Candida auris: Outbreak, surveillance and epidemiological monitoring in Northern Greece.

Candida auris is an emerging fungal pathogen associated with multi-drug resistance rates and widespread outbreaks in hospitals and healthcare units worldwide. Sequencing studies have revealed that different clonal lineages of the fungus seem to be prevalent among distinct geographical sites. The first case of C. auris in Northern Greece was reported in Thessaloniki in October 2022, almost 2 years after the first isolation in Greece (Athens 2019). The Mycology Laboratory of the Medical School of Aristotle University of Thessaloniki stands as the reference laboratory for fungal diseases in Northern Greece and a meticulous search for the yeast, in plenty of suspicious samples, has been run since 2019 in the Lab as well as a retrospective analysis of all its yeasts' collection, back to 2008, with negative results for the presence of C. auris. Here, are presented the findings concerning the outbreak and surveillance of C. auris in Northern Greece, mainly the region of Thessaloniki and the broader area of Macedonia, from October 2022 until August 2023. The isolates from Northern Greece continue to fall in Clade I and present with an almost equal and stable sensitivity profile until now.

The study concerns the outbreak of Candida auris in Northern Greece since October 2022 and the effort for surveillance and epidemiological monitoring. All isolates continue to fall in Clade I and present with an almost equal and stable sensitivity profile till now.

Nebulized Antibiotics for Healthcare- and Ventilator-Associated Pneumonia.

Global emergence of multidrug-resistant and extensive drug-resistant gram-negative bacteria has increased the risk of treatment failure, especially for healthcare- or ventilator-associated pneumonia (HAP/VAP). Nebulization of antibiotics, by providing high intrapulmonary antibiotic concentrations, represents a promising approach to optimize the treatment of HAP/VAP due to multidrug-resistant and extensive drug-resistant gram-negative bacteria, while limiting systemic antibiotic exposure. Aminoglycosides and colistin methanesulfonate are the most common nebulized antibiotics. Although optimal nebulized drug dosing regimen is not clearly established, high antibiotic doses should be administered using vibrating-mesh nebulizer with optimized ventilator settings to ensure safe and effective intrapulmonary concentrations. When used preventively, nebulized antibiotics reduced the incidence of VAP without any effect on mortality. This approach is not yet recommended and large randomized controlled trials should be conducted to confirm its benefit and explore the impact on antibiotic selection pressure. Compared with high-dose intravenous administration, high-dose nebulized colistin methanesulfonate seems to be more effective and safer in the treatment of ventilator-associated tracheobronchitis and VAP caused by multidrug resistant and extensive-drug resistant gram-negative bacteria. Adjunctive nebulized aminoglycosides could increase the clinical cure rate and bacteriological eradication in patients suffering from HAP/VAP due to multidrug-resistant and extensive drug-resistant gram-negative bacteria. As nebulized aminoglycosides broadly diffuse in the systemic circulation of patients with extensive bronchopneumonia, monitoring of plasma trough concentrations is recommended during the period of nebulization. Large randomized controlled trials comparing high dose of nebulized colistin methanesulfonate to high dose of intravenous colistin methanesulfonate or to intravenous new ß-lactams in HAP/VAP due to multidrug-resistant and extensive drug-resistant gram-negative bacteria are urgently needed.

Non-Respiratory Symptoms of Patients Infected with SARS-CoV-2 (Coronavirus Disease 2019): Lessons from Their Initial Presentation at the Hospital.

Background and objectives: As the COVID-19 pandemic spreads, it is becoming increasingly evident that this coronavirus is not limited to the respiratory system and that the musculoskeletal system can also be affected. The purpose of the present study was to describe non-respiratory symptoms of laboratory-confirmed COVID-19 cases. Materials and Methods: All patients with SARS-CoV-2 admitted to our hospital, between 1 August and 30 September 2020, were included in this retrospective study. Data were extracted from medical records. Epidemiological, clinical, laboratory and radiological characteristics at the initial presentation at the hospital were collected and analyzed. Results: A total of 79 COVID-19 patients were enrolled. The mean age of the patients was 44.08 years (age range, 18-87 years) and 59.5% were male. The most common symptoms were fatigue in 60 (75.9%) patients, followed by fever (73.4%), myalgia (51.9%), cough (41.8%), anosmia (38%) and arthralgia (36.7%). The muscles of the upper back and the knee joint were the most painful anatomic region and joint, respectively. The laboratory findings on admission showed that D-dimer, CRP and procalcitonin levels were increased, without significant gender differences (p > 0.05). Chest imaging demonstrated pneumonia in 20 (25.3%) patients. Conclusions: Our results indicate that from the onset of the symptoms of COVID-19 patients, musculoskeletal symptoms, such as fatigue, myalgia and arthralgia, were present in three-quarters of all patients. These findings could help elaborate updated triage and admission protocols for suspect COVID-19 patients at the hospital and Emergency Department presentation.

