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Objective: This study aimed to use systematic review and meta-analysis to establish the influence of antifungal therapy on pulmonary Candida colonisation of patients with mechanical ventilation (MV)., Design: Systematic review and meta-analysis., Data Sources: An extensive search was undertaken on publications from inception to 25 July 2023, through PubMed, Web of Science, Medline, Embase, China National Knowledge Infrastructure, Wanfang Data and VIP Databases., Eligibility Criteria for Selecting Studies: Randomised trials, cohort studies and case-control studies comparing the efficacy of antifungal treatment in immunocompetent patients with pulmonary Candida colonisation after invasive ventilation., Data Extraction and Synthesis: Two reviewers independently extracted the data and assessed the quality of studies. Dichotomous outcomes were expressed as ORs with 95% CIs. Continuous outcomes were expressed as standardised mean differences (SMD) with 95% CIs., Primary and Secondary Outcome Measures: The primary outcomes included intensive care unit (ICU), hospital, 28-day, and 90-day mortality. The secondary outcomes included ICU length of stay, MV duration and ventilator-associated pneumonia (VAP)., Results: Nine high-quality studies were included. According to the data collected from these nine studies, there is no significant evidence showing a difference between the therapy group treated with antifungal drugs and the control group without antifungal drugs in clinical outcomes, including ICU mortality (OR: 1.37; 95% CI 0.84 to 2.22), hospital mortality (OR: 1.17; 95% CI 0.57 to 2.38), 28-day mortality (OR: 0.71; 95% CI 0.45 to 1.14), 90-day mortality (OR: 0.76; 95% CI 0.35 to 1.63), ICU length of stay (SMD: -0.15; 95% CI -0.88 to 0.59), MV duration (SMD: 0.11; 95% CI -0.88 to 1.10) and VAP (OR: 1.54; 95% CI 0.56 to 4.20). Subgroup analysis of different treatment types indicates that the combined effect size is stable and unaffected by different treatment types including inhalation (OR: 2.32; 95% CI 0.30 to 18.09) and intravenous (OR: 0.65; 95% CI 0.13 to 3.34)., Conclusion: The application of antifungal treatment did not improve clinical outcomes in patients with MV. We do not suggest initiating antifungal treatment in patients with Candida pulmonary colonisation after invasive ventilation., Trial Registration Number: International Prospective Register of Systematic Reviews, CRD42020161138., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The 2016 IDSA guideline recommends a treatment duration of at least 7 days for hospital-acquired (HAP)/ventilator-associated pneumonia (VAP). The limited literature has demonstrated higher rates of recurrence for non-glucose fermenting gram-negative bacilli with short course therapy, raising the concern of optimal treatment duration for these pathogens. Therefore, we aimed to compare the outcomes for patients receiving shorter therapy treatment (≤ 8 days) versus longer regimen (> 8 days) for the treatment of multidrug resistant (MDR) Pseudomonas pneumonia., Methods: A single-center, retrospective cohort study was conducted to evaluate adult patients receiving an antimicrobial regimen with activity against MDR Pseudomonas aeruginosa in respiratory culture between 2017 and 2020 for a minimum of 6 consecutive days. Exclusion criteria were inmates, those with polymicrobial pneumonia, community-acquired pneumonia, and infections requiring prolonged antibiotic therapy., Results: Of 427 patients with MDR P. aeruginosa respiratory isolates, 85 patients were included. Baseline characteristics were similar among groups with a median age of 65.5 years and median APACHE 2 score of 20. Roughly 75% had ventilator-associated pneumonia. Compared to those who received ≤ 8 days of therapy, no difference was seen for clinical success in patients treated for more than 8 days (80% vs. 65.5%, p = 0.16). The number of 30-day and 90-day in-hospital mortality, 30-days relapse, and other secondary outcomes did not significantly differ among the treatment groups., Conclusions: Prolonging treatment duration beyond 8 days did not improve patient outcomes for MDR P. aeruginosa HAP/VAP., (© 2024. The Author(s).)

Background: As several recent studies have shown low mortality rates in burn injury induced ARDS early (≤7 days) after the burn, the Berlin criteria for the ARDS diagnosis in this setting may be disputed. Related to this issue, the present study investigated the incidence, trajectory and risk factors of early Acute Respiratory Distress Syndrome (ARDS) and outcome in burn patients, as per the Berlin criteria, along with the concurrent prevalence and influence of inhalation injury, and ventilator-acquired pneumonia (VAP)., Methods: Over a 2.5-year period, burn patients with Total Burn Surface Area (TBSA) exceeding 10% admitted to a national burn center were included. The subgroup of interest comprised patients with more than 48 h of ventilatory support. This group was assessed for ARDS, inhalation injury, and VAP., Results: Out of 292 admissions, 62 sustained burns > 10% TBSA. Of these, 28 (45%) underwent ventilatory support for over 48 h, almost all, 24 out of 28, meeting the criteria for ARDS early, within 7 days post-injury and with a P a O 2 /F i O 2 (PF) rat i o nadir at day 5. The mortality rate for this early ARDS group was under 10%, regardless of PF ratios (mean TBSA% 34,8%). Patients with concurrent inhalation injury and early ARDS showed significantly lower PF ratios (p < 0.001), and higher SOFA scores (p = 0.004) but without impact on mortality. Organ failure, indicated by SOFA scores, peaked early (day 3) and declined in the first week, mirroring PF ratio trends (p < 0.001)., Conclusions: The low mortality associated with early ARDS in burn patients in this study challenges the Berlin criteria's for the early ARDS diagnosis, which for its validity relies on that higher mortality is linked to worsening PF ratios. The finding suggests alternative mechanisms, leading to the early ARDS diagnosis, such as the significant impact of inhalation injury on early PF ratios and organ failure, as seen in this study. The concurrence of early organ failure with declining PF ratios, supports, as expected, the hypothesis of trauma-induced inflammation/multi-organ failure mechanisms contributing to early ARDS. The study highlights the complexity in differentiating between the contributions of inhalation injury to early ARDS and the related organ dysfunction early in the burn care trajectory. The Berlin criteria for the ARDS diagnosis may not be fully applicable in the burn care setting, where the low mortality significantly deviates from that described in the original Berlin ARDS criteria publication but is as expected when considering the actual not very extensive burn injury sizes/Baux scores as in the present study., Competing Interests: Declaration of Competing Interest On behalf of all co-authors, I hereby affirm no conflicts of interest associated with this manuscript., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Severe infections caused by carbapenem-resistant Acinetobacter baumannii (CRAB) have been reported increasingly over the past few years. Many in-vivo and in-vitro studies have suggested a possible role of intravenous fosfomycin for the treatment of CRAB infections., Methods: This multi-centre, retrospective study included patients treated with intravenous fosfomycin for severe infections caused by CRAB admitted consecutively to four hospitals in Italy from December 2017 to December 2022. The primary goal of the study was to evaluate the risk factors associated with 30-day mortality in the study population. A propensity score matched analysis was added to the model., Results: One hundred and two patients with severe infections caused by CRAB treated with an intravenous fosfomycin-containing regimen were enrolled in this study. Ventilator-associated pneumonia (VAP) was diagnosed in 59% of patients, primary bacteraemia in 22% of patients, and central-venous-catheter-related infection in 16% of patients. All patients were treated with a regimen containing intravenous fosfomycin, mainly in combination with cefiderocol (n=54), colistin (n=48) or ampicillin/sulbactam (n=18). Forty-eight (47%) patients died within 30 days. Fifty-eight (57%) patients experienced clinical therapeutic failure. Cox regression analysis showed that diabetes, primary bacteraemia and a colistin-containing regimen were independently associated with 30-day mortality, whereas adequate source control of infection, early 24-h active in-vitro therapy, and a cefiderocol-containing regimen were associated with survival. A colistin-based regimen, A. baumannii colonization and primary bacteraemia were independently associated with clinical failure. Conversely, adequate source control of infection, a cefiderocol-containing regimen, and early 24-h active in-vitro therapy were associated with clinical success., Conclusions: Different antibiotic regimens containing fosfomycin in combination can be used for treatment of severe infections caused by CRAB., (Copyright © 2024 Elsevier Ltd and International Society of Antimicrobial Chemotherapy. All rights reserved.)

Background: Re-intubation is necessary in 2% to 30% of cases of patients receiving a planned extubation. This procedure is associated with prolonged mechanical ventilation, a greater need for tracheostomy, a higher incidence of ventilator-associated pneumonia, and higher mortality. The aim of this study was to evaluate the effect of re-intubation within 48 h on mortality after planned extubation by using a randomized controlled trial database., Methods: Secondary analysis of a multi-center randomized trial, which evaluated the effect of reconnection to mechanical ventilation for 1 h after a successful spontaneous breathing trial, followed by extubation. The study included adult subjects who received invasive mechanical ventilation for > 12 h. The subjects were divided into an extubation failure group and an extubation success group. The outcome was in-hospital mortality. Two multivariate logistic regression models were constructed to identify independent factors associated with mortality., Results: Among the 336 subjects studied, extubation failed in 52 (15.4%) and they were re-intubated within 48 h. Most re-intubations occurred between 12 and 24 h after planned extubation (median [interquartile range] 16 [6-36] h). Mortality of the extubation failure group was higher both in the ICU (32.6% vs 6.6%; odds ratio [OR] 6.77, 95% CI 3.22-14.24; P < .001) and in-hospital (42.3% vs 14.0%; OR 4.47, 95% CI 2.34-8.51; P < .001) versus the extubation success group. Multivariate logistic regression analyses showed that re-intubation within 48 h was independently associated with both ICU mortality (OR 6.10, 95% CI 2.84-13.07; P < .001) and in-hospital mortality (OR 3.36, 95% CI 1.67-6.73; P = .001). In-hospital mortality was also associated with rescue noninvasive ventilation after extubation (OR 2.44, 95% CI 1.25-4.75; P = .009)., Conclusions: Re-intubation within 48 h after planned extubation was associated with mortality in subjects who were critically ill., Competing Interests: The authors have disclosed no conflicts of interest., (Copyright © 2024 by Daedalus Enterprises.)

