The yeast VAPs Scs2 and Scs22 are required for NVJ integrity and micronucleophagy.

Microautophagy degrades cargos in the vacuole by direct engulfment of the vacuolar membrane. Micronucleophagy selectively degrades a portion of the nucleus in budding yeast. The vacuole contacts the nucleus via the nucleus-vacuole junction (NVJ), and in micronucleophagy a portion of the nucleus containing nucleolar proteins is made to protrude into the vacuole at the NVJ, followed by abscission and degradation. Microautophagy and micronucleophagy are induced by inactivation of target of rapamycin complex 1 (TORC1) protein kinase after nutrient starvation. Here, we show that the VAMP-associated proteins (VAPs) Scs2 and its paralog Scs22 are required for NVJ integrity and micronucleophagic degradation of nucleolar proteins. On the other hand, nucleolar dynamics prerequisite for micronucleophagy were not impaired in VAP mutant cells. Finally, yeast VAPs were critical for viability during prolonged nutrient starvation. This study sheds light on the emerging role of VAP in adaptation in responses to nutrient starvation.

Prior carbapenem exposure increases the incidence of ventilator-associated pneumonia in critically Ill children.

BACKGROUND: Prior antibiotic exposure has been identified as a risk factor for VAP occurrence, making it a growing concern among clinical practitioners. But there is a lack of systematic research on the types of antibiotics and the duration of exposure that influence VAP occurrence in children at current. METHODS: We retrospectively reviewed 278 children admitted to the Pediatric Intensive Care Unit (PICU) and underwent invasive mechanical ventilation (MV) between January 2020 and December 2022. Of these, 171 patients with MV duration ≥ 48 h were included in the study, with 61 of them developing VAP (VAP group) and the remaining 110 as the non-VAP group. We analyzed the relationship between early antibiotic exposure and VAP occurrence. RESULTS: The incidence of VAP was 21.94% (61/278). The VAP group had significantly longer length of hospital stay (32.00 vs. 20.00 days, p<0.001), PICU stay(25.00 vs. 10.00 days, p<0.001), and duration of mechanical ventilation(16.00 vs. 6.00 days, p<0.001) compared to the non-VAP group. The mortality in the VAP group was significantly higher than that in the non-VAP group (36.07% vs. 21.82%, p = 0.044). The VAP group had a significantly higher rate of carbapenem exposure (65.57% vs. 41.82%, p = 0.003) and duration of usage (9.00 vs. 5.00 days, p = 0.004) than the non-VAP group. Vancomycin and/or linezolid exposure rates (57.38% vs. 40.00%, p = 0.029) and duration (8 vs. 4.5 days, p = 0.010) in the VAP group were significantly higher than that in the non-VAP group, either. Multivariate logistic regression analysis identified the use of carbapenem (≥ 7 days) (OR = 5.156, 95% CI: 1.881-14.137, p = 0.001), repeated intubation (OR = 3.575, 95% CI: 1.449-8.823, p = 0.006), and tracheostomy (OR = 5.767, 95% CI:1.686-19.729, p = 0.005) as the independent risk factors for the occurrence of VAP, while early intravenous immunoglobulin (IVIG) was a protective factor against VAP (OR = 0.426, 95% CI: 0.185-0.98, p = 0.045). CONCLUSION: Prior carbapenem exposure (more than 7 days) was an independent risk factor for the occurrence of VAP. For critically ill children, reducing carbapenem use and duration as much as possible should be considered.

Variations and National Perspectives on Evaluation and Management of Ventilator-Associated Pneumonia in Neonatal Intensive Care Units: An In-Depth Survey Analysis.

