in VAP patients. We also performed subgroup analyses. Furthermore, a comparative analysis of RDW and sequential organ failure assessment (SOFA) score and simplified acute physiology score II (SAPS II) were performed by receiver operating characteristic (ROC) curves. Results: The 30-day in-hospital mortality of VAP patients was approximately 19.05%. After adjusting all confounding factors, high RDW was associated with 30-day in-hospital mortality among VAP patients by using non-high RDW as the reference [hazard ratio (HR) =1.29, 95% confidence interval (CI): 1.01-1.63]. Additionally, the relationship was also robust in several populations, such as patients were younger than 60 years, or had not a history of congestive heart failure, or had a history of sepsis, or had not received renal replacement therapy, or had a duration of mechanical ventilation for more than 7 days. The result of ROC indicated that RDW had a better prognostic value in predicting 30-day in-hospital mortality for VAP patients than SOFA score and SAPS II score. Conclusion: High RDW level is associated with an increased 30-day in-hospital mortality. The RDW is a promising biomarker in predicting 30-day in-hospital mortality for patients admitted to the ICU, regardless of VAP. [ABSTRACT FROM AUTHOR]

Purpose: Lower respiratory tract infections (LRTI) are the most frequent infectious complication in patients admitted to the intensive care unit (ICU). We aim to report the clinical characteristics of ICU-admitted patients due to nosocomial LRTI and to describe their microbiology and clinical outcomes. Methods: A prospective observational study was conducted in 13 countries over two continents from 9th May 2016 until 16th August 2019. Characteristics and outcomes of ventilator-associated pneumonia (VAP), ventilator-associated tracheobronchitis (VAT), ICU hospital-acquired pneumonia (ICU-HAP), HAP that required invasive ventilation (VHAP), and HAP in patients transferred to the ICU without invasive mechanical ventilation were collected. The clinical diagnosis and treatments were per clinical practice and not per protocol. Descriptive statistics were used to compare the study groups. Results: 1060 patients with LRTI (72.5% male sex, median age 64 [50–74] years) were included in the study; 160 (15.1%) developed VAT, 556 (52.5%) VAP, 98 (9.2%) ICU-HAP, 152 (14.3%) HAP, and 94 (8.9%) VHAP. Patients with VHAP had higher serum procalcitonin (PCT) and Sequential Organ Failure Assessment (SOFA) scores. Patients with VAP or VHAP developed acute kidney injury, acute respiratory distress syndrome, multiple organ failure, or septic shock more often. One thousand eight patients had microbiological samples, and 711 (70.5%) had etiological microbiology identified. The most common microorganisms were Pseudomonas aeruginosa (18.4%) and Klebsiella spp (14.4%). In 382 patients (36%), the causative pathogen shows some antimicrobial resistance pattern. ICU, hospital and 28-day mortality were 30.8%, 37.5% and 27.5%, respectively. Patients with VHAP had the highest ICU, in-hospital and 28-day mortality rates. Conclusion: VHAP patients presented the highest mortality among those admitted to the ICU. Multidrug-resistant pathogens frequently cause nosocomial LRTI in this multinational cohort study. [ABSTRACT FROM AUTHOR]

