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Background: Predictors of ICU-acquired pulmonary aspergillosis (IPA) are not well-established in critically ill patients with ventilator-associated pneumonia (VAP), making IPA commonly misdiagnosed and anti-fungal therapy delayed. We aimed to develop a clinical score for prediction of IPA among patients with VAP. Methods: Mechanically ventilated patients who developed VAP in 4 ICUs in Bretagne, Western France, were included. The score was constructed in a learning cohort, based on predictors of IPA in logistic regression model, and validated in a validation cohort. Results: Among 1636 mechanically ventilated patients, 215 developed VAP but only 39 developed IPA (4 possible and 35 probable/putative) (18%). Most cases (31/39) were documented through a positive broncho-alveolar sample culture. Independent predictors of IPA were immunodepression (including onco-hematological disorder, immunomodulatory treatment, solid organ transplant, neutropenia < 0.5G/L and high-dose steroids ≥ 1 mg/kg/day of prednisolone equivalent) (p = 0.001; score = 1 point) and lymphocyte count at admission < 0.8 G/L (p = 0.019; score = 1 point). Operational values of the predictive score in the learning/validation cohort were 50%/52% sensitivity and 90%/87% specificity, respectively, for high PiPa score (score = 2) and 94%/91% sensitivity and 44%/46% specificity, respectively, for moderate PiPa score (score = 1). Finally, the AUC for the prediction of IPA was 0.783 in the learning cohort and 0.770 in the validation cohort. Conclusions: We evaluated a clinical score with good predictive value which may help to predict IPA in patient with VAP. External validation will be needed to confirm our preliminary findings. [ABSTRACT FROM AUTHOR]

Background: Ventilator acquired pneumonia (VAP) is a frequent and serious complication in ICU. Second episodes of VAP are common in trauma patients and may be related to severity of underlying conditions, treatment or bacterial factors of the first VAP. The aim of this study was to identify risk factors of second VAP episodes in trauma injured patients (defined as the development of a new pulmonary infection during or remotely following the first episode). Design: This is a single-center, retrospective cohort study of trauma injured patients who underwent a first episode of VAP between January 1, 2013 and December 31, 2020 at Beaujon Hospital. Results: A total of 533 patients with a first episode of VAP were analyzed, mostly with head and/or thoracic traumatic injury. A second episode of VAP occurred in one hundred sixty-seven patients (31.3%). The main risk factors found was the degree of hypoxemia at the time of the first episode [PaO2/FiO2 ratio 100–200, OR 3.12 (1.77–5.69); < 100, OR 5.80 (2.70–12.8)] and severe traumatic brain injury characterized by an initial GCS ≤ 8 [OR 1.65 (1.01–2.74)]. Conclusion: Depth of hypoxemia during the first VAP episode and severity of the initial brain injury are the main risk factors for VAP second episode in trauma injured patients. [ABSTRACT FROM AUTHOR]

Background: Even though the population-attributable fraction (PAF) is a well-established metric, it is often incorrectly estimated or interpreted not only in clinical application, but also in statistical research articles. The risk of bias is especially high in more complex time-to-event data settings.Methods: We explain how the PAF can be defined, identified and estimated in time-to-event settings with competing risks and time-dependent exposures. By using multi-state methodology and inverse probability weighting, we demonstrate how to reduce or completely avoid severe types of biases including competing risks bias, immortal time bias and confounding due to both baseline and time-varying patient characteristics.Results: The method is exemplarily applied to a real data set. Moreover, we estimate the number of deaths that were attributable to ventilator-associated pneumonia in France in the year 2016. The example demonstrates how, under certain simplifying assumptions, PAF estimates can be extrapolated to a target population of interest.Conclusions: Defining and estimating the PAF in advanced time-to-event settings within a framework that unifies causal and multi-state modelling enables to tackle common sources of bias and allows straightforward implementation with standard software packages. [ABSTRACT FROM AUTHOR]

Purpose: We aimed to determine whether interferon gamma-1b prevents hospital-acquired pneumonia in mechanically ventilated patients. Methods: In a multicenter, placebo-controlled, randomized trial conducted in 11 European hospitals, we randomly assigned critically ill adults, with one or more acute organ failures, under mechanical ventilation to receive interferon gamma-1b (100 µg every 48 h from day 1 to 9) or placebo (following the same regimen). The primary outcome was a composite of hospital-acquired pneumonia or all-cause mortality on day 28. The planned sample size was 200 with interim safety analyses after enrolling 50 and 100 patients. Results: The study was discontinued after the second safety analysis for potential harm with interferon gamma-1b, and the follow-up was completed in June 2022. Among 109 randomized patients (median age, 57 (41–66) years; 37 (33.9%) women; all included in France), 108 (99%) completed the trial. Twenty-eight days after inclusion, 26 of 55 participants (47.3%) in the interferon-gamma group and 16 of 53 (30.2%) in the placebo group had hospital-acquired pneumonia or died (adjusted hazard ratio (HR) 1.76, 95% confidence interval (CI) 0.94–3.29; P = 0.08). Serious adverse events were reported in 24 of 55 participants (43.6%) in the interferon-gamma group and 17 of 54 (31.5%) in the placebo group (P = 0.19). In an exploratory analysis, we found that hospital-acquired pneumonia developed in a subgroup of patients with decreased CCL17 response to interferon-gamma treatment. Conclusions: Among mechanically ventilated patients with acute organ failure, treatment with interferon gamma-1b compared with placebo did not significantly reduce the incidence of hospital-acquired pneumonia or death on day 28. Furthermore, the trial was discontinued early due to safety concerns about interferon gamma-1b treatment. [ABSTRACT FROM AUTHOR]

To compare the occurrence of healthcare-associated infections acquired in intensive care units (HAI-ICUs) in France among patients with COVID-19 and those without it in 2020 and the latter with that in patients before the COVID-19 pandemic. Multicentre HAI-ICU surveillance network (REA-REZO) data were used to identify 3 groups: 2019 patients (2019Control), a COVID-19 group (2020Cov), and a non–COVID-19 group (2020NonCov). The primary outcome was the occurrence of HAI-ICU (ventilator-associated pneumonia [VAP], bloodstream infections [BSIs], catheter-related bacteraemia). Standardized infection ratios of VAP were calculated for each quarter in 2020 and compared with those in 2019. A total of 30 105 patients were included in 2020: 23 798 in the 2020NonCov group, 4465 in 2020Cov group, and 39 635 patients in the 2019Control group. The frequency of VAP was strikingly greater in the 2020Cov group: 35.6 (33.4–37.8) episodes/1000 days of mechanical ventilation versus 18.4 (17.6–19.2) in the 2020NonCov group. VAP standardized infection ratio was high in 2020 patients, particularly during the 2 quarters corresponding to the 2 waves. BSI/1000 days were more frequent in the 2020Cov group (6.4% [6.4–6.4%] vs. 3.9% [3.8–3.9%] in the 2020NonCov group). VAP and BSI were also more frequent in the 2020NonCov group than in the 2019Control group. The microbial epidemiology was only slightly different. The data presented here indicate that HAI-ICUs were more frequent during the COVID-19 period, whether the patients were admitted for COVID-19 or, to a lesser extent, for another cause. This implies that managing patients with severe disease in a pandemic context carries risks for all patients. [ABSTRACT FROM AUTHOR]