De-escalation of antimicrobial therapy in ICU settings with high prevalence of multidrug-resistant bacteria: a multicentre prospective observational cohort study in patients with sepsis or septic shock.

BACKGROUND: De-escalation of empirical antimicrobial therapy, a key component of antibiotic stewardship, is considered difficult in ICUs with high rates of antimicrobial resistance. OBJECTIVES: To assess the feasibility and the impact of antimicrobial de-escalation in ICUs with high rates of antimicrobial resistance. METHODS: Multicentre, prospective, observational study in septic patients with documented infections. Patients in whom de-escalation was applied were compared with patients without de-escalation by the use of a propensity score matching by SOFA score on the day of de-escalation initiation. RESULTS: A total of 262 patients (mean age 62.2 ± 15.1 years) were included. Antibiotic-resistant pathogens comprised 62.9%, classified as MDR (12.5%), extensively drug-resistant (49%) and pandrug-resistant (1.2%). In 97 (37%) patients de-escalation was judged not feasible in view of the antibiotic susceptibility results. Of the remaining 165 patients, judged as patients with de-escalation possibility, de-escalation was applied in 60 (22.9%). These were matched to an equal number of patients without de-escalation. In this subset of 120 patients, de-escalation compared with no de-escalation was associated with lower all-cause 28 day mortality (13.3% versus 36.7%, OR 0.27, 95% CI 0.11-0.66, P = 0.006); ICU and hospital mortality were also lower. De-escalation was associated with a subsequent collateral decrease in the SOFA score. Cox multivariate regression analysis revealed de-escalation as a significant factor for 28 day survival (HR 0.31, 95% CI 0.14-0.70, P = 0.005). CONCLUSIONS: In ICUs with high levels of antimicrobial resistance, feasibility of antimicrobial de-escalation was limited because of the multi-resistant pathogens isolated. However, when de-escalation was feasible and applied, it was associated with lower mortality.

Antimicrobial Stewardship in Hematological Patients at the intensive care unit: a global cross-sectional survey from the Nine-i Investigators Network.

A global cross-sectional survey was performed to gather data on the current treatment of infections caused by multidrug-resistant (MDR) bacteria among hematological patients admitted to ICUs worldwide. The survey was performed in April 2019 using an electronic platform (SurveyMonkey®) being distributed among 83 physicians and completed by 48 (57.8%) responders. ESBL Enterobacteriaceae, carbapenem-resistant K. pneumoniae and carbapenem-resistant P. aeruginosa were the main concerns. Previous MDR infection (34% of responders), MDR colonization (20%) and previous antibiotic exposure within the last 3 months (20.5%) were considered the most relevant risk factors of bloodstream infection (BSI) due to MDR bacteria. In 48.8% of the ICUs, there was no antimicrobial stewardship (AMS) team focused on hematological patients. Updates on local epidemiology of MDR pathogens were provided in 98% of the centers, using phone or verbal communications (56.1% and 53.7%, respectively). In presence of febrile neutropenia, initial therapy consisted of anti-Gram-negative plus anti-Gram-positive antibiotics for 41% of participants. Antibiotic de-escalation and/or discontinuation of therapy were considered as a promising strategy for the prevention of MDR development (32.4%). Factors associated with antibiotic de-escalation were clinical improvement (43.6%) and neutrophil count recovery (12.8%). Infectious Disease consultation and AMS interventions were not determining factors for de-escalation decisions (more than 50% of responders). Infection control and educational programs were valued as necessary measures for implementation by ICU practitioners. These findings should guide future efforts on collaborative team working, improving compliance with adequate treatment protocols, implementing antimicrobial stewardship programs in critically ill hematological patients, and educational activities.

Hospital-wide antifungal prescription in Greek hospitals: a multicenter repeated point-prevalence study.

