Epidemiology of intra-abdominal infection and sepsis in critically ill patients: “AbSeS”, a multinational observational cohort study and ESICM Trials Group Project

Purpose: To describe the epidemiology of intra-abdominal infection in an international cohort of ICU patients according to a new system that classifies cases according to setting of infection acquisition (community-acquired, early onset hospital-acquired, and late-onset hospital-acquired), anatomical disruption (absent or present with localized or diffuse peritonitis), and severity of disease expression (infection, sepsis, and septic shock). Methods: We performed a multicenter (n = 309), observational, epidemiological study including adult ICU patients diagnosed with intra-abdominal infection. Risk factors for mortality were assessed by logistic regression analysis. Results: The cohort included 2621 patients. Setting of infection acquisition was community-acquired in 31.6%, early onset hospital-acquired in 25%, and late-onset hospital-acquired in 43.4% of patients. Overall prevalence of antimicrobial resistance was 26.3% and difficult-to-treat resistant Gram-negative bacteria 4.3%, with great variation according to geographic region. No difference in prevalence of antimicrobial resistance was observed according to setting of infection acquisition. Overall mortality was 29.1%. Independent risk factors for mortality included late-onset hospital-acquired infection, diffuse peritonitis, sepsis, septic shock, older age, malnutrition, liver failure, congestive heart failure, antimicrobial resistance (either methicillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci, extended-spectrum beta-lactamase-producing Gram-negative bacteria, or carbapenem-resistant Gram-negative bacteria) and source control failure evidenced by either the need for surgical revision or persistent inflammation. Conclusion: This multinational, heterogeneous cohort of ICU patients with intra-abdominal infection revealed that setting of infection acquisition, anatomical disruption, and severity of disease expression are disease-specific phenotypic characteristics associated with outcome, irrespective of the type of infection. Antimicrobial resistance is equally common in community-acquired as in hospital-acquired infection

Polymyxin-B hemoperfusion in septic patients: analysis of a multicenter registry

Background: In 2010, the EUPHAS 2 collaborative group created a registry with the purpose of recording data from critically ill patients suffering from severe sepsis and septic shock treated with polymyxin-B hemoperfusion (PMX-HP) for endotoxin removal. The aim of the registry was to verify the application of PMX-HP in the daily clinical practice. Methods: The EUPHAS 2 registry involved 57 centers between January 2010 and December 2014, collecting retrospective data of 357 patients (297 in Europe and 60 in Asia) suffering from severe sepsis and septic shock caused by proved or suspected infection related to Gram negative bacteria. All patients received atleast one cycle of extracorporeal endotoxin removal by PMX-HP. Results: Septic shock was diagnosed in 305 (85.4\ua0%) patients. The most common source of infection was abdominal (44.0\ua0%) followed by pulmonary (17.6\ua0%). Gram negative bacteria represented 60.6\ua0% of the pathogens responsible of infection. After 72\ua0h from the first cycle of PMX-HP, some of the SOFA score components significantly improved with respect to baseline: cardiovascular (2.16\ua0\ub1\ua01.77 from 3.32\ua0\ub1\ua01.29, p\ua0<\ua00.0001), respiratory (1.95\ua0\ub1\ua00.95 from 2.40\ua0\ub1\ua01.06, p\ua0<\ua00.001) and renal (1.84\ua0\ub1\ua01.77 from 2.23\ua0\ub1\ua01.62, p\ua0=\ua00.013). Overall 28-day survival rate was 54.5\ua0% (60.4\ua0% in abdominal and 47.5\ua0% in pulmonary infection). Patients with abdominal infection treated with PMX-HP within 24\ua0h from the diagnosis of septic shock had a 28-day survival rate of 64.5\ua0%. Patients showing a significantly cardiovascular improvement after PMX-HP had a 28-survival rate of 75\ua0% in comparison to the 39\ua0% of patients who did not (p\ua0<\ua00.001). Cox regression analysis found the variation of cardiovascular, respiratory and coagulation SOFA to be independent covariates for 28-day survival. In European patients were observed a higher 28-day (58.8 vs. 34.5\ua0%, p\ua0=\ua00.003), ICU (59 vs. 36.7\ua0%, p\ua0=\ua00.006) and hospital survival rate (53.2 vs. 35\ua0%, p\ua0=\ua00.02) than in Asian patients. However, the two populations were highly heterogeneous in terms of source of infection and severity scores at admission. Conclusion: The EUPHAS 2 is the largest registry conducted outside Japan on the clinical use of PMX-HP in septic patients. Data analysis confirmed the feasibility of PMX-HP to treat septic patients in daily clinical practice, showing clinical benefits associated with endotoxin removal without significant adverse events related to the extracorporeal technique. \ua9 2016, The Author(s)

Infections, antibiotic treatment and mortality in patients admitted to ICUs in countries considered to have high levels of antibiotic resistance compared to those with low levels

