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Background: Patients with acute brain injury are at high risk of ventilator-associated pneumonia (VAP). The benefit of short-term antibiotic prophylaxis remains debated. We aimed to establish the effect of an early, single dose of the antibiotic ceftriaxone on the incidence of early VAP in patients with severe brain injury who required mechanical ventilation., Methods: PROPHY-VAP was a multicentre, randomised, double-blind, placebo-controlled, assessor-masked, superiority trial conducted in nine intensive care units in eight French university hospitals. We randomly assigned comatose (Glasgow Coma Scale score [GCS] ≤12) adult patients (age ≥18 years) who required mechanical ventilation for at least 48 h after acute brain injury to receive intravenous ceftriaxone 2 g or placebo once within the 12 h following tracheal intubation. Participants did not receive selective oropharyngeal and digestive tract decontamination. The primary outcome was the proportion of patients developing early VAP from the 2nd to the 7th day of mechanical ventilation, confirmed by masked assessors. The analysis was reported in the modified intention-to-treat population, which comprised all randomly assigned patients except those who withdrew or did not give consent to continue and those who did not receive the allocated treatment because they met a criterion for non-eligibility. The trial is registered with ClinicalTrials.gov, NCT02265406., Findings: From Oct 14, 2015, to May 27, 2020, 345 patients were randomly assigned (1:1) to receive ceftriaxone (n=171) or placebo (n=174); 330 received the allocated intervention and 319 were included in the analysis (162 in the ceftriaxone group and 157 in the placebo group). 166 (52%) participants in the analysis were men and 153 (48%) were women. 15 patients did not receive the allocated intervention after randomisation and 11 withdrew their consent. Adjudication confirmed 93 cases of VAP, including 74 early infections. The incidence of early VAP was lower in the ceftriaxone group than in the placebo group (23 [14%] vs 51 [32%]; hazard ratio 0·60 [95% CI 0·38-0·95], p=0·030), with no microbiological impact and no adverse effects attributable to ceftriaxone., Interpretation: In patients with acute brain injury, a single ceftriaxone dose decreased the risk of early VAP. On the basis of our findings, we recommend that an early, single dose of ceftriaxone be included in all bundles for the prevention of VAP in patients with brain injury who require mechanical ventilation., Funding: French Ministry of Social Affairs and Health., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

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., Competing Interests: Declaration of interests BF reports personal fees from AM-Pharma, Aridis, Ashai-Kasai, Biomérieux, Enlivex, Ferring, Inotrem, Polyphor, and Transgene, outside the submitted work. JC reports personal fees from Combacte Magnet during the conduct of the study; personal fees from Bayer, Inotrem, Shionogi, and TiGenix (Takeda) outside the submitted work; and grants from Medimmune (AstraZeneca) outside the submitted work. PE reports personal fees from the COMBACTE-MAGNET Consortium during the conduct of the study. P-FD reports personal fees from the Associations pour la Promotion de la Réanimation Médicale, University Hospital, Tours, France during the conduct of the study. MJB reports grants from Jansen Vaccines, Merck, and Sanofi outside the submitted work; consultancy fees from Jansen Vaccines outside the submitted work; and Data and Safety Monitoring Board fees from Merck (all paid to the University Medical Center Utrecht) outside the submitted work. HSJ, OA, KS, PR, AR, VP, MTE, FD, YW, SC, and TBe report being employees of AstraZeneca. HSJ, OA, KS, PR, AR, VP, MTE, FD, YW, and SC report holding stock in AstraZeneca. HSJ, OA, KS, PR, AR, VP, MTE, FD, YW, SC report holding stock options in AstraZeneca. OA was an employee of AstraZeneca during the conduct of the study, and is now an employee of and holds stock options in Viela Bio. All other authors declare no competing interests., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Ventilator-associated pneumonia (VAP) is the most frequent health care-associated infection in severely ill patients, and aspiration of contaminated oropharyngeal content around the cuff of the tracheal tube is the main route of contamination., Research Question: Is continuous regulation of tracheal cuff pressure using a pneumatic device superior to manual assessment three times daily using a portable manometer (routine care) in preventing VAP in patients with severe trauma?, Study Design and Methods: In this open-label, randomized controlled superiority trial conducted in 13 French ICUs, adults (age ≥ 18 years) with severe trauma (Injury Severity Score > 15) and requiring invasive mechanical ventilation for ≥ 48 h were enrolled. Patients were randomly assigned (1:1) via a secure Web-based random number generator in permuted blocks of variable sizes to one of two groups according to the method of tracheal cuff pressure control. The primary outcome was the proportion of patients developing VAP within 28 days following the tracheal intubation, as determined by two assessors masked to group assignment, in the modified intention-to-treat population. This study is closed to new participants., Results: A total of 434 patients were recruited between July 31, 2015, and February 15, 2018, of whom 216 were assigned to the intervention group and 218 to the control group. Seventy-three patients (33.8%) developed at least one episode of VAP within 28 days following the tracheal intubation in the intervention group compared with 64 patients (29.4%) in the control group (adjusted subdistribution hazard ratio, 0.96; 95% CI, 0.76-1.20; P = .71). No serious adverse events related to the use of the pneumatic device were noted., Interpretation: Continuous regulation of cuff pressure of the tracheal tube using a pneumatic device was not superior to routine care in preventing VAP in patients with severe trauma., Clinical Trial Registration: ClinicalTrials.gov; No.: NCT02534974; URL: www.clinicaltrials.gov., (Copyright © 2021 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