The aim of the study was to evaluate antifungal prescriptions among hospitalized adult patients in Greek hospitals. This multicenter two-times, 1-day, point-prevalence study was carried out in 2015 and 2017 in five and six hospitals, respectively. Among the 5812 patients screened in both periods, antifungals were prescribed in 129 patients (73 in 2015 and 56 in 2017); antifungals were used as prophylaxis in 31 patients (24%), pre-emptively in 32 (25%), empirically in 38 (30%), and as targeted therapy in 28 (22%). Triazoles were the class most commonly used (65 patients; 50%), followed by echinocandins (59; 46%) and liposomal amphotericin B (12; 9%). The use of echinocandins was higher (P 0.009) in the ICU (16 out of 22 patients), as compared with those in other departments (40%). Antifungal treatment was deemed inappropriate in 32/129 patients (25%) (16% in 2015 versus 36% in 2017; P 0.014). Inappropriate antifungal administration was more common if indicated by the primary physician, as compared with an infectious disease specialist (35% versus 5%; P < 0.001). Candidemia represented the majority of microbiologically documented infections (12 out of 28). Only two cases of proven pulmonary aspergillosis were diagnosed. Fluconazole and echinocandins were most frequently prescribed for identified or presumptive fungal infections, while fluconazole or posaconazole was given most frequently as prophylaxis. Antifungal treatment has been, ultimately, proven unnecessary in one-fourth of cases, underlining the need of a nationwide antifungal stewardship program.

Factors associated with ventilator-associated events: an international multicenter prospective cohort study.

A secondary analysis of a prospective multicenter cohort was performed in six intensive care units (ICU) in four European countries (France, Greece, Spain and Turkey). The main objective was to identify factors associated with ventilator-associated events (VAEs) in adults who underwent mechanical ventilation (MV) ≥ 48 h. Secondary objectives were to identify: variables influencing VAE in the subpopulation with endotracheal intubation and in those subjects who were ventilated > 7 days. Subjects who had undergone MV ≥ 48 h were included. In subjects with multiple episodes of MV, only the first one was eligible. The adult definitions for VAEs were adjusted to the 2015 update of the CDC's 2013 National Healthcare Safety Network Association. Factors associated with VAE were estimated through multivariate Cox proportional hazards analysis. Among 163 adults (42 tracheostomies), 76 VAEs (34.9 VAEs/1,000 ventilator-days) were documented: 9 were Ventilator-Associated Conditions (VAC) and 67 Infection-related Ventilator-Associated Complications (IVAC)-plus (9 only IVAC and 58 Possible Ventilator-Associated Pneumonia). VAEs developed after a median of 6 days (interquartile range: 4-9). VAEs were independently associated with long-acting sedative/analgesic drugs (Hazard Ratio [HR]: 4.30), selective digestive decontamination (SDD) (HR: 0.38), and surgical/trauma admission (HR: 2.30). Among 116 subjects with endotracheal tube, SDD (HR: 0.21) and surgical/trauma admission (HR: 3.11) remained associated with VAE. Among 102 subjects ventilated >7 days, only long-acting sedative/analgesic agents (HR: 8.69) remained independently associated with VAE. In summary, SDD implementation and long-acting analgesic/sedative agents restriction prescription may prevent early and late VAEs, respectively. Bundles developed to prevent VAEs should include these two interventions.

Cumulative Evidence of Randomized Controlled and Observational Studies on Catheter-Related Infection Risk of Central Venous Catheter Insertion Site in ICU Patients: A Pairwise and Network Meta-Analysis.

BACKGROUND: Selection of central venous catheter insertion site in ICU patients could help reduce catheter-related infections. Although subclavian was considered the most appropriate site, its preferential use in ICU patients is not generalized and questioned by contradicted meta-analysis results. In addition, conflicting data exist on alternative site selection whenever subclavian is contraindicated. OBJECTIVE: To compare catheter-related bloodstream infection and colonization risk between the three sites (subclavian, internal jugular, and femoral) in adult ICU patients. DATA SOURCE: We searched MEDLINE, EMBASE, Cochrane Central Register of Controlled trials, CINAHL, and ClinicalTrials.gov. STUDY SELECTION: Eligible studies were randomized controlled trials and observational ones. DATA EXTRACTION: Extracted data were analyzed by pairwise and network meta-analysis. DATA SYNTHESIS: Twenty studies were included; 11 were observational, seven were randomized controlled trials for other outcomes, and two were randomized controlled trials for sites. We evaluated 18,554 central venous catheters: 9,331 from observational studies, 5,482 from randomized controlled trials for other outcomes, and 3,741 from randomized controlled trials for sites. Colonization risk was higher for internal jugular (relative risk, 2.25 [95% CI, 1.84-2.75]; I = 0%) and femoral (relative risk, 2.92 [95% CI, 2.11-4.04]; I = 24%), compared with subclavian. Catheter-related bloodstream infection risk was comparable for internal jugular and subclavian, higher for femoral than subclavian (relative risk, 2.44 [95% CI, 1.25-4.75]; I = 61%), and lower for internal jugular than femoral (relative risk, 0.55 [95% CI, 0.34-0.89]; I = 61%). When observational studies that did not control for baseline characteristics were excluded, catheter-related bloodstream infection risk was comparable between the sites. CONCLUSIONS: In ICU patients, internal jugular and subclavian may, similarly, decrease catheter-related bloodstream infection risk, when compared with femoral. Subclavian could be suggested as the most appropriate site, whenever colonization risk is considered and not, otherwise, contraindicated. Current evidence on catheter-related bloodstream infection femoral risk, compared with the other sites, is inconclusive.

