Association between selective digestive decontamination and decreased rate of acquired candidemia in mechanically ventilated ICU patients: a multicenter nationwide study.

BACKGROUND: Candidemia is a high-risk complication among intensive care unit (ICU) patients. While selective digestive decontamination (SDD) has been shown to be effective in preventing ICU-acquired bacterial secondary infection, its effects on ICU-acquired candidemia (ICAC) remain poorly explored. Therefore, we sought to assess the effects of SDD on ICAC. METHOD: Using the REA-REZO network, we included adult patients receiving mechanical ventilation for at least 48 h from January 2017 to January 2023. Non-parsimonious propensity score matching with a 1:1 ratio was performed to investigate the association between SDD and the rate of ICAC. RESULTS: A total of 94 437 patients receiving at least 48 h of mechanical ventilation were included throughout the study period. Of those, 3 001 were treated with SDD and 651 patients developed ICAC. The propensity score matching included 2 931 patients in the SDD group and in the standard care group. In the matched cohort analysis as well as in the overall population, the rate of ICAC was lower in patients receiving SDD (0.8% versus 0.3%; p = 0.012 and 0.7% versus 0.3%; p = 0.006, respectively). Patients with ICAC had higher mortality rate (48.4% versus 29.8%; p < 0.001). Finally, mortality rates as well as ICU length of stay in the matched populations did not differ according to SDD (31.0% versus 31.1%; p = 0.910 and 9 days [5-18] versus 9 days [5-17]; p = 0.513, respectively). CONCLUSION: In this study with a low prevalence of ICAC, SDD was associated with a lower rate of ICAC that did not translate to higher survival.

Effect of SARS-CoV-2 infection and pandemic period on healthcare-associated infections acquired in intensive care units.

OBJECTIVES: 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. METHODS: 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. RESULTS: 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. DISCUSSION: 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.

Attributable Mortality of Ventilator-associated Pneumonia Among Patients with COVID-19.

Rationale: Patients with a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are at higher risk of ventilator-associated pneumonia (VAP) and may have an increased attributable mortality (increased or decreased risk of death if VAP occurs in a patient) and attributable fraction (proportion of deaths that are attributable to an exposure) of VAP-related mortality compared with subjects without coronavirus disease (COVID-19). Objectives: Estimation of the attributable mortality of the VAP among patients with COVID-19. Methods: Using the REA-REZO surveillance network, three groups of adult medical ICU patients were computed: control group (patients admitted between 2016 and 2019; prepandemic patients), pandemic COVID-19 group (PandeCOV+), and pandemic non-COVID-19 group (PandeCOV-) admitted during 2020. The primary outcome was the estimation of attributable mortality and attributable fraction related to VAP in these patients. Using multistate modeling with causal inference, the outcomes related to VAP were also evaluated. Measurements and Main Results: A total of 64,816 patients were included in the control group, 7,442 in the PandeCOV- group, and 1,687 in the PandeCOV+ group. The incidence of VAP was 14.2 (95% confidence interval [CI], 13.9 to 14.6), 18.3 (95% CI, 17.3 to 19.4), and 31.9 (95% CI, 29.8 to 34.2) per 1,000 ventilation-days in each group, respectively. Attributable mortality at 90 days was 3.15% (95%, CI, 2.04% to 3.43%), 2.91% (95% CI, -0.21% to 5.02%), and 8.13% (95% CI, 3.54% to 12.24%), and attributable fraction of mortality at 90 days was 1.22% (95% CI, 0.83 to 1.63), 1.42% (95% CI, -0.11% to 2.61%), and 9.17% (95% CI, 3.54% to 12.24%) for the control, PandeCOV-, and PandeCOV+ groups, respectively. Except for the higher risk of developing VAP, the PandeCOV- group shared similar VAP characteristics with the control group. PandeCOV+ patients were at lower risk of death without VAP (hazard ratio, 0.62; 95% CI, 0.52 to 0.74) than the control group. Conclusions: VAP-attributable mortality was higher for patients with COVID-19, with more than 9% of the overall mortality related to VAP.

Increased Incidence of Ventilator-Acquired Pneumonia in Coronavirus Disease 2019 Patients: A Multicentric Cohort Study.

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.

Association between mortality and highly antimicrobial-resistant bacteria in intensive care unit-acquired pneumonia.

Data on the relationship between antimicrobial resistance and mortality remain scarce, and this relationship needs to be investigated in intensive care units (ICUs). The aim of this study was to compare the ICU mortality rates between patients with ICU-acquired pneumonia due to highly antimicrobial-resistant (HAMR) bacteria and those with ICU-acquired pneumonia due to non-HAMR bacteria. We conducted a multicenter, retrospective cohort study using the French National Surveillance Network for Healthcare Associated Infection in ICUs ("REA-Raisin") database, gathering data from 200 ICUs from January 2007 to December 2016. We assessed all adult patients who were hospitalized for at least 48 h and presented with ICU-acquired pneumonia caused by S. aureus, Enterobacteriaceae, P. aeruginosa, or A. baumannii. The association between pneumonia caused by HAMR bacteria and ICU mortality was analyzed using the whole sample and using a 1:2 matched sample. Among the 18,497 patients with at least one documented case of ICU-acquired pneumonia caused by S. aureus, Enterobacteriaceae, P. aeruginosa, or A. baumannii, 3081 (16.4%) had HAMR bacteria. The HAMR group was associated with increased ICU mortality (40.3% vs. 30%, odds ratio (OR) 95%, CI 1.57 [1.45-1.70], P < 0.001). This association was confirmed in the matched sample (3006 HAMR and 5640 non-HAMR, OR 95%, CI 1.39 [1.27-1.52], P < 0.001) and after adjusting for confounding factors (OR ranged from 1.34 to 1.39, all P < 0.001). Our findings suggest that ICU-acquired pneumonia due to HAMR bacteria is associated with an increased ICU mortality rate, ICU length of stay, and mechanical ventilation duration.