Introduction Infants in the neonatal intensive care unit (NICU) are vulnerable to ventilator-associated pneumonia (VAP), which increases their morbidity and mortality. There is a significant overlap of clinical features of neonatal VAP with other pulmonary pathologies, particularly in preterm infants, which can make the definitive diagnosis and management of VAP challenging. Objective Our study surveyed NICU providers across the United States to understand the perspectives and variations in neonatal VAP diagnostic and management practices. Methods The REDCap survey was distributed to the actively practicing members of the Section on Neonatal-Perinatal Medicine (SoNPM) of the American Academy of Pediatrics (AAP). We used descriptive statistics to analyze the data from the respondents. Results Of 254 respondents, the majority (86.6%, 220) were neonatologists and had a relatively even geographical distribution. Most (75.9%, 193) stated that they would perform a gram stain and respiratory culture as part of a sepsis workup irrespective of the patient's duration on invasive mechanical ventilation (IMV); 224 (88.2%) of providers preferred the endotracheal aspiration (ETA) technique to collect specimens. In cases where a positive respiratory culture was present, VAP (52.4%, 133) was the predominantly assigned diagnosis, followed by pneumonia (27.2%, 69) and ventilator-associated tracheitis (VAT) (9.8%, 25). Respondents reported a prescription of intravenous gentamicin (70%, 178) and vancomycin (41%, 105) as the initial empiric antibiotic drugs, pending final respiratory culture results. Most respondents (55.5%, 141) opted for seven days of antibiotics duration to treat VAP. The reported intra-departmental variation among colleagues in acquiring respiratory cultures and prescribing antibiotics for VAP was 48.8% (124) and 37.4% (95), respectively, with slightly more than half (53.5%, 136) of providers reporting having VAP prevention guidelines in their units. Conclusion The survey study revealed inconsistencies in the investigation, diagnostic nomenclature, choice of antibiotic, and treatment duration for neonatal VAP. Consequently, there is a pressing need for further research to establish a clear definition and evidence-based criteria for VAP.

Oxysterole-binding protein targeted by SARS-CoV-2 viral proteins regulates coronavirus replication.

Introduction: Oxysterol-binding protein (OSBP) is known for its crucial role in lipid transport, facilitating cholesterol exchange between the Golgi apparatus and endoplasmic reticulum membranes. Despite its established function in cellular processes, its involvement in coronavirus replication remains unclear. Methods: In this study, we investigated the role of OSBP in coronavirus replication and explored the potential of a novel OSBP-binding compound, ZJ-1, as an antiviral agent against coronaviruses, including SARS-CoV-2. We utilized a combination of biochemical and cellular assays to elucidate the interactions between OSBP and SARS-CoV-2 non-structural proteins (Nsps) and other viral proteins. Results: Our findings demonstrate that OSBP positively regulates coronavirus replication. Moreover, treatment with ZJ-1 resulted in reduced OSBP levels and exhibited potent antiviral effects against multiple coronaviruses. Through our investigation, we identified specific interactions between OSBP and SARS-CoV-2 Nsps, particularly Nsp3, Nsp4, and Nsp6, which are involved in double-membrane vesicle formation-a crucial step in viral replication. Additionally, we observed that Nsp3 a.a.1-1363, Nsp4, and Nsp6 target vesicle-associated membrane protein (VAMP)-associated protein B (VAP-B), which anchors OSBP to the ER membrane. Interestingly, the interaction between OSBP and VAP-B is disrupted by Nsp3 a.a.1-1363 and partially impaired by Nsp6. Furthermore, we identified SARS-CoV-2 orf7a, orf7b, and orf3a as additional OSBP targets, with OSBP contributing to their stabilization. Conclusion: Our study highlights the significance of OSBP in coronavirus replication and identifies it as a promising target for the development of antiviral therapies against SARS-CoV-2 and other coronaviruses. These findings underscore the potential of OSBP-targeted interventions in combating coronavirus infections.

Molecular characterization of NDM and OXA-48-like-producing Klebsiella pneumoniae ST16 and hypervirulent ST337 clone among two patients; a case report.

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.

The Ribosome Assembly Factor LSG1 Interacts with Vesicle-Associated Membrane Protein-Associated Proteins (VAPs).

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.

Exploring Ventilator-Associated Pneumonia: Microbial Clues and Biomarker Insights from a Retrospective Study.