Background: Antimicrobial resistance is an increasing concern in ICUs worldwide. Infection with an antibiotic resistant (ABR) strain of an organism is associated with greater mortality than infection with the non-resistant strain, but there are few data assessing whether being admitted to an intensive care unit (ICU) with high levels of antimicrobial resistance is associated with a worse outcome than being admitted to an ICU with low rates of resistance. The aim of this study was, therefore, to compare the characteristics of infections and antibiotic treatments and patient outcomes in patients admitted to ICUs in countries considered as having high levels of antibiotic resistance and those admitted to ICUs in countries considered as having low levels of antibiotic resistance. Methods: Data from the large, international EPIC II one-day point prevalence study on infections in patients hospitalized in ICUs were used. For the current study, we compared the data obtained from patients from two groups of countries: countries with reported MRSA rates of greater than= 25% (highABR: Greece, Israel, Italy, Malta, Portugal, Spain, and Turkey) and countries with MRSA rates of less than 5% (lowABR: Denmark, Finland, Netherlands, Norway, and Sweden). Results: On the study day, 1187/2204 (53.9%) patients in the HighABR ICUs were infected and 255/558 (45.7%) in the LowABR ICUs (P less than 0.01). Patients in the HighABR ICUs were more severely ill than those in the LowABR ICUs, as reflected by a higher SAPS II score (35.6 vs 32.7, P less than 0.05) and had longer median ICU (12 days vs 5 days) and hospital (24 days vs 16 days) lengths of stay. They also had higher crude ICU (20.0% vs 15.4%) and hospital (27.0% vs 21.5%) mortality rates (both P less than 0.05). However, after multivariable adjustment and matched pair analysis there were no differences in ICU or hospital mortality rates between High or LowABR ICU patients overall or among those with infections. Conclusions: Being hospitalized in an ICU in a region with high levels of antimicrobial resistance is not associated per se with a worse outcome

Infections, antibiotic treatment and mortality in patients admitted to ICUs in countries considered to have high levels of antibiotic resistance compared to those with low levels

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Infections, antibiotic treatment and mortality in patients admitted to ICUs in countries considered to have high levels of antibiotic resistance compared to those with low levels

Background: Antimicrobial resistance is an increasing concern in ICUs worldwide. Infection with an antibiotic resistant (ABR) strain of an organism is associated with greater mortality than infection with the non-resistant strain, but there are few data assessing whether being admitted to an intensive care unit (ICU) with high levels of antimicrobial resistance is associated with a worse outcome than being admitted to an ICU with low rates of resistance. The aim of this study was, therefore, to compare the characteristics of infections and antibiotic treatments and patient outcomes in patients admitted to ICUs in countries considered as having high levels of antibiotic resistance and those admitted to ICUs in countries considered as having low levels of antibiotic resistance.Methods: Data from the large, international EPIC II one-day point prevalence study on infections in patients hospitalized in ICUs were used. For the current study, we compared the data obtained from patients from two groups of countries: countries with reported MRSA rates of ≥ 25% (highABR: Greece, Israel, Italy, Malta, Portugal, Spain, and Turkey) and countries with MRSA rates of &lt; 5% (lowABR: Denmark, Finland, Netherlands, Norway, and Sweden).Results: On the study day, 1187/2204 (53.9%) patients in the HighABR ICUs were infected and 255/558 (45.7%) in the LowABR ICUs (P &lt; 0.01). Patients in the HighABR ICUs were more severely ill than those in the LowABR ICUs, as reflected by a higher SAPS II score (35.6 vs 32.7, P &lt; 0.05) and had longer median ICU (12 days vs 5 days) and hospital (24 days vs 16 days) lengths of stay. They also had higher crude ICU (20.0% vs 15.4%) and hospital (27.0% vs 21.5%) mortality rates (both P &lt; 0.05). However, after multivariable adjustment and matched pair analysis there were no differences in ICU or hospital mortality rates between High or LowABR ICU patients overall or among those with infections.Conclusions: Being hospitalized in an ICU in a region with high levels of antimicrobial resistance is not associated per se with a worse outcome. © 2014 Hanberger et al.; licensee BioMed Central Ltd

Phase-3 trial of recombinant human alkaline phosphatase for patients with sepsis-associated acute kidney injury (REVIVAL)

