Background: Reducing critically ill patients’ exposure to antibiotics is mandatory. In randomized controlled trials, procalcitonin (PCT)-guided algorithms (i.e., antibiotic therapy [ABT] should be stopped whenever PCT is less than 0.5 µg/L or is below 80% of the peak value) reduced the duration of (ABT) more than compliance with the current guidelines. However, the interest of such stopping rules in daily practice remains debated. Thus, we carried out a real-life study addressing this issue. Results: During the study period, 112 patients with sepsis upon intensive care unit admittance were included. The median age was 66 years (56–79). Half of the patients presented with acute respiratory failure. Pneumonia was diagnosed in 78% of them, and 41% met septic shock criteria. The initial ABT was empirical in most cases, and appropriateness rate to the isolated bacteria reached 71%. A median number of four PCT measurements was achieved in both groups. The compliance rate with the PCT algorithm was 54%. The median duration of ABT was 5 (4–7) days if the PCT algorithm was followed, as compared to 7 (5–10) days otherwise (p < 0.001). This ABT stopping rule allowed a 2-day reduction in the treatment duration as compared with those recommended by the guidelines (p < 0.001). The only independent factor associated with shorter treatment duration was compliance with the PCT algorithm (OR = 0.74, 95% CI [0.62; 0.88]; p < 0.001). Regarding safety, no difference in outcome was found between the two groups. Conclusions: Complying with one PCT-based stopping rule is associated with a significant reduction in the duration of ABT in septic critically ill patients, without apparent impact on patient outcomes.

Biofilm (BF) growth is believed to play a major role in the development of ventilator-associated pneumonia (VAP) in the intensive care unit. Despite concerted efforts to understand the potential implication of endotracheal tube (ETT)-BF dispersal, clinically relevant data are lacking to better characterize the impact of its mesostructure and microbiological singularity on the occurrence of VAP. We conducted a multicenter, retrospective observational study during the third wave of the COVID-19 pandemic, between March and May 2021. In total, 64 ETTs collected from 61 patients were included in the present BIOPAVIR study. Confocal microscopy acquisitions revealed two main morphological aspects of ETT-deposited BF: (1) a thin, continuous ribbon-shaped aspect, less likely monobacterial and predominantly associated with Enterobacter spp., Streptococcus pneumoniae or Viridans streptococci, and (2) a thicker, discontinuous, mushroom-shaped appearance, more likely characterized by the association of bacterial and fungal species in respiratory samples. The microbiological characterization of ETT-deposited BF found higher acquired resistance in more than 80% of analyzed BF phenotypes, compared to other colonization sites from the patient’s environment. These findings reveal BF as a singular microbiological compartment, and are of added clinical value, with a view to future ETT-deposited BF-based antimicrobial stewardship in critically ill patients. Trial registration NCT04926493. Retrospectively registered 15 June 2021.

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Med 2017;5:946–955. 6. Molyneaux PL, Cox MJ, Willis-Owen SA, Mallia P, Russell KE, Russell AM, et al. The role of bacteria in the pathogenesis and progression of idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 2014;190: 906–913. 7. Troy LK, Grainge C, Corte TJ, Williamson JP, Vallely MP, Cooper WA, et al.; Cryobiopsy versus Open Lung biopsy in the Diagnosis of Interstitial lung disease alliance (COLDICE) Investigators. Diagnostic accuracy of transbronchial lung cryobiopsy for interstitial lung disease diagnosis (COLDICE): a prospective, comparative study. Lancet Respir Med 2020;8:171–181. 8. Raghu G, Flaherty KR, Lederer DJ, Lynch DA, Colby TV, Myers JL, et al. Use of a molecular classifier to identify usual interstitial pneumonia in conventional transbronchial lung biopsy samples: a prospective validation study. Lancet Respir Med 2019;7:487–496. 9. Lukey PT, Harrison SA, Yang S, Man Y, Holman BF, Rashidnasab A, et al. A randomised, placebo-controlled study of omipalisib (PI3K/mTOR) in idiopathic pulmonary fibrosis. Eur Respir J 2019;53: 1801992. 10. Allden SJ, Ogger PP, Ghai P, McErlean P, Hewitt R, Toshner R, et al. The transferrin receptor CD71 delineates functionally distinct airway macrophage subsets during idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 2019;200:209–219. 11. Molyneaux PL, Willis-Owen SAG, Cox MJ, James P, Cowman S, Loebinger M, et al. Host-microbial interactions in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 2017;195: 1640–1650.