Background: Among strategies that aimed to prevent acquired infections (AIs), selective decontamination regimens have been poorly studied in the COVID-19 setting. We assessed the impact of a multiple-site decontamination (MSD) regimen on the incidence of bloodstream infections (BSI) and ventilator-associated pneumonia (VAP) in COVID-19 patients receiving mechanical ventilation. Methods: We performed an ancillary analysis of a multicenter retrospective observational study in 15 ICUs in western France. In addition to standard-care (SC), 3 ICUs used MSD, a variant of selective digestive decontamination, which consists of the administration of topical antibiotics four times daily in the oropharynx and the gastric tube, chlorhexidine body wash and a 5-day nasal mupirocin course. AIs were compared between the 3 ICUs using MSD (MSD group) and the 12 ICUs using SC. Results: During study period, 614 of 1158 COVID-19 patients admitted in our ICU were intubated for at least 48 h. Due to missing data in 153 patients, 461 patients were finally included of whom 89 received MSD. There were 34 AIs in the MSD group (2117 patient-days), as compared with 274 AIs in the SC group (8957 patient-days) (p < 0.001). MSD was independently associated with a lower risk of AI (IRR = 0.56 [0.38–0.83]; p = 0.004) (Table 2). When the same model was used for each site of infection, MSD remained independently associated with a lower risk of VAP (IRR = 0.52 [0.33–0.89]; p = 0.005) but not of BSI (IRR = 0.58, [0.25–1.34], p = 0.21). Hospital mortality was lower in the MSD group (16.9% vs 30.1%, p = 0.017). Conclusions: In ventilated COVID-19 patients, MSD was independently associated with lower AI incidence. [ABSTRACT FROM AUTHOR]

Background: Diagnosis of co/superinfection in patients with Acute Respiratory Distress Syndrome (ARDS) is challenging. The FilmArray Pneumonia plus Panel (bioMérieux, France), a new rapid multiplex Polymerase Chain Reaction (mPCR), has never been assessed on a blinded protected telescope catheter (PTC) samples, a very common diagnostic tool in patients under mechanical ventilation. We evaluated the performance of mPCR on PTC samples compared with conventional culture and its impact on antibiotic stewardship. Methods: Observational study in two intensive care units, conducted between March and July 2020, during the first wave of the COVID-19 pandemic in France. Results: We performed 125 mPCR on blinded PTC samples of 95 ARDS patients, including 73 (77%) SARS-CoV-2 cases and 28 (29%) requiring extracorporeal membrane oxygenation. Respiratory samples were drawn from mechanically ventilated patients either just after intubation (n = 48; 38%) or later for suspected ventilator-associated pneumonia (VAP) (n = 77; 62%). The sensitivity, specificity, positive, and negative predictive values of mPCR were 93% (95% CI 84–100), 99% (95% CI 99–100), 68% (95% CI 54–83), and 100% (95% CI 100–100), respectively. The overall coefficient of agreement between mPCR and standard culture was 0.80 (95% CI 0.68–0.89). Intensivists changed empirical antimicrobial therapy in only 14% (18/125) of cases. No new antibiotic was initiated in more than half of the CAP/HAP pneumonia-suspected cases (n = 29; 60%) and in more than one-third of those suspected to have VAP without affecting or delaying their antimicrobial therapy. Conclusions: Rapid mPCR was feasible on blinded PTC with good sensitivity and specificity. New antibiotics were not initiated in more than half of patients and more than one-third of VAP-suspected cases. Further studies are needed to assess mPCR potential in improving antibiotic stewardship. [ABSTRACT FROM AUTHOR]

Considering virus-related and drug-induced immunocompromised status of critically ill COVID-19 patients, we hypothesize that these patients would more frequently develop ventilator-associated pneumonia (VAP) than patients with ARDS from other viral causes. We conducted a retrospective observational study in two intensive care units (ICUs) from France, between 2017 and 2020. We compared bacterial co-infection at ICU admission and throughout the disease course of two retrospective longitudinally sampled groups of critically ill patients, who were admitted to ICU for either H1N1 or SARS-CoV-2 respiratory infection and depicted moderate-to-severe ARDS criteria upon admission. Sixty patients in the H1N1 group and 65 in the COVID-19 group were included in the study. Bacterial co-infection at the endotracheal intubation time was diagnosed in 33% of H1N1 and 16% COVID-19 patients (p = 0.08). The VAP incidence per 100 days of mechanical ventilation was 3.4 (2.2–5.2) in the H1N1 group and 7.2 (5.3–9.6) in the COVID-19 group (p < 0.004). The HR to develop VAP was of 2.33 (1.34–4.04) higher in the COVID-19 group (p = 0.002). Ten percent of H1N1 patients and 30% of the COVID-19 patients had a second episode of VAP (p = 0.013). COVID-19 patients have fewer bacterial co-infections upon admission, but the incidence of secondary infections increased faster in this group compared to H1N1 patients. [ABSTRACT FROM AUTHOR]

Objectives: Little is known about the epidemiology of ventilator-acquired pneumonia among coronavirus disease 2019 patients such as incidence or etiological agents. Some studies suggest a higher risk of ventilator-associated pneumonia in this specific population.Design: Cohort exposed/nonexposed study among the REA-REZO surveillance network.Setting: Multicentric; ICUs in France.Patients: The coronavirus disease 2019 patients at admission were matched on the age, sex, center of inclusion, presence of antimicrobial therapy at admission, patient provenance, time from ICU admission to mechanical ventilation, and Simplified Acute Physiology Score II at admission to the patients included between 2016 and 2019 within the same surveillance network (1:1).Interventions: None.Measurements and Main Results: The overall incidence of ventilator-associated pneumonia, the cumulative incidence, and hazard rate of the first and the second ventilator-associated pneumonia were estimated. In addition, the ventilator-associated pneumonia microbiological ecology and specific resistant pattern in coronavirus disease 2019 exposed and nonexposed patients were compared. Medication data were not collected. A total of 1,879 patients were included in each group. The overall incidence of ventilator-associated pneumonia was higher among coronavirus disease 2019 exposed patients (25.5; 95% CI [23.7-27.45] vs 15.4; 95% CI [13.7-17.3] ventilator-associated pneumonia per 1,000 ventilation days). The cumulative incidence was higher for the first and the second ventilator-associated pneumonia among the coronavirus disease 2019 exposed patients (respective Gray test p < 0.0001 and 0.0167). The microbiological ecology and resistance were comparable between groups with a predominance of Enterobacterales and nonfermenting Gram-negative bacteria. The documented resistance pattern was similar between groups, except for a lower rate of methicillin-resistant Staphylococcus aureus in the coronavirus disease 2019 exposed patient (6% vs 23%; p = 0.013).Conclusions: There was a higher incidence of ventilator-associated pneumonia occurring among coronavirus disease 2019 patient compared with the general ICU population, with a similar microbiological ecology and resistance pattern. [ABSTRACT FROM AUTHOR]

