Comparison of prognostic factors between bacteraemic and non-bacteraemic critically ill immunocompetent patients in community-acquired severe pneumococcal pneumonia: a STREPTOGENE sub-study.

BACKGROUND: The presence of bacteraemia in pneumococcal pneumonia in critically ill patients does not appear to be a strong independent prognostic factor in the existing literature. However, there may be a specific pattern of factors associated with mortality for ICU patients with bacteraemic pneumococcal community-acquired pneumonia (CAP). We aimed to compare the factors associated with mortality, according to the presence of bacteraemia or not on admission, for patients hospitalised in intensive care for severe pneumococcal CAP. METHODS: This was a post hoc analysis of data from the prospective, observational, multicentre STREPTOGENE study in immunocompetent Caucasian adults admitted to intensive care in France between 2008 and 2012 for pneumococcal CAP. Patients were divided into two groups based on initial blood culture (positive vs. negative) for Streptococcus pneumoniae. The primary outcome was hospital mortality, which was compared between the two groups using odds ratios according to predefined variables to search for a prognostic interaction present in bacterial patients but not non-bacteraemic patients. Potential differences in the distribution of serotypes between the two groups were assessed. The prognostic consequences of the presence or not of initial bi-antibiotic therapy were assessed, specifically in bacteraemic patients. RESULTS: Among 614 included patients, 274 had a blood culture positive for S. pneumoniae at admission and 340 did not. The baseline difference between the groups was more frequent leukopaenia (26% vs. 14%, p = 0.0002) and less frequent pre-hospital antibiotic therapy (10% vs. 16.3%, p = 0.024) for the bacteraemic patients. Hospital mortality was not significantly different between the two groups (p = 0.11). We did not observe any prognostic factors specific to the bacteraemic patient population, as the statistical comparison of the odds ratios, as an indication of the association between the predefined prognostic parameters and mortality, showed them to be similar for the two groups. Bacteraemic patients more often had invasive serotypes but less often serotypes associated with high case fatality rates (p = 0.003). The antibiotic regimens were similar for the two groups. There was no difference in mortality for patients in either group given a beta-lactam alone vs. a beta-lactam combined with a macrolide or fluoroquinolone. CONCLUSION: Bacteraemia had no influence on the mortality of immunocompetent Caucasian adults admitted to intensive care for severe pneumococcal CAP, regardless of the profile of the associated prognostic factors.

Venous-to-Arterial Carbon Dioxide Partial Pressure Difference: Predictor of Septic Patient Prognosis Depending on Central Venous Oxygen Saturation.

This study aimed to assess the viability of using the venous-to-arterial carbon dioxide partial pressure difference (P(v-a)CO2) to predict clinical worsening of septic shock, depending on central venous oxygen saturation (ScvO2). The prospective, observational, multicentric study conducted in three intensive care units (ICUs) included all patients with a septic shock episode during the first 6 h, with 122 patients assessed. Clinical worsening was defined as an increase of sequential organ failure assessment (SOFA) scores ≥1 (ΔSOFA ≥1) within 2 days. To assess the ability of P(v-a)CO2 to predict clinical worsening, univariate and multivariate analyses were performed according to ΔSOFA. A receiver-operating characteristic (ROC) analysis was used to confirm model predictions. Associations between P(v-a)CO2 and mortality were explored using correlations. Using multivariate analyses, two independent factors associated with ΔSOFA at least 1 were identified: an averaged 6-h value of lactate concentration (Lac [1-6]) (odds ratios [ORs], 2.43 [95% confidence interval, CI, 1.20-4.89]; P = 0.013) and an averaged 6-h value of P(v-a)CO2 (P(v-a)CO2 [1-6]) (OR, 1.49 [95% CI, 1.04-2.15]; P = 0.029). ROC analysis confirmed that Lac [1-6] and P(v-a)CO2 [1-6] were significantly associated with ΔSOFA at least 1, whereas ScvO2 [1-6] was not. Finally, ΔSOFA at least 1 was associated with higher 28-day (76% vs. 10%, P = 0.001) and ICU (83% vs. 12%, P = 0.001) mortality rates, which were higher in patients with P(v-a)CO2 [1-6] more than 5.8 mmHg (57% vs. 33%; P = 0.012). In conclusion, P(v-a)CO2 may help predict outcomes for septic shock patients regardless of ScvO2 values.

