A Nationwide, Prospective Study of Tracheal Intubation in Critically Ill Adults in Spain: Management, Associated Complications, and Outcomes.

OBJECTIVES: Our aims were to explore current intubation practices in Spanish ICUs to determine the incidence and risk factors of peri-intubation complications (primary outcome measure: major adverse events), the rate and factors associated with first-pass success, and their impact on mortality as well as the changes of the intubation procedure observed in the COVID-19 pandemic. DESIGN: Prospective, observational, and cohort study. SETTING: Forty-three Spanish ICU. PATIENTS: A total of 1837 critically ill adult patients undergoing tracheal intubation. The enrollment period was six months (selected by each center from April 16, 2019, to October 31, 2020). INTERVENTIONS: None. MEASUREMENT AND MAIN RESULTS: At least one major adverse peri-intubation event occurred in 40.4 % of the patients (973 major adverse events were registered) the most frequent being hemodynamic instability (26.5%) and severe hypoxemia (20.3%). The multivariate analysis identified seven variables independently associated with a major adverse event whereas the use of neuromuscular blocking agents (NMBAs) was associated with reduced odds of major adverse events. Intubation on the first attempt was achieved in 70.8% of the patients. The use of videolaryngoscopy at the first attempt was the only protective factor (odds ratio 0.43; 95% CI, 0.28-0.66; p < 0.001) for first-attempt intubation failure. During the COVID-19 pandemic, the use of videolaryngoscopy and NMBAs increased significantly. The occurrence of a major peri-intubation event was an independent risk factor for 28-day mortality. Cardiovascular collapse also posed a serious threat, constituting an independent predictor of death. CONCLUSIONS: A major adverse event occurred in up to 40% of the adults intubated in the ICU. Peri-intubation hemodynamic instability but not severe hypoxemia was identified as an independent predictor of death. The use of NMBAs was a protective factor for major adverse events, whereas the use of videolaringoscopy increases the first-pass success rate of intubation. Intubation practices changed during the COVID-19 pandemic.

Clustering COVID-19 ARDS patients through the first days of ICU admission. An analysis of the CIBERESUCICOVID Cohort.

BACKGROUND: Acute respiratory distress syndrome (ARDS) can be classified into sub-phenotypes according to different inflammatory/clinical status. Prognostic enrichment was achieved by grouping patients into hypoinflammatory or hyperinflammatory sub-phenotypes, even though the time of analysis may change the classification according to treatment response or disease evolution. We aimed to evaluate when patients can be clustered in more than 1 group, and how they may change the clustering of patients using data of baseline or day 3, and the prognosis of patients according to their evolution by changing or not the cluster. METHODS: Multicenter, observational prospective, and retrospective study of patients admitted due to ARDS related to COVID-19 infection in Spain. Patients were grouped according to a clustering mixed-type data algorithm (k-prototypes) using continuous and categorical readily available variables at baseline and day 3. RESULTS: Of 6205 patients, 3743 (60%) were included in the study. According to silhouette analysis, patients were grouped in two clusters. At baseline, 1402 (37%) patients were included in cluster 1 and 2341(63%) in cluster 2. On day 3, 1557(42%) patients were included in cluster 1 and 2086 (57%) in cluster 2. The patients included in cluster 2 were older and more frequently hypertensive and had a higher prevalence of shock, organ dysfunction, inflammatory biomarkers, and worst respiratory indexes at both time points. The 90-day mortality was higher in cluster 2 at both clustering processes (43.8% [n = 1025] versus 27.3% [n = 383] at baseline, and 49% [n = 1023] versus 20.6% [n = 321] on day 3). Four hundred and fifty-eight (33%) patients clustered in the first group were clustered in the second group on day 3. In contrast, 638 (27%) patients clustered in the second group were clustered in the first group on day 3. CONCLUSIONS: During the first days, patients can be clustered into two groups and the process of clustering patients may change as they continue to evolve. This means that despite a vast majority of patients remaining in the same cluster, a minority reaching 33% of patients analyzed may be re-categorized into different clusters based on their progress. Such changes can significantly impact their prognosis.

