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Abstract Objective The aim of this study was to describe the characteristics of patients admitted to the intensive care unit with severe pneumonia due to SARS-CoV-2, comparing them according to successive waves, and to identify prognostic factors for morbidity and mortality. Materials and methods This single-center retrospective observational descriptive study was conducted from March 10, 2020, to October 17, 2021. All adult patients admitted with SARS-CoV-2 pneumonia presenting acute respiratory failure were included. COVID 19 diagnosis was confirmed by RT-PCR testing of respiratory specimens. The primary endpoint was ICU mortality. Secondary endpoints were the occurrence of ventilator-associated pneumonia (VAP) or bronchopulmonary aspergillosis. Results Over the study period, 437 patients were included of whom 282 (65%) patients were ventilated for 9 [5;20] days. Among the studied population, 38% were treated for one or more episodes of VAP, and 22 (5%) for bronchopulmonary aspergillosis. ICU mortality was 26% in the first wave, then fell and stabilized at around 10% in subsequent waves (p = 0.02). Increased age, Charlson index, SOFA score and lactatemia on admission were predictive of mortality. Survival at 90 days was 85% (95% CI 82–88) and was unaffected by the presence of VAP. However, the occurrence of bronchopulmonary aspergillosis increased mortality to 36%. Conclusion In this study, we observed mortality in the lower range of those previously reported. Risk factors for mortality mainly included age and previous comorbidities. The prognosis of these critically ill Covid 19 patients improved over the four waves, underlining the likely beneficial effect of vaccination and dexamethasone.

Abstract Background Myceliophthora heterothallica belonging to Myceliophthora is considered as an environmental fungus and has not been reported to be pathogenic or colonizing in recent literature. The present case firstly reports a ventilation-associated pneumonia caused by Myceliophthora heterothallica among the aged adult. Case presentation A 67-years-old Asian female patient suffering from a sudden disturbance of consciousness for 3 h was admitted to our hospital. Cardiac arrest occurred during emergency transport, and sinus rhythm was restored after cardiopulmonary resuscitation. Invasive mechanical ventilation was given to this patient for respiratory failure. After mechanical ventilation, the lung CT images showed multiple cuneiform nodules arranging subpleural accompanying with ground-glass opacity. On the 5th day of mechanical ventilation, Myceliophthora heterothallica was cultured from endotracheal aspirates. Two methods, namely automatic microbial identification system and internal transcribed spacer sequencing were employed to identify this fungus. The present case firstly uncovered the colonization ability and pathogenicity of Myceliophthora heterothallica in the respiratory tract. After 28d of treatment with piperacillin-tazobactam, this patient weaned from the ventilator and recovered from consciousness with lung infection disappearance. Conclusions This is the first case report of ventilation-associated pneumonia in the aged patient caused by Myceliophthora heterothallica. This current case is worth for the clinical diagnosis and treatment of Myceliophthora heterothallica infection, and also enriches new pathogenic species found of thermothelomyces species.

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.

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 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.

A new approach to an automatable fiber impregnation and consolidation process for the manufacturing of fiber-reinforced composite parts is presented in this article. Therefore, a vacuum chamber sealing machine classically used in food packaging is modified for this approach—Vacuum Chamber Infusion (VCI). Dry fiber placement (DFP) preforms, made from 30 k carbon fiber tape, with different layer amounts and fiber orientations, are infused with the VCI and with the state-of-the-art process—Vacuum Assisted Process (VAP)—as the reference. VCI uses a closed system that is evacuated once, while VAP uses a permanently evacuated open system. Since process management greatly influences material properties, the mechanical properties, void content, and fiber volume fraction (FVF) are analyzed. In addition, the study aims to identify how the complexity of a resin infusion process can be reduced, the automation potential can be increased, and the number of consumables can be reduced. Comparable material characteristics and a reduction in consumables, setup complexity, and manufacturing time by a factor of four could be approved for VCI. A void content of less than 2% is measured for both processes and an FVF of 39% for VCI and 45% for VAP is achieved.

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

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.

This study aims to explore the diagnostic potential of blood lipid profiles in suspected ventilator-associated pneumonia (VAP). Early detection of VAP remains challenging for clinicians due to subjective clinical criteria and the limited effectiveness of current diagnostic tests. Blood samples from 20 patients, with ages between 6 months and 15 years, were collected at days 1, 3, 6, and 12, and an untargeted lipidomics analysis was performed using a Ultra high Pressure Liquid Chromatography hyphenated with High Resolution Mass Spectrometry UPLC-HRMS (TIMS-TOF/MS) platform. Patients were stratified based on modified pediatric clinical pulmonary index score (mCPIS) into high (mCPIS ≥ 6, n = 12) and low (mCPIS < 6, n = 8) VAP suspicion groups. With the untargeted lipid profiling, we were able to identify 144 lipid species from different lipid groups such as glycerophospholipids, glycerolipids, and sphingolipids, in the blood of children with VAP. Multivariate and univariate statistical analyses revealed a distinct distribution of blood lipid profiles between the studied groups, indicating the potential utility of lipid biomarkers in discriminating VAP presence. Additionally, specific lipids were associated with pharyngeal culture results, notably the presence of Klebsiella pneumoniae and Staphylococcus aureus, underscoring the importance of lipid profiling in identifying the microbial etiology of VAP.