Abstract Background No univocal recommendation exists for microbiological diagnosis of ventilator-associated pneumonia (VAP). Sampling of either proximal or distal respiratory tract likely impacts on the broad range of VAP incidence between cohorts. Immune biomarkers to rule-in/rule-out VAP diagnosis, although promising, have not yet been validated. COVID-19-induced ARDS made VAP recognition even more challenging, often leading to overdiagnosis and overtreatment. We evaluated the impact of different respiratory samples and laboratory techniques on VAP incidence and microbiological findings in COVID-19 patients. Methods Prospective single-centre cohort study conducted among COVID-19 mechanically ventilated patients in Policlinico Hospital (Milan, Italy) from January 2021 to May 2022. Microbiological confirmation of suspected VAP (sVAP) was based on concomitant endotracheal aspirates (ETA) and bronchoalveolar lavage (BAL). Conventional and fast microbiology (FILMARRAY® Pneumonia Panel plus, BALFAPPP) as well as immunological markers (immune cells and inflammatory cytokines) was analysed. Results Seventy-nine patients were included. Exposure to antibiotics and steroid therapy before ICU admission occurred in 51/79 (64.6%) and 60/79 (65.9%) patients, respectively. Median duration of MV at VAP suspicion was 6 (5–9) days. Incidence rate of microbiologically confirmed VAP was 33.1 (95% CI 22.1–44.0) and 20.1 (95% CI 12.5–27.7) according to ETA and BAL, respectively. Concordance between ETA and BAL was observed in 35/49 (71.4%) cases, concordance between BALFAPPP and BAL in 39/49 (79.6%) cases. With BAL as reference standard, ETA showed 88.9% (95% CI 70.8–97.7) sensitivity and 50.0% (95% CI 28.2–71.8) specificity (Cohen’s Kappa 0.40, 95% CI 0.16–0.65). BALFAPPP showed 95.0% (95% CI 75.1–99.9) sensitivity and 69% (95% CI 49.2–84.7) specificity (Cohen’s Kappa 0.60, 95% CI 0.39–0.81). BAL IL-1β differed significantly between VAP (135 (IQR 11–450) pg/ml) and no-VAP (10 (IQR 2.9–105) pg/ml) patients (P = 0.03). Conclusions In COVID-19 ICU patients, differences in microbial sampling at VAP suspicion could lead to high variability in VAP incidence and microbiological findings. Concordance between ETA and BAL was mainly limited by over 20% of ETA positive and BAL negative samples, while BALFAPPP showed high sensitivity but limited specificity when evaluating in-panel targets only. These factors should be considered when comparing results of cohorts with different sampling. BAL IL-1β showed potential in discriminating microbiologically confirmed VAP. Clinical Trial registration: NCT04766983, registered on February 23, 2021.

Background: Device-associated infections (DAIs) are important components of healthcare associated infection and are associated with increased morbidity and mortality. This study describes DAIs across different intensive care units (ICUs) in a hospital in Saudi Arabia. Methods: The study was conducted between 2017 and 2020 and followed the definitions of National Healthcare Safety Network (NHSN) for DAIs. The calculated the rates of ventilator-associated events (VAE), catheter-associated urinary tract infections (CAUTI) and central line-associated blood stream infections (CLABSI) followed NHSN definitions. Results: During the study period, there were 82 DAIs in adult ICUs and of these 16 (19.5%) were CLABSI, 26 (31.7%) were CAUTI and 40 (48.7%) were VAE. The overall rates for adult ICUs were 1.6, 1.9, 3.8 per 1000 device-days for CAUTI, CLABSI and VAE, respectively. The device-utilization ratio was 0.5, 0.6, and 0.48 for urinary catheters, central lines, and ventilators, respectively. VAE rates for medical and surgical ICU were about 2.8 times the rate in the coronary care unit and the rates were high in 2020 corresponding with the COVID-19 pandemic. Of the adult ICUS, medical ICU had a CLABSI rate of 2.13/1000 device-days and was about double the rate in surgical and cardiac ICU. For CAUTI, the rates per 1000 device-days were 2.19, 1.73, and 1.65 for medical, surgical, and coronary ICUs, respectively. The rate of CLABSI per 1000 device-days for pediatric and neonatal ICUs were 3.38 and 2.28, respectively. Conclusions: CAUTI was the most common infections among adult ICUs and medical ICU had higher rates than other adult ICUs. VAE rate was higher in the first year of the COVID-19 pandemic, indicating increased device-use, change in patients characteristics as well as possible change in practices across the ICUs.

Emergency nurses are responsible for the care of mechanically ventilated patients. Evidence-based care to prevent ventilator-associated pneumonia (VAP) must be initiated in the Emergency Department (ED) instead of after arrival in the critical care areas of the hospital. Nurses were surveyed assessing VAP prevention measures education, knowledge, and confidence. Nurses reported seldom to never monitoring patient/ventilator interactions (44.6%) and troubleshooting alarms (seldom/never: 48.9%) with confidence levels minimal (29.1%), moderate (54.1%) and high (14.5%). Nurses are responsible for titrating sedation but report contacting a respiratory therapist (RT) for all other ventilator management. ED nurses may not have the same exposure to VAP prevention education as their counterparts in the critical care areas. Increasing ED nurse knowledge and confidence in VAP prevention is necessary as EDs increasingly care for mechanically ventilated patients.

