Multidrug-resistant pathogens and ventilator-associated pneumonia in critically ill COVID-19 and non-COVID-19 patients: a prospective observational monocentric comparative study.

BACKGROUND: The COVID-19 pandemic has increased the incidence of ventilator-associated pneumonia (VAP) among critically ill patients. However, a comparison of VAP incidence in COVID-19 and non-COVID-19 cohorts, particularly in a context with a high prevalence of multidrug-resistant (MDR) organisms, is lacking. MATERIAL AND METHODS: We conducted a single-center, mixed prospective and retrospective cohort study comparing COVID-19 patients admitted to the intensive care unit (ICU) of the "Città della Salute e della Scienza" University Hospital in Turin, Italy, between March 2020 and December 2021 (COVID-19 group), with a historical cohort of ICU patients admitted between June 2016 and March 2018 (NON-COVID-19 group). The primary objective was to define the incidence of VAP in both cohorts. Secondary objectives were to evaluate the microbial cause, resistance patters, risk factors and impact on 28 days, ICU and in-hospital mortality, duration of ICU stay, and duration of hospitalization). RESULTS: We found a significantly higher incidence of VAP (51.9% - n = 125) among the 241 COVID-19 patients compared to that observed (31.2% - n = 78) among the 252 NON-COVID-19 patients. The median SOFA score was significantly lower in the COVID-19 group (9, Interquartile range, IQR: 7-11 vs. 10, IQR: 8-13, p < 0.001). The COVID-19 group had a higher prevalence of Gram-positive bacteria-related VAP (30% vs. 9%, p < 0.001), but no significant difference was observed in the prevalence of difficult-to-treat (DTR) or MDR bacteria. ICU and in-hospital mortality in the COVID-19 and NON-COVID-19 groups were 71% and 74%, vs. 33% and 43%, respectively. The presence of COVID-19 was significantly associated with an increased risk of 28-day all-cause hospital mortality (Hazard ratio, HR: 7.95, 95% Confidence Intervals, 95% CI: 3.10-20.36, p < 0.001). Tracheostomy and a shorter duration of mechanical ventilation were protective against 28-day mortality, while dialysis and a high SOFA score were associated with a higher risk of 28-day mortality. CONCLUSION: COVID-19 patients with VAP appear to have a significantly higher ICU and in-hospital mortality risk regardless of the presence of MDR and DTR pathogens. Tracheostomy and a shorter duration of mechanical ventilation appear to be associated with better outcomes.

Exploring the impact of dexmedetomidine on short-term outcomes in critically ill sepsis-associated encephalopathy patients.

OBJECTIVE: Dexmedetomidine has demonstrated potential in preclinical medical research as a protective agent against inflammatory injuries and a provider of neuroprotective benefits. However, its effect on the short-term prognosis of patients with sepsis-associated encephalopathy remains unclear. This study aims to explore the underlying value of dexmedetomidine in these patients. PATIENTS AND METHODS: This study enrolled patients with sepsis-associated encephalopathy from the Medical Information Mart for Intensive Care (MIMIC)-IV database, and they were divided into two groups based on dexmedetomidine therapy during hospitalization. Propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) were utilized to balance the inter-group baseline differences. Kaplan-Meier (KM) curves with log-rank test and subgroup analysis were also employed. The primary outcome was 28-day mortality, and the secondary outcomes were in-hospital mortality, intensive care unit (ICU) stay time, hospital stay time, and the incidence of ventilator-associated pneumonia (VAP). RESULTS: After PSM, 1,075 pairs of patients were matched. In contrast to the non-dexmedetomidine cohort, the dexmedetomidine cohort did not exhibit a shortened ICU [4.65 (3.16, 8.55) vs. 6.14 (3.66, 11.04), p<0.001] and hospital stay duration [10.04 (6.55, 15.93) vs. 12.76 (7.92, 19.95), p<0.001], and there was an elevated incidence of VAP [90 (8.4%) vs. 135 (12.6%), p=0.002]. The log-rank test for the KM curves of dexmedetomidine use and 28-day mortality was statistically significant (p<0.001). The results showed that dexmedetomidine was associated with improved 28-day mortality [hazard ratio (HR) 0.46, 95% confidence interval (CI) 0.35-0.61, p<0.001] and in-hospital mortality (HR 0.50, 95% CI 0.37-0.67, p<0.001) after adjusting for various confounders. In the following subgroup analysis, dexmedetomidine infusion was associated with decreased 28-day mortality in most subgroups. CONCLUSIONS: Dexmedetomidine administration was significantly associated with reduced short-term mortality among patients with sepsis-associated encephalopathy in the ICU. However, it also prolonged ICU and hospital stays and increased the incidence of VAP.