Host-pathogen interactions and prognosis of critically ill immunocompetent patients with pneumococcal pneumonia: the nationwide prospective observational STREPTOGENE study.

PURPOSE: To assess the relative importance of host and bacterial factors associated with hospital mortality in patients admitted to the intensive care unit (ICU) for pneumococcal community-acquired pneumonia (PCAP). METHODS: Immunocompetent Caucasian ICU patients with PCAP documented by cultures and/or pneumococcal urinary antigen (UAg Sp) test were included in this multicenter prospective study between 2008 and 2012. All pneumococcal strains were serotyped. Logistic regression analyses were performed to identify risk factors for hospital mortality. RESULTS: Of the 614 patients, 278 (45%) had septic shock, 270 (44%) had bacteremia, 307 (50%) required mechanical ventilation at admission, and 161 (26%) had a diagnosis based only on the UAg Sp test. No strains were penicillin-resistant, but 23% had decreased susceptibility. Of the 36 serotypes identified, 7 accounted for 72% of the isolates, with different distributions according to age. Although antibiotics were consistently appropriate and were started within 6 h after admission in 454 (74%) patients, 116 (18.9%) patients died. Independent predictors of hospital mortality in the adjusted analysis were platelets ≤ 100 × 109/L (OR, 7.7; 95% CI, 2.8-21.1), McCabe score ≥ 2 (4.58; 1.61-13), age > 65 years (2.92; 1.49-5.74), lactates > 4 mmol/L (2.41; 1.27-4.56), male gender and septic shock (2.23; 1.30-3.83 for each), invasive mechanical ventilation (1.78; 1-3.19), and bilateral pneumonia (1.59; 1.02-2.47). Women with platelets ≤ 100 × 109/L had the highest mortality risk (adjusted OR, 7.7; 2.8-21). CONCLUSIONS: In critically ill patients with PCAP, age, gender, and organ failures at ICU admission were more strongly associated with hospital mortality than were comorbidities. Neither pneumococcal serotype nor antibiotic regimen was associated with hospital mortality.

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.

Elevated Plasma Levels of sRAGE Are Associated With Nonfocal CT-Based Lung Imaging in Patients With ARDS: A Prospective Multicenter Study.

BACKGROUND: During ARDS, CT can reveal two distinct lung imaging patterns, focal or nonfocal, with different responses to positive end-expiratory pressure, recruitment maneuvers, and prone position. Nevertheless, their association with plasma biomarkers and their distinct functional/pathobiological mechanisms are unknown. The objective of this study was to characterize focal and nonfocal patterns of lung CT-based imaging with plasma markers of lung injury. METHODS: A prospective multicenter cohort study involving 119 consecutive patients with ARDS. Plasma biomarkers (soluble form of the receptor for advanced glycation end product [sRAGE], plasminogen activator inhibitor-1, soluble intercellular adhesion molecule-1, and surfactant protein-D) were measured within 24 h of ARDS onset. Lung CT scan was performed within the first 48 h to assess lung morphology. RESULTS: Thirty-two (27%) and 87 (73%) patients had focal and nonfocal ARDS, respectively. Plasma levels of sRAGE were significantly higher in nonfocal ARDS, compared with focal ARDS. A cut-off of 1,188 pg/mL differentiated focal from nonfocal ARDS with a sensitivity of 94% and a specificity of 84%. Nonfocal patterns were associated with higher 28- and 90-day mortality than focal patterns (31% vs 12%, P = .038 and 46% vs 21%, P = .026, respectively). Plasma levels of plasminogen activator inhibitor-1 were significantly higher in nonfocal ARDS. There was no difference in other biomarkers. CONCLUSIONS: Plasma sRAGE is associated with a nonfocal ARDS. Such novel findings may suggest a role for RAGE pathway in an underlying endotype of impaired alveolar fluid clearance and stimulate future research on the association between ARDS phenotypes and therapeutic responses.