The population-attributable fraction for time-dependent exposures and competing risks-A discussion on estimands.

The population-attributable fraction (PAF) quantifies the public health impact of a harmful exposure. Despite being a measure of significant importance, an estimand accommodating complicated time-to-event data is not clearly defined. We discuss current estimands of the PAF used to quantify the public health impact of an internal time-dependent exposure for data subject to competing outcomes. To overcome some limitations, we proposed a novel estimand that is based on dynamic prediction by landmarking. In a profound simulation study, we discuss interpretation and performance of the various estimands and their estimators. The methods are applied to a large French database to estimate the health impact of ventilator-associated pneumonia for patients in intensive care.

Trends of Incidence and Risk Factors of Ventilator-Associated Pneumonia in Elderly Patients Admitted to French ICUs Between 2007 and 2014.

OBJECTIVES: To assess trends and risk factors of ventilator-associated pneumonia according to age, particularly in the elderly admitted to French ICUs between 2007 and 2014. DESIGN: Multicenter, prospective French national Healthcare-Associated Infection surveillance network of ICUs ("Réseau REA-Raisin"). SETTINGS: Two-hundred fifty six ICUs in 246 settings in France. PATIENTS: Included were all adult patients hospitalized greater than or equal to 48 hours in ICUs participating in the network. INTERVENTIONS: Ventilator-associated pneumonia surveillance over time. MEASUREMENTS AND MAIN RESULTS: Overall and multidrug-resistant organism-related ventilator-associated pneumonia incidence rates were expressed per 1,000 intubation days at risk. Age was stratified into three groups: young (18-64 yr old), old (65-74 yr old), and very old (75+ yr old). Age-stratified multivariate mixed-effects Poisson regressions were undertaken to assess trends of ventilator-associated pneumonia incidence over time, with center as the random effect. Ventilator-associated pneumonia risk factors were also evaluated. Of 206,223 patients, 134,510 were intubated: 47.8% were young, 22.3% were old, and 29.9% were very old. Ventilator-associated pneumonia incidence was lower in the very old group compared with the young group (14.51; 95% CI, 16.95-17.70 vs 17.32; 95% CI, 16.95-17.70, respectively, p < 0.001). Methicillin-resistant Staphylococcus aureus and third-generation cephalosporin-resistant Enterobacteriaceae were identified more frequently in very old patients (p < 0.001 and 0.014, respectively). Age-stratified models disclosed that adjusted ventilator-associated pneumonia incidence decreased selectively in the young and old groups over time (adjusted incidence rate ratios, 0.88; 95% CI, 0.82-0.94; p < 0.001 and adjusted incidence rate ratios, 0.95; 95% CI, 0.86-1.04; p = 0.28, respectively). Male gender and trauma were independently associated with ventilator-associated pneumonia in the three age groups, whereas antibiotics at admission was a protective factor. Scheduled surgical ICU and immunodeficiency were risk factors of ventilator-associated pneumonia in the old group (p = 0.003). CONCLUSIONS: Ventilator-associated pneumonia incidence is lower but did not decrease over time in very old patients compared with young patients.

ICU-acquired candidaemia in France: Epidemiology and temporal trends, 2004-2013 - A study from the REA-RAISIN network.

OBJECTIVE: Candidaemia is a life-threatening infectious disease, associated with septic shock, multiple organ failure, and a high mortality rate. In France, reported data on the incidence of ICU-acquired candidaemia and the causative Candida species are scarce. The objective of this study was to determine temporal trends in epidemiology and risk factors of intensive care unit-acquired candidaemia (ICU-Cand) and ICU mortality among a very large population of ICU patients. METHOD: Demographics, patient risk factors, invasive device exposure and nosocomial infection in ICU patient were collected from 2004 to 2013 in a national network of 213 ICUs: REA-RAISIN. Incidence and risk factors for candidaemia and ICU mortality were assessed. RESULTS: Out of 246,459 ICU patients, 851 developed an ICU-cand, representing 0.3 per 1000 patients-days. The incidence rose sharply over time. Candida albicans was the main species. The overall and ICU mortality was 52.4% in ICU-cand patients. The main risk factors of ICU-cand were length of stay, severity of illness and antimicrobial therapy at ICU admission, immune status and use of invasive procedure. ICU-cand was an independent risk factor of mortality (OR: 1.53; 95%CI [1.40-1.70]); in a sub-group analysis, independent effects on mortality were observed with C. albicans (OR: 1.45 [1.23-1.71]), Candida tropicalis (OR: 2.11 [1.31-3.39]) and "other" Candida species (OR: 1.64 [1.09-2.45]). CONCLUSION: ICU candidaemia ranked sixth among bloodstream infections, and its average annual incidence was 0.3 per 1000 patients days. Despite of new therapy and international recommendation, the incidence rose sharply during the study period, and ICU mortality remained high.

Effect of standardized surveillance of intensive care unit-acquired infections on ventilator-associated pneumonia incidence.

In a multicenter surveillance of intensive care unit (ICU)-acquired infections, adjusted ventilator-associated pneumonia (VAP) incidence diminished by -1.0% per year (95% confidence interval [CI], -1.8 to -0.2; P = .02) in ICUs with continuous surveillance but increased by +16.1% (95% CI, 0.5%-34.1%; P = .04) in the year following surveillance disruption, suggesting a preventive effect of surveillance on VAP.