An amendment to this paper has been published and can be accessed via the original article.

Fluid overload in septic intensive care unit (ICU) patients is common and strongly associated with poor outcome. There is currently no treatment for capillary leak, which is mainly responsible for high positive fluid balance (FB) in sepsis. We hypothesized that increasing interstitial pressure with extensive corporeal compression would reduce FB. The objective of this study was to evaluate the feasibility, efficacy, and safety of a compression treatment during sepsis. This pilot, two-center, single-arm trial enrolled critically ill, non-surgical, septic patients receiving mechanical ventilation. The therapeutic intervention was the early application of compression bandages on more than 80% of the body surface. The primary outcome was negative net FB on day 7. The primary endpoint was reached in 29 of 45 patients (64%) with available data, for a planned objective of 26. By day 4, cumulative FB was 7280 ml [3300–9700]. SOFA- and aged-matched patients from a historical cohort had a significantly higher FB at 1, 2 and 7 days. Tolerance was good, although low-stage pressure ulcers were observed in 16 patients (26%). No effect on intra-abdominal pressure or respiratory plateau pressure was observed. In conclusion, corporeal compression demonstrated potential efficacy in limiting FB during septic shock, with acceptable feasibility and tolerance.

PurposeVentilator-associated pneumonia (VAP) increases exposure to antibiotics. Physicians are however reluctant to shorten treatment, arguing this could lead to failures and worse outcome. Monitoring procalcitonin (PCT) has proven effective for decreasing exposure to antibiotics in randomized controlled trials, but additional “real-life” studies are needed.Materials and methodsAll patients with VAP in whom ABT was stopped before death or discharge were included in this 5-year prospective cohort study. Patients in whom ABT was stopped in accordance with the algorithm (“PCT-guided” group: ABT withdrawal strongly encouraged if PCT < 0.5 ng/mL or < 80% peak value) were compared to those with ABT continuation despite PCT decrease (“not PCT-guided” group). The primary endpoint was ABT duration. The secondary endpoint was unfavorable VAP outcome (i.e. death or relapse).ResultsWe included 157 of the 316 patients with microbiologically-proven VAP. The algorithm was overruled in 81 patients (51.6%). ABT duration was significantly longer in these patients than in the PCT-guided group (9.5 vs. 8.0 days; p = .02), although baseline and VAP characteristics did not differ. The rate of unfavorable outcomes was comparable (46.9% vs. 51.3%; p = .69).ConclusionsPCT-guided ABT adherence appears safe for patients with VAP and is likely to reduce exposure to antibiotics.

We describe regional differences in therapy for bloodstream infection (BSI) caused by extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL-E) or carbapenemase-producing Enterobacteriaceae (CPE). Patients (n = 1482) in 12 countries from an observational study of BSI caused by ESBL-E or CPE were included. Multivariate logistic regression was used to calculate adjusted odds ratios (aORs) for the influence of country of recruitment on empirical use of β-lactam/β-lactamase inhibitors (BLBLIs) or carbapenems, targeted use of BLBLIs for ESBL-E and use of targeted combination therapy for CPE. Compared with Spain, BLBLI use for empirical therapy was least likely in sites from Israel (aOR 0.34, 95% CI 0.14–0.81), Greece (aOR 0.49, 95% CI 0.26–0.94) and Canada (aOR 0.31, 95% CI 0.11–0.88) but more likely in Italy (aOR 1.58, 95% CI 1.11–2.25) and Turkey (aOR 2.09, 95% CI 1.14–3.81). Empirical carbapenem use was more likely in sites from Taiwan (aOR 1.73, 95% CI 1.03–2.92) and USA (aOR 1.89, 95% CI 1.05–3.39) and less likely in Italy (aOR 0.44, 95% CI 0.28–0.69) and Canada (aOR 0.10, 95% CI 0.01–0.74). Targeted BLBLIs for ESBL-E was more likely in Italian sites. Treatment at sites within Israel, Taiwan, Turkey and Brazil was associated with less combination therapy for CPE. Although this study does not provide precise data on the relative prevalence of ESBL-E or CPE, significant variation in therapy exists across countries even after adjustment for patient factors. Better understanding of what influences therapeutic choices for these infections will aid antimicrobial stewardship efforts.