The Coronavirus Disease 2019 (COVID-19) has caused a global health crisis. Mortality predictors in critically ill patients remain under investigation. A retrospective cohort study included 201 patients admitted to the intensive care unit (ICU) due to COVID-19. Data on demographic characteristics, laboratory findings, and mortality were collected. Logistic regression analysis was conducted with various independent variables, including demographic characteristics, clinical factors, and treatment methods. The study aimed to identify key risk factors associated with mortality in an ICU. In an investigation of 201 patients comprising non-survivors (n = 80, 40%) and Survivors (n = 121, 60%), we identified several markers significantly associated with ICU mortality. Lower Interleukin 6 and White Blood Cells levels at both 24- and 48-hours post-ICU admission emerged as significant indicators of survival. The study employed logistic regression analysis to evaluate risk factors for in-ICU mortality. Analysis results revealed that demographic and clinical factors, including gender, age, and comorbidities, were not significant predictors of in-ICU mortality. Ventilator-associated pneumonia was significantly higher in Survivors, and the use of antibiotics showed a significant association with increased mortality risk in the multivariate model (OR: 11.2, p = 0.031). Our study underscores the significance of monitoring Il-6 and WBC levels within 48 hours of ICU admission, potentially influencing COVID-19 patient outcomes. These insights may reshape therapeutic strategies and ICU protocols for critically ill patients., Competing Interests: The authors declare no competing interests., (Copyright: © 2024 Bartoszewicz et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: We assessed the clinical effectiveness of cefiderocol (CFDC) in comparison with colistin (COL) for the treatment of carbapenem-resistant Acinetobacter baumannii (CRAB) bloodstream infections (BSI)., Materials/methods: Retrospective cohort study including adults with CRAB-BSI. Outcomes were mortality, clinical cure and adverse events during therapy. The average treatment effect of CFDC compared to COL was weighted with the inverse-probability treatment weight (IPTW)., Results: Overall, 104 patients were included (50 CFDC, 54 COL), median age 66.5 years, median Charlson Comorbidity Index 5, septic shock in 33.6% of patients. Primary BSI accounted for 43.3% of cases, followed by ventilator-associated pneumonia (VAP) (26%), catheter-related BSI (20.2%) and hospital-acquired pneumonia (HAP) (9.6%). Although not significantly, mortality at all time points was lower for CFDC than COL, while clinical cure was higher in CFDC than COL (66% vs. 44.4%, p = 0.027). Adverse events were more frequent in COL than CFDC-group (38.8% vs. 10%, p < 0.0001), primarily attributed to acute kidney injury (AKI) in the COL group. Patients with bacteremic HAP/VAP treated with CFDC had a significant lower 30-d mortality and higher clinical cure than COL (p = 0.008 and p = 0.0008, respectively). Increment of CCI (p = 0.005), ICU (p = 0.025), SARS-CoV2 (p = 0.006) and ECMO (p < 0.0001) were independently associated with 30-d mortality, while receiving CFDC was not associated with survival., Conclusions: CFDC could represent an effective and safe treatment option for CRAB BSI, especially in patients with bacteremic HAP/VAP and frail patients where the risk of acute renal failure during therapy should be avoided., (© 2024. The Author(s).)

Background: Extended illness-death models (a specific class of multistate models) are a useful tool to analyse situations like hospital-acquired infections, ventilation-associated pneumonia, and transfers between hospitals. The main components of these models are hazard rates and transition probabilities. Calculation of different measures and their interpretation can be challenging due to their complexity., Methods: By assuming time-constant hazards, the complexity of these models becomes manageable and closed mathematical forms for transition probabilities can be derived. Using these forms, we created a tool in R to visualize transition probabilities via stacked probability plots., Results: In this article, we present this tool and give some insights into its theoretical background. Using published examples, we give guidelines on how this tool can be used. Our goal is to provide an instrument that helps obtain a deeper understanding of a complex multistate setting., Conclusion: While multistate models (in particular extended illness-death models), can be highly complex, this tool can be used in studies to both understand assumptions, which have been made during planning and as a first step in analysing complex data structures. An online version of this tool can be found at https://eidm.imbi.uni-freiburg.de/ ., (© 2024. The Author(s).)

Introduction: We aimed to evaluate ventilator-associated pneumonia (VAP) incidence rate, risk factors, and isolated microorganisms in COVID-19 patients as the primary endpoint. Evaluation of VAP-associated intensive care unit (ICU) and hospital mortalities was the secondary endpoint., Materials and Methods: Records of patients admitted between March 2020- June 2021 to our pandemic ICU were reviewed and COVID-19 patients with VAP and non-VAP were evaluated retrospectively. Comorbidities, management, length of ICU stay, and outcomes of VAP and non-VAP patients, as well as risk factors for VAP mortality, were identified., Result: During the study period, 254 patients were admitted to the ICU. After the exclusion, the data of 208 patients were reviewed. In total, 121 patients required invasive mechanical ventilation, with 78 (64.5%) developing VAP. Length of ICU and hospital stays were longer in VAP patients (p<0.01 and p<0.01 respectively). Steroid use was higher in VAP patients, although it was not statistically significant (p= 0.06). APACHE II score (p<0.01) was higher in non-VAP patients. ICU mortality was high in both groups (VAP 70%, non-VAP 77%). VAP mortality was higher in males (p= 0.03) and in patients who required renal replacement therapy (p= 0.01). Length of ICU stay (p= 0.04), and length of hospital stay (p<0.01) were both high in VAP survivors. The most common isolated microorganisms were Acinetobacter spp. and Klebsiella spp. in VAP patients and most of them were extensively drug-resistant., Conclusions: Critically ill COVID-19 patients who required invasive mechanical ventilation developed VAP frequently. The length of ICU stay was longer in patients who developed VAP and ICU mortality was high in both VAP and non-VAP patients. The length of hospital and ICU stays among VAP survivors were also considerably high which is probably related to the long recovery period of COVID-19. The most frequently isolated microorganisms were Acinetobacter spp. and Klebsiella spp. in VAP patients.

Importance: The effectiveness of selective decontamination of the digestive tract (SDD) in critically ill adults receiving mechanical ventilation is uncertain., Objective: To determine whether SDD is associated with reduced risk of death in adults receiving mechanical ventilation in intensive care units (ICUs) compared with standard care., Data Sources: The primary search was conducted using MEDLINE, EMBASE, and CENTRAL databases until September 2022., Study Selection: Randomized clinical trials including adults receiving mechanical ventilation in the ICU comparing SDD vs standard care or placebo., Data Extraction and Synthesis: Data extraction and risk of bias assessments were performed in duplicate. The primary analysis was conducted using a bayesian framework., Main Outcomes and Measures: The primary outcome was hospital mortality. Subgroups included SDD with an intravenous agent compared with SDD without an intravenous agent. There were 8 secondary outcomes including the incidence of ventilator-associated pneumonia, ICU-acquired bacteremia, and the incidence of positive cultures of antimicrobial-resistant organisms., Results: There were 32 randomized clinical trials including 24 389 participants in the analysis. The median age of participants in the included studies was 54 years (IQR, 44-60), and the median proportion of female trial participants was 33% (IQR, 25%-38%). Data from 30 trials including 24 034 participants contributed to the primary outcome. The pooled estimated risk ratio (RR) for mortality for SDD compared with standard care was 0.91 (95% credible interval [CrI], 0.82-0.99; I2 = 33.9%; moderate certainty) with a 99.3% posterior probability that SDD reduced hospital mortality. The beneficial association of SDD was evident in trials with an intravenous agent (RR, 0.84 [95% CrI, 0.74-0.94]), but not in trials without an intravenous agent (RR, 1.01 [95% CrI, 0.91-1.11]) (P value for the interaction between subgroups = .02). SDD was associated with reduced risk of ventilator-associated pneumonia (RR, 0.44 [95% CrI, 0.36-0.54]) and ICU-acquired bacteremia (RR, 0.68 [95% CrI, 0.57-0.81]). Available data regarding the incidence of positive cultures of antimicrobial-resistant organisms were not amenable to pooling and were of very low certainty., Conclusions and Relevance: Among adults in the ICU treated with mechanical ventilation, the use of SDD compared with standard care or placebo was associated with lower hospital mortality. Evidence regarding the effect of SDD on antimicrobial resistance was of very low certainty.

Importance: Whether selective decontamination of the digestive tract (SDD) reduces mortality in critically ill patients remains uncertain., Objective: To determine whether SDD reduces in-hospital mortality in critically ill adults., Design, Setting, and Participants: A cluster, crossover, randomized clinical trial that recruited 5982 mechanically ventilated adults from 19 intensive care units (ICUs) in Australia between April 2018 and May 2021 (final follow-up, August 2021). A contemporaneous ecological assessment recruited 8599 patients from participating ICUs between May 2017 and August 2021., Interventions: ICUs were randomly assigned to adopt or not adopt a SDD strategy for 2 alternating 12-month periods, separated by a 3-month interperiod gap. Patients in the SDD group (n = 2791) received a 6-hourly application of an oral paste and administration of a gastric suspension containing colistin, tobramycin, and nystatin for the duration of mechanical ventilation, plus a 4-day course of an intravenous antibiotic with a suitable antimicrobial spectrum. Patients in the control group (n = 3191) received standard care., Main Outcomes and Measures: The primary outcome was in-hospital mortality within 90 days. There were 8 secondary outcomes, including the proportion of patients with new positive blood cultures, antibiotic-resistant organisms (AROs), and Clostridioides difficile infections. For the ecological assessment, a noninferiority margin of 2% was prespecified for 3 outcomes including new cultures of AROs., Results: Of 5982 patients (mean age, 58.3 years; 36.8% women) enrolled from 19 ICUs, all patients completed the trial. There were 753/2791 (27.0%) and 928/3191 (29.1%) in-hospital deaths in the SDD and standard care groups, respectively (mean difference, -1.7% [95% CI, -4.8% to 1.3%]; odds ratio, 0.91 [95% CI, 0.82-1.02]; P = .12). Of 8 prespecified secondary outcomes, 6 showed no significant differences. In the SDD vs standard care groups, 23.1% vs 34.6% had new ARO cultures (absolute difference, -11.0%; 95% CI, -14.7% to -7.3%), 5.6% vs 8.1% had new positive blood cultures (absolute difference, -1.95%; 95% CI, -3.5% to -0.4%), and 0.5% vs 0.9% had new C difficile infections (absolute difference, -0.24%; 95% CI, -0.6% to 0.1%). In 8599 patients enrolled in the ecological assessment, use of SDD was not shown to be noninferior with regard to the change in the proportion of patients who developed new AROs (-3.3% vs -1.59%; mean difference, -1.71% [1-sided 97.5% CI, -∞ to 4.31%] and 0.88% vs 0.55%; mean difference, -0.32% [1-sided 97.5% CI, -∞ to 5.47%]) in the first and second periods, respectively., Conclusions and Relevance: Among critically ill patients receiving mechanical ventilation, SDD, compared with standard care without SDD, did not significantly reduce in-hospital mortality. However, the confidence interval around the effect estimate includes a clinically important benefit., Trial Registration: ClinicalTrials.gov Identifier: NCT02389036.

In order to improve the nursing effect of respiratory critical illness, this paper combines the refined nursing method to explore the nursing plan of respiratory critical illness. Moreover, this paper uses the variable control method to explore the effects of nursing management, combines the hospital patient samples to conduct a controlled trial analysis, and conducts sample grouping according to the random grouping method. The patients in the control group are managed by traditional nursing management methods, the patients in the test group are managed by refined nursing management methods, and other conditions are basically the same. In addition, the experiment process variable control is carried out according to the mathematical statistics method, and the reasonable statistics and data processing are carried out. Through the comparison method, we can see that the refined management method proposed in this paper has a good effect in the nursing of respiratory critical illness., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Wenjuan Shi et al.)