Background: Staphylococcus aureus remains a common cause of ventilator-associated pneumonia, with little change in incidence over the past 15 years. We aimed to evaluate the efficacy of suvratoxumab, a monoclonal antibody targeting the α toxin, in reducing the incidence of S aureus pneumonia in patients in the intensive care unit (ICU) who are on mechanical ventilation.Methods: We did a multicentre, randomised, double-blind, placebo-controlled, parallel-group, phase 2 pilot trial at 31 hospitals in Belgium, the Czech Republic, France, Germany, Greece, Hungary, Portugal, Spain, and Switzerland. Eligible patients were in the ICU, aged ≥18 years, were intubated and on mechanical ventilation, were positive for S aureus colonisation of the lower respiratory tract, as assessed by quantitative PCR (qPCR) analysis of endotracheal aspirate, and had not been diagnosed with new-onset pneumonia. Patients were excluded if they had confirmed or suspected acute ongoing staphylococcal disease; had received antibiotics for S aureus infection for more than 48 h within 72 h of randomisation; had a Clinical Pulmonary Infection Score of 6 or higher; had an acute physiology and chronic health evaluation II score of 25 or higher with a Glasgow coma scale (GCS) score of more than 5, or an acute physiology and chronic health evaluation II score of at least 30 with a GCS score of 5 or less; had a Sequential Organ Failure Assessment score of 9 or higher; or had active pulmonary disease that would impair the ability to diagnose pneumonia. Colonised patients were randomly assigned (1:1:1), by use of an interactive voice or web response system, to receive either a single intravenous infusion of suvratoxumab 2000 mg, suvratoxumab 5000 mg, or placebo. Randomisation was done in blocks of size four, stratified by country and by whether patients had received systemic antibiotics for S aureus infection. Patients, investigators, and study staff involved in the treatment or clinical evaluation of patients were masked to patient assignment. The primary efficacy endpoint was the incidence of S aureus pneumonia at 30 days, as determined by a masked independent endpoint adjudication committee, in all patients who received their assigned treatment (modified intention-to-treat [ITT] population). Primary safety endpoints were the incidence of treatment-emergent adverse events at 30 days, 90 days, and 190 days after treatment, and the incidence of treatment-emergent serious adverse events, adverse events of special interest, and new-onset chronic disease at 190 days after treatment. All primary safety endpoints were assessed in the modified ITT population. This trial is registered with ClinicalTrials.gov (NCT02296320) and the EudraCT database (2014-001097-34).Findings: Between Oct 10, 2014, and April 1, 2018, 767 patients were screened, of whom 213 patients with confirmed S aureus colonisation of the lower respiratory tract were randomly assigned to the suvratoxumab 2000 mg group (n=15), the suvratoxumab 5000 mg group (n=96), or the placebo group (n=102). Two patients in the placebo group did not receive treatment after randomisation because their clinical conditions changed and they no longer met the eligibility criteria for dosing. As adjudicated by the data monitoring committee at an interim analysis, the suvratoxumab 2000 mg group was discontinued on the basis of predefined pharmacokinetic criteria. At 30 days after treatment, 17 (18%) of 96 patients in the suvratoxumab 5000 mg group and 26 (26%) of 100 patients in the placebo group had developed S aureus pneumonia (relative risk reduction 31·9% [90% CI -7·5 to 56·8], p=0·17). The incidence of treatment-emergent adverse events at 30 days were similar between the suvratoxumab 5000 mg group (87 [91%]) and the placebo group (90 [90%]). The incidence of treatment-emergent serious adverse events at 30 days were also similar between the suvratoxumab 5000 mg group (36 [38%]) and the placebo group (32 [32%]). No significant difference in the incidence of treatment-emergent adverse events between the two groups at 90 days (89 [93%] in the suvratoxumab 5000 mg group vs 92 [92%] in the placebo group) and at 190 days (93 [94%] vs 93 [93%]) was observed. 40 (40%) patients in the placebo group and 50 (52%) in the suvratoxumab 5000 mg group had a serious adverse event at 190 days. In the suvratoxumab 5000 mg group, one (1%) patient reported at least one treatment-emergent serious adverse event related to treatment, two (2%) patients reported an adverse event of special interest, and two (2%) reported a new-onset chronic disease.Interpretation: In patients in the ICU receiving mechanical ventilation with qPCR-confirmed S aureus colonisation of the lower respiratory tract, the incidence of S aureus pneumonia at 30 days was not significantly lower following treatment with 5000 mg suvratoxumab than with placebo. Despite these negative results, monoclonal antibodies still represent one promising therapeutic option to reduce antibiotic consumption that require further exploration and studies.Funding: AstraZeneca, with support from the Innovative Medicines Initiative Joint Undertaking. [ABSTRACT FROM AUTHOR]

Background: Patients with obesity are at higher risk for community-acquired and nosocomial infections. However, no study has specifically evaluated the relationship between obesity and ventilator-associated pneumonia (VAP).Research Question: Is obesity associated with an increased incidence of VAP?Study Design and Methods: This study was a post hoc analysis of the Impact of Early Enteral vs Parenteral Nutrition on Mortality in Patients Requiring Mechanical Ventilation and Catecholamines (NUTRIREA2) open-label, randomized controlled trial performed in 44 French ICUs. Adults receiving invasive mechanical ventilation and vasopressor support for shock and parenteral nutrition or enteral nutrition were included. Obesity was defined as BMI ≥ 30 kg/m2 at ICU admission. VAP diagnosis was adjudicated by an independent blinded committee, based on all available clinical, radiologic, and microbiologic data. Only first VAP episodes were taken into account. Incidence of VAP was analyzed by using the Fine and Gray model, with extubation and death as competing risks.Results: A total of 699 (30%) of the 2,325 included patients had obesity; 224 first VAP episodes were diagnosed (60 and 164 in obese and nonobese groups, respectively). The incidence of VAP at day 28 was 8.6% vs 10.1% in the two groups (hazard ratio, 0.85; 95% CI 0.63-1.14; P = .26). After adjustment on sex, McCabe score, age, antiulcer treatment, and Sequential Organ Failure Assessment at randomization, the incidence of VAP remained nonsignificant between obese and nonobese patients (hazard ratio, 0.893; 95% CI, 0.66-1.2; P = .46). Although no significant difference was found in duration of mechanical ventilation and ICU length of stay, 90-day mortality was significantly lower in obese than in nonobese patients (272 of 692 [39.3%] patients vs 718 of 1,605 [44.7%]; P = .02). In a subgroup of patients (n = 123) with available pepsin and alpha-amylase measurements, no significant difference was found in rate of abundant microaspiration of gastric contents, or oropharyngeal secretions between obese and nonobese patients.Interpretation: Our results suggest that obesity has no significant impact on the incidence of VAP. [ABSTRACT FROM AUTHOR]