Pulmonary co-infections by Pneumocystis jirovecii and Aspergillus fumigatus in non-HIV patients: A report of two cases and literature review.

Pneumocystis jirovecii is the causative agent of Pneumocystis pneumonia (PcP), a common and often life-threatening opportunistic infection in HIV-infected patients. However, non-HIV, immunocompromised patients are at risk of PcP as well, whereas the mortality appears to be higher among these patients. Pneumocystis co-infections with other microorganisms are less frequent and only sparse reports of combined PcP and invasive pulmonary fungal infections exist in the literature, especially in the non-HIV patients. Two cases of pulmonary co-infections by P. jirovecii and Aspergillus fumigatus are presented. Both patients were non-HIV infected, the first one was suffering from crescentic IgA nephropathy under immunosuppressive treatment and the second from resistant non-Hodgkin lymphoma under chemotherapy. Both patients were treated with intravenous trimethoprim/sulphamethoxazole (TMP/SMX) combined with voriconazole. The first patient showed gradual clinical improvement while the outcome for the second patient was unfavourable. In addition, a literature review of the previous published cases of co-infection by P. jirovecii and other fungi in non-HIV patients was performed. Our target was to provide comprehensive information on this kind of infections, highlighting the importance of clinical suspicion.

Intra-abdominal infection and sepsis in immunocompromised intensive care unit patients: Disease expression, microbial aetiology, and clinical outcomes.

We compared epidemiology of intra-abdominal infection (IAI) between immunocompromised and non-immunocompromised ICU patients and identified risk factors for mortality. We performed a secondary analysis on the "AbSeS" database, a prospective, observational study with IAI patients from 309 ICUs in 42 countries. Immunocompromised status was defined as either neutropenia or prolonged corticosteroids use, chemotherapy or radiotherapy in the past year, bone marrow or solid organ transplantation, congenital immunodeficiency, or immunosuppressive drugs use. Mortality was defined as ICU mortality at any time or 28-day mortality for those discharged earlier. Associations with mortality were assessed by logistic regression. The cohort included 2589 patients of which 239 immunocompromised (9.2 %), most with secondary peritonitis. Among immunocompromised patients, biliary tract infections were less frequent, typhlitis more frequent, and IAIs were more frequently healthcare-associated or early-onset hospital-acquired compared with immunocompetent patients. No difference existed in grade of anatomical disruption, disease severity, organ failure, pathogens, and resistance patterns. Septic shock was significantly more frequent in the immunocompromised population. Mortality was similar in both groups (31.1% vs. 28.9 %; p = 0.468). Immunocompromise was not a risk factor for mortality (OR 0.98, 95 % CI 0.66-1.43). Independent risk factors for mortality among immunocompromised patients included septic shock at presentation (OR 6.64, 95 % CI 1.27-55.72), and unsuccessful source control with persistent inflammation (OR 5.48, 95 % CI 2.29-12.57). In immunocompromised ICU patients with IAI, short-term mortality was similar to immunocompetent patients, despite the former presented more frequently with septic shock, and septic shock and persistent inflammation after source control were independent risk factors for death.

The role of centre and country factors on process and outcome indicators in critically ill patients with hospital-acquired bloodstream infections.