Background: It is essential to determine the distribution of the causative microorganisms in the region and the status of local antibiotic resistance for the proper treatment of hospital-acquired pneumonia/ventilator-associated pneumonia (HAP/VAP). This study aimed to investigate the occurrence and causative strains of HAP/VAP, distribution of resistant bacteria, use of antibiotics, and the ensuing outcomes of patients in Korea., Methods: A multicenter prospective observational cohort study was conducted among patients with HAP/VAP admitted to the medical intensive care unit of 5 tertiary referral centers between August 2012 and June 2015. Patients' demographic and clinical data were collected., Results: A total of 381 patients were diagnosed with HAP/VAP. Their median age was 69 (59-76) years and 71% were males. A majority of the patients (88%) had late-onset (> 5 days) HAP/VAP. One-quarter of the patients (n = 99) had at least one risk factor for multidrug-resistant (MDR) pathogens, such as prior intravenous antibiotic use within the last 90 days. Microbiological specimens were mostly obtained noninvasively (87%) using sputum or endotracheal aspirates. Pathogens were identified in 235 (62%) of the 381 patients. The most common bacterial pathogen was Acinetobacter baumannii (n = 89), followed by Staphylococcus aureus (n = 52), Klebsiella pneumoniae (n = 25) and Pseudomonas aeruginosa (n = 22). Most of isolated A. baumannii (97%) and S. aureus (88%) were multidrug resistant. The most commonly used empirical antibiotic regimens were carbapenem-based antibiotics (38%), followed by extended-spectrum penicillin/β-lactamase inhibitor (34%). Glycopeptide or linezolid were also used in combination in 54% of patients. The 28-day mortality rate of the patients with HAP/VAP was 30% and the 60-day mortality was 46%. Patients who used empirical antibiotics appropriately had significantly lower mortality rates than those who did not (28-day mortality: 25% vs. 40%, P = 0.032; 60-day mortality: 41% vs. 55%, P = 0.032, respectively). Administration of appropriate empirical antibiotics (odds ratio [OR], 0.282; confidence interval [CI], 0.092-0.859; P = 0.026), Day 7 treatment failure (OR, 4.515; CI, 1.545-13.192; P = 0.006), and APACHE II score on day 1 (OR, 1.326; CI, 0.988-1.779; P = 0.012) were the factors that determined the 28-day mortality in patients with HAP who had identified bacteria as pathogens., Conclusion: In HAP/VAP patients, there was a large burden of MDR pathogens, and their associated mortality rate was high. Proper selection of empirical antibiotics was significantly associated with the patient's prognosis; however, there was a discrepancy between major pathogens and empirical antibiotic therapy., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2021 The Korean Academy of Medical Sciences.)

Objective: The susceptibility to infection probably increases in COVID-19 patients due to a combination of virusand drug-induced immunosuppression. The reported rate of secondary infections was quite low in previous studies. The objectives of our study were to investigate the rate of secondary infections, risk factors for secondary infections and risk factors for mortality in COVID-19 critically ill patients., Methods: We performed a single-center retrospective study in mechanically ventilated critically ill COVID-19 patients admitted to our Critical Care Unit (CCU). We recorded the patients' demographic data; clinical data; microbiology data and incidence of secondary infection during CCU stay, including ventilator-associated pneumonia (VAP) and nosocomial bacteremia (primary and secondary)., Results: A total of 107 patients with a mean age 62.2 ± 10.6 years were included. Incidence of secondary infection during CCU stay was 43.0% (46 patients), including nosocomial bacteremia (34 patients) and VAP (35 patients). Age was related to development of secondary infection (65.2 ± 7.3 vs. 59.9 ± 12.2 years, p=0.007). Age ≥ 65 years and secondary infection were independent predictors of mortality (OR=2.692, 95% CI 1.068-6.782, p<0.036; and OR=3.658, 95% CI 1.385- 9.660, p=0.009, respectively). The hazard ratio for death within 90 days in the ≥ 65 years group and in patients infected by antimicrobial resistant pathogens was 1.901 (95% CI 1.198- 3.018; p= 0.005 by log-rank test) and 1.787 (95% CI 1.023-3.122; p= 0.036 by log-rank test), respectively., Conclusions: Our data suggest that the incidence of secondary infection and infection by antimicrobial resistant pathogens is very high in critically ill patients with COVID-19 with a significant impact on prognosis., (©The Author 2021. Published by Sociedad Española de Quimioterapia. This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0)(https://creativecommons.org/licenses/by-nc/4.0/).)

Following prolonged hospitalization that included broad-spectrum antibiotic exposure, a strain of Providencia rettgeri was cultured from the blood of a patient undergoing extracorporeal membrane oxygenation treatment for hypoxic respiratory failure due to COVID-19. The strain was resistant to all antimicrobials tested including the novel siderophore cephalosporin, cefiderocol. Whole genome sequencing detected ten antimicrobial resistance genes, including the metallo-β-lactamase bla NDM-1 , the extended-spectrum β-lactamase bla PER-1 , and the rare 16S methyltransferase rmtB2 .

Background: Mechanical ventilation (MV) is often applied in critically ill patients in intensive care unit (ICU) to protect the airway from aspiration, and supplement more oxygen. MV may result in ventilator-associated pneumonia (VAP) in ICU patients. This study was to estimate the 90-day and 180-day mortalities of ICU patients with VAP, and to explore the influence of VAP on the outcomes of ICU patients., Methods: Totally, 8182 patients who aged ≥18 years and received mechanical ventilation (MV) in ICU from Medical Information Mart for Intensive Care III (MIMIC III) database were involved in this study. All subjects were divided into the VAP group (n = 537) and the non-VAP group (n = 7626) based on the occurrence of VAP. Clinical data of all participants were collected. The effect of VAP on the prognosis of ICU patients was explored by binary logistic regression analysis., Results: The results delineated that the 90-day mortality of VAP patients in ICU was 33.33% and 180-day mortality was 37.62%. The 90-day and 180-day mortality rates were higher in the VAP group than in the non-VAP group. After adjusting the confounders including age, ethnicity, heart failure, septicemia, simplified acute physiology score II (SAPSII) score, sequential organ failure assessment (SOFA) score, serum lactate, white blood cell (WBC), length of ICU stay, length of hospital stay, length of ventilation, antibiotic treatment, Pseudomonas aeruginosa (P.aeruginosa), methicillin-resistant Staphylococcus aureus (MRSA), other pathogens, the risk of 90-day and 180-day mortalities in VAP patients were 1.465 times (OR = 1.465, 95%CI: 1.188-1.807, P < 0.001) and 1.635 times (OR = 1.635, 95%CI: 1.333-2.005, P < 0.001) higher than those in non-VAP patients, respectively., Conclusions: Our study revealed that ICU patients with VAP had poorer prognosis than those without VAP. The results of this study might offer a deeper insight into preventing the occurrence of VAP., (© 2021. The Author(s).)

Background: Previous studies reporting the causes of death in patients with severe COVID-19 have provided conflicting results. The objective of this study was to describe the causes and timing of death in patients with severe COVID-19 admitted to the intensive care unit (ICU)., Methods: We performed a retrospective study in eight ICUs across seven French hospitals. All consecutive adult patients (aged ≥ 18 years) admitted to the ICU with PCR-confirmed SARS-CoV-2 infection and acute respiratory failure were included in the analysis. The causes and timing of ICU deaths were reported based on medical records., Results: From March 1, 2020, to April 28, 287 patients were admitted to the ICU for SARS-CoV-2 related acute respiratory failure. Among them, 93 patients died in the ICU (32%). COVID-19-related multiple organ dysfunction syndrome (MODS) was the leading cause of death (37%). Secondary infection-related MODS accounted for 26% of ICU deaths, with a majority of ventilator-associated pneumonia. Refractory hypoxemia/pulmonary fibrosis was responsible for death in 19% of the cases. Fatal ischemic events (venous or arterial) occurred in 13% of the cases. The median time from ICU admission to death was 15 days (25th-75th IQR, 7-27 days). COVID-19-related MODS had a median time from ICU admission to death of 14 days (25th-75th IQR: 7-19 days), while only one death had occurred during the first 3 days since ICU admission., Conclusions: In our multicenter observational study, COVID-19-related MODS and secondary infections were the two leading causes of death, among severe COVID-19 patients admitted to the ICU.

Introduction: Severe coronavirus 2019 disease (CoViD-19) may lead to respiratory failure and mechanical ventilation. Therefore, ventilator associated pneumonia (VAP) may complicate the course of the disease. The aim of the current article was to investigate possible predictive factors for bacterial VAP on a retrospective manner, in a cohort of mechanically ventilated CoViD-19 patients. Additionally, determinant factors of lethality were analyzed., Methods: Medical records of patients hospitalized in the intensive care units (ICU) at the university hospital UZ Brussel during the epidemic were reviewed. VAP was defined following the National Healthcare Safety Network 2017 criteria. Univariate and multivariate logistic regressions analyses were performed., Results: Among the 39 patients included in the study, 54% were diagnosed with bacterial VAP. Case fatality rate was 44%, but 59% of the deceased patients had a do-not-resuscitate status. Multivariate logistic regression for prediction of VAP showed significant differences in duration of ICU hospitalization and in minimal lung compliance. Additional analyses were performed on CoViD-19 patients who were affected by bacterial respiratory superinfection. The responsible pathogens correspond to the commonly found bacteria in VAP. However, 71% of the isolated germs were multi-drug resistant and bacteraemia was reported in 38%. Multivariate analyses for prediction of lethality found significant difference in SOFA score., Conclusions: Mechanically ventilated CoViD-19 patients might frequently develop VAP. Longer ICU hospitalization was associated with pulmonary superinfection in the current cohort. Moreover, decreased minimal lung compliance was correlated to VAP and higher SOFA score at VAP diagnosis was associated with lethality., Competing Interests: Declaration of competing interest MLNGM is a member of the medical advisory Board of Pulsion Medical Systems (now fully integrated in Getinge, Solna, Sweden) and Serenno Medical (Tel Aviv, Israel), consults for Baxter, Maltron, ConvaTec, Acelity, Spiegelberg and Holtech Medical. All other authors declare that they hve no competing interests in relation to the content published in this manuscript., (Copyright © 2021 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Background: Mortality among patients with hospital-acquired pneumonia (HAP) is quite high; however, information on risk factors for short-term mortality in this population remains limited. The aim of the current study was to identify the risk factors for mortality in bedridden patients with HAP during a 3-month observation period., Methods: A secondary data analysis was conducted. In total, 1141 HAP cases from 25 hospitals were included in the analysis. Univariate and multilevel regression analyses were performed to identify the risk factors for mortality., Results: During the 3-month observation period, there were 189 deaths among bedridden patients with HAP. The mortality rate in this study was 16.56%. Multilevel regression analysis showed that ventilator-associated pneumonia (OR = 2.034, 95%CI: 1.256, 3.296, p = 0.004), pressure injuries (OR = 2.202, 95%CI: 1.258, 3.852, p = 0.006), number of comorbidities (OR = 1.076, 95%CI: 1.016,1.140, p = 0.013) and adjusted Charlson Comorbidity Index score (OR = 1.210, 95%CI: 1.090, 1.343, p<0.001) were associated with an increased risk of mortality, while undergoing surgery with general anaesthesia (OR = 0.582, 95%CI: 0.368, 0.920, p = 0.021) was associated with a decreased risk of mortality., Conclusions: The identification of risk factors associated with mortality is an important step towards individualizing care plans. Our findings may help healthcare workers select high-risk patients for specific interventions. Further study is needed to explore whether appropriate interventions against modifiable risk factors, such as reduced immobility complications or ventilator-associated pneumonia, could improve the prognoses., Competing Interests: The authors have declared that no competing interests exist.