Introduction: Because the risk of health-care associated infections (HAIs) is high in intensive care units, and HAIs are one of the causes of morbidity and mortality and affects the overall quality of health care, the continuous monitoring of HAIs in intensive care patients is essential.Aim and objectives: This descriptive cross-sectional study was carried out over a period of five years in a tertiary-care teaching hospital. The aim of the study was to investigate the main and specific types of health-care associated Infections and determine the microbiological profile and antimicrobial susceptibility rates of isolates in patients with HAI.Methods: The active surveillance method was used to detect HAIs in patients who spent over 48 hr in a targeted ICU. Patients with blood stream infections (BSI), central line-associated bloodstream infection (CLABSI), catheter-associated urinary tract infections (CAUTI) and ventilator-associated events (VAE) were included in the study. HAI were diagnosed based on the Centre for Disease Control (CDC)’s National Healthcare Safety Network (NHSN) updated definitions of HAIs.Results: A total of 121,051 patient days, including 7,989 central line days, 64,557 urinary catheter days, and 18,443 ventilator days, were recorded in the study population and 832 HAIs were diagnosed (incidence rate 6.9%). The overall rates of BSI, CLABSI, CAUTI and possible ventilator-associated pneumonia (p-VAP) were 3.7, 10.6, 2.1 and 13.4/1,000 device days, respectively. The most common organism isolated from BSI was (n=322, 29%), followed by 225 (n=225, 20.3%). 79.8% of strains were resistant to imipenem, 77.1% to ciprofloxacin and 76.4% to ampicillin. The most common organisms isolated from CAUTI were non-albicans species (n=38, 18%), followed by and spp (each n=33, each 15.7%). Conclusions: A trend of increasing resistance of to carbapenems was observed. Risk factor analysis showed invasive procedures during sepsis and organophosphorous poisoning as significant factors.

Background: No univocal recommendation exists for microbiological diagnosis of ventilator-associated pneumonia (VAP). Sampling of either proximal or distal respiratory tract likely impacts on the broad range of VAP incidence between cohorts. Immune biomarkers to rule-in/rule-out VAP diagnosis, although promising, have not yet been validated. COVID-19-induced ARDS made VAP recognition even more challenging, often leading to overdiagnosis and overtreatment. We evaluated the impact of different respiratory samples and laboratory techniques on VAP incidence and microbiological findings in COVID-19 patients. Methods: Prospective single-centre cohort study conducted among COVID-19 mechanically ventilated patients in Policlinico Hospital (Milan, Italy) from January 2021 to May 2022. Microbiological confirmation of suspected VAP (sVAP) was based on concomitant endotracheal aspirates (ETA) and bronchoalveolar lavage (BAL). Conventional and fast microbiology (FILMARRAY® Pneumonia Panel plus, BALFAPPP) as well as immunological markers (immune cells and inflammatory cytokines) was analysed. Results: Seventy-nine patients were included. Exposure to antibiotics and steroid therapy before ICU admission occurred in 51/79 (64.6%) and 60/79 (65.9%) patients, respectively. Median duration of MV at VAP suspicion was 6 (5–9) days. Incidence rate of microbiologically confirmed VAP was 33.1 (95% CI 22.1–44.0) and 20.1 (95% CI 12.5–27.7) according to ETA and BAL, respectively. Concordance between ETA and BAL was observed in 35/49 (71.4%) cases, concordance between BALFAPPP and BAL in 39/49 (79.6%) cases. With BAL as reference standard, ETA showed 88.9% (95% CI 70.8–97.7) sensitivity and 50.0% (95% CI 28.2–71.8) specificity (Cohen's Kappa 0.40, 95% CI 0.16–0.65). BALFAPPP showed 95.0% (95% CI 75.1–99.9) sensitivity and 69% (95% CI 49.2–84.7) specificity (Cohen's Kappa 0.60, 95% CI 0.39–0.81). BAL IL-1β differed significantly between VAP (135 (IQR 11–450) pg/ml) and no-VAP (10 (IQR 2.9–105) pg/ml) patients (P = 0.03). Conclusions: In COVID-19 ICU patients, differences in microbial sampling at VAP suspicion could lead to high variability in VAP incidence and microbiological findings. Concordance between ETA and BAL was mainly limited by over 20% of ETA positive and BAL negative samples, while BALFAPPP showed high sensitivity but limited specificity when evaluating in-panel targets only. These factors should be considered when comparing results of cohorts with different sampling. BAL IL-1β showed potential in discriminating microbiologically confirmed VAP. Clinical Trial registration: NCT04766983, registered on February 23, 2021. [ABSTRACT FROM AUTHOR]