Background: Our objective was to assess, through a qualitative, exploratory study, the thought processes of patients regarding the formulation of advance directives (AD) after a stay in the ICU. Methods: The study was conducted from May to July 2016 using telephone interviews performed by four senior ICU physicians. Inclusion criteria were: patients discharged from ICU to home > 3 months earlier. Semi-directive interviews with patients focused on 5 main points surrounding AD. Results: In total, among 159 eligible patients, data from 94 (59%) were available for analysis. Among all those interviewed, 83.5% had never heard of "advance directives''. Only 2% had executed AD before ICU admission, and 7% expressed a desire to prepare AD further to their ICU stay. Among the barriers to preparation of AD, lack of information was the main reason cited for not executing AD. Patients noted the following in their AD: withdrawal of life-support in case of vegetative/minimally conscious state or when there is no longer any hope, in case of uncontrollable pain, and if impossible to wean from mechanical ventilation. Conclusion: The ideal time to engage patients in these discussions is most likely well before an acute health event occurs, although this warrants further investigation both before and after ICU admissions. (C) 2017 Societe francaise d'anesthesie et de reanimation (Sfar). Published by Elsevier Masson SAS. All rights reserved.

Background: Among septic patients admitted to the intensive care unit (ICU), early recognition of those with the highest risk of death is of paramount importance. We evaluated the prognostic value of Procalcitonin (PCT), mid regional-proadrenomedullin (MR-proADM), copeptine and CT-proendothelin 1 (CT-ProET 1) concentrations. Methods: This was a prospective cohort study, which included 173 septic patient admitted to one ICU. Blood samples for biomarker measurements were obtained upon admission and on day 5. The predictive value of each biomarker regarding the risk of death at day 28 was assessed. The fluid balance was evaluated from admission to day 5. Results: All cause ICU mortality was 36.4%. All the biomarkers except CT-ProET-1 were significantly more elevated in the non-survivors than in the survivors upon day 1. This was especially true for MR-proADM (8.6 [5.9] vs. 4.4 [3.9] nmol/L; P < 0.0001) and for the CT-proET-1/MR-proADM ratio (52.9 [22.4] vs. 31.3 [26.6] arbitrary units; P < 0.0001). The best AUROCC values on day 1 were obtained with MR-ProADM and the CT-proET-1/MR-proADM ratio as well (0.75 [0.67–0.85] and 0.82 [0.75–0.89]; 95% CI, respectively). An improved accuracy was achieved on day 5. Moreover, MR-ProADM baseline levels and fluid balance over the 5-day period following ICU admission were strongly correlated (Rho = 0.41; P < 0.001). Conclusions: In patients admitted to the ICU with sepsis, MR-ProADM on admission was the best predictor of short-term clinical outcome if compared with others. This could be related to its ability to predict fluid sequestration.