Treatment of ventilated patients with gram-negative pneumonia (GNP) is often unsuccessful. We aimed to assess the efficacy and safety of nebulized amikacin (NA) as adjunctive therapy to systemic antibiotics in this patient population. PubMed, Embase, China national knowledge infrastructure, Wanfang, and the Cochrane database were searched for randomized controlled trials (RCTs) investigating the effect of NA as adjunctive therapy in ventilated adult patients with GNP. Heterogeneity was explored using subgroup analysis and sensitivity analysis. The Grading of recommendations assessment, development, and evaluation approach was used to assess the certainty of the evidence. Thirteen RCTs with 1733 adults were included. The pooled results showed NA had better microbiologic eradication (RR = 1.51, 95% CI 1.35 to 1.69, P < 0.0001) and improved clinical response (RR = 1.23; 95% CI 1.13 to 1.34; P < 0.0001) when compared with control. Meanwhile, overall mortality, pneumonia associated mortality, duration of mechanical ventilation, length of stay in ICU and change of clinical pneumonia infection scores were similar between NA and control groups. Additionally, NA did not add significant nephrotoxicity while could cause more bronchospasm. The use of NA adjunctive to systemic antibiotics therapy showed better benefits in ventilated patients with GNP. More well-designed RCTs are still needed to confirm our results.

Ventilator-associated pneumonia (VAP) is one of the most frequent ICU-acquired infections and a leading cause of death among patients in Intensive Care Unit (ICU). The South East Asian Region is a part of the world with limited health resources where infectious diseases are still underestimated. We aimed to review the literature in this part of the world to describe incidence, mortality and microbiological evidence of VAP and explore preventive and control strategies. We selected 24 peer-reviewed articles published from January 1, 2000 to September 1, 2020 from electronic databases and manual searching for observational studies among adult patients diagnosed with VAP expressed per thousand days admitted in ICU. The VAP rates ranged from 2.13 to 116 per thousand days, varying among different countries of this region. A significant rate of mortality was observed in 13 studies ranging from 16.2% to 74.1%. Gram negative organisms like Acinetobacter spp., Pseudomonas aeruginosa and Klebsiella pneumoniae and Gram-positive organisms like Staphylococcus aureus and Enterococcus species were frequently found. Our findings suggest an alarming situation of VAP among patients of most of the countries of this region with increasing incidence, mortality and antibiotic resistance. Thus, there is an urgent need for cost effective control and preventive measures like interventional studies and educational programs on staff training, hand hygiene, awareness on antibiotic resistance, implementation of antibiotic stewardship programs and appropriate use of ventilator bundle approach., Competing Interests: The authors have declared that no competing interests exist.

Background: Ventilator-associated pneumonia (VAP) is the most common hospital-acquired infection (HAI) in intensive care units (ICUs). Ventilator-associated event (VAE), a more objective definition, has replaced traditional VAP surveillance and is now widely used in the USA. However, the adoption outside the USA is limited. This study aims to describe the epidemiology and clinical outcomes of VAEs in China, based on a prospectively maintained registry., Methods: An observational study was conducted using an ICU-HAI registry in west China. Patients that were admitted to ICUs and underwent mechanical ventilation (MV) between April 1, 2015, and December 31, 2018, were included. The characteristics and outcomes were compared between patients with and without VAEs. The rates of all VAEs dependent on different ICUs were calculated, and the pathogen distribution of patients with possible VAP (PVAP) was described., Results: A total of 20,769 ICU patients received MV, accounting for 21,723 episodes of mechanical ventilators and 112,697 ventilator-days. In all, we identified 1882 episodes of ventilator-associated condition (VAC) events (16.7 per 1000 ventilator-days), 721 episodes of infection-related ventilator-associated complications (IVAC) events (6.4 per 1000 ventilator-days), and 185 episodes of PVAP events (1.64 per 1000 ventilator-days). The rates of VAC varied across ICUs with the highest incidence in surgical ICUs (23.72 per 1000 ventilator-days). The median time from the start of ventilation to the onset of the first VAC, IVAC, and PVAP was 5 (3-8), 5 (3-9), and 6 (4-13) days, respectively. The median length of hospital stays was 28.00 (17.00-43.00), 30.00 (19.00-44.00), and 30.00 (21.00-46.00) days for the three VAE tiers, which were all longer than that of patients without VAEs (16.00 [12.00-23.00]). The hospital mortality among patients with VAEs was more than three times of those with non-VAEs., Conclusions: VAE was common in ICU patients with ≥ 4 ventilator days. All tiers of VAEs were highly correlated with poor clinical outcomes, including longer ICU and hospital stays and increased risk of mortality. These findings highlight the importance of VAE surveillance and the development of new strategies to prevent VAEs.

Background: Ventilator-associated pneumonia (VAP) is a common nocosomial infection in intensive care unit (ICU). Local microbiological surveillance of pathogens and resistance patterns for early-onset VAP (EOVAP) and late-onset VAP (LOVAP) will help to choose appropriate empiric antibiotics., Objective: To compare the multi-drug resistant (MDR) pathogens, treatment outcomes, and factors associated with hospital mortality of VAP., Method: A cross-sectional study between 1 January 2015 and 31 December 2017 at Srinagarind hospital, Khon Kaen University was conducted. The demographic data, causative pathogens, hospital length of stay (LOS), ICU LOS, mechanical ventilator (MV) days, and hospital mortality were retrospectively reviewed., Results: One hundred and ninety patients were enrolled; 42 patients (22%) were EOVAP and 148 patients (78%) were LOVAP. Acinetobacter baumannii was the most common pathogen in both groups (50% EOVAP vs 52.7% LOVAP). MDR pathogens were significant greater in LOVAP (81.8%) than EOVAP (61.9%) (p = 0.007). The EOVAP had a significantly better ICU LOS [median (interquartile range, IQR) 20.0 (11.0, 30.0) vs. 26.5 (17.0, 43.0) days], hospital LOS [median (IQR) 26.5 (15.0, 44.0) vs. 35.5 (24.0, 56.0) days] shorter MV days [median (IQR) 14.0 (10.0, 29.0) vs. 23.0 (14.0, 35.5) days] and lower hospital mortality (16.7% vs 35.1%) than LOVAP (p < 0.05). The factor associated with hospital mortality was having simplified acute physiology (SAP) II score ≥ 40 with an adjusted odds ratio (aOR) of 2.22 [95% confidence interval (CI), 1.08-4.54, p = 0.02]., Conclusion: LOVAP had significantly higher MDR pathogens, MV days, ICU LOS, hospital LOS and hospital mortality than EOVAP. A broad-spectrum antibiotic to cover MDR pathogens should be considered in LOVAP. The factor associated with hospital mortality of VAP was a SAPII score ≥ 40.