Optimizing Diagnosis and Management of Community-acquired Pneumonia in the Emergency Department.

Pneumonia is split into 3 diagnostic categories: community-acquired pneumonia (CAP), health care-associated pneumonia, and ventilator-associated pneumonia. This classification scheme is driven not only by the location of infection onset but also by the predominant associated causal microorganisms. Pneumonia is diagnosed in over 1.5 million US emergency department visits annually (1.2% of all visits), and most pneumonia diagnosed by emergency physicians is CAP.

Ventilator-associated pneumonia related to extended-spectrum beta-lactamase producing Enterobacterales during severe acute respiratory syndrome coronavirus 2 infection: risk factors and prognosis.

BACKGROUND: Patients infected with the severe acute respiratory syndrome coronavirus 2 (SARS-COV 2) and requiring mechanical ventilation suffer from a high incidence of ventilator associated pneumonia (VAP), mainly related to Enterobacterales. Data regarding extended-spectrum beta-lactamase producing Enterobacterales (ESBL-E) VAP are scarce. We aimed to investigate risk factors and outcomes of ESBL-E related VAP among critically ill coronavirus infectious disease-19 (COVID-19) patients who developed Enterobacterales related VAP. PATIENTS AND METHODS: We performed an ancillary analysis of a multicenter prospective international cohort study (COVID-ICU) that included 4929 COVID-19 critically ill patients. For the present analysis, only patients with complete data regarding resistance status of the first episode of Enterobacterales related VAP (ESBL-E and/or carbapenem-resistant Enterobacterales, CRE) and outcome were included. RESULTS: We included 591 patients with Enterobacterales related VAP. The main causative species were Enterobacter sp (n = 224), E. coli (n = 111) and K. pneumoniae (n = 104). One hundred and fifteen patients (19%), developed a first ESBL-E related VAP, mostly related to Enterobacter sp (n = 40), K. pneumoniae (n = 36), and E. coli (n = 31). Eight patients (1%) developed CRE related VAP. In a multivariable analysis, African origin (North Africa or Sub-Saharan Africa) (OR 1.7 [1.07-2.71], p = 0.02), time between intubation and VAP (OR 1.06 [1.02-1.09], p = 0.002), PaO2/FiO2 ratio on the day of VAP (OR 0.997 [0.994-0.999], p = 0.04) and trimethoprim-sulfamethoxazole exposure (OR 3.77 [1.15-12.4], p = 0.03) were associated with ESBL-E related VAP. Weaning from mechanical ventilation and mortality did not significantly differ between ESBL-E and non ESBL-E VAP. CONCLUSION: ESBL-related VAP in COVID-19 critically-ill patients was not infrequent. Several risk factors were identified, among which some are modifiable and deserve further investigation. There was no impact of resistance of the first Enterobacterales related episode of VAP on outcome.

Association of antibiotic duration and all-cause mortality in a prospective study of patients with ventilator-associated pneumonia in a tertiary-level critical care unit in Southern India.

OBJECTIVES: To estimate all-cause mortality in ventilator-associated pneumonia (VAP) and determine whether antibiotic duration beyond 8 days is associated with reduction in all-cause mortality in patients admitted with VAP in the intensive care unit. DESIGN: A prospective cohort study of patients diagnosed with VAP based on the National Healthcare Safety Network definition and clinical criteria. SETTING: Single tertiary care hospital in Southern India. PARTICIPANTS: 100 consecutive adult patients diagnosed with VAP were followed up for 28 days postdiagnosis or until discharge. OUTCOME MEASURES: The incidence of mortality at 28 days postdiagnosis was measured. Tests for association and predictors of mortality were determined using χ2 test and multivariate Cox regression analysis. Secondary outcomes included baseline clinical parameters such as age, underlying comorbidities as well as measuring total length of stay, number of ventilator-free days and antibiotic-free days. RESULTS: The overall case fatality rate due to VAP was 46%. There was no statistically significant difference in mortality rates between those receiving shorter antibiotic duration (5-8 days) and those on longer therapy. Among those who survived until day 9, the observed risk difference was 15.1% between both groups, with an HR of 1.057 (95% CI 0.26 to 4.28). In 70.4% of isolates, non-fermenting Gram-negative bacilli were identified, of which the most common pathogen isolated was Acinetobacter baumannii (62%). CONCLUSION: In this hospital-based cohort study, there is insufficient evidence to suggest that prolonging antibiotic duration beyond 8 days in patients with VAP improves survival.