Background and Objectives: Ventilator-associated pneumonia (VAP) is a common complication in critically ill patients receiving mechanical ventilation. The incidence rates of VAP vary, and it poses significant challenges due to microbial resistance and the potential for adverse outcomes. This study aims to explore the microbial profile of VAP and evaluate the utility of biomarkers and illness severity scores in predicting survival. Materials and Methods: A retrospective cohort study was conducted involving 130 patients diagnosed with VAP. Microbial analysis of bronchoalveolar lavage (BAL) fluid, as well as measurements of C-reactive protein (CRP) and procalcitonin (PCT) levels, were performed. Sequential Organ Failure Assessment (SOFA) and Acute Physiology and Chronic Health Evaluation II (APACHE II) scores were calculated to assess illness severity. Statistical analyses were conducted to determine correlations and associations. Results: The study revealed that Klebsiella pneumoniae (K. pneumoniae) (50.7%) and Pseudomonas aeruginosa (P. aeruginosa) (27.69%) were the most identified microorganisms in VAP cases. SOFA (p-value < 0.0001) and APACHE II (p-value < 0.0001) scores were effective in assessing the severity of illness and predicting mortality in VAP patients. Additionally, our investigation highlighted the prognostic potential of CRP levels (odds ratio [OR]: 0.980, 95% confidence interval [CI] 0.968 to 0.992, p = 0.001). Elevated levels of CRP were associated with reduced survival probabilities in VAP patients. Conclusion: This study highlights the microbial profile of VAP and the importance of biomarkers and illness severity scores in predicting survival. Conclusions: The findings emphasize the need for appropriate management strategies to combat microbial resistance and improve outcomes in VAP patients.

Surveillance of ventilator associated pneumonia in a network of indian hospitals using modified definitions: a pilot study.

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).

Expression of Vascular Adhesion Protein-1 and Thrombospondin-1 in Gingival Crevicular Fluid of Patients with Periodontitis and Non-Alcoholic Fatty Liver Disease.

Purpose: Non-alcoholic fatty liver disease (NAFLD) represents a heterogeneous spectrum of liver diseases that encompass simple steatosis, non-alcoholic steatohepatitis (NASH), and advanced fibrosis or cirrhosis. Periodontitis is a chronic infectious disease with multiple causal factors that presents a complex interaction between the microbial biofilm and the host's immune response. The aim of this study was to investigate the concentrations of Vascular Adhesion Protein-1 (VAP-1) and Thrombospondin-1 (TSP-1) in patients with coexisting periodontitis and NAFLD. Patients and Methods: This study included 48 patients, who were dental and periodontal assessed. Of these patients, 25 were diagnosed with NAFLD. After performing the periodontal clinical examination, gingival crevicular fluid (GCF) samples were collected. Enzyme-linked immunosorbent assay (ELISA) dedicated kits tests were used for the detection and quantitative determination of VAP-1 and TSP-1 in GCF samples. Statistical methods were applied for the comparison and correlation of data. Results: VAP-1 and TSP-1 levels showed significant differences between all test and control groups (p<0.0001). Statistically significant correlations (p<0.05) between VAP-1 and periodontal and liver parameters were found in patients with NAFLD and periodontitis. Conclusion: Periodontal inflammation is more marked in patients with periodontitis-NAFLD association. Vascular adhesion and angiogenesis could be affected in patients with periodontitis and NAFLD. These findings could suggest that addressing periodontal inflammation in individuals with the periodontitis-NAFLD association may have a broader impact on vascular adhesion and angiogenesis, highlighting the interplay between oral health and liver conditions for comprehensive patient care.

Six-year evaluation of device-associated nosocomial infections in intensive care units.

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 clinic-based 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.

Bundle care approach to reduce device associated infections in post-living-donor-liver transplantation in a tertiary care hospital, Egypt.

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.

Coordination of oxysterol binding protein 1 and VAP-A/B modulates the generation of cholesterol and viral inclusion bodies to promote grass carp reovirus replication.