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).

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.)

Introduction: The preventive impact of hospital-acquired infection (HAI) surveillance is difficult to assess. Our objective was to investigate the effect of HAI surveillance disruption on ventilator-associated pneumonia (VAP) incidence., Methods: A quasi-experimental study with an intervention group and a control group was conducted between 1 January 2004 and 31 December 2010 in two intensive care units (ICUs) of a university hospital that participated in a national HAI surveillance network. Surveillance was interrupted during the year 2007 in unit A (intervention group) and was continuous in unit B (control group). Period 1 (pre-test period) comprised patients hospitalized during 2004 to 2006, and period 2 (post-test period) involved patients hospitalized during 2008 to 2010. Patients hospitalized ≥ 48 hours and intubated during their stay were included. Multivariate Poisson regression was fitted to ascertain the influence of surveillance disruption., Results: A total of 2,771 patients, accounting for 19,848 intubation-days at risk, were studied; 307 had VAP. The VAP attack rate increased in unit A from 7.8% during period 1 to 17.1% during period 2 (P <0.001); in unit B, it was 7.2% and 11.2% for the two periods respectively (P = 0.17). Adjusted VAP incidence rose in unit A after surveillance disruption (incidence rate ratio = 2.17, 95% confidence interval 1.05 to 4.47, P = 0.036), independently of VAP trend; no change was observed in unit B. All-cause mortality and length of stay increased (P = 0.028 and P = 0.038, respectively) in unit A between periods 1 and 2. In unit B, no change in mortality was observed (P = 0.22), while length of stay decreased between periods 1 and 2 (P = 0.002)., Conclusions: VAP incidence, length of stay and all-cause mortality rose after HAI surveillance disruption in ICU, which suggests a specific effect of HAI surveillance on VAP prevention and reinforces the role of data feedback and counselling as a mechanism to facilitate performance improvement.

Using a multi-level logistic regression model, we determined whether there was any relationship between alcohol-based hand-rub consumption and prevalence of device-associated infections (DAIs) in French healthcare facilities (HCFs). Two national databases were used: the 2006 French prevalence survey of nosocomial infections, and the 2006 French infection control indicator database which includes alcohol-based hand-rub consumption as an indicator (ICSHA: indicateur de consommation de solution hydro-alcoolique). Only patients with at least one medical device (urinary catheter, vascular catheter or tracheal tube) who were present in an HCF for at least two days were included in the analysis. A multi-level statistical analysis was performed to assess the joint effect of patient-level and hospital-level variables. In all, 814 HCFs, each with a minimum of 15 study patients, were included, giving a total of 53,459 patients. The overall prevalence of DAI was 6.7% (95% confidence interval: 6.4-6.9). The median value of ICSHA was 37.2%. There was no association between DAI prevalence and ICSHA, but all patient-level variables were associated with DAI prevalence. Patient-level variables explain 25% of the hospital-level variation in DAI prevalence, although 60% of this variation remains unexplained when both patient and hospital variables are included in the model. To further assess any association between DAI prevalence and hand hygiene, additional studies on hand hygiene practices specifically associated with invasive medical device manipulation are required., (Copyright © 2011 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.)