Background: AKT3 appears to play a role in lung cancer. However, its role in ventilator-associated pneumonia is still unclear. Therefore, this study aimed to investigate the role of AKT3 in macrophages during ventilator-associated pneumonia. Methods: The mRNA level of AKT3, Data from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), The data is analyzed using the Xiantao academic analysis tool. Additionally, the roles of AKT3 in ventilator-associated pneumonia (VAP) were investigated through in vivo experiments. Results: AKT3 was differentially expressed in various normal and tumor tissues. Functional enrichment analysis indicated the immunomodulatory function and inflammatory response of AKT3 in lung cancer. Depletion of macrophages protected against lung epithelial cells and significantly decreased MMP9, MMP19, FTH, and FTL expression levels and increased GPX4 expression levels, while partially reversing the changes in macrophage. Mechanistically, macrophage depletion attenuates ferroptosis of lung epithelial cells by modulating AKT3 following VAP. Conclusion: Collectively, this study suggests the need for further validation of the immunoregulatory function of AKT3 in lung cancer. Additionally, macrophage depletion mitigates lung injury by modulating the AKT3/GPX4 pathway in the context of VAP. [ABSTRACT FROM AUTHOR]

When considering the vesicle-associated membrane protein-associated protein (VAP) family, major receptors at the surface of the endoplasmic reticulum (ER), it appears that VAP-A and VAP-B paralogs largely overlap in structure and function, and that specific features to distinguish these two proteins hardly exist or are poorly documented. Here, we question the degree of redundancy between VAP-A and VAP-B: is one simply a backup plan, in case of loss of function of one of the two genes, or are there molecular and functional divergences that would explain their maintenance during evolution? [ABSTRACT FROM AUTHOR]

Background: Nearly 10% of COVID-19 cases will require admission to the intensive care unit (ICU). Our aim was to assess the clinical and microbiological outcomes of secondary infections among critically ill COVID-19 adult patients treated with/without immunomodulation. Methods: A prospective observational cohort study was performed between 2020 and 2022 at a single ICU. The diagnosis and severity classification were established by the ECDC and WHO criteria, respectively. Eligible patients were included consecutively at admission, and followed for +30 days post-inclusion. Bloodstream-infections (BSIs), ventilator-associated bacterial pneumonia (VAP), and COVID-19-associated invasive pulmonary aspergillosis (CAPA) were defined according to international guidelines. Patient stratification was performed by immunomodulatory therapy administration (dexamethasone, tocilizumab, baricitinib/ruxolitinib). The primary outcome was any microbiologically confirmed major infectious complication, secondary outcomes were invasive mechanical ventilation (IMV) requirement and all-cause mortality. Results: Altogether, 379 adults were included. At baseline, 249/379 (65.7%) required IMV and 196/379 (51.7%) had a cytokine storm. At +30 days post-inclusion, the rate of any microbiologically confirmed major infectious complication was 151/379 (39.8%), IMV requirement and all-cause mortality were 303/379 (79.9%) and 203/379 (53.6%), respectively. There were no statistically significant outcome differences after stratification. BSI, VAP, and CAPA episodes were mostly caused by Enterococcus faecalis (27/124, 22.1%), Pseudomonas aeruginosa (26/91, 28.6%), and Aspergillus fumigatus (20/20, 100%), respectively. Concerning the primary outcome, Kaplan–Meier analysis showed similar probability distributions between the treatment subgroups (118/299, 39.5% vs. 33/80, 41.3%, log-rank p = 0.22), and immunomodulation was not retained as its independent predictor in multivariate logistic regression. Conclusions: Secondary infections among critically ill COVID-19 adult patients represent a relevant burden, probably irrespective of immunomodulatory treatment. [ABSTRACT FROM AUTHOR]