Background: Patients treated with mechanical ventilation in intensive care units (ICUs) have a high risk of developing respiratory tract infections (RTIs). Ventilator-associated pneumonia (VAP) has been estimated to affect 5% to 40% of patients treated with mechanical ventilation for at least 48 hours. The attributable mortality rate of VAP has been estimated at about 9%. Selective digestive decontamination (SDD), which consists of the topical application of non-absorbable antimicrobial agents to the oropharynx and gastroenteric tract during the whole period of mechanical ventilation, is often used to reduce the risk of VAP. A related treatment is selective oropharyngeal decontamination (SOD), in which topical antibiotics are applied to the oropharynx only. This is an update of a review first published in 1997 and updated in 2002, 2004, and 2009., Objectives: To assess the effect of topical antibiotic regimens (SDD and SOD), given alone or in combination with systemic antibiotics, to prevent mortality and respiratory infections in patients receiving mechanical ventilation for at least 48 hours in ICUs., Search Methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), which contains the Cochrane Acute Respiratory Infections (ARI) Group's Specialised Register, PubMed, and Embase on 5 February 2020. We also searched the WHO ICTRP and ClinicalTrials.gov for ongoing and unpublished studies on 5 February 2020. All searches included non-English language literature. We handsearched references of topic-related systematic reviews and the included studies., Selection Criteria: Randomised controlled trials (RCTs) and cluster-RCTs assessing the efficacy and safety of topical prophylactic antibiotic regimens in adults receiving intensive care and mechanical ventilation. The included studies compared topical plus systemic antibiotics versus placebo or no treatment; topical antibiotics versus no treatment; and topical plus systemic antibiotics versus systemic antibiotics., Data Collection and Analysis: We used standard methodological procedures expected by Cochrane., Main Results: We included a total of 41 trials involving 11,004 participants (five new studies were added in this update). The minimum duration of mechanical ventilation ranged from 2 (19 studies) to 6 days (one study). Thirteen studies reported the mean length of ICU stay, ranging from 11 to 33 days. The percentage of immunocompromised patients ranged from 0% (10 studies) to 22% (1 study). The reporting quality of the majority of included studies was very poor, so we judged more than 40% of the studies as at unclear risk of selection bias. We judged all studies to be at low risk of performance bias, though 47.6% were open-label, because hospitals usually have standardised infection control programmes, and possible subjective decisions on who should be tested for the presence or absence of RTIs are unlikely in an ICU setting. Regarding detection bias, we judged all included studies as at low risk for the outcome mortality. For the outcome RTIs, we judged all double-blind studies as at low risk of detection bias. We judged five open-label studies as at high risk of detection bias, as the diagnosis of RTI was not based on microbiological exams; we judged the remaining open-label studies as at low risk of detection bias, as a standardised set of diagnostic criteria, including results of microbiological exams, were used. Topical plus systemic antibiotic prophylaxis reduces overall mortality compared with placebo or no treatment (risk ratio (RR) 0.84, 95% confidence interval (CI) 0.73 to 0.96; 18 studies; 5290 participants; high-certainty evidence). Based on an illustrative risk of 303 deaths in 1000 people this equates to 48 (95% CI 15 to 79) fewer deaths with topical plus systemic antibiotic prophylaxis. Topical plus systemic antibiotic prophylaxis probably reduces RTIs (RR 0.43, 95% CI 0.35 to 0.53; 17 studies; 2951 participants; moderate-certainty evidence). Based on an illustrative risk of 417 RTIs in 1000 people this equates to 238 (95% CI 196 to 271) fewer RTIs with topical plus systemic antibiotic prophylaxis. Topical antibiotic prophylaxis probably reduces overall mortality compared with no topical antibiotic prophylaxis (RR 0.96, 95% CI 0.87 to 1.05; 22 studies, 4213 participants; moderate-certainty evidence). Based on an illustrative risk of 290 deaths in 1000 people this equates to 19 (95% CI 37 fewer to 15 more) fewer deaths with topical antibiotic prophylaxis. Topical antibiotic prophylaxis may reduce RTIs (RR 0.57, 95% CI 0.44 to 0.74; 19 studies, 2698 participants; low-certainty evidence). Based on an illustrative risk of 318 RTIs in 1000 people this equates to 137 (95% CI 83 to 178) fewer RTIs with topical antibiotic prophylaxis. Sixteen studies reported adverse events and dropouts due to adverse events, which were poorly reported with sparse data. The certainty of the evidence ranged from low to very low., Authors' Conclusions: Treatments based on topical prophylaxis probably reduce respiratory infections, but not mortality, in adult patients receiving mechanical ventilation for at least 48 hours, whereas a combination of topical and systemic prophylactic antibiotics reduces both overall mortality and RTIs. However, we cannot rule out that the systemic component of the combined treatment provides a relevant contribution in the observed reduction of mortality. No conclusion can be drawn about adverse events as they were poorly reported with sparse data., (Copyright © 2021 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Background: Early distinguishing ventilator-associated tracheobronchitis (VAT) and ventilator-associated pneumonia (VAP) remains difficult in the daily practice. However, this question appears clinically relevant, as treatments of VAT and VAP currently differ. In this study, we assessed the accuracy of sepsis criteria according to the Sepsis-3 definition in the early distinction between VAT and VAP., Methods: Retrospective single-center cohort, including all consecutive patients with a diagnosis of VAT (n = 70) or VAP (n = 136), during a 2-year period. Accuracy of sepsis criteria according to Sepsis-3, total SOFA and respiratory SOFA, calculated at time of microbiological sampling were assessed in differentiating VAT from VAP, and in predicting mortality on ICU discharge., Results: Sensitivity and specificity of sepsis criteria were found respectively at 0.4 and 0.91 to distinguish VAT from VAP, and at 0.38 and 0.75 for the prediction of mortality in VA-LRTI. A total SOFA ≥ 6 and a respiratory SOFA ≥ 3 were identified as the best cut-offs for these criteria in differentiating VAT from VAP, with sensitivity and specificity respectively found at 0.63 and 0.69 for total SOFA, and at 0.49 and 0.7 for respiratory SOFA. Additionally, for prediction of mortality, a total SOFA ≥ 7 and a respiratory SOFA = 4 were identified as the best-cut-offs, respectively yielding sensitivity and specificity at 0.56 and 0.61 for total SOFA, and at 0.22 and 0.95 for respiratory SOFA., Conclusions: Sepsis criteria according to the Sepsis-3 definition show a high specificity but a low sensitivity for the diagnosis of VAP. Our results do not support the use of these criteria for the early diagnosis of VAP in patients with VA-LRTI., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: SN received fees from MSD, Pfizer, Gilead, BioMérieux, and Bio Rad for lectures. Other authors declare that they have no competing interest. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Background: Ventilator-associated pneumonia (VAP) is defined as pneumonia developing in people who have received mechanical ventilation for at least 48 hours. VAP is a potentially serious complication in these patients who are already critically ill. Oral hygiene care (OHC), using either a mouthrinse, gel, swab, toothbrush, or combination, together with suction of secretions, may reduce the risk of VAP in these patients., Objectives: To assess the effects of oral hygiene care (OHC) on incidence of ventilator-associated pneumonia in critically ill patients receiving mechanical ventilation in hospital intensive care units (ICUs)., Search Methods: Cochrane Oral Health's Information Specialist searched the following databases: Cochrane Oral Health's Trials Register (to 25 February 2020), the Cochrane Central Register of Controlled Trials (CENTRAL) (the Cochrane Library, 2020, Issue 1), MEDLINE Ovid (1946 to 25 February 2020), Embase Ovid (1980 to 25 February 2020), LILACS BIREME Virtual Health Library (1982 to 25 February 2020) and CINAHL EBSCO (1937 to 25 February 2020). We also searched the VIP Database (January 2012 to 8 March 2020). The US National Institutes of Health Trials Registry (ClinicalTrials.gov) and the World Health Organization International Clinical Trials Registry Platform were searched for ongoing trials. No restrictions were placed on the language or date of publication when searching the electronic databases., Selection Criteria: We included randomised controlled trials (RCTs) evaluating the effects of OHC (mouthrinse, gel, swab, toothbrush or combination) in critically ill patients receiving mechanical ventilation for at least 48 hours., Data Collection and Analysis: At least two review authors independently assessed search results, extracted data and assessed risk of bias in included studies. We contacted study authors for additional information. We reported risk ratio (RR) for dichotomous outcomes and mean difference (MD) for continuous outcomes, using the random-effects model of meta-analysis when data from four or more trials were combined., Main Results: We included 40 RCTs (5675 participants), which were conducted in various countries including China, USA, Brazil and Iran. We categorised these RCTs into five main comparisons: chlorhexidine (CHX) mouthrinse or gel versus placebo/usual care; CHX mouthrinse versus other oral care agents; toothbrushing (± antiseptics) versus no toothbrushing (± antiseptics); powered versus manual toothbrushing; and comparisons of other oral care agents used in OHC (other oral care agents versus placebo/usual care, or head-to-head comparisons between other oral care agents). We assessed the overall risk of bias as high in 31 trials and low in two, with the rest being unclear. Moderate-certainty evidence from 13 RCTs (1206 participants, 92% adults) shows that CHX mouthrinse or gel, as part of OHC, probably reduces the incidence of VAP compared to placebo or usual care from 26% to about 18% (RR 0.67, 95% confidence intervals (CI) 0.47 to 0.97; P = 0.03; I 2 = 66%). This is equivalent to a number needed to treat for an additional beneficial outcome (NNTB) of 12 (95% CI 7 to 128), i.e. providing OHC including CHX for 12 ventilated patients in intensive care would prevent one patient developing VAP. There was no evidence of a difference between interventions for the outcomes of mortality (RR 1.03, 95% CI 0.80 to 1.33; P = 0.86, I 2 = 0%; 9 RCTs, 944 participants; moderate-certainty evidence), duration of mechanical ventilation (MD -1.10 days, 95% CI -3.20 to 1.00 days; P = 0.30, I 2 = 74%; 4 RCTs, 594 participants; very low-certainty evidence) or duration of intensive care unit (ICU) stay (MD -0.89 days, 95% CI -3.59 to 1.82 days; P = 0.52, I 2 = 69%; 5 RCTs, 627 participants; low-certainty evidence). Most studies did not mention adverse effects. One study reported adverse effects, which were mild, with similar frequency in CHX and control groups and one study reported there were no adverse effects. Toothbrushing (± antiseptics) may reduce the incidence of VAP (RR 0.61, 95% CI 0.41 to 0.91; P = 0.01, I 2 = 40%; 5 RCTs, 910 participants; low-certainty evidence) compared to OHC without toothbrushing (± antiseptics). There is also some evidence that toothbrushing may reduce the duration of ICU stay (MD -1.89 days, 95% CI -3.52 to -0.27 days; P = 0.02, I 2 = 0%; 3 RCTs, 749 participants), but this is very low certainty. Low-certainty evidence did not show a reduction in mortality (RR 0.84, 95% CI 0.67 to 1.05; P = 0.12, I 2 = 0%; 5 RCTs, 910 participants) or duration of mechanical ventilation (MD -0.43, 95% CI -1.17 to 0.30; P = 0.25, I 2 = 46%; 4 RCTs, 810 participants)., Authors' Conclusions: Chlorhexidine mouthwash or gel, as part of OHC, probably reduces the incidence of developing ventilator-associated pneumonia (VAP) in critically ill patients from 26% to about 18%, when compared to placebo or usual care. We did not find a difference in mortality, duration of mechanical ventilation or duration of stay in the intensive care unit, although the evidence was low certainty. OHC including both antiseptics and toothbrushing may be more effective than OHC with antiseptics alone to reduce the incidence of VAP and the length of ICU stay, but, again, the evidence is low certainty. There is insufficient evidence to determine whether any of the interventions evaluated in the studies are associated with adverse effects., (Copyright © 2020 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Background: Recently intravenous (IV) and aerosolized (ASZ) colistin have been used for treating ventilator-associated pneumonia (VAP) due to colistin susceptible multidrug-resistant Gram-negative bacteria (MDR-GNB). Colistin has limited lung penetration. We compared the efficacy and safety of IV-alone versus IV+ASZ-colistin for treating VAP in neonates., Methods: This retrospective matched case-control study was performed at NICU of the Aga Khan University Hospital, Pakistan between January 2015 and December 2018. Sixteen neonates with MDR-GNB associated VAP received IV-ASZ-colistin and were matched for date of birth, gestational age, birth weight, Apgar score, antenatal steroid history, disease severity, and duration of mechanical ventilation with 16 control neonates who received IV-colistin alone., Results: Both groups had similar MDR-GNB isolates and Acinetobacter baumannii (78%) was the most common pathogen. No colistin-resistant strain was isolated. Duration of IV-colistin and concomitant antibiotics use was significantly ( p < 0.05) shorter in the IV-ASZ-colistin group. Significantly ( p < 0.05) higher clinical cure and microbial eradication, along with lower ventilatory requirements, mortality rate, and colistin induced nephrotoxicity and electrolyte imbalance was observed in the IV-ASZ-colistin group., Conclusions: With better lung penetration, ASZ-colistin offers effective and safe microbiological and clinical benefits as adjunctive or alternate treatment of VAP due to colistin susceptible MDR-GNB in neonates.