Strategies to reduce curative antibiotic therapy in intensive care units (adult and paediatric).

Emerging resistance to antibiotics shows no signs of decline. At the same time, few new antibacterials are being discovered. There is a worldwide recognition regarding the danger of this situation. The urgency of the situation and the conviction that practices should change led the Société de Réanimation de Langue Française (SRLF) and the Société Française d'Anesthésie et de Réanimation (SFAR) to set up a panel of experts from various disciplines. These experts met for the first time at the end of 2012 and have since met regularly to issue the following 67 recommendations, according to the rigorous GRADE methodology. Five fields were explored: i) the link between the resistance of bacteria and the use of antibiotics in intensive care; ii) which microbiological data and how to use them to reduce antibiotic consumption; iii) how should antibiotic therapy be chosen to limit consumption of antibiotics; iv) how can antibiotic administration be optimized; v) review and duration of antibiotic treatments. In each institution, the appropriation of these recommendations should arouse multidisciplinary discussions resulting in better knowledge of local epidemiology, rate of antibiotic use, and finally protocols for improving the stewardship of antibiotics. These efforts should contribute to limit the emergence of resistant bacteria.

Outcome of acute mesenteric ischemia in the intensive care unit: a retrospective, multicenter study of 780 cases.

BACKGROUND: In the intensive care unit (ICU), the outcomes of patients with acute mesenteric ischemia (AMI) are poorly documented. This study aimed to determine the risk factors for death in ICU patients with AMI. METHODS: A retrospective, observational, non-interventional, multicenter study was conducted in 43 ICUs of 38 public institutions in France. From January 2008 to December 2013, all adult patients with a diagnosis of AMI during their hospitalization in ICU were included in a database. The diagnosis was confirmed by at least one of three procedures (computed tomography scan, gastrointestinal endoscopy, or upon surgery). To determine factors associated with ICU death, we established a logistic regression model. Recursive partitioning analysis was applied to construct a decision tree regarding risk factors and their interactions most critical to determining outcomes. RESULTS: The death rate of the 780 included patients was 58 %. Being older, having a higher sequential organ failure assessment (SOFA) severity score at diagnosis, and a plasma lactate concentration over 2.7 mmol/l at diagnosis were independent risk factors of ICU mortality. In contrast, having a prior history of peripheral vascular disease or an initial surgical treatment were independent protective factors against ICU mortality. Using age and SOFA severity score, we established an ICU mortality score at diagnosis based on the cutoffs provided by recursive partitioning analysis. Probability of survival was statistically different (p < 0.001) between patients with a score from 0 to 2 and those with a score of 3 and 4. CONCLUSION: Acute mesenteric ischemia in ICU patients was associated with a 58 % ICU death rate. Age and SOFA severity score at diagnosis were risk factors for mortality. Plasma lactate concentration over 2.7 mmol/l was also an independent risk factor, but values in the normal range did not exclude the diagnosis of AMI.

Effect of statin therapy on mortality in patients with ventilator-associated pneumonia: a randomized clinical trial.