Abstract Background The role of upper airways microbiota and its association with ventilator-associated pneumonia (VAP) development in mechanically ventilated (MV) patients is unclear. Taking advantage of data collected in a prospective study aimed to assess the composition and over-time variation of upper airway microbiota in patients MV for non-pulmonary reasons, we describe upper airway microbiota characteristics among VAP and NO-VAP patients. Methods Exploratory analysis of data collected in a prospective observational study on patients intubated for non-pulmonary conditions. Microbiota analysis (trough 16S-rRNA gene profiling) was performed on endotracheal aspirates (at intubation, T0, and after 72 h, T3) of patients with VAP (cases cohort) and a subgroup of NO-VAP patients (control cohort, matched according to total intubation time). Results Samples from 13 VAP patients and 22 NO-VAP matched controls were analyzed. At intubation (T0), patients with VAP revealed a significantly lower microbial complexity of the microbiota of the upper airways compared to NO-VAP controls (alpha diversity index of 84 ± 37 and 160 ± 102, in VAP and NO_VAP group, respectively, p-value

Abstract Background Up to 48% of ventilated coronavirus disease 2019 (COVID-19) patients develop ventilator-associated pneumonia (VAP) during hospitalization in an ICU. Dysbiotic oral microbiota can colonize the lower respiratory tract and lead to VAP. It is recommended to introduce oral care strategies in the ICU to prevent VAP. In this study, we observed the impact of an oral hygienic protocol with tooth brushing on cultivable oral bacteriota, the incidence of HAI and patient safety among mechanically ventilated COVID-19 patients in an ICU setting. Methods In this prospective cohort study, we recruited 56 adult COVID-19 patients who qualified for mechanical ventilation. Patients were divided into 2 groups depending on the oral care procedure: standard and extended oral procedures with tooth brushing. Oral bacteriota samples were taken first within 36 h and after 7 days of intubation. Microorganisms were identified by MALDI/TOF mass spectrometry. bacterial health care-associated infection (HAI) cases were retrospectively analyzed by etiology. A PFGE study was performed for Klebsiella pneumoniae to check for clonal spreading of strains from oral bacteriota samples and HAI cases. Results We observed significant dysbiosis and a decrease in cultivable oral bacteriota diversity, with a high frequency of potentially pathogenic species, including Acinetobacter baumannii and K. pneumoniae. The HAI incidence rate was high (55.2/1000 patient-days), most commonly of K. pneumoniae and A. baumannii etiologies, which correlated with the presence of A. baumannii and K. pneumoniae in the oral samples. Strains isolated from VAP cases were the same as oral isolates in 8 cases. The procedure with tooth brushing led to less frequent identification of A. baumannii in oral samples (55.6% vs. 5.3%, p = 0.001); however, it did not decrease the incidence of HAIs. Conclusions Dysbiotic oral bacteriota is an important source of respiratory pathogens. The introduction of tooth brushing in oral hygiene protocols in an ICU setting was effective in decreasing the extent of oral bacteriota dysbiosis; however, it did not reduce the risk of HAIs or mortality. Trial registration: 1072.6120.333.2020.