Purpose: We explore the hypothesis that critically ill patients developing ICU-acquired pneumonia (ICU-AP) have worse outcomes and an altered inflammatory response if their ICU admission was sepsis-related., Methods: Prospective cohort study in two centers. Patients with ICU-AP were evaluated according to their previous exposure to sepsis at ICU-admission. Demographic variables, comorbidities, severity scores at admission and at the time of acquisition of ICU-AP, and serum biomarkers of the inflammatory response were evaluated., Primary Outcome: 90-day mortality., Secondary Outcomes: ICU and hospital length of stay, mortality at days 28 and 180, in-hospital mortality, ventilator-free days (day-28), and inflammatory response. Propensity scoring weighted the risk of previously-acquired sepsis. Multivariate analysis evaluated the risk of mortality by day-90. Sensitivity analyses evaluated the primary outcome in different subgroups., Results: Of 341 patients enrolled, 147 had sepsis on ICU-admission. Adjusted risk of mortality at 90 days did not differ overall [hazard ratio (HR) = 0.94(CI:0.65-1.37)], nor in subpopulations with a confirmed etiology of pneumonia [HR = 0.93(CI:0.57-1.53)] or sepsis [HR = 0.91(0.54-1.55)], ventilator-associated pneumonia (VAP) [HR = 1.01(CI:0.61-1.68)], nor non-VAP ICU-AP [HR = 0.83(CI:0.40-1.71)]. No differences were found in clinical secondary outcomes, the inflammatory response was similar., Conclusions: Previous sepsis does not appear to predispose to higher mortality nor worse outcomes in patients who develop ICU-acquired pneumonia., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests., (Copyright © 2020. Published by Elsevier Inc.)

Introduction: Severe acute respiratory syndrome coronavirus2 has caused a global pandemic of coronavirus disease 2019 (COVID-19). High-density lipoproteins (HDLs), particles chiefly known for their reverse cholesterol transport function, also display pleiotropic properties, including anti-inflammatory or antioxidant functions. HDLs and low-density lipoproteins (LDLs) can neutralize lipopolysaccharides and increase bacterial clearance. HDL cholesterol (HDL-C) and LDL cholesterol (LDL-C) decrease during bacterial sepsis, and an association has been reported between low lipoprotein levels and poor patient outcomes. The goal of this study was to characterize the lipoprotein profiles of severe ICU patients hospitalized for COVID-19 pneumonia and to assess their changes during bacterial ventilator-associated pneumonia (VAP) superinfection., Methods: A prospective study was conducted in a university hospital ICU. All consecutive patients admitted for COVID-19 pneumonia were included. Lipoprotein levels were assessed at admission and daily thereafter. The assessed outcomes were survival at 28 days and the incidence of VAP., Results: A total of 48 patients were included. Upon admission, lipoprotein concentrations were low, typically under the reference values ([HDL-C] = 0.7[0.5-0.9] mmol/L; [LDL-C] = 1.8[1.3-2.3] mmol/L). A statistically significant increase in HDL-C and LDL-C over time during the ICU stay was found. There was no relationship between HDL-C and LDL-C concentrations and mortality on day 28 (log-rank p = 0.554 and p = 0.083, respectively). A comparison of alive and dead patients on day 28 did not reveal any differences in HDL-C and LDL-C concentrations over time. Bacterial VAP was frequent (64%). An association was observed between HDL-C and LDL-C concentrations on the day of the first VAP diagnosis and mortality ([HDL-C] = 0.6[0.5-0.9] mmol/L in survivors vs. [HDL-C] = 0.5[0.3-0.6] mmol/L in nonsurvivors, p = 0.036; [LDL-C] = 2.2[1.9-3.0] mmol/L in survivors vs. [LDL-C] = 1.3[0.9-2.0] mmol/L in nonsurvivors, p = 0.006)., Conclusion: HDL-C and LDL-C concentrations upon ICU admission are low in severe COVID-19 pneumonia patients but are not associated with poor outcomes. However, low lipoprotein concentrations in the case of bacterial superinfection during ICU hospitalization are associated with mortality, which reinforces the potential role of these particles during bacterial sepsis., Competing Interests: The authors have declared that no competing interests exist.

Objectives: To analyse the use of polymyxins for the treatment of ventilator-associated pneumonia (VAP) at a teaching hospital where carbapenem-resistant gram-negative bacteria are endemic., Patients and Methods: This was a historical cohort study of patients receiving polymyxins to treat VAP in ICUs at a public university hospital in southern Brazil between January 1, 2017 and January 31, 2018., Results: During the study period, 179 cases of VAP were treated with polymyxins. Of the 179 patients, 158 (88.3%) were classified as having chronic critical illness. Death occurred in 145 cases (81.0%). Multivariate analysis showed that the factors independently associated with mortality were the presence of comorbidities (P<0.001) and the SOFA score of the day of polymyxin prescription (P<0.001). Being a burn patient was a protective factor for mortality (P<0.001). Analysis of the 14-day survival probability showed that mortality was higher among the patients who had sepsis or septic shock at the time of polymyxin prescription (P = 0.028 and P<0.001, respectively). Acinetobacter baumannii was identified as the etiological agent of VAP in 121 cases (67.6%). In our cohort, polymyxin consumption and the incidence density of VAP were quite high., Conclusions: In our study, comprised primarily of chronically critically ill patients, there was a high prevalence of VAP caused by multidrug-resistant bacteria, consistent with healthcare-associated infections in low- and middle-income countries. Presence of comorbidities and the SOFA score at the time of polymyxin prescription were predictors of mortality in this cohort. Despite aggressive antimicrobial treatment, mortality was high, stressing the need for antibiotic stewardship., Competing Interests: The authors have declared that no competing interests exist.

Introduction: Nosocomial pneumonia develops after ≥48 h of hospitalisation and is classified as ventilator-associated pneumonia (VAP) and hospital-acquired pneumonia (HAP); the latter may require mechanical ventilation (V-HAP) or not (NV-HAP)., Main Findings: VAP and HAP affect a significant proportion of hospitalised patients and are characterised by poor clinical outcomes. Among them, V-HAP has the greatest 28-day mortality rate followed by VAP and NV-HAP (27.8% versus 18% versus 14.5%, respectively). However, no differences in terms of pathophysiology, underlying microbiological pathways and subsequent therapy have been identified. International guidelines suggest specific flow charts to help clinicians in the therapeutic management of such diseases; however, there are no specific recommendations beyond VAP and HAP classification. HAP subtypes are scarcely considered as different entities and the lack of data from the clinical scenario limits any final conclusion. Hopefully, recent understanding of the pathophysiology of such diseases, as well as the discovery of new therapies, will improve the outcome associated with such pulmonary infections., Conclusion: Nosocomial pneumonia is a multifaced disease with features of pivotal interest in critical care medicine. Due to the worrisome data on mortality of patients with nosocomial pneumonia, further prospective studies focused on this topic are urgently needed., Competing Interests: Conflict of interest: M.S. Vallecoccia has nothing to disclose. Conflict of interest: C. Dominedò has nothing to disclose. Conflict of interest: S.L. Cutuli has nothing to disclose. Conflict of interest: I. Martin-Loeches reports personal fees from MSD, outside the submitted work. Conflict of interest: A. Torres has nothing to disclose. Conflict of interest: G. De Pascale has nothing to disclose., (Copyright ©ERS 2020.)

Purpose: Studies have shown that lung-ultrasound may be superior to chest x-ray (CXR) in diagnosing ventilator-associated pneumonia (VAP). This study investigated whether the use of lung-ultrasound monitoring could detect VAP earlier and improve patient outcome., Methods: This was a single-center diagnostic randomized controlled trial. In the control group, VAP was diagnosed using a combination of CXR and clinical findings. In the intervention group, VAP was diagnosed using a combination of lung-ultrasound and clinical findings. The primary outcome measured was ventilator free days (VFD). Secondary outcomes were ICU mortality, length of stay in ICU, change in Sequential Organ Failure Score at day 4 compared to day 0 (delta SOFA), antibiotic duration and ventilator days., Results: We randomized intubated patients until 44 VAP diagnosis was made in each group. VFD was higher in the intervention group than in the control group (7.80+/- 9.7 days versus 3.7+/- 6.4 days, p = .044). There were no differences between the groups in terms of ICU mortality (p=.104), ICU length of stay, (p = .058), ventilator days, (p = .081), delta SOFA (p = .10) and antibiotic duration (p = .70)., Conclusion: The use of lung-ultrasound monitoring for diagnosis of VAP improves patient outcome when compared to the standard diagnostic strategy that relies on CXR., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Ventilator-associated pneumonia (VAP) might be increased in cases with intra-abdominal hypertension (IAH). However, despite animal experimentation and physiological studies on humans in favor of this hypothesis, there is no definitive clinical data that IAH is associated with VAP. We therefore aimed to study whether IAH is a risk factor for increased incidence of VAP in critical care patients. This 1-center prospective observational cohort study was conducted in the intensive care unit of the University Hospital of Larissa, Greece, during 2013 to 2015. Consecutive patients were recruited if they presented risk factors for IAH at admission and were evaluated systematically for IAH and VAP for a 28-day period., Results: Forty-five (36.6%) of 123 patients presented IAH and 45 (36.6%) presented VAP; 24 patients presented VAP following IAH. Cox regression analysis showed that VAP was independently associated with IAH (1.06 [1.01-1.11]; P = .053), while there was an indication for an independent association between VAP and abdominal surgery (1.62 [0.87-3.03]; P = .11] and chronic obstructive pulmonary disease (1.79 [0.96-3.37]; P = .06)., Conclusions: Intra-abdominal hypertension is an independent risk factor for increased VAP incidence in critically ill patients who present risk factors for IAH at admission to the ICU.

Introduction: Ventilator-associated pneumonia (VAP) has been considered as a healthcare-associated infection with high mortality. Acinetobacter baumannii and Klebsiella pneumoniae are the common causes of VAPs around the world., Methodology: This research was a retrospective observational study in the intensive care unit (ICU) in a tertiary referral collegiate hospital in Tehran between March 2016 and May 2018. Patients who fulfilled VAP due to documented Multidrug Resistant Acinetobacter baumannii (MDR-AB) or Extended Spectrum Beta Lactamase-producing Klebsiella pneumoniae (ESBL-KP) criteria were enrolled. General demographic features, duration of hospital stay, antimicrobial treatment regimens, duration of ICU admission, the period of mechanical ventilation (MV) and 30-day mortality were documented and compared., Results: 210 patients were found with clinical, microbiological and radiological evidence of VAP. In total, 76 patients with MDR-AB and 76 patients with ESBL-KP infections were matched in the final analysis. Duration of hospitalization in the patients with MDR-AB was significantly more than that of patients infected with ESBL-KP (p-value: 0.045). Patients diagnosed with MDR-AB VAP had a 65.8% mortality rate compared to 42.1% in the ESBL-KP infection group (p = 0.003)., Conclusions: Results of the present study demonstrated that VAPs caused by MDR-AB may be more hazardous than ESBL-KP VAPs because they could be accompanied by a longer hospitalization course and even a higher mortality., Competing Interests: No Conflict of Interest is declared, (Copyright (c) 2020 Mohammadreza Salehi, Sirous Jafari, Lida Ghafouri, Hossein Malekafzali Ardakani, Alireza Abdollahi, Mohammad Taghi Beigmohammadi, Seyed Ali Dehghan Manshadi, Mohammad Mehdi Feizabadi, Masoud Ramezani, Hamidreza Abtahi, Arash Seifi.)