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: 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.

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.

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.

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

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

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).

Eman E Hegazy,1 Marwa Gamal Bahey,1 Alaa Mohammed Abo Hagar,2 Amira Abdelgalil Elkholy,3 Esraa A Mohamed1 1Department of Medical Microbiology and Immunology, Faculty of Medicine, Tanta University, Tanta, Egypt; 2Department of Anesthesiology, Surgical Intensive Care and Pain Medicine, Faculty of Medicine, Tanta University, Tanta, Egypt; 3Department of Chest Diseases, Faculty of Medicine, Tanta University, Tanta, EgyptCorrespondence: Eman E Hegazy, Tel +20 10 99008274, Email dr_emanhegazy2010@yahoo.comBackground: Ventilator-associated pneumonia (VAP) caused by carbapenem-resistant gram-negative bacteria has been proven to be an escalating public health challenge in Egypt owing to its high mortality rate and raised health care costs.Purpose: Detection of carbapenem-resistant gram-negative bacilli among VAP patients, genotypic identification of carbapenemase genes in the isolated strains with evaluation of their impact on patient outcome and detection of carbapenemase-producing enterobacterales by MASTDISCS combi Carba plus disc system.Methods: Broncho-alveolar lavage fluid (BALF) and endotracheal aspirate were collected aseptically from clinically suspected VAP patients. Pathogen identification and antibiotic sensitivity testing were done. Carbapenemase-encoding genes (blaKPC, blaNDM, and blaOXA-48) were tested by PCR in all carbapenem-resistant gram-negative isolates. Performance of MASTDISCS combi Carba plus in isolated Enterobacterales was assessed in relation to the PCR results.Results: Eighty-three carbapenem-resistant gram-negative isolates were detected. The most frequent pathogens were Klebsiella pneumoniae, Acinetobacter baumannii and Pseudomonas aeruginosa representing 34.9%, 20.5% and 18.1%, respectively. blaKPC was the predominant gene. Patients with persistent mechanical ventilation less than 15 days and Pseudomonas aeruginosa infection were significantly associated with a higher death rate. MAST-Carba plus had the highest sensitivity, specificity, positive and negative predictive values for detecting OXA-48 carbapenemases representing 81.8%, 92.5%, 75% and 94.9%, respectively.Conclusion: Worse outcome in VAP patients was associated with carbapenem-resistant gram-negative bacilli. MASTDISCS combi Carba plus is an efficient simple method for identification of different carbapenemases among enterobacterales.Keywords: Mast DISCS, carbapenemase, enterobacterales, ventilator-associated pneumonia, VAP

Objectives: To date limited information about cefiderocol use is provided by real life studies. Our aim is to evaluate characteristics and outcome of patients with Gram-negative infections with limited therapeutic options treated with cefiderocol in combination or monotherapy. Methods: We retrospectively collected data on demographical, clinical characteristics and clinical cure, in-hospital and 30-days mortality, microbiological failure and Clostridioides difficile infections of all patients ≥ 18 years old treated with cefiderocol for ≥ 48 h. Results: There were 18 patients of which 14 (77.8%) treated with cefiderocol in combination and 4 (22.2%) with monotherapy. Median age was 54.5 (IQR 35.25–65.75) vs 70.5 (IQR 57.5–78.25) years old, respectively and ward of admission was the ICU in the 78.57% vs 100% of cases. In the 50% vs 100% of cases infections were VAP with concomitant bloodstream infections. Median SOFA score was 10 (IQR 4.5–12.5) vs 5 (IQR 4–6) and APACHE II score was 13.5 (IQR 7.5–18) vs 16 (IQR 8.5–23.5), respectively. Isolated pathogen was carbapenems-resistant Acinetobacter baumannii in 78.57% vs 100% of cases. Median duration of cefiderocol treatment was 9.5 (IQR 7–13.25) vs 9 days (IQR 5.5–12.5) and in 77.8% patients it was used in combination therapy, of which 57.1% were colistin-spairing regimens. Clinical cure was achieved in 64.29% for combination therapy vs 75% of monotherapy treated patients, 30-days mortality rate was 28.57% vs 25% and 30-day ICU admission rate was 14.29% vs 50%, respectively. No statistically significant differences were observed between combination therapy and monotherapy treated patients. Conclusions: To date, no differences have been demonstrated between cefiderocol monotherapy or combination. Further studies are required to understand whether cefiderocol combination therapy could provide an advantage in outcome in seriously-ill patients.