Automated surveillance of non-ventilator-associated hospital-acquired pneumonia (nvHAP): a systematic literature review.

BACKGROUND: Hospital-acquired pneumonia (HAP) and its specific subset, non-ventilator hospital-acquired pneumonia (nvHAP) are significant contributors to patient morbidity and mortality. Automated surveillance systems for these healthcare-associated infections have emerged as a potentially beneficial replacement for manual surveillance. This systematic review aims to synthesise the existing literature on the characteristics and performance of automated nvHAP and HAP surveillance systems. METHODS: We conducted a systematic search of publications describing automated surveillance of nvHAP and HAP. Our inclusion criteria covered articles that described fully and semi-automated systems without limitations on patient demographics or healthcare settings. We detailed the algorithms in each study and reported the performance characteristics of automated systems that were validated against specific reference methods. Two published metrics were employed to assess the quality of the included studies. RESULTS: Our review identified 12 eligible studies that collectively describe 24 distinct candidate definitions, 23 for fully automated systems and one for a semi-automated system. These systems were employed exclusively in high-income countries and the majority were published after 2018. The algorithms commonly included radiology, leukocyte counts, temperature, antibiotic administration, and microbiology results. Validated surveillance systems' performance varied, with sensitivities for fully automated systems ranging from 40 to 99%, specificities from 58 and 98%, and positive predictive values from 8 to 71%. Validation was often carried out on small, pre-selected patient populations. CONCLUSIONS: Recent years have seen a steep increase in publications on automated surveillance systems for nvHAP and HAP, which increase efficiency and reduce manual workload. However, the performance of fully automated surveillance remains moderate when compared to manual surveillance. The considerable heterogeneity in candidate surveillance definitions and reference standards, as well as validation on small or pre-selected samples, limits the generalisability of the findings. Further research, involving larger and broader patient populations is required to better understand the performance and applicability of automated nvHAP surveillance.

[The dynamic monitoring of gastric residual volume by ultrasound was used to guide the early nutritional treatment of patients with severe mechanical ventilation to gradually achieve the standard].

OBJECTIVE: To explore the application value of dynamic monitoring of gastric residual volume (GRV) in achieving different target energy in severe mechanical ventilation patients. METHODS: A prospective randomized controlled study was conducted. Forty-two patients with mechanical ventilation admitted to the department of critical care medicine of General Hospital of Ningxia Medical University from July to December 2022 were enrolled. According to the random number table method, patients were divided into GRV guided enteral nutrition by traditional gastric juice pumpback method (control group, 22 patients) and GRV guided enteral nutrition by bedside ultrasound (test group, 20 patients). General data were collected from both groups, and clinical indicators such as hypersensitive C-reactive protein (hs-CRP), interleukin-6 (IL-6), neutrophil percentage (Neut%), procalcitonin (PCT), absolute lymphocytes (LYM), prealbumin (PA), and retinol-binding protein (RBP) were dynamically observed. Inflammation, infection, immunity, nutritional indicators, and the incidence of reflux/aspiration, ventilator-associated pneumonia (VAP) were compared between the two groups, and further compared the proportion of patients with respectively to reach the target energy 25%, 50%, and 70% on days 1, 3, and 5 of initiated enteral nutrition. RESULTS: (1) There were no significant differences in gender, age, body mass index (BMI), duration of mechanical ventilation, and acute physiology and chronic health evaluation II (APACHE II), sequential organ failure assessment (SOFA), severe nutritional risk score (NUTRIC) at admission between the two groups, indicating comparability. (2) On day 1 of initiated enteral nutrition, there were no significant differences in infection, inflammation, immunity and nutrition indicators between the two groups. On day 3 of initiated enteral nutrition, the hs-CRP in the test group was lower than that control group, LYM and PA were higher than those control group [hs-CRP (mg/L): 129.60±75.18 vs. 185.20±63.74, LYM: 1.00±0.84 vs. 0.60±0.41, PA (mg/L): 27.30±3.66 vs. 22.30±2.55, all P < 0.05]. On day 5 of initiated enteral nutrition, the hs-CRP, Neut%, PCT in the test group were lower than those control group, LYM and PA were higher than those control group [hs-CRP (mg/L): 101.70±54.32 vs. 148.40±36.35, Neut%: (85.50±7.66)% vs. (92.90±6.01)%, PCT (µg/L): 0.7 (0.3, 2.7) vs. 3.6 (1.2, 7.5), LYM: 1.00±0.68 vs. 0.50±0.38, PA (mg/L): 27.10±4.57 vs. 20.80 ± 3.51, all P < 0.05]. There were no significantly differences in IL-6 and RBP between the two groups at different time points. (3) The proportion of 50% and 70% of achieved target energy in the test group on day 3, day 5 of initiated enteral nutrition were higher than those of the control group (70.0% vs. 36.4%, 70.0% vs. 36.4%, both P < 0.05). (4) The incidence of reflux/aspiration and VAP in the test group on day 5 of initiated enteral nutrition were significantly lower than those control group (incidence of reflux/aspiration: 5.0% vs. 28.6%, incidence of VAP: 10.0% vs. 36.4%, both P < 0.05). CONCLUSIONS: Dynamic monitoring of GRV by bedside ultrasound can accurately improve the proportion of 50% of achieved target energy on day 3 and 75% on day 5 in severe mechanical ventilation patients, improve the patient's inflammation, immune and nutritional status, and can prevent the occurrence of reflux/aspiration and VAP.