Similar to other RNA viruses, grass carp reovirus, the causative agent of the hemorrhagic disease, replicates in cytoplasmic viral inclusion bodies (VIBs), orchestrated by host proteins and lipids. The host pathways that facilitate the formation and function of GCRV VIBs are poorly understood. This work demonstrates that GCRV manipulates grass carp oxysterol binding protein 1 (named as gcOSBP1) and vesicle-associated membrane protein-associated protein A/B (named as gcVAP-A/B), 3 components of cholesterol transport pathway, to generate VIBs. By siRNA-mediated knockdown, we demonstrate that gcOSBP1 is an essential host factor for GCRV replication. We reveal that the nonstructural proteins NS80 and NS38 of GCRV interact with gcOSBP1, and that the gcOSBP1 is recruited by NS38 and NS80 for promoting the generation of VIBs. gcOSBP1 increases the expression of gcVAP-A/B and promotes the accumulation of intracellular cholesterol. gcOSBP1 also interacts with gcVAP-A/B for forming gcOSBP1-gcVAP-A/B complexes, which contribute to enhance the accumulation of intracellular cholesterol and gcOSBP1-mediated generation of VIBs. Inhibiting cholesterol accumulation by lovastatin can completely abolish the effects of gcOSBP1 and/or gcVAP-A/B in promoting GCRV infection, suggesting that cholesterol accumulation is vital for gcOSBP1- and/or gcVAP-A/B-mediated GCRV replication. Thus, our results, which highlight that gcOSBP1 functions in the replication of GCRV via its interaction with essential viral proteins for forming VIBs and with host gcVAP-A/B, provide key molecular targets for obtaining anti-hemorrhagic disease grass carp via gene editing technology.

Visualized and pH-responsive hydrogel antibacterial coating for ventilator-associated pneumonia.

Ventilator-associated pneumonia (VAP) is a common healthcare-acquired infection often arising during artificial ventilation using endotracheal intubation (ETT), which offers a platform for bacterial colonization and biofilm development. In particular, the effects of prolonged COVID-19 on the respiratory system. Herein, we developed an antimicrobial coating (FK-MEM@CMCO-CS) capable of visualizing pH changes based on bacterial infection and releasing meropenem (MEM) and FK13-a1 in a controlled manner. Using a simple dip-coating process with controlled loading, chitosan was cross-linked with sodium carboxymethyl cellulose oxidation (CMCO) and coated onto PVC-based ETT to form a hydrogel coating. Subsequently, the coated segments were immersed in an indicator solution containing bromothymol blue (BTB), MEM, and FK13-a1 to fabricate the FK-MEM@CMCO-CS coating. In vitro studies have shown that MEM and FK13-a1 can be released from coatings in a pH-responsive manner. Moreover, anti-biofilm and antibacterial adhesion results showed that FK-MEM@CMCO-CS coating significantly inhibited biofilm formation and prevented their colonization of the coating surface. In the VAP rat model, the coating inhibited bacterial growth, reduced lung inflammation, and had good biocompatibility. The coating can be applied to the entire ETT and has the potential for industrial production.

Efficacy and Safety of Ceftazidime-Avibactam Alone versus Ceftazidime-Avibactam Plus Fosfomycin for the Treatment of Hospital-Acquired Pneumonia and Ventilator-Associated Pneumonia: A Multicentric Retrospective Study from the SUSANA Cohort.

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.

Novel Antibiotics for Gram-Negative Nosocomial Pneumonia.

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

Predictors of treatment failure following early antibiotic discontinuation in culture-negative, ventilator-associated pneumonia: an observational study.

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.

Association between anion gap and the 30-day mortality of patients with ventilator-associated pneumonia: a study of the MIMIC-III database.

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

Antimicrobial resistance pattern in aerobic bacteria isolated from endotracheal aspirate in ventilator-associated pneumonia: Ten years observation from a tertiary care hospital.

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.

The Clinical Pulmonary Infection Score Combined with Procalcitonin and Lung Ultrasound (CPIS-PLUS), a Good Tool for Ventilator Associated Pneumonia Early Diagnosis in Pediatrics.

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