Introduction and purpose: hospital-acquired pneumonia and ventilator-associated pneumonia are common risk factors for morbidity and mortality. They are difficult to diagnose and treat due to the large number of factors that may contribute to the deterioration of the clinical condition of critically ill patients. In this article, the authors summarize the diagnosis, treatment and prevention of these diseases based on current guidelines, the latest research and other scientific works. Material and metod: sources available in the PubMed database were analyzed using the following keywords: "pneumonia", "hospital-acquired pneumonia", "ventilator-associated pneumonia", "HAP", "VAP", publications related to the subject of the work were selected and used. Conclusion: A patient with HAP or VAP should undergo non-invasive testing such as blood and sputum cultures and nasal swabs to isolate the pathogen responsible for the infection and to adjust antibiotic therapy. The procalcitonin level can be used in conjunction with the clinical assessment to assess the adjustment of the duration of treatment. Patients with HAP or VAP who are immunocompromised, haemodynamically unstable, or cannot be sampled from the lower respiratory tract for microbiological testing should be treated with empiric antibiotics based on individual risk factors and antibiotic resistance.

Introduction. Ventilator-associated pneumonia (VAP) is a common hospital-acquired infection in children, leading to an increase in morbidity and mortality. A previous study in 2013 showed that VAP rates decreased dramatically after implementation of a VAP bundle and appointing a VAP coordinator. As part of a ‘Plan, Do, Study, Act’ cycle, it was necessary to evaluate the efficacy of these interventions. Objective. To evaluate the VAP rate in the paediatric intensive care unit (PICU) over 2 years (2017 - 2018), and to describe the causative organisms and antibiotic sensitivity/resistance patterns during this period. Methods. This was a retrospective, descriptive study using the existing PICU VAP database as well as clinical folders. Results. Over the 2 years, 31 VAP cases were identified. The VAP rate for 2017 was 4.0/1 000 ventilator days and 5.4/1 000 ventilator days for 2018. Compliance with the VAP bundle was 68% in 2017 and 70% in 2018. The median (interquartile range (IQR)) duration of ventilation in 2017 was 9 (6 -12) days and 15 (11 - 28) days in 2018. The median (IQR) length of PICU stay in 2017 was 11 (8 - 22) days and 25 (17 - 37) days in 2018. The most common cultured organism was an extended-spectrum beta-lactamase (ESBL) Klebsiella pneumoniae sensitive to amikacin and carbapenems. Conclusion. Our VAP rate has not decreased since 2013. It is imperative that we improve compliance with the VAP bundle, in order to reduce VAP rates. K. pneumoniae and Pseudomonas aeruginosa were the most common organisms causing VAPs and empiric use of piptazobactam and amikacin is still appropriate.

ABSTRACT: Background: One of the most important public health concerns is the ever-growing problem of antibiotic resistance. Importantly, the rate of introduction of new molecules into clinical practice has slowed down considerably. Moreover, the rapid emergence of resistance shortens the effective ‘lifespan’ of these molecules. Objective: The quality of care before and after active intervention and feedback was evaluated in patients diagnosed with sepsis/septic shock or ventilator-associated pneumonia (VAP) in the ICUs of Hacettepe University Adult and Oncology Hospitals. Results: There was a significant increase in total scores. Significant improvements were achieved in the management of these patients in terms of requests for necessary diagnostic tests, and the prolonged infusion of beta-lactam agents. Conclusion: Implementation of an ASP in centers where antimicrobial management of ICU patients is largely controlled by infectious diseases specialists remains a feasible strategy that leads to better patient care.

Abstract Background Diagnosing ventilator-associated pneumonia (VAP) in an intensive care unit (ICU) is a complex process. Our aim was to collect, evaluate and represent the information relating to current clinical practice for the diagnosis of VAP in UK NHS ICUs, and to explore the potential value and role of a novel diagnostic for VAP, which uses optical molecular alveoscopy to visualise the alveolar space. Methods Qualitative study performing semi-structured interviews with clinical experts. Interviews were recorded, transcribed, and thematically analysed. A flow diagram of the VAP patient pathway was elicited and validated with the expert interviewees. Fourteen clinicians were interviewed from a range of UK NHS hospitals: 12 ICU consultants, 1 professor of respiratory medicine and 1 professor of critical care. Results Five themes were identified, relating to [1] current practice for the diagnosis of VAP, [2] current clinical need in VAP diagnostics, [3] the potential value and role of the technology, [4] the barriers to adoption and [5] the evidence requirements for the technology, to help facilitate a successful adoption. These themes indicated that diagnosis of VAP is extremely difficult, as is the decision to stop antibiotic treatment. The analysis revealed that there is a clinical need for a diagnostic that provides an accurate and timely diagnosis of the causative pathogen, without the long delays associated with return of culture results, and which is not dangerous to the patient. It was determined that the technology would satisfy important aspects of this clinical need for diagnosing VAP (and pneumonia, more generally), but would require further evidence on safety and efficacy in the patient population to facilitate adoption. Conclusions Care pathway analysis performed in this study was deemed accurate and representative of current practice for diagnosing VAP in a UK ICU as determined by relevant clinical experts, and explored the value and role of a novel diagnostic, which uses optical technology, and could streamline the diagnostic pathway for VAP and other pneumonias.