Mohd Saleem,1 Azharuddin Sajid Syed Khaja,1 Ashfaque Hossain,2 Fahaad Alenazi,3 Kamaleldin B Said,1 Soha Abdallah Moursi,1 Homoud Abdulmohsin Almalaq,4 Hamza Mohamed,5 Ehab Rakha,6,7 Mohammed Salem Alharbi,8 Salma Ahmed Ali Babiker,9 Kauser Usman10 1Department of Pathology, College of Medicine, University of Hail, Hail, Kingdom of Saudi Arabia; 2Department of Medical Microbiology and Immunology, RAK Medical and Health Sciences University, Ras Al Khaimah, United Arab Emirates; 3Department of Pharmacology, College of Medicine, University of Hail, Hail, Kingdom of Saudi Arabia; 4Hail Health Cluster, King Khalid Hospital, College of Pharmacy, King Saud University, Riyadh, Kingdom of Saudi Arabia; 5Anatomy Department, Faculty of Medicine, Northern Border University, Arar, Kingdom of Saudi Arabia; 6Laboratory Department, King Khalid Hospital, Hail, Kingdom of Saudi Arabia; 7Clinical Pathology Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt; 8Department of Internal Medicine, College of Medicine, University of Hail, Hail, Kingdom of Saudi Arabia; 9Department of Family Medicine, Hail University Medical Clinics, University of Hail, Hail, Kingdom of Saudi Arabia; 10Department of Internal Medicine, King George’s Medical University, Lucknow, IndiaCorrespondence: Azharuddin Sajid Syed Khaja, Department of Pathology, College of Medicine, University of Hail, Hail, Kingdom of Saudi Arabia, Tel +966 59 184 9573, Email skazharuddin@uoh.edu.saPurpose: Ventilator-associated pneumonia (VAP) is associated with a higher mortality risk for critical patients in the intensive care unit (ICU). Several strategies, including using β-lactam antibiotics, have been employed to prevent VAP in the ICU. However, the lack of a gold-standard method for VAP diagnosis and a rise in antibiotic-resistant microorganisms have posed challenges in managing VAP. The present study is designed to identify, characterize, and perform antimicrobial susceptibility of the microorganisms from different clinical types of infections in ICU patients with emphasis on VAP patients to understand the frequency of the latter, among others.Patients and Methods: A 1-year prospective study was carried out on patients in the ICU unit at a tertiary care hospital, Hail, Saudi Arabia.Results: A total of 591 clinically suspected hospital-acquired infections (HAI) were investigated, and a total of 163 bacterial isolates were obtained from different clinical specimens with a high proportion of bacteria found associated with VAP (70, 43%), followed by CAUTI (39, 24%), CLABSI (25, 15%), and SSI (14, 8.6%). Klebsiella pneumoniae was the most common isolate 39 (24%), followed by Acinetobacter baumannii 35 (21.5%), Pseudomonas aeruginosa 25 (15.3%), and Proteus spp 23 (14%). Among the highly prevalent bacterial isolates, extended-spectrum beta-lactamase was predominant 42 (42.4%).Conclusion: Proper use of antibiotics, continuous monitoring of drug sensitivity patterns, and taking all precautionary measures to prevent beta-lactamase-producing organisms in clinical settings are crucial and significant factors in fending off life-threatening infections for a better outcome.Keywords: ICU, VAP, ESBL, Klebsiella pneumoniae, Acinetobacter baumannii

BackgroundAKT3 appears to play a role in lung cancer. However, its role in ventilator-associated pneumonia is still unclear. Therefore, this study aimed to investigate the role of AKT3 in macrophages during ventilator-associated pneumonia.MethodsThe mRNA level of AKT3, Data from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), The data is analyzed using the Xiantao academic analysis tool. Additionally, the roles of AKT3 in ventilator-associated pneumonia (VAP) were investigated through in vivo experiments.ResultsAKT3 was differentially expressed in various normal and tumor tissues. Functional enrichment analysis indicated the immunomodulatory function and inflammatory response of AKT3 in lung cancer. Depletion of macrophages protected against lung epithelial cells and significantly decreased MMP9, MMP19, FTH, and FTL expression levels and increased GPX4 expression levels, while partially reversing the changes in macrophage. Mechanistically, macrophage depletion attenuates ferroptosis of lung epithelial cells by modulating AKT3 following VAP.ConclusionCollectively, this study suggests the need for further validation of the immunoregulatory function of AKT3 in lung cancer. Additionally, macrophage depletion mitigates lung injury by modulating the AKT3/GPX4 pathway in the context of VAP.