Background: The aim of this study is to determine whether severe COVID-19 patients harbour a higher risk of ICU-acquired pneumonia. Methods: This retrospective multicentre cohort study comprised all consecutive patients admitted to seven ICUs for severe COVID-19 pneumonia during the first COVID-19 surge in France. Inclusion criteria were laboratory-confirmed SARS-CoV-2 infection and requirement for invasive mechanical ventilation for 48 h or more. Control groups were two historical cohorts of mechanically ventilated patients admitted to the ICU for bacterial or non-SARS-CoV-2 viral pneumonia. The outcome of interest was the development of ICU-acquired pneumonia. The determinants of ICU-acquired pneumonia were investigated in a multivariate competing risk analysis. Result: One hundred and seventy-six patients with severe SARS-CoV-2 pneumonia admitted to the ICU between March 1st and 30th June of 2020 were included into the study. Historical control groups comprised 435 patients with bacterial pneumonia and 48 ones with viral pneumonia. ICU-acquired pneumonia occurred in 52% of COVID-19 patients, whereas in 26% and 23% of patients with bacterial or viral pneumonia, respectively (p < 0.001). Times from initiation of mechanical ventilation to ICU-acquired pneumonia were similar across the three groups. In multivariate analysis, the risk of ICU-acquired pneumonia remained independently associated with underlying COVID-19 (SHR = 2.18; 95 CI 1.2–3.98, p = 0.011). Conclusion: COVID-19 appears an independent risk factor of ICU-acquired pneumonia in mechanically ventilated patients with pneumonia. Whether this is driven by immunomodulatory properties by the SARS-CoV-2 or this is related to particular processes of care remains to be investigated. [ABSTRACT FROM AUTHOR]

In a prospective, nationwide study in France of Escherichia coli responsible for pneumonia in patients receiving mechanical ventilation, we determined E. coli antimicrobial susceptibility, phylotype, O-type, and virulence factor gene content. We compared 260 isolates with those of 2 published collections containing commensal and bacteremia isolates. The preponderant phylogenetic group was B2 (59.6%), and the predominant sequence type complex (STc) was STc73. STc127 and STc141 were overrepresented and STc95 underrepresented in pneumonia isolates compared with bacteremia isolates. Pneumonia isolates carried higher proportions of virulence genes sfa/foc, papGIII, hlyC, cnf1, and iroN compared with bacteremia isolates. Virulence factor gene content and antimicrobial drug resistance were higher in pneumonia than in commensal isolates. Genomic and phylogenetic characteristics of E. coli pneumonia isolates from critically ill patients indicate that they belong to the extraintestinal pathogenic E. coli pathovar but have distinguishable lung-specific traits. [ABSTRACT FROM AUTHOR]

Summary Background Non-invasive ventilation has never been compared with high-flow oxygen to determine whether it reduces the risk of severe hypoxaemia during intubation. We aimed to determine if preoxygenation with non-invasive ventilation was more efficient than high-flow oxygen in reducing the risk of severe hypoxaemia during intubation. Methods The FLORALI-2 multicentre, open-label trial was done in 28 intensive care units in France. Adult patients undergoing tracheal intubation for acute hypoxaemic respiratory failure (a partial pressure of arterial oxygen [PaO 2 ] to fraction of inspired oxygen [FiO 2 ] ratio of ≤300 mm Hg) were randomly assigned (1:1; block size, four participants) to non-invasive ventilation or high-flow oxygen during preoxygenation, with stratification by PaO 2 /FiO 2 ratio (≤200 mm Hg vs >200 mm Hg). Key exclusion criteria were intubation for cardiac arrest, altered consciousness (defined as a Glasgow coma score of less than eight points), other contraindications to non-invasive ventilation (recent laryngeal, oesophageal, or gastric surgery, and substantial facial fractures), pulse oximetry not available, pregnant or breastfeeding women, and refusal to participate. The primary outcome was the occurrence of severe hypoxaemia (pulse oximetry <80%) during the procedure, assessed in the intention-to-treat population. This trial is registered with ClinicalTrials.gov , number NCT02668458. Findings Between April 15, 2016, and Jan 8, 2017, 2079 patients were intubated in the 28 participating units, and 322 were enrolled. We excluded five patients with no recorded data, two who withdrew consent or were under legal protection, one who was not intubated, and one who had a cardiac arrest. Of the 313 patients included in the intention-to-treat analysis, 142 were assigned to non-invasive ventilation and 171 to high-flow oxygen therapy. Severe hypoxaemia occurred in 33 (23%) of 142 patients after preoxygenation with non-invasive ventilation and 47 (27%) of 171 with high-flow oxygen (absolute difference −4·2%, 95% CI −13·7 to 5·5; p=0·39). In the 242 patients with moderate-to-severe hypoxaemia (PaO 2 /FiO 2 ≤200 mm Hg), severe hypoxaemia occurred less frequently after preoxygenation with non-invasive ventilation than with high-flow oxygen (28 [24%] of 117 patients vs 44 [35%] of 125; adjusted odds ratio 0·56, 0·32 to 0·99, p=0·0459). Serious adverse events did not differ between treatment groups, with the most common immediate complications being systolic arterial hypotension (70 [49%] patients in the non-invasive ventilation group vs 86 [50%] patients in the high-flow oxygen group) and chest infiltrate on x-ray (28 [20%] vs 33 [19%]), and the most common late complications being death at day 28 (53 [37%] vs 58 [34%]) and ventilator-associated pneumonia during ICU stay (31 [22%] vs 35 [20%]). Interpretation In patients with acute hypoxaemic respiratory failure, preoxygenation with non-invasive ventilation or high-flow oxygen therapy did not change the risk of severe hypoxaemia. Future research should explore the effect of preoxygenation method in patients with moderate-to-severe hypoxaemia at baseline. Funding French Ministry of Health. [ABSTRACT FROM AUTHOR]

BACKGROUND: In a previous study of subjects suspected of having ventilator-associated pneumonia, a rapid susceptibility testing approach by using ETEST (BioMérieux) strips directly applied to bronchoalveolar lavage samples provided valuable information at hour 24. The primary objective of this study was to assess a new direct specimen testing by using an even more-rapid E-test approach (at hour 10), which could promote an early de-escalation of the antimicrobial therapy. METHODS: Twenty-eight subjects with ventilator-associated pneumonia admitted to a medical ICU were prospectively included. In parallel with standard routine methods, E-test strips were directly applied onto agar plates seeded with bronchoalveolar lavage samples and were analyzed after 10 h of incubation. E-test results were used to identify potential drug choices by simulating clinical decision making if the microscopy results had been available at the point of care. These choices were analyzed for concordance with the narrowest adequate antimicrobial therapy according to the Minimum Inhibitory Concentrations (MICs) provided by the reference method (ie, the laboratory routine diagnostic). RESULTS: At hour 10, direct specimen testing was readable in 18 of 28 bronchoalveolar lavage samples (64%). Total agreement between the 10-h direct specimen testing approach and the laboratory routine diagnostic approach was 90%, with a sensitivity of 83% and a specificity of 95%, with 8% major errors and 3% very major errors. The concordance between the 2 tests was very good (kappa = 0.79). If the 10-h E-test results were taken into account, then an early de-escalation strategy would have been possible in 10 of 18 cases (55%) at hour 10. CONCLUSIONS: This rapid susceptibility testing approach provided early (10 h) and valuable information that could lead to an early adjustment of empirical antimicrobial treatment in a ventilator-associated pneumonia setting. [ABSTRACT FROM AUTHOR]