Objectives:Ventilator-associated pneumonia is frequent in ICUs. Extended-spectrum &bgr;-lactamase–producing Enterobacteriaceae are difficult-to-treat pathogens likely to cause ventilator-associated pneumonia. We sought to assess the interest of screening for extended-spectrum &bgr;-lactamase–producing Enterobacteriaceae rectal carriage as a way to predict their involvement in ventilator-associated pneumonia. Design:A retrospective cohort study of patients with suspected ventilator-associated pneumonia in a medical ICU was conducted. Patients:Every patient admitted between January 2006 and August 2013 was eligible if subjected to mechanical ventilation for more than 48 hours. Each patient with suspected ventilator-associated pneumonia was included in the cohort. Active surveillance culture for extended-spectrum &bgr;-lactamase–producing Enterobacteriaceae detection was routinely performed in all patients at admission and then weekly throughout the study period. Extended-spectrum &bgr;-lactamase colonization was defined by the isolation of at least one extended-spectrum &bgr;-lactamase–producing Enterobacteriaceae from rectal swab culture. Interventions:None. Measurements and Main Results:Among 587 patients with suspected ventilator-associated pneumonia, 40 (6.8%) were colonized with extended-spectrum &bgr;-lactamase–producing Enterobacteriaceae prior to the development of pneumonia. Over the study period, 20 patients (3.4%) had ventilator-associated pneumonia caused by extended-spectrum &bgr;-lactamase–producing Enterobacteriaceae; of whom, 17 were previously detected as being colonized with extended-spectrum &bgr;-lactamase–producing Enterobacteriaceae. Sensitivity and specificity of prior extended-spectrum &bgr;-lactamase–producing Enterobacteriaceae colonization as a predictor of extended-spectrum &bgr;-lactamase–producing Enterobacteriaceae involvement in ventilator-associated pneumonia were 85.0% and 95.7%, respectively. The positive and negative predictive values were 41.5% and 99.4%, respectively. The positive likelihood ratio was 19.8. Conclusions:Screening for extended-spectrum &bgr;-lactamase–producing Enterobacteriaceae digestive colonization by weekly active surveillance cultures could reliably exclude the risk of the involvement of such pathogens in patients with ventilator-associated pneumonia in low-prevalence area.

Introduction: Ventilator-associated pneumonia (VAP) is the most commonly acquired infection in intensive care units (ICU). Its outcome is related, at least in part, to the host's response. Statins have anti-inflammatory effects and may thus improve the outcome. We aimed to assess the impact of prior statin use in the setting of VAP.Methods: A six-year cohort study was conducted in a French ICU at a teaching hospital. All of the patients with suspected VAP were included. Baseline characteristics, outcomes, statin exposure, and the description of suspected episodes were collected prospectively. The primary endpoint was 30-day mortality. Patients who were taking statins before admission to the ICU whether or not treatment was continued thereafter ('previous users' group) were compared to those without prior statin therapy ('statin-naive' group). A survival analysis using a Cox model was conducted in the whole cohort and in the subgroup of prior statin users.Results: Among the 349 patients included, 93 (26.6%) had taken statins. At baseline, these patients were at higher risk of complications than statin-naive ones (for example, older, more likely to be men and to have underlying diseases, greater simplified acute physiology score II (SAPS II)). There was, however, no difference regarding severity at the time VAP was suspected (sequential organ failure assessment (SOFA): 9.0 (4.0 to 16.0) versus 8.0 (4.0 to 17.0); P = 0.11). Nonetheless, 30-day mortality in statin users was not different from that in statin-naive patients (35.5% versus 26.2%, respectively; adjusted hazard ratio (HR) = 1.23 (0.79 to 1.90) 95% confidence interval (CI); P = 0.36). In contrast, after limiting analysis to prior statin users and adjusting for potential confounders, those who continued the treatment had better survival than those who did not (HR = 0.47; (0.22 to 0.97) 95% CI; P = 0.04).Conclusions: Statin continuation in prior users could provide protective effects in patients with suspected VAP.