Objective: To assess whether ventilator-associated lower respiratory tract infections (VA-LRTIs) are associated with mortality in critically ill patients with acute respiratory distress syndrome (ARDS)., Materials and Methods: Post hoc analysis of prospective cohort study including mechanically ventilated patients from a multicenter prospective observational study (TAVeM study); VA-LRTI was defined as either ventilator-associated tracheobronchitis (VAT) or ventilator-associated pneumonia (VAP) based on clinical criteria and microbiological confirmation. Association between intensive care unit (ICU) mortality in patients having ARDS with and without VA-LRTI was assessed through logistic regression controlling for relevant confounders. Association between VA-LRTI and duration of mechanical ventilation and ICU stay was assessed through competing risk analysis. Contribution of VA-LRTI to a mortality model over time was assessed through sequential random forest models., Results: The cohort included 2960 patients of which 524 fulfilled criteria for ARDS; 21% had VA-LRTI (VAT = 10.3% and VAP = 10.7%). After controlling for illness severity and baseline health status, we could not find an association between VA-LRTI and ICU mortality (odds ratio: 1.07; 95% confidence interval: 0.62-1.83; P = .796); VA-LRTI was also not associated with prolonged ICU length of stay or duration of mechanical ventilation. The relative contribution of VA-LRTI to the random forest mortality model remained constant during time. The attributable VA-LRTI mortality for ARDS was higher than the attributable mortality for VA-LRTI alone., Conclusion: After controlling for relevant confounders, we could not find an association between occurrence of VA-LRTI and ICU mortality in patients with ARDS.

Clinical prediction models play a key role in risk stratification, therapy assignment and many other fields of medical decision making. Before they can enter clinical practice, their usefulness has to be demonstrated using systematic validation. Methods to assess their predictive performance have been proposed for continuous, binary, and time-to-event outcomes, but the literature on validation methods for discrete time-to-event models with competing risks is sparse. The present paper tries to fill this gap and proposes new methodology to quantify discrimination, calibration, and prediction error (PE) for discrete time-to-event outcomes in the presence of competing risks. In our case study, the goal was to predict the risk of ventilator-associated pneumonia (VAP) attributed to Pseudomonas aeruginosa in intensive care units (ICUs). Competing events are extubation, death, and VAP due to other bacteria. The aim of this application is to validate complex prediction models developed in previous work on more recently available validation data., (© 2019 The Authors. Biometrical Journal published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Although several guidelines recommend subglottic secretion drainage as a strategy for prevention of ventilator-associated pneumonia (VAP), its use is not widespread. With the aim to assess the effectiveness of subglottic secretion drainage for preventing VAP and to improve other outcomes such as mortality, duration of mechanical ventilation and length of stay in the intensive care unit (ICU) or hospital, an electronic search of the Cochrane Library, MEDLINE, Web of Science and Embase was undertaken. Nine systematic reviews with meta-analysis (in the overview of reviews) and 20 randomised controlled trials (in the updated meta-analysis) were included.In the overview of reviews, all systematic reviews with meta-analysis included found a positive effect of subglottic secretion drainage in the reduction of incidence of VAP. In the updated meta-analysis, subglottic secretion drainage significantly reduced VAP incidence (risk ratio (RR) 0.56, 95% CI 0.48-0.63; I 2 =0%, p=0.841) and mortality (RR 0.88, 95% CI 0.80-0.97; I 2 =0%, p=0.888).This is the first study that has found a decrease of mortality associated with the use of subglottic secretion drainage. In addition, subglottic secretion drainage is an effective measure to reduce VAP incidence, despite not improving the duration of mechanical ventilation and ICU and/or hospital length of stay., Competing Interests: Conflict of interest: D.P Pozuelo-Carracosa has nothing to disclose. Conflict of interest: A. Herráiz-Adillo has nothing to disclose. Conflict of interest: C. Alvarez-Bueno has nothing to disclose. Conflict of interest: J.M. Añón has nothing to disclose. Conflict of interest: V. Martínez-Vizcaíno has nothing to disclose. Conflict of interest: I. Cavero-Redondo has nothing to disclose., (Copyright ©ERS 2020.)

Background: Herpes simplex virus (HSV) replication can be detected in the respiratory secretions of a high proportion of ventilated intensive care unit (ICU) patients. However, the clinical significance remains poorly defined. We investigated whether patients with ventilator-associated pneumonia not responding to antibiotics and in whom high levels of HSV could be detected in respiratory secretions benefit from acyclovir treatment., Methods: Respiratory secretions (bronchoalveolar lavage fluid or tracheal aspirates) were tested for HSV replication by quantitative real-time PCR. ICU survival times, clinical parameters, and radiographic findings were retrospectively compared between untreated and acyclovir treated patients with high (> 10 5 HSV copies/mL) and low (10 3 -10 5 HSV copies/mL) viral load., Results: Fifty-seven low and 69 high viral load patients were identified. Fewer patients with high viral load responded to antibiotic treatment (12% compared to 40% of low load patients, p = 0.001). Acyclovir improved median ICU survival (8 vs 22 days, p = 0.014) and was associated with a significantly reduced hazard ratio for ICU death (HR = 0.31, 95% CI 0.11-0.92, p = 0.035) in high load patients only. Moreover, circulatory and pulmonary oxygenation function of high load patients improved significantly over the course of acyclovir treatment: mean norepinephrine doses decreased from 0.05 to 0.02 μg/kg body weight/min between days 0 and 6 of treatment (p = 0.049), and median PaO 2 /FiO 2 ratio increased from 187 to 241 between day 3 and day 7 of treatment (p = 0.02). Chest radiographic findings also improved significantly (p < 0.001)., Conclusions: In patients with ventilator-associated pneumonia, antibiotic treatment failure, and high levels of HSV replication, acyclovir treatment was associated with a significantly longer time to death in the ICU and improved circulatory and pulmonary function. This suggests a causative role for HSV in this highly selected group of patients.

Background: Acinetobacter baumannii has become a common pathogen causing hospital-acquired infections (HAIs). Although acquiring any nosocomial infection is associated with increased mortality, we do not know if the acquisition of Acinetobacter infection confers a worse prognosis as compared to non-Acinetobacter-related HAI. The aim of the current study is to compare the clinical outcomes of ventilator-associated pneumonia (VAP) and central line associated blood stream infections (CLABSIs) caused by A. baumannii with those caused by other bacterial pathogens., Materials and Methods: This prospective cohort study was conducted among critically ill adults admitted to a tertiary care hospital in South India from January 2013 to June 2014. We enrolled patients who developed new-onset fever ≥48 h after admission and fulfilled pre-specified criteria for VAP or CLABSI. The patients were followed up until the primary outcomes of death or hospital discharge., Results: During the study period, 4047 patients were admitted in the intensive care units, among which 129 eligible HAI events were analysed. Of these, 95 (73.6%) were VAP, 34 (26.4%) were CLABSI, 78 (60.4%) were A. baumannii-related HAI (AR-HAI) and 51 (39.6%) were non-A. baumannii-related HAI (NAR-HAI). Mortality among AR-HAI was 57.6% compared to 39.2% in NAR-HAI (P = 0.04) which on multivariate analysis did not achieve statistical significance, although the trend persisted (odds ratio [OR] = 4.2, 95% confidence interval [CI]: 0.95-18.4, P = 0.06). The acquisition of VAP due to A. baumannii was associated with poor ventilator outcomes even after adjusting for confounders (adjusted OR = 3.5, 95% CI: 1.07-11.6, P = 0.04)., Conclusion: In our cohort of critically ill adults with VAP and CLABSI, AR-HAI was associated with poor ventilator outcomes and a trend towards higher mortality. These findings add to the evidence suggesting that A. baumannii is a dangerous pathogen, perhaps even more so than others., Competing Interests: None

Objectives: The primary objective was to identify the proportion of patients on mechanical ventilation (MV) beyond day 10, the recently defined time of onset of Persistent Critical Illness (PerCI). The secondary objective was to identify underlying diagnoses, intensive care unit (ICU) based therapies, relevant complications, and outcomes of patients with PerCI., Subjects: 100 PerCI patients and 100 age, sex, mechanical ventilation for >24 h, acute physiology and chronic health score (APACHE III) and co-morbidity score-matched controls., Main Results: The maximum proportion of PerCI patients requiring invasive MV beyond day 10 was 66%. PerCI patients were more likely to have respiratory, septic, or neurosurgical admission diagnoses (p = .01). In the first 10 ICU days, they received multiple types of ICU-based treatments for longer duration and had a higher incidence rate of ventilator-associated pneumonia (VAP) (p = .008). Hospital discharge destination differed significantly (p≤.001), with greater mortality (34% vs. 22%) and discharge to chronic care facility (11% vs. 0%)., Conclusions: Mechanical ventilation beyond day 10 affected only two thirds of PerCI patients. However, VAP was a key complication in such patients. Discharge to chronic care facilities and hospital mortality were more common in PerCI patients., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Purpose: Ventilator associated-lower respiratory tract infections (VA-LRTIs), either ventilator-associated pneumonia (VAP) or tracheobronchitis (VAT), accounts for most nosocomial infections in intensive care units (ICU) including. Our aim was to determine if appropriate antibiotic treatment in patients with VA-LRTI will effectively reduce mortality in patients who had cardiovascular failure., Methods: This was a pre-planned subanalysis of a large prospective cohort of mechanically ventilated patients for at least 48 h in eight countries in two continents. Patients with a modified Sequential Organ Failure Assessment (mSOFA) cardiovascular score of 4 (at the time of VA-LRTI diagnosis and needed be present for at least 12 h) were defined as having cardiovascular failure., Results: VA-LRTI occurred in 689 (23.2%) out of 2960 patients and 174 (25.3%) developed cardiovascular failure. Patients with cardiovascular failure had significantly higher ICU mortality than those without (58% vs. 26.8%; p < 0.001; OR 3.7; 95% CI 2.6-5.4). A propensity score analysis found that the presence of inappropriate antibiotic treatment was an independent risk factor for ICU mortality in patients without cardiovascular failure, but not in those with cardiovascular failure. When the propensity score analysis was conducted in patients with VA-LRTI, the use of appropriate antibiotic treatment conferred a survival benefit for patients without cardiovascular failure who had only VAP., Conclusions: Patients with VA-LRTI and cardiovascular failure did not show an association to a higher ICU survival with appropriate antibiotic treatment. Additionally, we found that in patients without cardiovascular failure, appropriate antibiotic treatment conferred a survival benefit for patients only with VAP., Trial Registry: ClinicalTrials.gov, number NCT01791530.