Background: Early-onset ventilator-associated pneumonia (EOVAP) occurs frequently in severe traumatic brain-injured patients, but potential consequences on cerebral oxygenation and outcome have been poorly studied. The objective of this study was to describe the incidence, risk factors for, and consequences on cerebral oxygenation and outcome of EOVAP after severe traumatic brain injury (TBI).Methods: We conducted a retrospective, observational study including all intubated TBI admitted in the trauma center. An EOVAP was defined as a clinical pulmonary infection score >6, and then confirmed by an invasive method. Patient characteristics, computed tomography (CT) scan results, and outcome were extracted from a prospective register of all intubated TBI admitted in the intensive care unit (ICU). Data concerning the cerebral oxygenation monitoring by PbtO2 and characteristics of EOVAP were retrieved from patient files. Multivariate logistic regression models were developed to determine the risk factors of EOVAP and to describe the factors independently associated with poor outcome at 1-year follow-up.Results: During 7 years, 175 patients with severe TBI were included. The overall incidence of EOVAP was 60.6% (47.4/1000 days of ventilation). Significant risk factors of EOVAP were: therapeutic hypothermia (OR 3.4; 95% CI [1.2-10.0]), thoracic AIS score ≥3 (OR 2.4; 95% CI [1.1-5.7]), and gastric aspiration (OR 5.2, 95% CI [1.7-15.9]). Prophylactic antibiotics administration was a protective factor against EOVAP (OR 0.3, 95% CI [0.1-0.8]). EOVAP had negative consequences on cerebral oxygenation. The PbtO2 was lower during EOVAP: 23.5 versus 26.4 mmHg (p <0.0001), and there were more brain hypoxia episodes: 32 versus 27% (p = 0.03). Finally, after adjusting for confounders, an EOVAP was an independent factor associated with unfavorable neurologic functional outcome at the 1-year follow-up (OR 2.71; 95% CI [1.01-7.25]).Conclusions: EOVAP is frequent after a severe TBI (overall rate: 61%), with therapeutic hypothermia, severe thoracic lesion, and gastric aspiration as main risk factors. EOVAP had a negative impact on cerebral oxygenation measured by PbtO2 and was independently associated with unfavorable outcome at 1-year follow-up. This suggests that all precautions available should be taken to prevent EOVAP in this population. [ABSTRACT FROM AUTHOR]

BACKGROUND Neuromuscular blockers used to prevent shivering during therapeutic hypothermia in comatose patients after out-of-hospital cardiac arrest are associated with adverse events. OBJECTIVE TO assess the influence of a nurse-implemented protocol on use of neuromuscular blockers in patients treated with 24-hour therapeutic hypothermia after out-of-hospital cardiac arrest. METHODS A before and after study was done in a 24-bed cardiac arrest center. During the before period, paralysis was maintained by continuous infusion of vecuronium during therapeutic hypothermia. During the after period, a nurse-implemented protocol was used to strictly control use of neuromuscular blockers. The primary outcome measure was duration of infusion of neuromuscular blockers; secondary end points included rates of ventilator-associated pneumonia and intensive care unit mortality. RESULTS Among the 22 patients in the before group and the 23 patients in the after group, most were men (78%) with a median age of 66 years. Baseline characteristics were similar between the 2 groups. Median duration of sedation was 36 hours, shorter in the after group (34 hours) than in the before group (38 hours; P = .02). Median duration of infusion of neuromuscular blockers was significantly shorter in the after group (6 hours) than in the before group (33 hours; P < .001). Ventilator-associated pneumonia occurred more frequently in the before group (45%) than in the after group (13%; P = .02). Overall intensive care unit mortality rate was 58%, similar in both groups (P = .44). CONCLUSION Use of a nurse-implemented protocol to reduce use of neuromuscular blockers is feasible. [ABSTRACT FROM AUTHOR]

Background: Ventilator-associated pneumonia (VAP) is the most common infection in intubated critically ill patients. Microaspiration of the contaminated gastric and oropharyngeal secretions is the main mechanism involved in the pathophysiology of VAP. Tracheal cuff plays an important role in stopping the progression of contaminated secretions into the lower respiratory tract. Previous in vitro studies suggested that conical cuff shape might be helpful in improving tracheal sealing. However, clinical studies found conflicting results. The aim of this study is to determine the impact of conical tracheal cuff shape on the microaspiration of gastric contents in critically ill patients.Methods/design: This prospective cluster randomized controlled crossover open-label trial is currently being conducted in ten French intensive care units (ICUs). Patients are allocated to intubation with a polyvinyl chloride (PVC) standard (barrel)-shaped or a PVC conical-shaped tracheal tube. The primary objective is to determine the impact of the conical shaped tracheal cuff on abundant microaspiration of gastric contents. Secondary outcomes include the incidence of microaspiration of oropharyngeal secretions, tracheobronchial colonization, VAP and ventilator-associated events. Abundant microaspiration is defined as the presence of pepsin at significant level (>200 ng/ml) in at least 30 % of the tracheal aspirates. Pepsin and amylase are quantitatively measured in all tracheal aspirates during the 48 h following inclusion. Quantitative tracheal aspirate culture is performed at inclusion and twice weekly. We plan to recruit 312 patients in the participating ICUs.Discussion: BEST Cuff is the first randomized controlled study evaluating the impact of PVC tracheal-cuff shape on gastric microaspirations in patients receiving invasive mechanical ventilation. Enrollment began in June 2014 and is expected to end in October 2015.Trial Registration: ClinicalTrials.gov Identifier: NCT01948635 (registered 31 August 2013). [ABSTRACT FROM AUTHOR]

Aims: Modifications of antimicrobials' pharmacokinetic parameters have been reported in critically ill patients, resulting in a risk of treatment failure. We characterized amikacin pharmacokinetic variability in critically ill patients with ventilator-associated pneumonia (VAP) and evaluated several dosing regimens. Methods: We conducted a prospective multicenter study in critically ill patients with presumptive diagnosis of Gram-negative bacilli (GNB) VAP. Patients empirically received imipenem and a single-dose of amikacin, which was administered as a 30-min infusion (20 mg/kg). Concentrations were measured 0.5, 1, 8, 16, and 24 h after beginning of infusion. Pharmacokinetic parameters were estimated using a population approach. Main pharmacodynamic target was a ratio ≥10 between the concentration achieved 1 h after beginning of infusion ( C) and the minimal inhibitory concentration of the liable bacteria (MIC). We simulated individual C for several dosing regimens by Monte Carlo method and computed C/MIC ratios for MICs from 0.5 to 64 mg/L. Results: Sixty patients (47 males), median (range) age, and body weight, 61.5 years (28-84) and 78 kg (45-126), respectively, were included. Amikacin median C was 45 mg/L (22-87). Mean value (between-patients variability) for CL, V1, Q, and V2 were 4.3 L/h (31 %), 15.9 L (22 %), 12.1 L/h (27 %), and 21.4 L (47 %), respectively. CL increased with CrCL ( p < 0.001) and V1 with body weight ( p < 0.001) and PaO/FIO ratio ( p < 0.001). With a 25 mg/kg regimen, the pharmacodynamic target was achieved in 20 and 96 % for a MICs of 8 and 4 mg/L, respectively. Conclusion: Amikacin clearance was decreased and its volume of distribution was increased as previously reported. A ≥25 mg/kg single-dose is needed for empirical treatment of GNB-VAP. [ABSTRACT FROM AUTHOR]