Acinetobacter baumannii is a Gram-negative saprophytic rod inhabiting both moist niches and dry surfaces. The wide spread of the microbe in the environment by means of minimal nutritional requirements and exceptional survival capabilities give the opportunities to occupy hospital niches, and thus to create threats for hospitalized patients. This bacterium may be a part of the human microbiota as an opportunistic pathogen which upon the host’s weakening, causes less or more serious diseases. A. baumannii is an etiological factor of ventilator-associated pneumonia, which is especially dangerous for patients in intensive care units (in Poland every fifth patient suffers from such infection). Due to the increasing multidrug resistance of A. baumannii, this bacterium belongs to the group of priority pathogens. Fighting such dangerous bacteria is difficult due to their natural resistance as well as acquired resistance mechanisms in response to environmental threats. The unique ability of A. baumannii to cause diseases and acquire resistance to numerous antibiotics, make it necessary to control and prevent these infections.

Abstract Studies have shown that a ventilator associated pneumonia (VAP) bundle significantly decreases VAP rates. In this study, we evaluated existing knowledge, practices, and adherence of nurses and infection control preventionists (ICP) to the VAP bundles of care in the intensive care unit (ICU) by using qualitative and quantitative tools. Of 60 participants (56 nurses and 4 ICPs), mean knowledge score regarding specific evidence-based VAP guidelines was 5 (range 3–8) out of 10 points. Self-reported adherence to the VAP bundle ranged from 38.5 to 100%, with perfect compliance to head of bed elevation, and poorest compliance with readiness to extubate. Overall VAP median bundle compliance was 84.6%. Knowledge regarding specific components of VAP prevention is lacking. Formal training and interactive educational sessions should be performed regularly to assess the competency of key personnel regarding the VAP bundle, especially in the context of rapid nurse turnover. Incentives for retention of nurses should also be considered, so that knowledge of hospital specific initiatives such as the VAP bundles of care can be cultivated over time.

Abstract Background The link between oral bacteria and respiratory infections is well documented. Dental plaque has the potential to be colonized by respiratory pathogens and this, together with microaspiration of oral bacteria, can lead to pneumonia particularly in the elderly and critically ill. The provision of adequate oral care is therefore essential for the maintenance of good oral health and the prevention of respiratory complications. Main body Numerous oral care practices are utilised for intubated patients, with a clear lack of consensus on the best approach for oral care. This narrative review aims to explore the oral-lung connection and discuss in detail current oral care practices to identify shortcomings and offer suggestions for future research. The importance of adequate oral care has been recognised in guideline interventions for the prevention of pneumonia, but practices differ and controversy exists particularly regarding the use of chlorhexidine. The oral health assessment is also an important but often overlooked element of oral care that needs to be considered. Oral care plans should ideally be implemented on the basis of an individual oral health assessment. An oral health assessment prior to provision of oral care should identify patient needs and facilitate targeted oral care interventions. Conclusion Oral health is an important consideration in the management of the critically ill. Studies have suggested benefit in the reduction of respiratory complication such as Ventilator Associated Pneumonia associated with effective oral health care practices. However, at present there is no consensus as to the best way of providing optimal oral health care in the critically ill. Further research is needed to standardise oral health assessment and care practices to enable development of evidenced based personalised oral care for the critically ill.

Artificial respiration is saving lives especially in the COVID-19 pandemic, but it also carries the risk to cause ventilator-associated pneumonia (VAP). VAP is one of the most common and severe nosocomial infections, often leading to death and adding a major economic burden to the healthcare system. To prevent a proliferation of microbial pathogens that cause VAP, an endotracheal tube (ETT) equipped with blue LEDs (LED-ETT) was developed. This blue wavelength exhibits antimicrobial properties but may also harm human tracheal cells at higher irradiances. Therefore, the aim of this study was to find the minimal required irradiance for microbial reduction of 1 log level in 24 h by applying LED-ETTs. A LED-ETT with 48 blue LEDs (450 nm) was fixed in a glass tube, which served as a trachea model. The investigation was carried out with irradiations of 4.2, 6.6 and 13.4 mW/cm² at 37 °C for 24 h. The experiments were performed with Acinetobacter kookii as a surrogate of Acinetobacter baumannii, which is classified as critical by the WHO. Samples of A. kookii suspensions were taken every 4 h during irradiation from the trachea model. Bacteria concentrations were quantified by determining colony forming units (CFU)/ml. A homogeneous irradiance of only 4.2 mW/cm² generated by the blue LEDs, at a LED forward current of 3.125 mA, is sufficient to achieve a 1 log reduction of A. kookii within 24 h. The total irradiation dose within this period was 360 J/cm2. Human cells survive this dose without cellular damage. Previous studies revealed that the pathogen A. baumannii is even more sensitive to blue light than A. kookii. Therefore, blue LED-ETTs are expected to reduce A. baumannii without harming human tracheal cells.