Background: Routine application of chlorhexidine oral rinse is recommended to reduce risk of ventilator-associated pneumonia (VAP) in mechanically ventilated patients. Recent reappraisal of the evidence from two meta-analyses suggests chlorhexidine may cause excess mortality in non-cardiac surgery patients and does not reduce VAP. Mechanisms for possible excess mortality are unclear. The CHORAL study will evaluate the impact of de-adopting chlorhexidine and implementing an oral care bundle (excluding chlorhexidine) on mortality, infection-related ventilator-associated complications (IVACs), and oral health status., Methods: The CHORAL study is a stepped wedge, cluster randomized controlled trial in six academic intensive care units (ICUs) in Toronto, Canada. Clusters (ICU) will be randomly allocated to six sequential steps over a 14-month period to de-adopt oral chlorhexidine and implement a standardized oral care bundle (oral assessment, tooth brushing, moisturization, and secretion removal). On study commencement, all clusters begin with a control period in which the standard of care is oral chlorhexidine. Clusters then begin crossover from control to intervention every 2 months according to the randomization schedule. Participants include all mechanically ventilated adults eligible to receive the standardized oral care bundle. The primary outcome is ICU mortality; secondary outcomes are IVACs and oral health status. We will determine demographics, antibiotic usage, mortality, and IVAC rates from a validated local ICU clinical registry. With six clusters and 50 ventilated patients on average each month per cluster, we estimate that 4200 patients provide 80% power after accounting for intracluster correlation to detect an absolute reduction in mortality of 5.5%. We will analyze our primary outcome of mortality using a generalized linear mixed model adjusting for time to account for secular trends. We will conduct a process evaluation to determine intervention fidelity and to inform interpretation of the trial results., Discussion: The CHORAL study will inform understanding of the effectiveness of de-adoption of oral chlorhexidine and implementation of a standardized oral care bundle for decreasing ICU mortality and IVAC rates while improving oral health status. Our process evaluation will inform clinicians and decision makers about intervention delivery to support future de-adoption if justified by trial results., Trial Registration: ClinicalTrials.gov, NCT03382730 . Registered on December 26, 2017.

BACKGROUND As a common nosocomial infection, ventilator-associated pneumonia (VAP) often has high mortality. This study aimed to assess the risk factor for mortality owing to VAP. MATERIAL AND METHODS This retrospective clinical audit study screened medical records between the period of January 2014 and December 2017. All patients under mechanical ventilation MV) for ≥72 hours were screened against previously reported diagnostic criteria for VAP. The medical records were obtained for cases of documented diagnosis of VAP. RESULTS In all, 145 patients (5.0%) diagnosed with VAP were included in the study; the morbidity of VAP was 19.5 episodes per 1000 days of MV. The 30-day mortality rate was 42.8%. Univariate logistic analysis showed that elevated neutrophil-to-lymphocyte ratio (NLR), high blood urea nitrogen/albumin (BUN/ALB) ratio, Multidrug-resistant organism infection, and a higher sequential organ failure assessment (SOFA) score were risk factors for mortality caused by VAP. In the second multivariate analysis, elevated NLR levels (P=0.038), high BUN/ALB ratio (P=0.016), multidrug-resistant organism infections (P=0.036), and a higher SOFA score (P<0.001) were still associated with the 30-day mortality rate. CONCLUSIONS The 30-day mortality rate of VAP was high. Blood NLR and BUN/ALB levels can be used as risk factors to assess the 30-day VAP-related mortality to help clinicians improve the prognosis of VAP.

Ventilator-associated pneumonia (VAP) affects up to 30 per cent of ICU patients and has been associated with increased morbidity and mortality. We identified factors associated with prolonged latency of VAP and evaluated its effects on survival and additional outcomes. We also determined the sensitivity of various clinical definitions of VAP, including the Centers for Disease Control and Prevention (CDC) 2013 criteria. We hypothesized that the CDC 2013 criteria would have poor sensitivity. We collected data on 102 subjects who developed VAP between 2012 and 2017. We conducted a Kaplan-Meier survival analysis with Cox proportional hazards regression and generalized linear models/ANOVA to look at predictor variables along with multivariate models for each outcome. White patients, nonsurgical patients, patients with renal failure, altered mental status, increased FiO₂, and increased positive end-expiratory pressure had worse survival. Trauma patients, patients with positive sputum cultures, and patients with suspected pneumonia had better survival. Sensitivity of the CDC 2013 criteria was only 44.1 per cent. Our results emphasize the importance of having a high index of suspicion for VAP in ventilator-dependent patients. The 2013 CDC criteria failed to detect 55.9 per cent of confirmed VAP cases. These results are concerning because undetected VAP can have devastating consequences for patients.

Background: The link between bacterial resistance and prognosis remains controversial. Predominant pathogen causing ventilator-associated pneumonia (VAP) is Pseudomonas aeruginosa (Pa), which has increasingly become multidrug resistant (MDR). The aim of this study was to evaluate the relationship between MDR VAP Pa episodes and 30-day mortality., Methods: From a longitudinal prospective French multicenter database (2010-2016), Pa VAP onset and physiological data were recorded. MDR was defined as non-susceptibility to at least 1 agent in 3 or more antimicrobial categories. To analyze if MDR episodes were associated with greater in-hospital 30-day mortality, we performed a multivariate survival analysis using the multivariate nonlinear frailty model., Results: A total of 230 patients presented 286 Pa VAP. A maximum of 3 episodes per patient was observed; 73 episodes were MDR and 213 were susceptible. In the multivariate model, factors independently associated with 30-day mortality included hospitalization in the 6 months preceding the first episode (hazard ratio [HR], 2.31; 95% confidence interval [CI], 1.50-3.60; P = .0002), chronic renal failure (HR, 2.34; 95% CI, 1.15-4.77; P = .0196), and Pa VAP recurrence (HR, 2.29; 95% CI, 1.79-4.87; P = .032). Finally, MDR Pa VAP was not associated with death (HR, 0.87; 95% CI; 0.52-1.45; P = .59)., Conclusions: This study did not identify a relationship between the resistance profile of Pseudomonas aeruginosa and mortality., (Copyright © 2019 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Ventilator-associated pneumonia (VAP) is a well-known, life-threatening disease that persists despite preventative measures and approved antibiotic therapies. This prospective observational study investigated bacterial airway colonization, and whether its detection and quantification in the endotracheal aspirate (ETA) is useful for identifying mechanically ventilated ICU patients who are at risk of developing VAP., Methods: 240 patients admitted to 3 ICUs at the Lahey Hospital and Medical Center (Burlington, MA) between June 2014 and June 2015 and mechanically ventilated for > 2 days were included. ETA samples and clinical data were collected. Airway colonization was assessed, and subsequently categorized into "heavy" and "light" by semi-quantitative microbiological analysis of ETAs. VAP was diagnosed retrospectively by the study sponsor according to a pre-specified pneumonia definition., Results: Pathogenic bacteria were isolated from ETAs of 125 patients. The most common species isolated was S. aureus (56.8%), followed by K. pneumoniae, P. aeruginosa, and E. coli (35.2% combined). VAP was diagnosed in 85 patients, 44 (51.7%) with no bacterial pathogen, 18 associated with S. aureus and 18 Gram-negative-only cases, and 5 associated with other Gram-positive or mixed species. A higher proportion of patients who were heavily colonized with S. aureus developed VAP (32.4%) associated with S. aureus compared to those lightly colonized (17.6%). The same tendency was seen for patients heavily and lightly colonized with Gram-negative pathogens (30.0 and 0.0%, respectively). Detection of S. aureus in the ETA preceded S. aureus VAP by approximately 4 days, while Gram-negative organisms were first detected 2.5 days prior to Gram-negative VAP. VAP was associated with significantly longer duration of mechanical ventilation and hospitalization regardless of microbiologic cause when compared to patients who did not develop VAP., Conclusions: The overall VAP rate was 35%. Heavy tracheal colonization supported identification of patients at higher risk of developing a corresponding S. aureus or Gram-negative VAP. Detection of bacterial ETA-positivity tended to precede VAP.

Background: Ventilator-associated events (VAE), using objective diagnostic criteria, are the preferred quality indicator for patients requiring mechanical ventilation (MV) for greater than 48 hours. We aim to identify the occurrence of VAE in our trauma population, the impact on survival, and length of stay, as compared to the traditional definition of ventilator-associated pneumonia (VAP)., Methods: This retrospective review included adult trauma patients, who were Washington residents, admitted between 2012 and 2017, and required at least 3 days of MV. Exclusions included patients with Abbreviated Injury Scale head score greater than 4 and burn related mechanisms of injury. We matched trauma registry data with our institutional, physician-adjudicated, and culture-confirmed ventilator event database. We compared the clinical outcomes of ventilator-free days, intensive care unit length of stay, hospital length of stay, and likelihood of death between VAE and VAP., Results: One thousand five hundred thirty-three trauma patients met criteria; 124 (8.1%) patients developed VAE, 114 (7.4%) patients developed VAP, and 63 (4.1%) patients met criteria for both VAE and VAP. After adjusted analyses, patients with VAE were more likely to die (hazard ratio [HR], 2.86; 95% confidence interval [CI], 1.44-5.68), than those with VAP, as well those patients with neither diagnosis (HR, 2.83; 95% CI, 1.83-4.38). Patients with VAP were no more likely to die (HR, 1.55; 95% CI, 0.91-2.68) than those with neither diagnosis. Patients with VAE had fewer ventilator-free days than those with VAP (HR, -2.71; 95% CI, -4.74 to -0.68)., Conclusion: Critically injured trauma patients who develop VAE are three times more likely to die and utilize almost 3 days more MV than those that develop VAP. The objective criteria of VAE make it a promising indicator on which quality indicator efforts should be focused. Future studies should be aimed at identification of modifiable risk factors for VAE and their impact on outcome, as these patients are at high risk for death., Level of Evidence: Retrospective cohort study, level III.

Purpose: To compare bacteria recovered by standard cultures and metataxonomics, particularly with regard to ventilator-associated pneumonia (VAP) pathogens, and to determine if the presence of particular bacteria or microbiota in tracheal and oropharyngeal secretions during the course of intubation was associated with the development of VAP., Methods: In this case-control study, oropharyngeal secretions and endotracheal aspirate were collected daily in mechanically ventilated patients. Culture and metataxonomics (16S rRNA gene-based taxonomic profiling of bacterial communities) were performed on serial upper respiratory samples from patients with late-onset definite VAP and their respective controls., Results: Metataxonomic analyses showed that a low relative abundance of Bacilli at the time of intubation in the oropharyngeal secretions was strongly associated with the subsequent development of VAP. On the day of VAP, the quantity of human and bacterial DNA in both tracheal and oropharyngeal secretions was significantly higher in patients with VAP than in matched controls with similar ventilation times. Molecular techniques identified the pathogen(s) of VAP found by culture, but also many more bacteria, classically difficult to culture, such as Mycoplasma spp. and anaerobes., Conclusions: Molecular analyses of respiratory specimens identified markers associated with the development of VAP, as well as important differences in the taxa abundance between VAP and controls. Further prospective trials are needed to test the predictive value of these markers, as well as the relevance of uncultured bacteria in the pathogenesis of VAP.