ERS/ESICM/ESCMID/ALAT guidelines for the management of severe community-acquired pneumonia.

BACKGROUND: Severe community-acquired pneumonia (sCAP) is associated with high morbidity and mortality, and while European and non-European guidelines are available for community-acquired pneumonia, there are no specific guidelines for sCAP. MATERIALS AND METHODOLOGY: The European Respiratory Society (ERS), European Society of Intensive Care Medicine (ESICM), European Society of Clinical Microbiology and Infectious Diseases (ESCMID) and Latin American Thoracic Association (ALAT) launched a task force to develop the first international guidelines for sCAP. The panel comprised a total of 18 European and four non-European experts, as well as two methodologists. Eight clinical questions for sCAP diagnosis and treatment were chosen to be addressed. Systematic literature searches were performed in several databases. Meta-analyses were performed for evidence synthesis, whenever possible. The quality of evidence was assessed with GRADE (Grading of Recommendations, Assessment, Development and Evaluation). Evidence to Decision frameworks were used to decide on the direction and strength of recommendations. RESULTS: Recommendations issued were related to diagnosis, antibiotics, organ support, biomarkers and co-adjuvant therapy. After considering the confidence in effect estimates, the importance of outcomes studied, desirable and undesirable consequences of treatment, cost, feasibility, acceptability of the intervention and implications to health equity, recommendations were made for or against specific treatment interventions. CONCLUSIONS: In these international guidelines, ERS, ESICM, ESCMID and ALAT provide evidence-based clinical practice recommendations for diagnosis, empirical treatment and antibiotic therapy for sCAP, following the GRADE approach. Furthermore, current knowledge gaps have been highlighted and recommendations for future research have been made.

Evaluation of health outcomes after the implementation of rotational thromboelastometry in patients undergoing cardiac surgery.

BACKGROUND: Viscoelastic tests (rotational thromboelastometry, ROTEM®), together with the implementation of a specific algorithm for coagulation management in cardiac surgery, enable perioperative coagulopathy to be better controlled. METHODS: Retrospective cohort study including 675 patients who underwent cardiac surgery with cardiopulmonary bypass. The incidence of allogeneic blood transfusions and clinical postoperative complications were analyzed before and after ROTEM® implementation. RESULTS: Following viscoelastic testing and the implementation of a specific algorithm for coagulation management, the incidence of any allogeneic blood transfusion decreased (41.4% vs 31.9%, p = .026) during the perioperative period. In the group monitored with ROTEM®, decreased incidence of transfusion was observed for packed red blood cells (31.3% vs 19.8%, p = .002), fresh frozen plasma (9.8% vs 3.8%, p = .008), prothrombin complex concentrate administration (0.9% vs 0.3%, p = .599) and activated recombinant factor VII (0.3% vs 0.0%, p = .603). Increased incidence was observed for platelet transfusion (4.8% vs 6.8%, p = .530) and fibrinogen concentrate (0.9% vs 3.5%, p = .066), tranexamic acid (0.0% vs 0.6%, p = .370) and protamine administration (0.6% vs 0.9%, p = .908). Similar results were observed in the postoperative period, but with a decreased incidence of platelet transfusion (4.8% vs 3.8%, p = .813). In addition, statistically significant reductions were detected in the incidence of postoperative bleeding (9.5% vs 5.3%, p = .037), surgical reexploration (6.0% vs 2.9%, p = .035), and length of Intensive Care Unit (ICU) stay (6.0 days vs 5.3 days, p = .026). CONCLUSIONS: The monitoring of hemostasis by ROTEM® in cardiac surgery, was associated with decreased incidence of allogeneic blood transfusion, clinical hematologic postoperative complications and lengths of ICU stay.

Effectiveness and safety of the Space GlucoseControl system for glycaemia control in caring for postoperative cardiac surgical patients.