Probable Non-Ventilator-Associated Hospital-Acquired Pneumonia: A Case Report.

INTRODUCTION: Non-ventilator-associated hospital-acquired pneumonia is a preventable health care-associated infection accounting for 1 in 14 hospital deaths. Clinical factors influencing this condition include oral health and bacteria and oral care. This case report addresses diagnostics and clinical variables related to non-ventilator-associated hospital-acquired pneumonia and emphasizes the importance of prevention. CLINICAL FINDINGS: A 90-year-old woman was admitted to the hospital with shortness of breath and generalized weakness from new-onset atrial fibrillation and suspected heart failure exacerbation. During the hospitalization, her oral health status declined and oral bacterial colonization shifted, with Neisseria becoming the most common oral bacterial genus around the time of development of probable non-ventilator-associated hospital-acquired pneumonia. DIAGNOSIS: The patient had new respiratory symptoms and a chest radiograph positive for pneumonia on day 4 and was subsequently diagnosed with probable non-ventilator-associated hospital-acquired pneumonia. INTERVENTIONS: Intravenous antibiotic treatment was initiated. Oral care was completed on only 2 of 7 days. The patient received limited ambulation assistance and encouragement from staff and family members. No dysphagia screening was documented. OUTCOMES: On day 6, the patient was discharged with oral antibiotics to her independent living facility with home health care. CONCLUSIONS: Consistent oral care, early and frequent physical activity, and measures aimed to reduce aspiration risk are key interventions for all hospitalized patients to prevent non-ventilator-associated hospital-acquired pneumonia. Further research is warranted to assess shifts in oral bacteria and general oral health during hospitalization, which could provide clinically meaningful data on risk for non-ventilator-associated hospital-acquired pneumonia.

Data quality review of the Brazilian nosocomial infections surveillance system.

BACKGROUND: Surveillance of healthcare-associated infections (HAIs) is an essential component of hospital infection prevention and control systems. We aimed to assess the quality of the data compiled by the Brazilian HAI Surveillance System from pediatric (PICUs) and neonatal intensive care units (NICUs), between 2012 and 2021. METHODS: Data Quality Review, including adherence, completeness, internal consistency, consistency over time, and consistency of population trend, were computed at both national and state levels based on quality metrics from World Health Organization Toolkit. Incidence rates (or incidence density) of ventilator-associated pneumonia (VAP) and central line-associated bloodstream infection (CLABSI) were obtained from the Brazilian National Nosocomial Infections Surveillance (NNIS) system. Data on sepsis-related mortality, spanning the period from 2012 to 2021, were extracted from the Brazilian National Health Service database (DATASUS). Additionally, correlations between sepsis-related mortality and incidence rates of VAP or CLABSI were calculated. RESULTS: Throughout the majority of the study period, adherence to VAP reporting remained below 75%, exhibiting a positive trend post-2016. Widespread outliers, as well as inconsistencies over time and in population trends, were evident across all 27 states. Only four states maintained consistent adherence levels above 75% for more than 8 years regarding HAI incidence rates. Notably, CLABSI in NICUs boasted the highest reporting adherence among all HAIs, with 148 periods out of 270 (54.8%) exhibiting reporting adherence surpassing 75%. Three states achieved commendable metrics for CLABSI in PICUs, while five states demonstrated favorable results for CLABSI in NICUs. CONCLUSIONS: While adherence to HAI report is improving among Brazilian states, an important room for improvement in the Brazilian NNIS exists. Additional efforts should be made by the Brazilian government to improve the reliability of HAI data, which could serve as valuable guidance for hospital infection prevention and control policies.