PURPOSE: The primary objective of this study was to evaluate the associations between centre/country-based factors and two important process and outcome indicators in patients with hospital-acquired bloodstream infections (HABSI). METHODS: We used data on HABSI from the prospective EUROBACT-2 study to evaluate the associations between centre/country factors on a process or an outcome indicator: adequacy of antimicrobial therapy within the first 24 h or 28-day mortality, respectively. Mixed logistical models with clustering by centre identified factors associated with both indicators. RESULTS: Two thousand two hundred nine patients from two hundred one intensive care units (ICUs) were included in forty-seven countries. Overall, 51% (n = 1128) of patients received an adequate antimicrobial therapy and the 28-day mortality was 38% (n = 839). The availability of therapeutic drug monitoring (TDM) for aminoglycosides everyday [odds ratio (OR) 1.48, 95% confidence interval (CI) 1.03-2.14] or within a few hours (OR 1.79, 95% CI 1.34-2.38), surveillance cultures for multidrug-resistant organism carriage performed weekly (OR 1.45, 95% CI 1.09-1.93), and increasing Human Development Index (HDI) values were associated with adequate antimicrobial therapy. The presence of intermediate care beds (OR 0.63, 95% CI 0.47-0.84), TDM for aminoglycoside available everyday (OR 0.66, 95% CI 0.44-1.00) or within a few hours (OR 0.51, 95% CI 0.37-0.70), 24/7 consultation of clinical pharmacists (OR 0.67, 95% CI 0.47-0.95), percentage of vancomycin-resistant enterococci (VRE) between 10% and 25% in the ICU (OR 1.67, 95% CI 1.00-2.80), and decreasing HDI values were associated with 28-day mortality. CONCLUSION: Centre/country factors should be targeted for future interventions to improve management strategies and outcome of HABSI in ICU patients.

Hospital-acquired bloodstream infections in critically ill cirrhotic patients: a post-hoc analysis of the EUROBACT-2 international cohort study.

BACKGROUND: Hospital-acquired bloodstream infections are common in the intensive care unit (ICU) and have a high mortality rate. Patients with cirrhosis are especially susceptible to infections, yet there is a knowledge gap in the epidemiological distinctions in hospital-acquired bloodstream infections between cirrhotic and non-cirrhotic patients in the ICU. It has been suggested that cirrhotic patients, present a trend towards more gram-positive infections, and especially enterococcal infections. This study aims to describe epidemiological differences in hospital-acquired bloodstream infections between cirrhotic and non-cirrhotic patients hospitalized in the ICU regarding infection sources, microorganisms and mortality. METHODS: Using prospective Eurobact-2 international cohort study data, we compared hospital-acquired bloodstream infections sources and microorganisms in cirrhotic and non-cirrhotic patients. The association between Enterococcus faecium and cirrhosis was studied using a multivariable mixed logistic regression. The association between cirrhosis and mortality was assessed by a multivariable frailty Cox model. RESULTS: Among the 1059 hospital-acquired bloodstream infections patients included from 101 centers, 160 had cirrhosis. Hospital-acquired bloodstream infection source in cirrhotic patients was primarily abdominal (35.6%), while it was pulmonary (18.9%) for non-cirrhotic (p < 0.01). Gram-positive hospital-acquired bloodstream infections accounted for 42.3% in cirrhotic patients compared to 33.2% in non-cirrhotic patients (p = 0.02). Hospital-acquired bloodstream infections in cirrhotic patients were most frequently caused by Klebsiella spp (16.5%), coagulase-negative Staphylococci (13.7%) and E. faecium (11.5%). E. faecium bacteremia was more frequent in cirrhotic patients (11.5% versus 4.5%, p < 0.01). After adjusting for possible confounding factors, cirrhosis was associated with higher E. faecium hospital-acquired bloodstream infections risk (Odds ratio 2.5, 95% CI 1.3-4.5, p < 0.01). Cirrhotic patients had increased mortality compared to non-cirrhotic patients (Hazard Ratio 1.3, 95% CI 1.01-1.7, p = 0.045). CONCLUSIONS: Critically ill cirrhotic patients with hospital-acquired bloodstream infections exhibit distinct epidemiology, with more Gram-positive infections and particularly Enterococcus faecium.

Epidemiology and risk factors for mortality in critically ill patients with pancreatic infection.

Background: The AbSeS-classification defines specific phenotypes of patients with intra-abdominal infection based on the (1) setting of infection onset (community-acquired, early onset, or late-onset hospital-acquired), (2) presence or absence of either localized or diffuse peritonitis, and (3) severity of disease expression (infection, sepsis, or septic shock). This classification system demonstrated reliable risk stratification in intensive care unit (ICU) patients with intra-abdominal infection. This study aimed to describe the epidemiology of ICU patients with pancreatic infection and assess the relationship between the components of the AbSeS-classification and mortality. Methods: This was a secondary analysis of an international observational study ("AbSeS") investigating ICU patients with intra-abdominal infection. Only patients with pancreatic infection were included in this analysis (n=165). Mortality was defined as ICU mortality within 28 days of observation for patients discharged earlier from the ICU. Relationships with mortality were assessed using logistic regression analysis and reported as odds ratio (OR) and 95% confidence interval (CI). Results: The overall mortality was 35.2% (n=58). The independent risk factors for mortality included older age (OR=1.03, 95% CI: 1.0 to 1.1 P=0.023), localized peritonitis (OR=4.4, 95% CI: 1.4 to 13.9 P=0.011), and persistent signs of inflammation at day 7 (OR=9.5, 95% CI: 3.8 to 23.9, P<0.001) or after the implementation of additional source control interventions within the first week (OR=4.0, 95% CI: 1.3 to 12.2, P=0.013). Gram-negative bacteria were most frequently isolated (n=58, 49.2%) without clinically relevant differences in microbial etiology between survivors and non-survivors. Conclusions: In pancreatic infection, a challenging source/damage control and ongoing pancreatic inflammation appear to be the strongest contributors to an unfavorable short-term outcome. In this limited series, essentials of the AbSeS-classification, such as the setting of infection onset, diffuse peritonitis, and severity of disease expression, were not associated with an increased mortality risk.ClinicalTrials.gov number: NCT03270345.