Purpose: Ilofotase alfa is a human recombinant alkaline phosphatase with reno-protective effects that showed improved survival and reduced Major Adverse Kidney Events by 90 days (MAKE90) in sepsis-associated acute kidney injury (SA-AKI) patients. REVIVAL, was a phase-3 trial conducted to confirm its efficacy and safety. Methods: In this international double-blinded randomized-controlled trial, SA-AKI patients were enrolled < 72 h on vasopressor and < 24 h of AKI. The primary endpoint was 28-day all-cause mortality. The main secondary endpoint was MAKE90, other secondary endpoints were (i) days alive and free of organ support through day 28, (ii) days alive and out of the intensive care unit (ICU) through day 28, and (iii) time to death through day 90. Prior to unblinding, the statistical analysis plan was amended, including an updated MAKE90 definition. Results: Six hundred fifty patients were treated and analyzed for safety; and 649 for efficacy data (ilofotase alfa n = 330; placebo n = 319). The observed mortality rates in the ilofotase alfa and placebo groups were 27.9% and 27.9% at 28 days, and 33.9% and 34.8% at 90 days. The trial was stopped for futility on the primary endpoint. The observed proportion of patients with MAKE90A and MAKE90B were 56.7% and 37.4% in the ilofotase alfa group vs. 64.6% and 42.8% in the placebo group. Median [interquartile range (IQR)] days alive and free of organ support were 17 [0–24] and 14 [0–24], number of days alive and discharged from the ICU through day 28 were 15 [0–22] and 10 [0–22] in the ilofotase alfa and placebo groups, respectively. Adverse events were reported in 67.9% and 75% patients in the ilofotase and placebo group. Conclusion: Among critically ill patients with SA-AKI, ilofotase alfa did not improve day 28 survival. There may, however, be reduced MAKE90 events. No safety concerns were identified

Antimicrobial Lessons From a Large Observational Cohort on Intra-abdominal Infections in Intensive Care Units

Severe intra-abdominal infection commonly requires intensive care. Mortality is high and is mainly determined by disease-specific characteristics, i.e. setting of infection onset, anatomical barrier disruption, and severity of disease expression. Recent observations revealed that antimicrobial resistance appears equally common in community-acquired and late-onset hospital-acquired infection. This challenges basic principles in anti-infective therapy guidelines, including the paradigm that pathogens involved in community-acquired infection are covered by standard empiric antimicrobial regimens, and second, the concept of nosocomial acquisition as the main driver for resistance involvement. In this study, we report on resistance profiles of Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Enterococcus faecalis and Enterococcus faecium in distinct European geographic regions based on an observational cohort study on intra-abdominal infections in intensive care unit (ICU) patients. Resistance against aminopenicillins, fluoroquinolones, and third-generation cephalosporins in E. coli, K. pneumoniae and P. aeruginosa is problematic, as is carbapenem-resistance in the latter pathogen. For E. coli and K. pneumoniae, resistance is mainly an issue in Central Europe, Eastern and South-East Europe, and Southern Europe, while resistance in P. aeruginosa is additionally problematic in Western Europe. Vancomycin-resistance in E. faecalis is of lesser concern but requires vigilance in E. faecium in Central and Eastern and South-East Europe. In the subcohort of patients with secondary peritonitis presenting with either sepsis or septic shock, the appropriateness of empiric antimicrobial therapy was not associated with mortality. In contrast, failure of source control was strongly associated with mortality. The relevance of these new insights for future recommendations regarding empiric antimicrobial therapy in intra-abdominal infections is discussed

Candida bloodstream infections in intensive care units: analysis of the extended prevalence of infection in intensive care unit study

Item does not contain fulltextOBJECTIVES: To provide a global, up-to-date picture of the prevalence, treatment, and outcomes of Candida bloodstream infections in intensive care unit patients and compare Candida with bacterial bloodstream infection. DESIGN: A retrospective analysis of the Extended Prevalence of Infection in the ICU Study (EPIC II). Demographic, physiological, infection-related and therapeutic data were collected. Patients were grouped as having Candida, Gram-positive, Gram-negative, and combined Candida/bacterial bloodstream infection. Outcome data were assessed at intensive care unit and hospital discharge. SETTING: EPIC II included 1265 intensive care units in 76 countries. PATIENTS: Patients in participating intensive care units on study day. INTERVENTIONS: None. MEASUREMENT AND MAIN RESULTS: Of the 14,414 patients in EPIC II, 99 patients had Candida bloodstream infections for a prevalence of 6.9 per 1000 patients. Sixty-one patients had candidemia alone and 38 patients had combined bloodstream infections. Candida albicans (n = 70) was the predominant species. Primary therapy included monotherapy with fluconazole (n = 39), caspofungin (n = 16), and a polyene-based product (n = 12). Combination therapy was infrequently used (n = 10). Compared with patients with Gram-positive (n = 420) and Gram-negative (n = 264) bloodstream infections, patients with candidemia were more likely to have solid tumors (p < .05) and appeared to have been in an intensive care unit longer (14 days [range, 5-25 days], 8 days [range, 3-20 days], and 10 days [range, 2-23 days], respectively), but this difference was not statistically significant. Severity of illness and organ dysfunction scores were similar between groups. Patients with Candida bloodstream infections, compared with patients with Gram-positive and Gram-negative bloodstream infections, had the greatest crude intensive care unit mortality rates (42.6%, 25.3%, and 29.1%, respectively) and longer intensive care unit lengths of stay (median [interquartile range]) (33 days [18-44], 20 days [9-43], and 21 days [8-46], respectively); however, these differences were not statistically significant. CONCLUSION: Candidemia remains a significant problem in intensive care units patients. In the EPIC II population, Candida albicans was the most common organism and fluconazole remained the predominant antifungal agent used. Candida bloodstream infections are associated with high intensive care unit and hospital mortality rates and resource use