OBJECTIVE: : We investigated the overall immune response to pathogens in brain-injured patients, and assessed its relationship to nosocomial pneumonia. DESIGN: : Observational study. SETTING: : Two surgical ICUs of a single institution. PATIENTS: : Severe brain-injured patients (n = 32) requiring mechanical ventilation and sex- and age-matched healthy donors (n = 25). INTERVENTIONS: : None. MEASUREMENTS AND MAIN RESULTS: : We evaluated, ex vivo, the ability of peripheral blood mononuclear cells from brain injury patients to develop an effective granulomatous response to mycobacteria. Thirty-two consecutive patients (25 traumatic brain injured and seven subarachnoid hemorrhage) were included. Median Glasgow Coma Scale was 7 (5-8). Thirteen (41%) patients developed nosocomial pneumonia. Peripheral blood mononuclear cells from brain-injured patients with nosocomial pneumonia generated significantly fewer mature granulomas compared with brain-injured patients without nosocomial pneumonia and with healthy donors. The percentage of multinucleated giant cells was lower in brain-injured patients without nosocomial pneumonia (1% [range: 0%-7%]) and in brain-injured patients with nosocomial pneumonia (4% [range: 2%-5%]) compared with healthy donors (20% [range: 15%-28%]). The blood levels of [gamma][delta] T cells were significantly increased in brain-injured patients without nosocomial pneumonia (66% [range: 34%-69%]) compared with healthy donors (23% [range: 8%-61%]) and was not altered in brain-injured patients with nosocomial pneumonia (31% [range: 12%-44%]). The percentage of [gamma][delta] T cells in granulomas was significantly decreased in brain injury patients with nosocomial pneumonia (5% [range: 4%-43%]) compared with healthy donors (43% [range: 19%-54%]) and was not significantly altered in brain-injured patients without nosocomial pneumonia (26% [range: 10%-41%]). The blood levels of natural killer cells were not altered in brain-injured patients. The percentage of natural killer cells in granulomas was significantly decreased in brain-injured patients with nosocomial pneumonia (3% [range: 1%-9%]) compared with brain-injured patients without nosocomial pneumonia (16% [range: 6%-29%]) and with healthy donors (17% [range: 10%-29%]). CONCLUSIONS: : Brain-injured patients experienced a maturation defect of the ex vivo granulomatous response involving monocytes as well as natural killer cells and [gamma][delta] T cells. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: To compare risk factors of early- (E) and late-onset (L) ventilator-associated pneumonia (VAP). Materials and Methods: An epidemiological survey based on a nosocomial infection surveillance program of 11 intensive care units (ICUs) of university teaching hospitals in Lyon, France, was conducted. A total of 7236 consecutive ventilated patients, older than 18 years and hospitalized in ICUs for at least 48 hours, were studied between 1996 and 2002. Data during ICU stay, patient-dependent risk factors, device exposure, nosocomial infections occurrence, and outcome were collected. The cutoff point definition between E-VAP (≤6 days) and L-VAP (>six days) was based on the daily hazard rate of VAP. Results: The VAP incidence rate was 13.1%, 356 (37.6%) E-VAP (within 6 days of admission) and 590 (62.4%) L-VAP were reported. Independent risk factor for E-VAP vs L-VAP was surgical diagnostic category (odds ratio [OR], 1.49 [95% confidence interval, 1.07-2.07]), whereas independent risk factors for L-VAP vs E-VAP were older age (OR, 1.01 [1.01-1.02]), high Simplified Acute Physiology Score II (OR, 1.01 [1.00-1.02]), infection on admission (OR=2.22 [1.61-3.03]), another nosocomial infection before VAP (OR, 5.88 [3.33-11.11]), and exposure to central venous catheter before VAP (OR, 4.76 [1.04-20.00]). Conclusions: E-VAP and L-VAP have different risk factors, highlighting the need for developing specific preventive measures. [Copyright &y& Elsevier]

Background: The management of suspected ventilator-associated pneumonia (VAP) is traditionally based on either a clinical or a "bacteriological" approach. Direct examination of specimens may provide a valuable help to both approaches.Objective: The objective was to test an algorithm for the management of suspected pneumonia based on severity criteria and Gram stains of specimens, including early treatment of patients with a positive Gram stain of a protected telescoping catheter specimen and awaiting culture results in patients with either Gram stains of endotracheal aspirate and protected specimen both being negative, or only positive endotracheal aspirate (EA), except in the presence of the severity criteria.Methods: Observational study including 76 first episodes of suspected pneumonia in 4 units. We assessed the rates of correctly diagnosed episodes and of those treated empirically (i.e., ultimately confirmed pneumonia), or appropriately not receiving such therapy (non-confirmed pneumonia), based on protected specimen culture results.Results: When adhered to, the algorithm allowed early appropriate management in 80% of patients, including 83% of those with confirmed pneumonia, and 74% of those without confirmed infection. The rate of appropriately managed episodes using this algorithm was significantly higher than that using a strategy based on the modified clinical pulmonary infection score (CPIS) alone (80 vs. 50%, p<0.001). The empiric regimen was adequate in 86% of confirmed episodes.Conclusion: A strategy based on severity criteria and Gram stain examination of respiratory tract specimens allows correct identification and appropriate management of more than 80% of mechanically ventilated patients who need or do not need therapy for suspected pneumonia. [ABSTRACT FROM AUTHOR]