COVID-19-Associated Pulmonary Aspergillosis (CAPA) in Northern Greece during 2020-2022: A Comparative Study According to the Main Consensus Criteria and Definitions.

Coronavirus disease 2019 (COVID-19)-associated pulmonary aspergillosis (CAPA) has emerged as an important complication among patients with acute respiratory failure due to SARS-CoV-2 infection. Almost 2.5 years since the start of the COVID-19 pandemic, it continues to raise concerns as an extra factor that contributes to increased mortality, which is mostly because its diagnosis and management remain challenging. The present study utilises the cases of forty-three patients hospitalised between August 2020 and February 2022 whose information was gathered from ten ICUs and special care units based in northern Greece. The main aim was to describe the gained experience in diagnosing CAPA, according to the implementation of the main existing diagnostic consensus criteria and definitions, and present the different classification of the clinical cases due to the alternative algorithms.

Epidemiology and outcomes of hospital-acquired bloodstream infections in intensive care unit patients: the EUROBACT-2 international cohort study.

PURPOSE: In the critically ill, hospital-acquired bloodstream infections (HA-BSI) are associated with significant mortality. Granular data are required for optimizing management, and developing guidelines and clinical trials. METHODS: We carried out a prospective international cohort study of adult patients (≥ 18 years of age) with HA-BSI treated in intensive care units (ICUs) between June 2019 and February 2021. RESULTS: 2600 patients from 333 ICUs in 52 countries were included. 78% HA-BSI were ICU-acquired. Median Sequential Organ Failure Assessment (SOFA) score was 8 [IQR 5; 11] at HA-BSI diagnosis. Most frequent sources of infection included pneumonia (26.7%) and intravascular catheters (26.4%). Most frequent pathogens were Gram-negative bacteria (59.0%), predominantly Klebsiella spp. (27.9%), Acinetobacter spp. (20.3%), Escherichia coli (15.8%), and Pseudomonas spp. (14.3%). Carbapenem resistance was present in 37.8%, 84.6%, 7.4%, and 33.2%, respectively. Difficult-to-treat resistance (DTR) was present in 23.5% and pan-drug resistance in 1.5%. Antimicrobial therapy was deemed adequate within 24 h for 51.5%. Antimicrobial resistance was associated with longer delays to adequate antimicrobial therapy. Source control was needed in 52.5% but not achieved in 18.2%. Mortality was 37.1%, and only 16.1% had been discharged alive from hospital by day-28. CONCLUSIONS: HA-BSI was frequently caused by Gram-negative, carbapenem-resistant and DTR pathogens. Antimicrobial resistance led to delays in adequate antimicrobial therapy. Mortality was high, and at day-28 only a minority of the patients were discharged alive from the hospital. Prevention of antimicrobial resistance and focusing on adequate antimicrobial therapy and source control are important to optimize patient management and outcomes.

Comparison of Oligon catheters and chlorhexidine-impregnated sponges with standard multilumen central venous catheters for prevention of associated colonization and infections in intensive care unit patients: a multicenter, randomized, controlled study.