IMPORTANCE: Observational studies have reported that statin use may be associated with improved outcomes of various infections. Ventilator-associated pneumonia (VAP) is the most common infection in the intensive care unit (ICU) and is associated with substantial mortality. OBJECTIVE: To determine whether statin therapy can decrease day-28 mortality in patients with VAP. DESIGN, SETTING, AND PARTICIPANTS: Randomized, placebo-controlled, double-blind, parallel-group, multicenter trial performed in 26 intensive care units in France from January 2010 to March 2013. For power to detect an 8% absolute reduction in the day-28 mortality rate, we planned to enroll 1002 patients requiring invasive mechanical ventilation for more than 2 days and having suspected VAP, defined as a modified Clinical Pulmonary Infection Score of 5 or greater. The futility stopping rules were an absolute increase in day-28 mortality of at least 2.7% with simvastatin compared with placebo after enrollment of the first 251 patients. INTERVENTIONS: Participants were randomized to receive simvastatin (60 mg) or placebo, started on the same day as antibiotic therapy and given until ICU discharge, death, or day 28, whichever occurred first. MAIN OUTCOMES AND MEASURES: Primary outcome was day-28 mortality. Day-14, ICU, and hospital mortality rates were determined, as well as duration of mechanical ventilation and Sequential Organ Failure Assessment (SOFA) scores on days 3, 7, and 14. RESULTS: The study was stopped for futility at the first scheduled interim analysis after enrollment of 300 patients, of whom all but 7% in the simvastatin group and 11% in the placebo group were naive to statin therapy at ICU admission. Day-28 mortality was not lower in the simvastatin group (21.2% [95% CI, 15.4% to 28.6%) than in the placebo group (15.2% [95% CI, 10.2% to 22.1%]; P = .10; hazard ratio, 1.45 [95% CI, 0.83 to 2.51]); the between-group difference was 6.0% (95% CI, -3.0% to 14.9%). In statin-naive patients, day-28 mortality was 21.5% (95% CI, 15.4% to 29.1%) with simvastatin and 13.8% (95% CI, 8.8% to 21.0%) with placebo (P = .054) (between-group difference, 7.7% [95%CI, -1.8% to 16.8%). There were no significant differences regarding day-14, ICU, or hospital mortality rates; duration of mechanical ventilation; or changes in SOFA score. CONCLUSIONS AND RELEVANCE: In adults with suspected VAP, adjunctive simvastatin therapy compared with placebo did not improve day-28 survival. These findings do not support the use of statins with the goal of improving VAP outcomes. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01057758.

Bacterial ventilator-associated pneumonia: bronchoalveolar lavage results are not influenced by dilution.

OBJECTIVE: This study was designed to determine if bronchoalveolar lavage (BAL) quantitative culture results can be used confidently for the diagnosis of bacterial ventilator-associated pneumonia (VAP) without taking dilution into account. DESIGN: Prospective observational cohort study. SETTING: A 12-bed medical ICU in a teaching hospital. PATIENTS: A total of 241 BAL (three 50-mL aliquots) were performed in 127 patients presenting a suspicion of VAP. INTERVENTIONS: All consecutive adults who were ventilated more than 48 h were included if VAP was clinically suspected. A dilution factor, k, was developed according to the formula: dilution factor k = concentration of urea in plasma/concentration of urea in lavage fluid recovered. Using this dilution factor, the quantitative bacterial counts were interpreted accordingly with a corrected positive threshold at 10(5) colony forming unit (CFU) mL(-1). MEASUREMENTS AND RESULTS: Eighty-nine BAL with at least one micro-organism > or = 10(4) CFU mL(-1) were identified (37%). In 176 BAL (73%), k ranged from 10 to 100. Median k was 24.4 (9.7-40.2) in VAP group and 24.6 (13.1-57.8) in patients without pneumonia (NS). Among the 25 BAL with micro-organism counts of 10(4) CFU mL(-1), 3 had a dilution factor lower than 10, resulting in corrected counts below the threshold of 10(5) CFU mL(-1). Two out of 15 patients with micro-organism counts of 10(3) CFU mL(-1) had corrected micro-organism counts of 10(5) CFU mL(-1). Finally, only five BAL (2.1%) were misclassified when the dilution correction factor was applied. CONCLUSIONS: Using urea as dilution factor, we showed that BAL dilution variations did not alter the interpretation of BAL quantitative bacterial culture when administrating three aliquots of 50 mL of saline.