Objective: To determine the incidence, risk factors, and clinical relevance of viral ventilator-associated pneumonia (VAP) in an adult intensive care unit (ICU).Design: Prospective observational study.Setting: A 22-bed adult medical ICU in a university hospital.Patients: All consecutive adult patients ventilated more than 48 h in a 9-month period including regular seasonal viral infections.Interventions: A tracheobronchial aspirate upon enrollment and at the time of VAP suspicion.Measurements and Results: All respiratory specimens were tested in culture, indirect immunofluorescence assay, and PCR or RT-PCR for virological assessment. Patients were followed until ICU discharge or death. One hundred thirty-nine patients were included. Upon enrollment, a respiratory virus was detected in the tracheobronchial aspirate in 25% of patients (35 of 139). The incidence of VAP, defined according to clinical daily evaluation, was 28% (39 of 139 patients). A bacteria was documented in 74% of cases, whereas no case of a causative viral infection was encountered among VAP patients; however, herpes simplex virus type-1 (HSV 1) infection was detected in respiratory specimens of 31% of VAP (12 of 39).Conclusions: We found a high incidence of HSV-1 infection in VAP patients; however, nosocomial viral VAP is likely to be rare in ICU, as assessed by the absence of respiratory virus-induced VAP identified in this prospective cohort study. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the potential ability of an algorithm based on the clinical pulmonary infection score (CPIS) to identify and treat patients with bacterial ventilator-associated pneumonia (VAP) compared to a strategy based on quantitative cultures of bronchoscopic specimens.Design: Retrospective cohort study.Setting: Thirty-one critical care units across France.Patients: Two hundred and one patients clinically suspected of having VAP who had been included in the "invasive strategy" group of the French multicenter randomized trial and for whose quantitative cultures bronchoscopic specimens were obtained. CPIS was determined retrospectively, based on data that had been collected for the initial study.Interventions: None.Measurements and Results: The clinical pulmonary infection score was determined on days 1 and 3, and compared in patients identified as having developed VAP or not, as defined by bronchoscopic specimen culture results. On day 3 138 of the 201 patients (69%) had a CPIS of more than 6 that would have required prolonged antimicrobial therapy based on the algorithm. In contrast, based on bronchoscopy, only 88 (44%) patients were considered to have VAP (kappa coefficient for concordance between the two strategies, 0.33). While the sensitivity of CPIS more than 6 on day 3 for identifying VAP was 89%, its specificity was only 47%, leading to potentially unnecessary treatment of 60 (53%) of the 113 patients without VAP as diagnosed by bronchoscopy.Conclusion: A strategy based on the CPIS to decide which patients with suspected VAP should receive prolonged administration of antibiotics would appear to over-prescribe these agents, as compared to a strategy based on bronchoscopy. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the impact of continuous subglottic suctioning and semi-recumbent body position on bacterial colonisation of the lower respiratory tract.Design: A randomised controlled trial.Setting: The ten-bed medical ICU of a French university hospital.Patients: Critically ill patients expected to require mechanical ventilation for more than 5 days.Interventions: Patients were randomly assigned to receive either continuous suctioning of subglottic secretions and semi-recumbent body position or to receive standard care and supine position.Measurements and Results: Oropharyngeal and tracheal secretions were sampled daily and quantitatively cultured. All included patients were followed up from day 1 (intubation) to day 10, extubation or death. Ninety-seven samples of oropharynx and trachea were analysed (40 for the suctioning group and 57 for the control group). The median bacterial counts in trachea were 6.6 Log10 CFU/ml (interquartile range, IQR, 4.4-8.3) in patients who received continuous suctioning and 5.1 Log10 CFU/ml (IQR 3.6-5.5) in control patients. Most of the patients were colonised in the trachea after 1 day of mechanical ventilation (75% in the suctioning group, 80% in the control group). No significant difference was found in the daily bacterial counts in the oropharynx and in the trachea between the two groups of patients.Conclusion: Tracheal colonisation in long-term mechanically ventilated ICU patients was not modified by the use of continuous subglottic suctioning and semi-recumbent body position. [ABSTRACT FROM AUTHOR]

(1) Background: Leclercia adecarboxylata (L. adecarboxylata) is a gram-negative bacillus of the Enterobacteriaceae family, which is uncommonly isolated from clinical specimens. L. adecarboxylata is considered as an aquatic opportunistic pathogen and most of the human infections are polymicrobial and usually occur in immunocompromised hosts. (2) Methods: In this retrospective study, we included all L. adecarboxylata strains since the introduction of MALDI-TOF MS in the Microbiology Department of Nord Franche-Comté Hospital, France (from 1 March 2015 to 31 July 2019). We studied demographic characteristics, comorbidities, characteristics of the current infection and outcome as well as antimicrobial susceptibility testing in all isolates. (3) Results: A total of 8 samples were identified (in 6 patients (4M/2F), with a recurrent L. adecarboxylata infection in 2 patients). The patients' mean age was 66.2 years (range: 19–84). All patients were considered as immunocompetent, except a peritoneal dialysis patient with kidney transplantation. An exposition to an aquatic environment was identified in one patient. The most prevalent clinical feature was catheter-associated male urinary tract infection (in 3 cases) followed by ventilator-associated pneumonia (in 2 cases). One of 6 patients presented L. adecarboxylata bacteremia. L. adecarboxylata was part of a polymicrobial infection in 4 patients. The isolates showed a high susceptibility to all tested antibiotics, except one strain, which was resistant to fosfomycin. All patients with L. adecarboxylata infection were treated with antibiotics with a favorable outcome. (4) Conclusion: This study confirms the pathogenicity of L. adecarboxylata, even in immunocompetent patients, with a high susceptibility to antibiotics. [ABSTRACT FROM AUTHOR]

Background: The COVID-19 pandemic is responsible for many hospitalizations in intensive care units (ICU), with widespread use of invasive mechanical ventilation (IMV) which exposes patients to the risk of ventilator-associated pneumonia (VAP). The characteristics of VAP in COVID-19 patients remain unclear., Methods: We retrospectively collected data on all patients hospitalized for COVID-19 during the first phase of the epidemic in one of the seven ICUs of the Pays-de-Loire region (North-West France) and who were on invasive mechanical ventilation for more than 48 h. We studied the characteristics of VAP in these patients. VAP was diagnosed based on official recommendations, and we included only cases of VAP that were confirmed by a quantitative microbiological culture., Findings: We analyzed data from 188 patients. Of these patients, 48.9% had VAP and 19.7% experienced multiple episodes. Our study showed an incidence of 39.0 VAP per 1000 days of IMV (until the first VAP episode) and an incidence of 33.7 VAP per 1000 days of IMV (including all 141 episodes of VAP). Multi-microbial VAP accounted for 39.0% of all VAP, and 205 pathogens were identified. Enterobacteria accounted for 49.8% of all the isolated pathogens. Bacteremia was associated in 15 (10.6%) cases of VAP. Pneumonia was complicated by thoracic empyema in five cases (3.5%) and by pulmonary abscess in two cases (1.4%). Males were associated with a higher risk of VAP (sHR 2.24 CI95% [1.18; 4.26] p = 0.013)., Interpretation: Our study showed an unusually high incidence of VAP in patients admitted to the ICU for severe COVID-19, even though our services were not inundated during the first wave of the epidemic. We also noted a significant proportion of enterobacteria. VAP-associated complications (abscess, empyema) were not exceptional., Registration: As an observational study, this study has not been registered.

The impact of mechanical ventilation on the daily costs of intensive care unit (ICU) care is largely unknown. We thus conducted a systematic search for studies measuring the daily costs of ICU stays for general populations of adults (age ≥18 years) and the added costs of mechanical ventilation. The relative increase in the daily costs was estimated using random effects meta regression. The results of the analyses were applied to a recent study calculating the excess length-of-stay associated with ICU-acquired (ventilator-associated) pneumonia, a major complication of mechanical ventilation. The search identified five eligible studies including a total of 54 766 patients and ~238 037 patient days in the ICU. Overall, mechanical ventilation was associated with a 25.8% (95% CI 4.7%-51.2%) increase in the daily costs of ICU care. A combination of these estimates with standardised unit costs results in approximate daily costs of a single ventilated ICU day of €1654 and €1580 in France and Germany, respectively. Mechanical ventilation is a major driver of ICU costs and should be taken into account when measuring the financial burden of adverse events in ICU settings.

The article discusses a study conducted in the Paediatric Intensive Care Unit (PICU) of Robert-Debre Hospital, Paris, France to assess variability in CuffPress when using pressure regulator (PR). It cites the main advantage of using PR in potentially preventing weaning failures by reducing incidence of airway mucosal necrosis and ventilator acquired pneumonia. It suggests that using PR may alleviate nursing staff workload and prevent pressure drops caused by manual monitoring of CuffPress.