OBJECTIVE: To evaluate silver-impregnated (Oligon) central venous catheters and chlorhexidine-gluconate-impregnated sponges for reducing catheter-related colonization and infection, nonbacteremic or bacteremic. DESIGN: Multicenter, prospective, randomized, controlled study. SETTING: Five general intensive care units in Greece. PATIENTS: Intensive care unit patients requiring a multilumen central venous catheter between June 2006 and May 2008. INTERVENTIONS: Patients were randomly assigned to receive a standard catheter (standard group), a standard catheter plus chlorhexidine-gluconate-impregnated sponge (chlorhexidine-gluconate-impregnated sponge group), or an Oligon catheter (Oligon group). Catheter colonization was defined as a positive quantitative tip culture (≥10 colony-forming units/mL), catheter-related infection was defined by the previous criterion plus clinical evidence of sepsis, and bacteremia catheter-related infection as catheter-related infection plus a positive peripheral blood culture with the same micro-organism as in the catheter tip. MEASUREMENTS AND MAIN RESULTS: Data were obtained from 465 patients, 156 in the standard-group, 150 in the chlorhexidine-gluconate-impregnated sponge group, and 159 in the Oligon-group. Colonization occurred in 24 (15.4%) standard catheters, 21 (14%) in the chlorhexidine-gluconate-impregnated sponge group, and 25 (15.7%) in the Oligon catheters (p = .35) (20.9, 19.9, 21.8/1000 catheter-days, respectively). Catheter-related infections were recorded in nine (5.8%) standard catheters, six (4%) in the chlorhexidine-gluconate-impregnated sponge group, and seven (4.4%) in the Oligon catheters (p = .58) (7.8/1,000, 5.7/1,000, 6.1/1,000 catheter-days, respectively). No difference was observed between the chlorhexidine- gluconate-impregnated sponge group and the standard group regarding catheter colonization (hazard ratio 1.21; 95% confidence interval 0.56-2.61; p = .64) and catheter-related infections (hazard ratio 0.65; 95% confidence interval 0.23-1.85; p = .42). The Oligon catheter did not reduce colonization or catheter-related infections when compared with the standard catheter (colonization: hazard ratio 1.0; 95% confidence interval 0.46-2.21; p = .98; catheter-related infection: hazard ratio 0.72; 95% confidence interval 0.27-1.95; p = .52). Seven patients (1.5%, 2.09/1,000 catheter-days) presented bacteremic catheter-related infections. Central venous catheters inserted either in the internal jugular or the femoral vein had greater risk to be colonized than catheters inserted in the subclavian vein (internal jugular vs. subclavian: hazard ratio 3.29; 95% confidence interval 1.26-8.61; p = .01; femoral vs. subclavian: hazard ratio 3.36; 95% confidence interval 1.17-9.65; p = .02). Acinetobacter baumannii was the predominant pathogen (37.1% episodes of colonization, 36.4% catheter-related infections, 57.1% bacteremic catheter-related infections). CONCLUSION: For short-term (median duration 7 days) central venous catheters in intensive care units with high prevalence of multiresistant Gram-negative bacteria, chlorhexidine-impregnated sponges and Oligon catheters as single preventive measures did not reduce catheter colonization or catheter-related infections. As a result of the limited amount of events, no conclusion could be reached regarding bacteremic catheter-related infections. The femoral site was the most frequently colonized insertion site in all types of catheters.

The importance of colonization pressure in multiresistant Acinetobacter baumannii acquisition in a Greek intensive care unit.

INTRODUCTION: We investigated the role of colonization pressure on multiresistant Acinetobacter baumannii acquisition and defined patient-related predictors for carriage at admission and acquisition during hospitalization in intensive care unit (ICU) patients. METHODS: This was a 12-month, prospective, cohort study of all patients admitted to a single ICU of a tertiary hospital. Screening samples were collected at ICU admission to identify imported carriers, and weekly during hospitalization to identify acquisition. Colonization pressure (carriers' patient-days × 100/all patients' patient-days) and the absolute number of carriers were calculated weekly, and the statistical correlation between these parameters and acquisition was explored. Multivariable analysis was performed to identify predictors for A. baumannii carriage at admission and acquisition during hospitalization. A. baumannii isolates were genotyped by repetitive-extragenic-palindromic polymerase chain reaction (PCR; rep-PCR). RESULTS: At ICU admission, 284 patients were screened for carriage. A. baumannii was imported in 16 patients (5.6%), and acquisition occurred in 32 patients (15.7%). Acquisition was significantly correlated to weekly colonization pressure (correlation coefficient, 0.379; P = 0.004) and to the number of carriers per week (correlation coefficient, 0.499; P <0.001). More than one carrier per week significantly increased acquisition risk (two to three carriers, odds ratio (OR), 12.66; P = 0.028; more than four carriers, OR, 25.33; P = 0.004). Predictors of carriage at admission were infection at admission (OR, 11.03; confidence interval (CI), 3.56 to 34.18; P < 0.01) and hospitalization days before ICU (OR, 1.09; CI, 1.01 to 1.16; P = 0.02). Predictors of acquisition were a medical reason for ICU admission (OR, 5.11; CI, 1.31 to 19.93; P = 0.02), duration of antibiotic administration in the unit (OR, 1.24; CI, 1.12 to 1.38; P < 0.001), and duration of mechanical ventilation (OR, 1.08; CI, 1.04 to 1.13; P = 0.001). All strains were multiresistant. Rep-PCR analysis showed one dominant cluster. CONCLUSIONS: Acquisition of multiresistant A. baumannii in ICU patients is strongly correlated to colonization pressure. High levels of colonization pressure and more than two carriers per week independently increase acquisition risk. Patient-related factors, such as infection at admission and long hospitalization before the ICU, can identify imported A. baumannii carriers. Medical patients with extended administration of antibiotics and long duration of mechanical ventilation in the ICU were the most vulnerable to acquisition.