In this research, silver-seeded PVC was synthesised and modified to combat ventilator-associated pneumonia by preventing bacterial adherence. The silver-seeded PVC was synthesised by in situ deposition of silver particles, and the silver-seeded PVC was further modified by reacting with 3,3,4,4,5,5,6,6,7,7,8,8,9,9,10,10,10-heptadecafluoro-1-decanethiol to create a superhydrophobic surface with static water contact angle more than 150°. The silver-coated PVC and superhydrophobic silver-coated PVC both exhibited excellent anti-adherent activity against MRSA and Pseudomonas aeruginosa.

ABSTRACT The impact of syndromic molecular diagnosis in the management of nosocomial infections caused by multidrug-resistant (MDR) and extensively drug-resistant (XDR) pathogens has been incompletely characterized. We evaluated the performance of a molecular syndromic platform (BioFire FilmArray-Pneumonia plus Panel) in patients with pneumonia in the intensive care unit (ICU) of a University Hospital in Greece over a 2-year period. We evaluated 79 consecutive patients diagnosed with pneumonia in the ICU (2018–2020), including 55 patients with ventilator associated pneumonia (VAP). We included 40 control patients diagnosed with pneumonia in the ICU the year before the study (2017–2018). We identified 16 cases of VAP due to XDR bacterial pathogens. We found an excellent agreement (89.4% 76/85 reported results) between the results of syndromic platform and conventional cultures of tracheal aspirates. The molecular syndromic test significantly improved time to diagnosis versus conventional culture (3.5 h vs 72 h, P

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 Introduction Pseudomonas aeruginosa is a common cause of ventilator-associated pneumonia (VAP). Rapid and accurate detection of lower respiratory tract colonization and/or infection with P. aeruginosa may advise targeted preventive (antibody-based) strategies and antibiotic therapy. To investigate this, we compared semi-quantitative culture results from 80 endotracheal aspirates (ETA) collected from mechanically-ventilated patients, to two culture and two non-culture-based methods for detection of P. aeruginosa. Methods P. aeruginosa-positive (n = 40) and -negative (n = 40) ETAs from mechanically ventilated patients analyzed initally by (i) routine semi-quantitative culture, were further analyzed with (ii) quantitative culture on chromogenic ChromID P. aeruginosa and blood agar; (iii) enrichment in brain heart infusion broth followed by plating on blood agar and ChromID P. aeruginosa; (iv) O-antigen acetylase gene-based TaqMan qPCR; and (v) GeneXpert PA PCR assay. Results Of the 80 ETA samples included, one sample that was negative for P. aeruginosa by semi-quantitative culture was found to be positive by the other four methods, and was included in an “extended” gold standard panel. Based on this extended gold standard, both semi-quantitative culture and the GeneXpert PA assay showed 97.6% sensitivity and 100% specificity. The quantitative culture, enrichment culture and O-antigen acetylase gene-based TaqMan qPCR had a sensitivity of 97.6%, 89.5%, 92.7%, and a specificity of 97.4%, 100%, and 71.1%, respectively. Conclusion This first evaluation of the GeneXpert PA assay with ETA samples found it to be as sensitive and specific as the routine, hospital-based semi-quantitative culture method. Additionally, the GeneXpert PA assay is easy to perform (hands-on time ≈ 5 min) and rapid (≈ 55 min assay time). The combination of the high sensitivity and high specificity together with the rapid acquisition of results makes the GeneXpert PA assay a highly recommended screening technique. Where this equipment is not available, semi-quantitative culture remains the most sensitive of the culture methods evaluated here for P. aeruginosa detection in ETA samples.

Abstract Background Ventilator-associated pneumonia (VAP) is a major health problem for people intubated in intensive care units (ICUs), leading to increased mortality rates, hospital stay, and treatment costs. In the present study, the core pathogens causing VAP in Beni-Suef University's Hospital, Egypt, was investigated over a study period of 2 years (2017–2019). Results Of a total of 213 patients subjected to mechanical ventilation, 60 have developed VAP during their stay in the ICU. The mortality rate reached 41.7% among VAP patients. Sixty bacteria were isolated from an endotracheal aspirate of hospitalized patients. The different isolates were cultured followed by running biochemical tests, sensitivity assays, and automated VITEK®2 System analysis. Unexpectedly, all the isolates were Gram-negative bacteria. Klebsiella pneumoniae were the main pathogen encountered (27/60 isolates) followed by Acientobacter baumannnii (7/60) and other microorganisms belonging to the genera Moraxella, Escherichia, and Pseudomonas (11/60). Antibiotic sensitivity testing was performed via the VITEK®2 System using up to 16 different antibiotics representing 8 different antibiotic classes and subclasses (aminoglycosides, carbapenems, fluoroquinolones, penicillin/β-lactamase inhibitor, extended-spectrum cephalosporins, aminopenicillins, aminopenicillins/β-lactamase inhibitor, folic acid synthesis inhibitor). Majority of the isolates (28/60) showed a remarkable extensive drug resistance (XDR) pattern, while 15 isolates were multi-drug resistant (MDR) and only 6 were pan-drug resistant (PDR) with regard to antibiotics under evaluation. Conclusion The association of VAP with multi-drug-resistant bacteria is alarming, and rapid management is crucial. Identification of core pathogens is essential for identifying the most appropriate technique for infection control.