Objective: To establish whether continuous subglottic suctioning (CSS) could be cost-effective., Design: Cost-benefit analysis, based on a hypothetical replacement of conventional ventilation (CV) with CSS., Setting: A surgical intensive care unit (SICU) of a tertiary care university hospital in France., Patients: All consecutive patients receiving ventilation in the SICU in 2006., Methods: Efficacy data for CSS were obtained from the literature and applied to the SICU of our hospital. Costs for CV and CSS were provided by the hospital pharmacy; costs for ventilator-associated pneumonia (VAP) were obtained from the literature. The cost per averted VAP episode was calculated, and a sensitivity analysis was performed on VAP incidence and on the number of tubes required for each patient., Results: At our SICU in 2006, 416 patients received mechanical ventilation for 3,487 ventilation-days, and 32 VAP episodes were observed (7.9 episodes per 100 ventilated patients; incidence density, 9.2 episodes per 10,000 ventilation-days). Based on the hypothesis of a 29% reduction in the risk of VAP with CSS than CV, 9 VAP episodes could have been averted. The additional cost of CSS for 2006 was estimated to be €10,585.34. The cost per averted VAP episode was €1,176.15. Assuming a VAP cost of €4,387, a total of 3 averted VAP episodes would neutralize the additional cost. For a low VAP incidence of 6.6%, the cost per averted VAP would be €1,323. If each patient required 2 tubes during ventilation, the cost would be €1,383.69 per averted VAP episode., Conclusion: Replacement of CV with CSS was cost-effective even when assuming the most pessimistic scenario of VAP incidence and costs.

Background: Ventilator-associated pneumonia (VAP), the most common hospital-acquired infection in intensive care units, increases mortality and health care costs. We describe the long-term impact of a multifaceted program for decreasing VAP rates that markedly improved compliance with 8 targeted preventive measures., Methods: We compared VAP rates during a 45-month baseline period and a 30-month intervention period in a cohort of patients who received mechanical ventilation for > 48 h. VAP was diagnosed on the basis of quantitative cultures of distal specimens. VAP incidence density rates were expressed as total VAP episodes over total mechanical ventilation duration and as first VAP episodes over mechanical ventilation duration at VAP or hospital discharge. We used segmented regression analysis and a Cox proportional hazard model to assess the impact of the program on first VAP occurrence., Results: Baseline and intervention VAP rates were 22.6 and 13.1 total VAP episodes over total mechanical ventilation duration per 1000 ventilation-days, respectively, and 26.1 and 14.9 first VAP episodes over mechanical ventilation duration at VAP or hospital discharge per 1000 procedure-days, respectively (P < .001). VAP rates decreased by 43% in both statistical analyses and remained significant after adjustment for confounders (Cox adjusted hazard ratio, 0.58; 95% confidence interval, 0.46-0.72; P < .001). Daily VAP hazard rates on ventilation days 5, 10, and 15 were 2.6%, 3.5%, and 3.4%, respectively, during the baseline period and 1.4%, 2.3%, and 2%, respectively, during the intervention period., Conclusion: Our preventive program produced sustained VAP rate decreases in the long term. However, VAP rates remained substantial despite high compliance with preventive measures, suggesting that eliminating VAP in the intensive care unit may be an unrealistic goal.