Poor timing and failure of source control are risk factors for mortality in critically ill patients with secondary peritonitis.

PURPOSE: To describe data on epidemiology, microbiology, clinical characteristics and outcome of adult patients admitted in the intensive care unit (ICU) with secondary peritonitis, with special emphasis on antimicrobial therapy and source control. METHODS: Post hoc analysis of a multicenter observational study (Abdominal Sepsis Study, AbSeS) including 2621 adult ICU patients with intra-abdominal infection in 306 ICUs from 42 countries. Time-till-source control intervention was calculated as from time of diagnosis and classified into 'emergency' (< 2 h), 'urgent' (2-6 h), and 'delayed' (> 6 h). Relationships were assessed by logistic regression analysis and reported as odds ratios (OR) and 95% confidence interval (CI). RESULTS: The cohort included 1077 cases of microbiologically confirmed secondary peritonitis. Mortality was 29.7%. The rate of appropriate empiric therapy showed no difference between survivors and non-survivors (66.4% vs. 61.3%, p = 0.1). A stepwise increase in mortality was observed with increasing Sequential Organ Failure Assessment (SOFA) scores (19.6% for a value ≤ 4-55.4% for a value > 12, p < 0.001). The highest odds of death were associated with septic shock (OR 3.08 [1.42-7.00]), late-onset hospital-acquired peritonitis (OR 1.71 [1.16-2.52]) and failed source control evidenced by persistent inflammation at day 7 (OR 5.71 [3.99-8.18]). Compared with 'emergency' source control intervention (< 2 h of diagnosis), 'urgent' source control was the only modifiable covariate associated with lower odds of mortality (OR 0.50 [0.34-0.73]). CONCLUSION: 'Urgent' and successful source control was associated with improved odds of survival. Appropriateness of empirical antimicrobial treatment did not significantly affect survival suggesting that source control is more determinative for outcome.

Epidemiology and age-related mortality in critically ill patients with intra-abdominal infection or sepsis: an international cohort study.

OBJECTIVE: To describe epidemiology and age-related mortality in critically ill older adults with intra-abdominal infection. METHODS: A secondary analysis was undertaken of a prospective, multi-national, observational study (Abdominal Sepsis Study, ClinicalTrials.gov #NCT03270345) including patients with intra-abdominal infection from 309 intensive care units (ICUs) in 42 countries between January and December 2016. Mortality was considered as ICU mortality, with a minimum of 28 days of observation when patients were discharged earlier. Relationships with mortality were assessed by logistic regression analysis. RESULTS: The cohort included 2337 patients. Four age groups were defined: middle-aged patients [reference category; 40-59 years; n=659 (28.2%)], young-old patients [60-69 years; n=622 (26.6%)], middle-old patients [70-79 years; n=667 (28.5%)] and very old patients [≥80 years; n=389 (16.6%)]. Secondary peritonitis was the predominant infection (68.7%) and was equally prevalent across age groups. Mortality increased with age: 20.9% in middle-aged patients, 30.5% in young-old patients, 31.2% in middle-old patients, and 44.7% in very old patients (P<0.001). Compared with middle-aged patients, young-old age [odds ratio (OR) 1.62, 95% confidence interval (CI) 1.21-2.17], middle-old age (OR 1.80, 95% CI 1.35-2.41) and very old age (OR 3.69, 95% CI 2.66-5.12) were independently associated with mortality. Other independent risk factors for mortality included late-onset hospital-acquired intra-abdominal infection, diffuse peritonitis, sepsis/septic shock, source control failure, liver disease, congestive heart failure, diabetes and malnutrition. CONCLUSIONS: For ICU patients with intra-abdominal infection, age >60 years was associated with mortality; patients aged ≥80 years had the worst prognosis. Comorbidities and overall disease severity further compromised survival. As all of these factors are non-modifiable, it remains unclear how to improve outcomes.