Does organophosphorus poisoning increase the risk of staphylococcal ventilator associated pneumonia? - a retrospective study.

INTRODUCTION: The aim of this study was to determine the clinical predictors of staphylococcal ventilator-associated pneumonia (VAP) and to compare the outcomes of staphylococcal VAP with non-staphylococcal VAP. METHODOLOGY: A retrospective observational study was conducted among adult patients admitted to the medical intensive care unit (MICU) in a tertiary care hospital in India from January 2017 to December 2019. The patients were grouped based on their diagnosis into staphylococcal and non-staphylococcal VAP, and the baseline characteristics, clinical parameters, co-morbidities, and outcome parameters were compared. RESULTS: Out of 2129 MICU admissions, 456 patients with microbiologically confirmed VAP were included, of which 69 (15.1%) had staphylococcal VAP, and the remaining 387 (84.9%) had non-staphylococcal VAP. Organophosphorus (OP) poisoning was identified as an independent predictor of staphylococcal VAP (odds ratio: 2.57; 95% CI: 1.4 to 4.73). The median duration of mechanical ventilation before VAP diagnosis was less in the staphylococcal VAP group (4 vs. 5 days; p = 0.004). The staphylococcal group also showed a better in-hospital outcome. CONCLUSIONS: OP poisoning was an independent predictor of staphylococcal VAP. Staphylococcal VAP was diagnosed earlier in patients than non-staphylococcal VAP. Screening for nasal carriage for Staphylococcus, especially in patients with OP poisoning at the time of MICU admission, may help guide antibiotic therapy.

The impact of obesity on ventilator-associated pneumonia, a US nationwide study.

BACKGROUND: Ventilator-associated pneumonia (VAP) is one of the leading causes of mortality in patients with critical care illness. Since obesity is highly prevalent, we wanted to study its impact on the outcomes of patients who develop VAP. METHODS: Using the National Inpatient Sample (NIS) database from 2017 to 2020, we conducted a retrospective study of adult patients with a principal diagnosis of VAP with a secondary diagnosis with or without obesity according to 10th revision of the International Statistical Classification of Diseases (ICD-10) codes. Several demographics, including age, race, and gender, were analyzed. The primary endpoint was mortality, while the secondary endpoints included tracheostomy, length of stay in days, and patient charge in dollars. Multivariate logistic regression model analysis was used to adjust for confounders, with a p-value less than 0.05 considered statistically significant. RESULTS: The study included 3832 patients with VAP, 395 of whom had obesity. The mean age in both groups was around 58 years, and 68% of the group with obesity were females compared to 40% in females in the group without obesity. Statistically significant comorbidities in the obesity group included a Charlson Comorbidity Index score of three and above, diabetes mellitus, hypertension, chronic kidney disease, and sleep apnea. Rates and odds of mortality were not significantly higher in the collective obesity group 39 (10%) vs. 336 (8.5%), p-value 0.62, adjusted odds ratio 1.2, p-value 0.61). The rates and odds of tracheostomy were higher in the obesity group but not statistically significant. Obese patients were also found to have a longer hospitalization. Upon subanalysis of the data, no evidence of racial disparities was found in the care of VAP for both the obese and control groups. CONCLUSIONS: Obesity was not found to be an independent risk factor for worse outcomes in patients who develop VAP in the intensive care unit.

Bacterial profiles detected in ventilator-associated pneumonia in Japan: A systematic review.