BACKGROUND: Hyperglycaemia is a very common complication in post-cardiac surgical patients, and as such, it must be properly managed. For this purpose, the enhanced Model Predictive Control algorithm for glycaemia control has been implemented into a nurse-led device called Space GlucoseControl (SGC) that aims to achieve a safe and effective blood glucose control in a better way than the traditional "paper-based" protocols. PURPOSE: The aim of the study was to know the effectiveness and safety of the SGC in glycaemia control in cardiosurgical adult patients in the immediate postoperative period in the intensive care unit. METHODS: A prospective before-and-after intervention study was conducted. One hundred sixty cardiosurgical adult patients with hyperglycaemia were selected: 80 in the control group from May to November 2018 and 80 in the intervention group (use of the SGC device) from January to December 2019. The primary outcome was the percentage of time within the target range (140-180 mg/dL in the control group and 100-160 mg/dL in the intervention group). RESULTS: The percentage of time within the target range was significantly higher in the SGC group than in the control group (70.5% [58.25-80] vs 54.83% [36.09-75], p < 0.001). The range was also achieved earlier with the SGC (5 [3-6.875] hours vs 7 [4-11] hours; p < 0.05). The first blood glucose value after reaching the target range was higher in the control group, with statistical significance (p < 0.05). There were no hypoglycaemia episodes in the control group. However, during SGC treatment, six episodes of hypoglycaemia occurred, and all of them were nonsevere (mean value = 61 mg/dL). CONCLUSION: The SGC is useful to achieve a faster tight glycaemic control, with a higher percentage of time within the target range, although episodes of nonsevere hypoglycaemia could be observed.

Timing of antibiotic therapy in the ICU.

Severe or life threatening infections are common among patients in the intensive care unit (ICU). Most infections in the ICU are bacterial or fungal in origin and require antimicrobial therapy for clinical resolution. Antibiotics are the cornerstone of therapy for infected critically ill patients. However, antibiotics are often not optimally administered resulting in less favorable patient outcomes including greater mortality. The timing of antibiotics in patients with life threatening infections including sepsis and septic shock is now recognized as one of the most important determinants of survival for this population. Individuals who have a delay in the administration of antibiotic therapy for serious infections can have a doubling or more in their mortality. Additionally, the timing of an appropriate antibiotic regimen, one that is active against the offending pathogens based on in vitro susceptibility, also influences survival. Thus not only is early empiric antibiotic administration important but the selection of those agents is crucial as well. The duration of antibiotic infusions, especially for ß-lactams, can also influence antibiotic efficacy by increasing antimicrobial drug exposure for the offending pathogen. However, due to mounting antibiotic resistance, aggressive antimicrobial de-escalation based on microbiology results is necessary to counterbalance the pressures of early broad-spectrum antibiotic therapy. In this review, we examine time related variables impacting antibiotic optimization as it relates to the treatment of life threatening infections in the ICU. In addition to highlighting the importance of antibiotic timing in the ICU we hope to provide an approach to antimicrobials that also minimizes the unnecessary use of these agents. Such approaches will increasingly be linked to advances in molecular microbiology testing and artificial intelligence/machine learning. Such advances should help identify patients needing empiric antibiotic therapy at an earlier time point as well as the specific antibiotics required in order to avoid unnecessary administration of broad-spectrum antibiotics.

The evolution of the ventilatory ratio is a prognostic factor in mechanically ventilated COVID-19 ARDS patients.