A secondary analysis of a prospective multicenter cohort was performed in six intensive care units (ICU) in four European countries (France, Greece, Spain and Turkey). The main objective was to identify factors associated with ventilator-associated events (VAEs) in adults who underwent mechanical ventilation (MV) ≥ 48 h. Secondary objectives were to identify: variables influencing VAE in the subpopulation with endotracheal intubation and in those subjects who were ventilated > 7 days. Subjects who had undergone MV ≥ 48 h were included. In subjects with multiple episodes of MV, only the first one was eligible. The adult definitions for VAEs were adjusted to the 2015 update of the CDC's 2013 National Healthcare Safety Network Association. Factors associated with VAE were estimated through multivariate Cox proportional hazards analysis. Among 163 adults (42 tracheostomies), 76 VAEs (34.9 VAEs/1,000 ventilator-days) were documented: 9 were Ventilator-Associated Conditions (VAC) and 67 Infection-related Ventilator-Associated Complications (IVAC)-plus (9 only IVAC and 58 Possible Ventilator-Associated Pneumonia). VAEs developed after a median of 6 days (interquartile range: 4-9). VAEs were independently associated with long-acting sedative/analgesic drugs (Hazard Ratio [HR]: 4.30), selective digestive decontamination (SDD) (HR: 0.38), and surgical/trauma admission (HR: 2.30). Among 116 subjects with endotracheal tube, SDD (HR: 0.21) and surgical/trauma admission (HR: 3.11) remained associated with VAE. Among 102 subjects ventilated >7 days, only long-acting sedative/analgesic agents (HR: 8.69) remained independently associated with VAE. In summary, SDD implementation and long-acting analgesic/sedative agents restriction prescription may prevent early and late VAEs, respectively. Bundles developed to prevent VAEs should include these two interventions.

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.)

Introduction: Respiratory tract Candida spp. colonization is associated with more frequent bacterial ventilator-associated pneumonia (VAP). However, this colonization could be causally related to VAP or simply reflect the immune paralysis associated with multiple organ failure., Objective: To prospectively evaluate the relationship between Candida spp. colonization and bacterial VAP in mechanically ventilated patients with multiple organ failure., Inclusion: Patients receiving mechanical ventilation for > 4 days and presenting multiple organ failure were included. Tracheal colonization with Candida spp. was evaluated at inclusion (day 0, D0) and every 4 days until extubation. Quantitative proximal and tracheal cultures were performed at each VAP episode. Monocyte human leukocyte antigen-DR isotype (mHLA-DR) expression and the ratio of polymononuclear leukocytes to lymphocytes were used to evaluate immunoparalysis at D0 and D7. The relationship between fungal colonization and VAP was modelled using cause-specific models for repeated events with adjustment for time-dependent confounders and immune factors., Results: A total of 213 patients, with a median age of 64, simplified acute physiology score II (SAPS II) score 55 and sequential organ failure assessment (SOFA) score 10, mainly admitted for medical reasons (n = 197, 92%), were enrolled in 2012-2015. The median ICU stay was 24 days and the mortality rate was 32% (69 cases). Median mHLA-DR was 5916 Ab-bound/cell [3863-8934]; median lymphocyte count, 0.9Giga/L [0.6-1.3]; neutrophil-to-lymphocyte ratio, 10.9 [6.5-19.7]. Overall, 146 cases (68.5%) had tracheal colonization with Candida spp. An episode of VAP occurred (either for the first or only time) in 62 (29.1%) cases 5.5 days (median) after D0; a second episode occurred in 12 (5.6%) cases, 15.5 days (median) after D0. After adjustment, bronchial colonization with Candida was not associated with VAP [adjusted cause-specific hazard ratio = 0.98 (0.59-1.65), p = 0.95]., Conclusion: In patients with mechanical ventilation for more than 4 days and multiple organ failure, bronchial colonization with Candida spp. was not associated with VAP, even after adjustment for immune function.

Background: Ventilator-associated pneumonia (VAP) accounts for 25% of infections in intensive care units. Compared to a long duration (LD) of antibiotic therapy, a short duration (SD) has a comparable clinical efficacy with less antibiotic use and less multidrug-resistant (MDR) pathogen emergence, with the exception of documented VAP of non-fermenting Gram-negative bacilli (NF-GNB), including Pseudomonas aeruginosa (PA). These results have led the American Thoracic Society to recommend SD therapy for VAP, except for PA-VAP. Thus the beneficial effect of SD therapy in PA-VAP is still a matter of debate. We aimed to assess the non-inferiority of a short duration of antibiotics (8 days) versus prolonged antibiotic therapy (15 days) in PA-VAP.Methods/design: The impact of the duration of antibiotics on clinical events in patients with Pseudomonas aeruginosa ventilator-associated pneumonia (iDIAPASON) trial is a randomized, open-labeled non-inferiority controlled trial, conducted in 34 French intensive care units (ICUs), comparing two groups of patients with PA-VAP according to the duration (8 days or 15 days) of effective antibiotic therapy against PA. The primary outcome is a composite endpoint combining day 90 mortality and PA-VAP recurrence rate during hospitalization in the ICU. Furthermore, durations of mechanical ventilation and hospitalization, as well as number and types of extrapulmonary infections or acquisition of MDR pathogens during the hospitalization in the ICU will be recorded. Recurrence with predefined criteria (clinical suspicion of VAP associated with a positive quantitative culture of a respiratory sample) will be evaluated by two independent experts.Discussion: Demonstrating that an SD (8 days) versus LD (15 days) therapy strategy in PA-VAP treatment is safe and not associated with an increased mortality or recurrence rate could lead to a change in practices and guidelines in the management of antibiotic therapy of this frequent ICU complication. This strategy could lead to decreased antibiotic exposure during hospitalization in the ICU and in turn reduce the acquisition and the spread of MDR pathogens.Trial Registration: ClinicalTrials.gov: NCT02634411 . Registered on 19 November 2015. [ABSTRACT FROM AUTHOR]

Objective: Ventilator-associated pneumonia (VAP) is the most common hospital-acquired infection in intensive care unit (ICU). The aim of the study was to evaluate the follow-up of the guidelines for VAP prevention., Study Design: Retrospective, observational and multicenter study., Patients and Methods: During one year, all patients with mechanical ventilation over 48 hours were included in the CCLIN-Ouest Network. The demographic characteristics of the patients, the use of specific protocol for VAP prevention and the density of incidence of VAP were recorded. The use of a protocol for preventing VAP (absence, incomplete, complete and care bundle (i.e. complete prevention of VAP with weaning mechanical protocol and sedation protocol)) was collected., Results: 26 ICU with 5742 patients were included. Ten ICU (38%; 2595 patients) had no protocol for VAP prevention, eight ICU (31%; 1821 patients) had an incomplete protocol, five ICU (19%; 561 patients) had a complete protocol and three ICU (12%; 765 patients) had a care bundle. The density of incidence of VAP was 14.8‰ (Interquartile range [IQR]: 10.2-0.1) for no protocol group, 15.6‰ [IQR: 12.6-6.2] for incomplete protocol group, 11.0‰ [IQR: 9.1-14.0] for complete protocol group and 12.9‰ [5-7,7-9,9-12] for care bundle group (P=0.742)., Conclusions: The compliance to prevention of VAP was poor. Proposals for improving practice are discussed., (Copyright © 2013. Published by Elsevier SAS.)