The primary objective of this study was to identify the predominant organisms associated with ventilator-associated pneumonia (VAP) in Japan. Studies on VAP conducted in Japan were systematically reviewed, and seven studies with a total of 374 cases were included. The detection rate of each bacterium and multidrug-resistant (MDR) pathogen was analyzed using the inverse variance method. Pseudomonas aeruginosa was identified as the predominant pathogen in 29.2 % of cases, followed by methicillin-resistant Staphylococcus aureus (MRSA) (12.0 %), and Klebsiella spp. (9.5 %). An integrated analysis revealed a detection rate of 57.8 % (95 % confidence interval: 48.7%-66.8 %) for MDR pathogens. This review highlights P. aeruginosa and MRSA as the predominant VAP-associated organisms in Japan, with a significant prevalence of MDR pathogens. This analysis provides valuable insights based on the regional distribution of bacteria detected in VAP, which is critical for selecting appropriate empirical therapy.

Nation-wide survey of oral care practice in Japanese intensive care units: A descriptive study.

Oral care for critically ill patients helps provide comfort and prevent ventilator-associated pneumonia. However, a standardized protocol for oral care in intensive care units is currently unavailable. Thus, this study aimed to determine the overall oral care practices, including those for intubated patients, in Japanese intensive care units. We also discuss the differences in oral care methods between Japanese ICUs and ICUs in other countries. This study included all Japanese intensive care units meeting the authorities' standard set criteria, with a minimum of 0.5 nurses per patient at all times and admission of adult patients requiring mechanical ventilation. An online survey was used to collect data. Survey responses were obtained from one representative nurse per intensive care unit. Frequency analysis was performed, and the percentage of each response was calculated. A total of 609 hospitals and 717 intensive care units nationwide participated; among these, responses were collected from 247 intensive care units (34.4%). Of these, 215 (87.0%) and 32 (13.0%) reported standardized and non-standardized oral care, respectively. Subsequently, the data from 215 intensive care units that provided standardized oral care were analyzed in detail. The most common frequency of practicing oral care was three times a day (68.8%). Moreover, many intensive care units provided care at unequal intervals (79.5%), mainly in the morning, daytime, and evening. Regarding oral care methods, 96 (44.7%) respondents used only a toothbrush, while 116 (54.0%) used both a toothbrush and a non-brushing method. The findings of our study reveal current oral care practices in ICUs in Japan. In particular, most ICUs provide oral care three times a day at unequal intervals, and almost all use toothbrushes as a common tool for oral care. The results suggest that some oral care practices in Japanese ICUs differ from those in ICUs in other countries.

Co-immobilization of Ciprofloxacin and Chlorhexidine as a Broad-Spectrum Antimicrobial Dual-Drug Coating for Poly(vinyl chloride) (PVC)-Based Endotracheal Tubes.

The endotracheal tube (ETT) affords support for intubated patients, but the increasing incidence of ventilator-associated pneumonia (VAP) is jeopardizing its application. ETT surfaces promote (poly)microbial colonization and biofilm formation, with a heavy burden for VAP. Devising safe, broad-spectrum antimicrobial materials to tackle the ETT bioburden is needful. Herein, we immobilized ciprofloxacin (CIP) and/or chlorhexidine (CHX), through polydopamine (pDA)-based functionalization, onto poly(vinyl chloride) (PVC) surfaces. These surfaces were characterized regarding physicochemical properties and challenged with single and polymicrobial cultures of VAP-relevant bacteria (Pseudomonas aeruginosa, Acinetobacter baumannii, Klebsiella pneumoniae, Staphylococcus aureus, Staphylococcus epidermidis) and fungi (Candida albicans). The coatings imparted PVC surfaces with a homogeneous morphology, varied wettability, and low roughness. The antimicrobial immobilization via pDA chemistry was still evidenced by infrared spectroscopy. Coated surfaces exhibited sustained CIP/CHX release, retaining prolonged (10 days) activity. CIP/CHX-coated surfaces evidencing no A549 lung cell toxicity displayed better antibiofilm outcomes than CIP or CHX coatings, preventing bacterial attachment by 4.1-7.2 Log10 CFU/mL and modestly distressingC. albicans. Their antibiofilm effectiveness was endured toward polymicrobial consortia, substantially inhibiting the adhesion of the bacterial populations (up to 8 Log10 CFU/mL) within the consortia in dual- and even inP. aeruginosa/S. aureus/C. albicans triple-species biofilms while affecting fungal adhesion by 2.7 Log10 CFU/mL (dual consortia) and 1 Log10 CFU/mL (triple consortia). The potential of the dual-drug coating strategy in preventing triple-species adhesion and impairing bacterial viability was still strengthened by live/dead microscopy. The pDA-assisted CIP/CHX co-immobilization holds a safe and robust broad-spectrum antimicrobial coating strategy for PVC-ETTs, with the promise laying in reducing VAP incidence.