BACKGROUND: Mortality due to COVID-19 is high, especially in patients requiring mechanical ventilation. The purpose of the study is to investigate associations between mortality and variables measured during the first three days of mechanical ventilation in patients with COVID-19 intubated at ICU admission. METHODS: Multicenter, observational, cohort study includes consecutive patients with COVID-19 admitted to 44 Spanish ICUs between February 25 and July 31, 2020, who required intubation at ICU admission and mechanical ventilation for more than three days. We collected demographic and clinical data prior to admission; information about clinical evolution at days 1 and 3 of mechanical ventilation; and outcomes. RESULTS: Of the 2,095 patients with COVID-19 admitted to the ICU, 1,118 (53.3%) were intubated at day 1 and remained under mechanical ventilation at day three. From days 1 to 3, PaO2/FiO2 increased from 115.6 [80.0-171.2] to 180.0 [135.4-227.9] mmHg and the ventilatory ratio from 1.73 [1.33-2.25] to 1.96 [1.61-2.40]. In-hospital mortality was 38.7%. A higher increase between ICU admission and day 3 in the ventilatory ratio (OR 1.04 [CI 1.01-1.07], p = 0.030) and creatinine levels (OR 1.05 [CI 1.01-1.09], p = 0.005) and a lower increase in platelet counts (OR 0.96 [CI 0.93-1.00], p = 0.037) were independently associated with a higher risk of death. No association between mortality and the PaO2/FiO2 variation was observed (OR 0.99 [CI 0.95 to 1.02], p = 0.47). CONCLUSIONS: Higher ventilatory ratio and its increase at day 3 is associated with mortality in patients with COVID-19 receiving mechanical ventilation at ICU admission. No association was found in the PaO2/FiO2 variation.

Intensive care nurses' experiences during the COVID-19 pandemic: A qualitative study.

BACKGROUND: Because of the COVID-19 pandemic, health care systems worldwide are working under challenging conditions. Patients, who are seriously ill, require intensive care admission. In fighting COVID-19, nurses are frontline health care workers and, as such, have a great responsibility providing needed specialized patient care in intensive care units (ICU). However, working conditions and emotional factors have an impact on the quality of the care provided. AIM: The purpose of the present study was to explore and describe the experiences and perceptions of nurses working in an ICU during the COVID-19 global pandemic. STUDY DESIGN: Qualitative research was undertaken, using an empirical approach and inductive content analysis techniques. METHODS: The selected population consisted of ICU nurses from a tertiary teaching hospital in Spain. Data were obtained via semi-structured videocall interviews from Apr 12th to Apr 30th, 2020. Subsequently, transcribed verbatims were analysed using the template analysis model of Brooks. FINDINGS: A total of 17 nurses comprised the final sample after data saturation. Four main themes emerged from the analysis and 13 subthemes: "providing nursing care," "psychosocial aspects and emotional lability," "resources management and safety" and "professional relationships and fellowship." CONCLUSION: Providing health care by intensive care nursing professionals, during the COVID-19 pandemic, has shown both strong and weak points in the health care system. Nursing care has been influenced by fear and isolation, making it hard to maintain the humanization of the health care. RELEVANCE TO CLINICAL PRACTICE: Implications for practice include optimizing resource management (human and material), providing psychological support, and adequate training for ICU nurses, as well as high-quality protocols for future emergency situations.

Managing Acinetobacter baumannii infections.

PURPOSE OF REVIEW: We reviewed recent data about epidemiology of Acinetobacter baumannii, resistance mechanisms, and therapeutic options for severe infections caused by multidrug-resistant strains. RECENT FINDINGS: A. baumannii is a major cause of nosocomial infections affecting mainly to debilitating patients in the ICU, although the spread to regular wards and to long-term care facilities is increasing. It is characterized by its great persistence in the environment and to have an extraordinary capability to develop resistance to all antimicrobials.Carbapenems may not be considered the treatment of choice in areas with high rates of carbapenem-resistant A. baumannii. Nowadays, polymyxins are the antimicrobials with the greatest level of in-vitro activity against A. baumannii. Colistin is the most widely used in clinical practice although polymyxin B seems to be associated with less renal toxicity. Colistin is administered intravenously as its inactive prodrug colistimethate. A loading dose of 9 million IU and subsequently high, extended-interval maintenance doses (4.5 million IU/12 h) are recommended. Combination therapy instead of monotherapy increases the rates of microbiological eradication although no clinical study has demonstrated a reduction in clinical outcomes (mortality or length of stay). SUMMARY: The optimal treatment for multidrug-resistant A. baumannii nosocomial infections has not been established. There are no compelling data to recommend combination therapy for severe A. baumannii infections.