Summary: Background: The available scientific evidence suggests a significant association between oral bacteria and the incidence of ventilator-associated pneumonia (VAP). Aims: The aim of this study was to determine the effectiveness of an oral health protocol in the prevention of ventilator-associated pneumonia. Methods: In this multi-center RCT, conducted in the intensive care units of neurological patients in three general teaching hospitals of two provinces located in the west of the Iran, a consecutive sample of 200 intubated patients were initially recruited. Patients were randomly allocated to the intervention (received oral health care based on evidence-based oral health protocol) or control (routine oral health care) groups. Both groups received their prescribed treatment regimen for seven consecutive days. The percentage of VAP diagnoses as main outcome assessed using clinical pulmonary infection score (CPIS). Findings: The rate of VAP in the intervention and control groups was 5% and 64%, respectively. The intervention reduced the risk of VAP by 97% and this difference was statistically significant (P

Background: Specialized diets enriched with immune nutrients could be an important supplement in patients (pts) with acute traumatic brain injury (TBI). Omega-3 and arginine may interact with immune response and microbiota. No data are available about the role of the specialized diets in modulating the lung microbiota, and little is known about the influence of lung microbiota structure in development of ventilator-associated pneumonia (VAP) in TBI pts. The aims of this study are to evaluate the impact of specific nutrients on the lung microbiota and the variation of lung microbiota in TBI pts developing VAP. Methods: A cohort of 31 TBI pts requiring mechanical ventilation in ICU was randomized for treatment with specialized (16pts) or standard nutrition (15pts). Alpha and beta diversity of lung microbiota were analyzed from bronco Alveolar Lavage (BAL) samples collected at admission and 7 days post-ICU admission in both groups. A further analysis was carried out on the same samples retrospectively grouped in VAP or no VAP pts. Results: None developed VAP in the first week. Thereafter, ten out of thirty-one pts developed VAP. The BAL microbiota on VAP group showed significant differences in beta diversity and Staphylococcus and Acinetobacter Genera were high. The specialized nutrition had influence on beta diversity that reached statistical significance only in Bray–Curtis distance. Conclusion: Our data suggest that TBI patients who developed VAP during ICU stay have different structures of BAL microbiota either at admission and at 7 days post-ICU admission, while no correlation has been observed between different enteral formulas and microbiota composition in terms of richness and evenness. These findings suggest that targeting the lung microbiota may be a promising approach for preventing infections in critically ill patients. [ABSTRACT FROM AUTHOR]

Device-associated infections (DAIs) are important components of healthcare associated infection and are associated with increased morbidity and mortality. This study describes DAIs across different intensive care units (ICUs) in a hospital in Saudi Arabia. The study was conducted between 2017 and 2020 and followed the definitions of National Healthcare Safety Network (NHSN) for DAIs. The calculated the rates of ventilator-associated events (VAE), catheter-associated urinary tract infections (CAUTI) and central line-associated blood stream infections (CLABSI) followed NHSN definitions. During the study period, there were 82 DAIs in adult ICUs and of these 16 (19.5%) were CLABSI, 26 (31.7%) were CAUTI and 40 (48.7%) were VAE. The overall rates for adult ICUs were 1.6, 1.9, 3.8 per 1000 device-days for CAUTI, CLABSI and VAE, respectively. The device-utilization ratio was 0.5, 0.6, and 0.48 for urinary catheters, central lines, and ventilators, respectively. VAE rates for medical and surgical ICU were about 2.8 times the rate in the coronary care unit and the rates were high in 2020 corresponding with the COVID-19 pandemic. Of the adult ICUS, medical ICU had a CLABSI rate of 2.13/1000 device-days and was about double the rate in surgical and cardiac ICU. For CAUTI, the rates per 1000 device-days were 2.19, 1.73, and 1.65 for medical, surgical, and coronary ICUs, respectively. The rate of CLABSI per 1000 device-days for pediatric and neonatal ICUs were 3.38 and 2.28, respectively. CAUTI was the most common infections among adult ICUs and medical ICU had higher rates than other adult ICUs. VAE rate was higher in the first year of the COVID-19 pandemic, indicating increased device-use, change in patients characteristics as well as possible change in practices across the ICUs. [ABSTRACT FROM AUTHOR]