Membrane contact sites (MCS) are crucial for nonvesicular trafficking-based interorganelle communication. Endoplasmic reticulum (ER)–organelle tethering occurs in part through the interaction of the ER resident protein VAP with FFAT motif-containing proteins. FFAT motifs are characterized by a seven amino acidic core surrounded by acid tracks. We have previously shown that the human intracellular bacterial pathogen Chlamydia trachomatis establishes MCS between its vacuole (the inclusion) and the ER through expression of a bacterial tether, IncV, displaying molecular mimicry of eukaryotic FFAT motif cores. Here, we show that multiple layers of host cell kinase-mediated phosphorylation events govern the assembly of the IncV–VAP tethering complex and the formation of ER-Inclusion MCS. Via a C-terminal region containing three CK2 phosphorylation motifs, IncV recruits CK2 to the inclusion leading to IncV hyperphosphorylation of the noncanonical FFAT motif core and serine-rich tracts immediately upstream of IncV FFAT motif cores. Phosphorylatable serine tracts, rather than genetically encoded acidic tracts, accommodate Type III-mediated translocation of IncV to the inclusion membrane, while achieving full mimicry of FFAT motifs. Thus, regulatory components and post-translational modifications are integral to MCS biology, and intracellular pathogens such as C. trachomatis have evolved complex molecular mimicry of these eukaryotic features.

Ventilator-associated pneumonia (VAP) is associated with increased hospital stay and high morbidity and mortality in critically ill patients. The aims of this study were to (i) determine the incidence of multidrug-resistant (MDR) pathogens in the first episodes of VAP and to assess potential differences in bacterial profiles of subjects with early- versus late-onset VAP. This was a retrospective cohort study over a period of 18 months including all patients who had a first episode of VAP confirmed by positive bacterial culture. Subjects were distributed into two groups according to the number of intubation days: early-onset VAP (n = 46). The most frequently isolated bacteria were A. baumannii, 53% (n = 32); P. aeruginosa in 37% (n = 22); Enterobacterales in 28% (n = 17) and S. aureus in 5% (n = 3). Ninety-seven percent of the bacteria were MDR. The VAP group comprised 36 (60%) episodes of early-onset VAP and 24 (40%) episodes of late-onset VAP. There was no significant difference in the distribution of the bacterial isolates, nor in terms of antibacterial resistances between early- and late-onset VAPs. Our data support recent observations that there is no microbiological difference in the prevalence of potential MDR pathogens or in their resistance profiles associated with early- versus late-onset VAPs, especially in countries with high rates of MDR bacteria.

Introduction: Hospital-acquired infection (HAI) rates were reported to have declined in healthcare settings during the Covid-19 pandemic. Needless to mention that HAI is of paramount interest and relevance to a primary care physician who need to care from womb to tomb inside pandemic. Objectives: This study was conducted to find the impact of Covid-19 pandemic on the four parameters of HAIs, namely, catheter-associated urinary tract infections (CAUTI), central-line-associated bloodstream infections (CLABSI), ventilator-associated pneumonia (VAP) and surgical site infections (SSIs) with hand hygiene compliance rates among healthcare workers. Materials and Methods: This retrospective data mining was undertaken in a 700 bed multispecialty teaching hospital in the Eastern India which was a Government of Bihar approved speciality Covid Care Hospital. Data from the monthly routine infection control monitoring and surveillance activities was collated from January 2019 to December 2020. Control charts with upper and lower control limit set at mean ± 1 SD were used to monitor monthly trends of HAIs. Results: The CAUTI rates reduced by 28.01%; the CLABSI rates declined by 37.61%, the SSI rates reduced by 62.39%, while the highest VAP rates were reported in November 2019 (1.9 per 1000 ventilator days). The hand hygiene compliance rates from January 2019 to December 2020 among different healthcare staffs showed a sharply rising trend. Conclusion: Covid-19 pandemic highlighted paramount importance regarding compliance to hand hygiene and implementation of standard infection control practices as recommended by World Health Organisation and Centres for Diseases Control and Prevention (CDC), which can drastically reduce range of HAIs.