Purpose: Probiotics have been shown to be able to restore a non-pathogenic digestive flora, to prevent digestive colonization by pathogenic bacteria, and to modulate immunity. The aim of this study was to assess the effects of prophylactic probiotic administration in patients ventilated for up to 2 days., Methods: This study was performed as a double-blind, concealed randomized, placebo-controlled trial in a French medical intensive care unit (ICU). Adult patients mechanically ventilated for a period of more than 48 h received enterally administered probiotics (Ergyphilus, 2 x 10(10) lactic acid bacteria, mostly Lactobacillus rhamnosus GG, once a day) or placebo until successful weaning., Results: A total of 167 patients were included. The two groups were comparable at baseline. The 28-day mortality rates were not different in the probiotic (25.3%) and placebo groups (23.7%). Mortality rates in ICU and at 90 days were also unaffected by the treatment. The incidence of ICU-acquired infections did not differ significantly except for that of catheter-related bloodstream infections that was lowered by probiotics. On a prespecified subgroup analysis, we found a reduction of the 28-day mortality among severe sepsis patients (total n = 101) treated with probiotics (n = 52) with an odds ratio (OR) for death at 0.38 (95% CI 0.16-0.93, p = 0.035). By contrast, probiotics were associated with a higher mortality rate in non-severe sepsis patients (OR 3.09, 95% CI 0.87-11.01, p = 0.08)., Conclusions: Although numerous uncertainties remain (type and the number of strains to use, delay and length of administration), and despite an acceptable safety profile, the daily prophylactic administration of probiotics cannot be encouraged in the critically ill patient.

Purpose: Prevention of ventilator-associated pneumonia (VAP) requires a complex approach that should include factors affecting healthcare workers' (HCWs) behavior. This study attempted to assess change of individual factors throughout a multifaceted program focusing on VAP prevention., Methods: The prevention program involved all HCWs in a 20-bed medical intensive care unit (ICU) and included a multidisciplinary task force, an educational session, direct observations and performance feedback, technical improvements, and reminders. Knowledge, beliefs, and perceptions (cognitive factors) were assessed with a test and a self-reporting questionnaire based on social-cognitive theories. They were completed before and 1 and 12 months after the educational session., Results: Of the 100 HCWs initially evaluated, 84 were present 1 year later. Overall, individual factors (knowledge and cognitive factors) changed positively and significantly, immediately after the educational session. Five cognitive factors were significantly associated with knowledge: perceived susceptibility, seriousness, knowledge, benefits, and self-efficacy (P < 0.05). The other factors, i.e., perceived barriers, subjective and behavioral norm, intention to perform action, and motivation, were not. The positive cognitive change was significantly reinforced at 1 year. Three distinct cognitive profiles derived from answers to the baseline questionnaire were individualized. The positive impact of our behavioral approach was highest for the HCW group with the lowest baseline cognitive profiles., Conclusions: Behavior changed gradually throughout the program and was especially pronounced for HCWs with the lowest baseline cognitive profiles.

Background: Early-onset ventilator associated pneumonia (EOVAP) are frequent in head-trauma patients, but specific risk factors are poorly studied in this population., Methods: We conducted a retrospective cohort study in a surgical intensive care unit. Consecutive severe head-trauma patients admitted from January 2000 to December 2002 were studied. Microorganisms, and risks factors for EOVAP were analyzed., Results: During the 3-year period, 161 patients were studied; 21.1% of them developed an EOVAP. On univariate analysis 6 variables were associated with EOVAP: early enteral feeding, barbiturate use, immunosuppression, mean Simplified Acute Physiology Score 2, acute respiratory distress syndrome, and initial neurosurgery procedures. On multivariate analysis, enteral feeding >2000 Kcal before day 5 [odds ratio (OR): 0.33, 95% confidence interval (CI): 0.21-0.85] and initial neurosurgical procedure (OR: 0.36, 95% CI: 0.15-0.89) remained protective factors for EOVAP, whereas immunosuppression (OR: 7.15, 95% CI: 1.66-30.73) and barbiturate use (OR: 2.68, 95% CI: 1.06-6.80) remained risk factors for EOVAP. EOVAP was also significantly associated with a longer duration of mechanical ventilation (14.0 vs. 11.0 d, P=0.024), and a longer sedation duration (8.3 vs. 5.8 d P=0.005). Methicillin-susceptible Staphylococcus aureus was the most common pathogen involved in EOVAP (46%)., Conclusions: We demonstrate for the first time that early enteral feeding is a protective factor for EOVAP, and this result could have clinical implications for the prevention of EOVAP after traumatic brain injury. This study also confirms that barbiturate use is an important risk factor of EOVAP whereas Methicillin-susceptible S. aureus was found to be the main pathogen involved in EOVAP.