Background: Ventilator associated pneumonia (VAP) is defined by the American College of Surgeons Trauma Quality Improvement Program (ACS TQIP) using laboratory findings, pathophysiologic signs/symptoms, and imaging criteria. However, many critically ill trauma patients meet the non-specific laboratory and sign/symptom thresholds for VAP, so the TQIP designation of VAP depends heavily upon imaging evidence. We hypothesized that physician opinions widely vary regarding chest radiograph findings significant for VAP. Patients and Methods: The TQIP Spring 2021 Benchmark Report (BR) was used to identify 14 patients with VAP at an academic Level 1 Trauma Center. Critically ill trauma patients (n = 7) who spent at least four days intubated and met TQIP's laboratory and sign/symptom thresholds for VAP but did not appear as VAPs on the BR comprised the control group. For each deidentified patient, four successive chest radiographic images were compiled and arranged chronologically. Cases and controls were randomly arranged in digital format. Blinded physicians (n = 27) were asked to identify patients with VAP based solely on imaging evidence. Results: Radiographic evidence of VAP was highly subjective (Krippendorff α = 0.134). Among physicians of the same job description, inter-rater reliability remained low (α = 0.137 for trauma attending physicians; α = 0.141 for trauma fellows; α = 0.271 for radiologists). When majority judgment was compared to the TQIP BR, there was disagreement between the two tests (Cohen κ = -0.071; sensitivity, 64.3%; specificity, 28.6%). Conclusions: Current definitions of VAP rely on subjective imaging interpretation and ignore the reality that there are numerous explanations for opacities on CXR. The inconsistency of physicians' imaging interpretation and protean physiologic findings for VAP in trauma patients should preclude the current definition of VAP from being used as a quality improvement metric in TQIP. [ABSTRACT FROM AUTHOR]

Light-inducible dimerization protein modules enable precise temporal and spatial control of biological processes in non-invasive fashion. Among them, Magnets are small modules engineered from the Neurospora crassa photoreceptor Vivid by orthogonalizing the homodimerization interface into complementary heterodimers. Both Magnets components, which are well-tolerated as protein fusion partners, are photoreceptors requiring simultaneous photoactivation to interact, enabling high spatiotemporal confinement of dimerization with a single excitation wavelength. However, Magnets require concatemerization for efficient responses and cell preincubation at 28°C to be functional. Here we overcome these limitations by engineering an optimized Magnets pair requiring neither concatemerization nor low temperature preincubation. We validated these 'enhanced' Magnets (eMags) by using them to rapidly and reversibly recruit proteins to subcellular organelles, to induce organelle contacts, and to reconstitute OSBP-VAP ER-Golgi tethering implicated in phosphatidylinositol-4-phosphate transport and metabolism. eMags represent a very effective tool to optogenetically manipulate physiological processes over whole cells or in small subcellular volumes.

Mechanically ventilated patients are at risk of several complications, including ventilator-associated pneumonia (VAP). VAP is the most common nosocomial infection in this group of hospitalized patients. As a nosocomial infection, it is an undesirable event and is associated with prolonged hospitalization, high costs, and high mortality. To minimize the incidence and provide safe care for mechanically ventilated patients, it is recommended that VAP prevention procedures be developed and implemented, which take into account the general principles of infection prevention such as hand hygiene, isolation, and personal protective equipment, as well as risk factors associated with the treatment, which include, among others, patient position, nutrition, oral hygiene, and tracheobronchial toilet. Knowledge of ventilator operation and decontamination of medical equipment are also of great importance in the prevention of VAP. Collaboration between the patient care staff and the and the infection control team is equally important. Effective VAP surveillance systems can significantly reduce the risk of its occurrence. The aim of this study is to present the issues of VAP with particular emphasis on risk factors for the disease, nursing care, and epidemiological surveillance on the basis of a literature review. The work is dedicated to both epidemiological nurses employed in infection control teams and nurses working in intensive care units, where patients requiring mechanical ventilation are hospitalized, as well as representatives of other professions (e.g. physiotherapists, nutritionists) taking care of patients hospitalized in intensive care units (ICUs).