Desirability of Outcome Ranking and Response Adjusted for Antibiotic Risk (DOOR/RADAR) Post Hoc Analysis Supports Equipoise for Antibiotic Initiation Strategies in Intensive Care Unit-Acquired Pneumonia.

Background: Pneumonia is the most common intensive care unit (ICU)-acquired infection and source of potential sepsis in ICU populations but can be difficult to diagnose in real-time. Despite limited data, rapid initiation of antibiotic agents is endorsed by society guidelines. We hypothesized that a post hoc analysis of a recent randomized pilot study would show no difference between two antibiotic initiation strategies. Patients and Methods: The recent Trial of Antibiotic Restraint in Presumed Pneumonia (TARPP) was a pragmatic cluster-randomized pilot of antibiotic initiation strategies for patients with suspected ICU-acquired pneumonia. Participating ICUs were cluster-randomized to either an immediate initiation protocol or a specimen-initiated protocol where a gram stain was required for initiation of antibiotics. Patients in the study were divided into one of seven mutually exclusive outcome rankings (desirability of outcome ranking; DOOR): (1) Survival, No Pneumonia, No adverse events; (2) Survival, Pneumonia, No adverse events; (3) Survival, No Pneumonia, ventilator-free-alive days ≤14; (4) Survival, Pneumonia, ventilator-free-alive days ≤14; (5) Survival, No Pneumonia, Subsequent episode of suspected pneumonia; (6) Survival, Pneumonia, Subsequent episode of suspected pneumonia; and (7) Death. These rankings were further refined using the duration of antibiotics prescribed for pneumonia (response adjusted for antibiotic risk; RADAR). Results: There were 186 patients enrolled in the study. After applying the DOOR analysis, a randomly selected patient was equally likely to have a better outcome in specimen-initiated arm as in the immediate initiation arm (DOOR probability: 50.8%; 95% confidence interval [CI], 42.7%-58.9%). Outcome probabilities were similar after applying the RADAR analysis (52.5%; 95% CI, 44.2%-60.6%; p = 0.31). Conclusions: We found that patients for whom antibiotic agents were withheld until there was objective evidence (specimen-initiated group) had similar outcome rankings to patients for whom antibiotic agents were started immediately. This supports the findings of the TARPP pilot trial and provides further evidence for equipoise between these two treatment strategies.

Interleukin-36 receptor antagonist stimulation in vitro inhibits peripheral and lung-resident T cell response isolated from patients with ventilator-associated pneumonia.

Interleukin-36 (IL-36) cytokine family members play an immunomodulatory function to immune cells through IL-36 receptor signaling pathway. However, the regulatory role of IL-36 exerted on T cells is not completely elucidated in patients with ventilator-associated pneumonia (VAP). For this purpose, this study enrolled 51 VAP patients and 27 controls. IL-36 levels were measured by ELISA. The mRNA levels of IL-36 receptor subunits were determined by real-time PCR. CD4+ and CD8+ T cells were enriched, and stimulated with recombinant IL-36 receptor antagonist (IL-36RA). The influence of IL-36RA on transcription factors and cytokine secretions by CD4+ T cells was investigated. The modulatory function of IL-36RA on CD8+ T cells was assessed by measuring target cell death and cytokine secretions. There were no significant differences in serum IL-36 levels between VAP patients and controls. Only IL-36RA, but not IL-36α, IL-36ß, or IL-36γ, in bronchoalveolar lavage fluid was elevated in infection site of VAP patients. IL-36 receptor subunits in CD4+ and CD8+ T cells were comparable between VAP patients and controls. 10 ng/mL of IL-36RA stimulation dampened peripheral effector CD4+ T cell response isolated from both VAP patients and controls. Target cell death mediated by CD8+ T cells isolated from BAFL of VAP patients was suppressed by 100 ng/mL of IL-36RA stimulation in vitro. The down-regulations of perforin, granzyme B, interferon-γ, tumor necrosis factor-α, and Fas ligand following IL-36RA stimulation in vitro were responsible for reduced CD8+ T cell-mediated cytotoxicity. IL-36RA revealed an immunosuppressive property for T cell response in vitro, and may be involved in the protective mechanism in VAP patients.