BACKGROUND:Invasive candidiasis (IC) is a life-threatening ICU-acquired infection. A strong correlation between time to antifungal therapy (AFT) administration and outcome has been established. Empirical therapy benefit should be balanced with the risk of echinocandin overuse. We assessed therefore a decision rule that aimed at guiding empirical therapy.METHODS:A 45-month prospective cohort study in a teaching medical ICU. All of the patients with suspected IC (uncontrolled sepsis despite broad spectrum antibiotics without any bacterial proven infection in patients with Candida score ≥ 3 points including multifocal Candida sp. colonization) were eligible. The primary endpoint was proven IC diagnosis (i.e., candidemia) following treatment onset. Timing of AFT administration was also investigated in those latter patients. Antifungal therapy step-down and discontinuation was done according to international guidelines in patients with candidemia. Otherwise, echinocandin discontinuation was encouraged in patients without proven IC, excepting when a clinical improvement was achieved without any other explanation that antifungals initiation (i.e., probable IC). In addition, a survival multivariate analysis using a Cox model was conducted.RESULTS:Fifty-one patients were given an echinocandin with respect to our decision rule. Among them, candidemia was diagnosed thereafter in 9 patients. Over the same period, antifungal therapy was triggered by candidemia announcement (i.e., definite therapy) in 12 patients who did not fulfill criteria for empirical therapy before. Time elapsed from candidemia onset to echinocandin therapy initiation was shortened (0.4 [0.5] vs. 2.4 [2.8] hours; p = 0.04) when it was given empirically. In addition, 18 patients clinically improved under empirical antifungal therapy without any obvious other explanation, despite IC remained unproven. Moreover, echinocandin exposure duration was independently related to survival in those patients. Over the same period, our predefined criteria for empirical therapy were overruled in 55 cases. None of them develop IC thereafter. Finally, Our decision rule allowed IC early recognition of proven/probable IC with sensitivity, specificity, positive and negative predictive value of 69.2%, 82.1%, 69.2% and 82.1%, respectively.CONCLUSION:Implementation of pragmatic guidelines for empirical AFT based on CS and fungal colonization assessment could be useful in selecting patients who really benefit from an echinocandin.

PURPOSE:We investigated incidence, risk factors for new-onset atrial fibrillation (NAF), and prognostic impact during septic shock in medical Intensive Care Unit (ICU) patients. METHODS:Prospective, observational study in a university hospital. Consecutive patients from 03/2011 to 05/2013 with septic shock were eligible. Exclusion criteria were age <18 years, history of AF, transfer with prior septic shock. Included patients were equipped with long-duration (7 days) Holter ECG monitoring. NAF was defined as an AF episode lasting >30 seconds. Patient characteristics, infection criteria, cardiovascular parameters, severity of illness, support therapies were recorded. RESULTS:Among 66 patients, 29(44%) developed NAF; 10 (34%) would not have been diagnosed without Holter ECG monitoring. NAF patients were older, with more markers of heart failure (troponin and NT-pro-BNP), lower left ventricular ejection fraction (LVEF), longer QRS duration and more nonsustained supra ventricular arrhythmias (<30s) on day 1 than patients who maintained sinus rhythm. By multivariate analysis, age (OR: 1.06; p = 0.01) and LVEF<45% (OR: 13.01, p = 0.03) were associated with NAF. NAF did not predict 28 or 90 day mortality. CONCLUSIONS:NAF is common, especially in older patients, and is associated with low ejection fraction. We did not find NAF to be independently associated with higher mortality.

Candida spp. airway colonization could promote development of ventilator-associated pneumonia (VAP) caused by Pseudomonas aeruginosa, a potentially multidrug-resistant (MDR) bacteria, and worsen the outcome of VAP regardless of pathogen. We therefore address the question of the risk of MDR bacteria isolation within the airway of patients with suspected VAP, whether Candida spp. is present or not.Prospective observational study in a teaching hospital.Consecutive patients with suspected VAP were included. Respiratory tract secretions were seeded on specific medium for yeast isolation in addition to standard culture. Outcome as well as presence of MDR bacteria were assessed according to fungal colonization.323 suspected VAP were analysed. Among these, 181 (56 %) cases presented with Candida spp. airway colonization. Colonized and noncolonized patients were similar regarding baseline characteristics, prior exposure to antibiotics and VAP severity. However, mortality rate was greater in patients with fungal airway colonization than in those without (44.2 versus 31.0 %, respectively; p = 0.02). In addition, MDR bacteria isolation was 31.5 % in patients with Candida spp. colonization versus 23.2 % in those without (p = 0.13). Moreover, Candida spp. airway colonization was one independent risk factor for MDR bacteria isolation [odds ratio (OR) = 1.79, 95 % confidence interval 1.05-3.05; p = 0.03], in addition to the time elapsed between intensive care unit (ICU) admission and VAP suspicion.In patients with suspected VAP, Candida spp. airway colonization is frequent and associated with increased risk for MDR bacteria isolation. This could worsen outcome and should therefore be considered when choosing an empiric antibiotic therapy.