How should we treat acinetobacter pneumonia?

PURPOSE OF REVIEW: To describe recent data about Acinetobacter baumannii pneumonia epidemiology and the therapeutic options including adjunctive nebulized therapy. RECENT FINDINGS: A. baumannii is a major cause of nosocomial pneumonia in certain geographic areas affecting mainly debilitated patients, with prolonged hospitalization and broad-spectrum antimicrobials. Inappropriate empirical treatment has clearly been associated with increased mortality in A. baumannii pneumonia. Carbapenems may not be considered the treatment of choice in areas with high rates of carbapenem-resistant A. baumannii. Nowadays, polymyxins are the antimicrobials with the greatest level of in-vitro activity. Colistin is the antimicrobial most widely used although polymyxin B is associated with less renal toxicity. It is clear that lung concentrations of polymyxins are suboptimal in a substantial proportion of patients. This issue has justified the use of combination therapy or adjunctive nebulized antibiotics. Current evidence does not allow us to recommend combination therapy for A. baumannii pneumonia. Regarding nebulized antibiotics, it seems reasonable to use in patients who are nonresponsive to systemic antibiotics or A. baumannii isolates with colistin minimum inhibitory concentrations close to the susceptibility breakpoints. Cefiderocol, a novel cephalosporin active against A. baumannii, may represent an attractive therapeutic option if ongoing clinical trials confirm preliminary results. SUMMARY: The optimal treatment for multidrug-resistant A. baumannii pneumonia has not been established. New therapeutic options are urgently needed. Well designed, randomized controlled trials must been conducted to comprehensively evaluate the effectiveness and safety of nebulized antibiotics for the treatment of A. baumannii pneumonia.

Usefulness of guideline recommendations for prognosis in patients with candidemia.

We aimed to analyze whether the lack of inclusion of specific recommendations for the management of candidemia is an independent risk factor for early and overall mortality. Multicenter study of adult patients with candidemia in 13 hospitals. We assessed the proportion of patients on whom nine specific ESCMID and IDSA guidelines recommendations had been applied, and analyzed its impact on mortality. 455 episodes of candidemia were documented. Patients who died within the first 48 hours were excluded. Sixty-two percent of patients received an appropriate antifungal treatment. Either echinocandin or amphotericin B therapy were administered in 43% of patients presenting septic shock and in 71% of those with neutropenia. Sixty-one percent of patients with breakthrough candidemia underwent a change in antifungal drug class. Venous catheters were removed in 79% of cases. Follow-up blood cultures were performed in 72% of cases. Ophthalmoscopy and echocardiogram were performed in 48% and 50% of patients, respectively. Length of treatment was appropriate in 78% of cases. Early (2-7 days) and overall (2-30 days) mortality were 8% and 27.7%, respectively. Inclusion of less than 50% of the specific recommendations was independently associated with a higher early (HR = 7.02, 95% CI: 2.97-16.57; P < .001) and overall mortality (HR = 3.55, 95% CI: 2.24-5.64; P < .001). In conclusion, ESCMID and IDSA guideline recommendations were not performed on a significant number of patients. Lack of inclusion of these recommendations proved to be an independent risk factor for early and overall mortality.

A case of pan-resistant Burkholderia cepacia complex bacteremic pneumonia, after lung transplantation treated with a targeted combination therapy.

We describe a case of one patient with cystic fibrosis who developed a pan-resistant Burkholderia cepacia complex rapidly progressive bacteraemic pneunonia, following bilateral lung transplantation. The patient was treated with a targeted combination antibiotic therapy (meropenem plus ceftazidime/avibactam plus high doses of nebulized colistimethate sodium). Evolution of the disease was complicated by multiple organ system dysfunction. Finally, clinical improvement and microbiological cure was achieved.

Colistin versus meropenem in the empirical treatment of ventilator-associated pneumonia (Magic Bullet study): an investigator-driven, open-label, randomized, noninferiority controlled trial.