Introduction: The Portuguese National Registry of Transcatheter Aortic Valve Implantation records prospectively the characteristics and outcomes of transcatheter aortic valve implantation (TAVI) procedures in Portugal. Objectives: To assess the 30-day and one-year outcomes of TAVI procedures in Portugal. Methods: We compared TAVI results according to the principal access used (transfemoral (TF) vs. non-transfemoral (non-TF)). Cumulative survival curves according to access route, other procedural and clinical variables were obtained. The Valve Academic Research Consortium-2 (VARC-2) composite endpoint of early (30-days) safety was assessed. VARC-2 predictors of 30-days and 1-year all-cause mortality were identified. Results: Between January 2007 and December 2018, 2346 consecutive patients underwent TAVI (2242 native, 104 valve-in-valve; mean age 81±7 years, 53.2% female, EuroSCORE-II - EuroS-II, 4.3%). Device success was 90.1% and numerically lower for non-TF (87.0%). Thirty-day all-cause mortality was 4.8%, with the TF route rendering a lower mortality rate (4.3% vs. 10.1%, p=0.001) and higher safety endpoint (86.4% vs. 72.6%, p5% (p5% (p

ObjectiveThe purpose of this study was to investigate the key nursing factors associated with ventilator-associated pneumonia (VAP) in critical care patients.MethodsThrough the quality control platform of Hebei Province, questionnaires were sent to intensive care nurses in 32 tertiary hospitals in Hebei Province, China to collect data concerning the incidence of VAP and the status of the nursing staff. All the data were analyzed using an independent t-test and a one-way analysis of variance (ANOVA). The Pearson correlation coefficient was used to analyse the correlation between the nursing factors and the incidence of VAP. Multivariate logistic regression analysis was used to determine the risk factors affecting VAP.ResultsIn terms of nursing, the incidence of VAP was affected by the differential nursing strategies. Multivariate logistic regression analysis showed that the incidence of VAP was significantly associated with the following six variables: the ratio of nurses to beds (p = 0.000), the ratio of nurses with a bachelor's degree or higher (p = 0.000), the ratio of specialist nurses (p = 0.000), the proportion of nurses with work experience of 5–10 years (p = 0.04), the number of patients nurses were responsible for at night (p = 0.01) and the frequency of oral care (p = 0.000).ConclusionThe incidence of VAP is closely related to nursing factors. In terms of nursing human resources, even junior nurses (less experienced nurses) can play an essential role in reducing VAP. In addition, to reduce VAP, the number of patients that nurses are responsible for at night should be reduced as much as possible, and improving nursing qualifications.

Background: The purpose of this study was to investigate and predict ventilator-associated pneumonia (VAP) in the two groups of patients who received either proton pump inhibitors (Pantoprazole) or histamine H2 antagonist (Ranitidine). Methods: Patients in ICU received Pantoprazole or Ranitidine as stress-related mucosal injury and GI bleeding prophylaxis. The incidence rate of VAP and GI bleeding was estimated in each group during ICU stay. Chi-Square and Multivariate Logistic Regression Test were used for data analysis. P.value less than 0.05 was considered significant. Data analysis was performed through SPSS version 19.0. Results: The incidence rate of VAP in the Ranitidine and Pantoprazole groups was 44.7% and 37.3% respectively (p=0.3). According to the multivariable logistic regression analysis, length of mechanical ventilation ≥ 4 days was a predictive factor for VAP only in the Pantoprazole group (OR: 1.8, 95% CI: 1.56-1.90, p=0.006). No relationship between GI bleeding incidence and stress ulcer prophylaxis was found (p=0.4). Kaplan-Meier curve showed no significant difference between the two groups of Ranitidine and Pantoprazole (p=0.4) in survival time according to the length of ICU stay. Conclusion: According to the results, there was no difference between the two groups in terms of VAP, GI bleeding and stress ulcer. Due to the lower cost of Ranitidine, it may be a more appropriate choice for GI bleeding prophylaxis in ICU patients.

Abstract Background Aerosolized antibiotic administration offers the theoretical advantages of achieving high drug concentrations at the infection site together with lower systemic absorption. This study aims to compare the effect of combining nebulized amikacin with intravenous amikacin to the effect of the usual intravenous route alone in the treatment of patients with ventilator-associated pneumonia and its impact on the duration of mechanical ventilation, laboratory, and clinical picture of the patients. Results This study was carried out on 64 mechanically ventilated patients with Gram-negative VAP. The patients were divided into 2 groups. Group A included 32 patients treated with nebulized amikacin plus IV amikacin, and group B included 32 patients treated with IV amikacin alone. The duration of treatment for both groups was 8 days with a daily assessment of Clinical Pulmonary Infection Score (CPIS) and monitoring of clinical and laboratory parameters. Sputum cultures were obtained thereafter. In our study, the CPIS score and overall ICU mortality were less in the nebulized than in the IV group but the difference failed to be statistically significant. Increase of oxygenation level (Pao2/Fio2 ratio), organism clearance, decrease in serum creatinine level, duration of mechanical ventilation, and length of ICU stay were significantly different in favor of group A than group B. Conclusion Nebulized and IV amikacin offered better oxygenation, organism clearance, less nephrotoxicity, and less duration of mechanical ventilation and ICU stay than the IV group. Combined and IV routes were comparable regarding the decrease in CPIS score and ICU mortality with no significant difference between them. However, we prefer to use the combined regimen for the mentioned reasons. Further large-scale studies are required to confirm these findings and to establish a definite conclusion.

Abstract In accordance with the recommendations of, amongst others, the Surviving Sepsis Campaign and the recently published European treatment guidelines for hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP), in the event of a patient with such infections, empirical antibiotic treatment must be appropriate and administered as early as possible. The aim of this manuscript is to update treatment protocols by reviewing recently published studies on the treatment of nosocomial pneumonia in the critically ill patients that require invasive respiratory support and patients with HAP from hospital wards that require invasive mechanical ventilation. An interdisciplinary group of experts, comprising specialists in anaesthesia and resuscitation and in intensive care medicine, updated the epidemiology and antimicrobial resistance and established clinical management priorities based on patients’ risk factors. Implementation of rapid diagnostic microbiological techniques available and the new antibiotics recently added to the therapeutic arsenal has been reviewed and updated. After analysis of the categories outlined, some recommendations were suggested, and an algorithm to update empirical and targeted treatment in critically ill patients has also been designed. These aspects are key to improve VAP outcomes because of the severity of patients and possible acquisition of multidrug-resistant organisms (MDROs).

Introduction: Ventilator-associated pneumonia (VAP) is the most frequent intensive care unit (ICU) acquired infection among patients receiving mechanical ventilation. Accurate clinical and microbiologic diagnosis of VAP is essential not only for selection of appropriate antimicrobials but also to prevent their misuse. As the organisms and their sensitivity pattern may differ in every ICU, the knowledge of the resident flora and their behaviour should be known for successful treatment. Methods: The study was conducted to evaluate the organisms responsible for VAP and their Antibiotic Sensitivity Pattern for the study setting. A prospective, open, epidemiological clinical study was performed in a tertiary care hospital in Nepal. 100 patients admitted to ICU and Mechanically Ventilated were evaluated about VAP. Clinical Pulmonary Infection Score (CPIS) was used to diagnose VAP. Results: Among 60 patients ventilated for more than 48 hours, 25 (41.6%) developed VAP. The VAP was caused predominantly by Klebsiella pneumonia in 34.5% of cases, followed by Acinetobacter calcoaceticus baumanni in 27.6%, Acinetobacter wolffi and Pseudomonas aeruginosa in 13.8% each and Escheresia coli in 10.3%. The most sensitive antibiotics were Colistin, followed by Polymyxin B and Amikacin with sensitivity rates of 67%, 60% and 58%, respectively. Conclusion: Based on these results, an empiric approach to antibiotic treatment can be made tailored to the specific settings. Given the magnitude of drug resistance and its implicated financial and societal burden, there is an urgent need for broad implementation of Antibiotic Stewardship programs across all health care settings.

Neuregulins (NRGs) signal via ErbB receptors to regulate neural development, excitability, synaptic and network activity, and behaviors relevant to psychiatric disorders. Bidirectional signaling between NRG2/ErbB4 and NMDA receptors is thought to homeostatically regulate GABAergic interneurons in response to increased excitatory neurotransmission or elevated extracellular glutamate levels. Unprocessed proNRG2 forms discrete clusters on cell bodies and proximal dendrites that colocalize with the potassium channel Kv2.1 at specialized endoplasmic reticulum-plasma membrane (ER-PM) junctions, and NMDA receptor activation triggers rapid dissociation from ER-PM junctions and ectodomain shedding by ADAM10. Here, we elucidate the mechanistic basis of proNRG2 clustering at ER-PM junctions and its regulation by NMDA receptors. Importantly, we demonstrate that proNRG2 promotes the formation of ER-PM junctions by directly binding the ER-resident membrane tether VAP, like Kv2.1. The proNRG2 intracellular domain harbors two non-canonical, low-affinity sites that cooperatively mediate VAP binding. One of these is a cryptic and phosphorylation-dependent VAP binding motif that is dephosphorylated following NMDA receptor activation, thus revealing how excitatory neurotransmission promotes the dissociation of proNRG2 from ER-PM junctions. Therefore, proNRG2 and Kv2.1 can independently function as VAP-dependent organizers of neuronal ER-PM junctions. Based on these and prior studies, we propose that proNRG2 and Kv2.1 serve as co-regulated downstream effectors of NMDA receptors to homeostatically regulate GABAergic interneurons.