BACKGROUND: Colistin is recommended in the empirical treatment of ventilator-associated pneumonia (VAP) with a high prevalence of carbapenem-resistant gram-negative bacilli (CR-GNB). However, the efficacy and safety of colistin are not well defined. METHODS: A multicenter prospective randomized trial conducted in 32 European centers compared the efficacy and safety of colistin (4.5 million unit loading dose followed by a maintenance dose of 3 million units every 8 h) versus meropenem (2 g every 8 h), both in combination with levofloxacin (500 mg every 12 h) for 7-14 days in patients with late VAP. Between May 2012 and October 2015, 232 patients were randomly assigned to the 2 treatment groups. The primary endpoint was mortality at 28 days after randomization in the microbiologically modified intention-to-treat (mMITT) population. Secondary outcomes included clinical and microbiological cure, renal function at the end of the treatment, and serious adverse events. The study was interrupted after the interim analysis due to excessive nephrotoxicity in the colistin group; therefore, the sample size was not achieved. RESULTS: A total of 157 (67.7%) patients were included in the mMITT population, 36 of whom (22.9%) had VAP caused by CR-GNB. In the mMITT population, no significant difference in mortality between the colistin group (19/82, 23.2%) and the meropenem group (19/75, 25.3%) was observed, with a risk difference of - 2.16 (- 15.59 to 11.26, p = 0.377); the noninferiority of colistin was not demonstrated due to early termination and limited number of patients infected by carbapenem-resistant pathogens. Colistin plus levofloxacin increased the incidence of renal failure (40/120, 33.3%, versus 21/112, 18.8%; p = 0.012) and renal replacement therapy (11/120, 9.1%, versus 2/112, 1.8%; p = 0.015). CONCLUSIONS: This study did not demonstrate the noninferiority of colistin compared with meropenem, both combined with levofloxacin, in terms of efficacy in the empirical treatment of late VAP but demonstrated the greater nephrotoxicity of colistin. These findings do not support the empirical use of colistin for the treatment of late VAP due to early termination. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01292031. Registered 9 February 2011.

Developing definitions for invasive fungal diseases in critically ill adult patients in intensive care units. Protocol of the FUNgal infections Definitions in ICU patients (FUNDICU) project.

BACKGROUND: The reliability of diagnostic criteria for invasive fungal diseases (IFD) developed for severely immunocompromised patients is questionable in critically ill adult patients in intensive care units (ICU). OBJECTIVES: To develop a standard set of definitions for IFD in critically ill adult patients in ICU. METHODS: Based on a systematic literature review, a list of potential definitions to be applied to ICU patients will be developed by the ESCMID Study Group for Infections in Critically Ill Patients (ESGCIP) and the ESCMID Fungal Infection Study Group (EFISG) chairpersons. The proposed definitions will be evaluated by a panel of 30 experts using the RAND/UCLA appropriateness methods. The panel will rank each of the proposed definitions on a 1-9 scale trough a dedicated questionnaire, in two rounds: one remote and one face-to-face. Based on their median rank and the level of agreement across panel members, selected definitions will be organised in a main consensus document and in an executive summary. The executive summary will be made available online for public comments. CONCLUSIONS: The present consensus project will seek to provide standard definitions for IFD in critically ill adult patients in ICU, with the ultimate aims of improving their clinical outcome and facilitating the comparison and generalizability of research findings.

Initial Antifungal Strategy Reduces Mortality in Critically Ill Patients With Candidemia: A Propensity Score-Adjusted Analysis of a Multicenter Study.

OBJECTIVE: The objective of this study was to evaluate the impact of the empirical therapy with fluconazole or an echinocandin on 30- and 90-day mortality in critically ill patients with candidemia. The outcome of patients in whom the empirical echinocandin was deescalated to fluconazole was also assessed. DESIGN: Retrospective, observational multicenter study. SETTING: Medical and surgical ICUs in nine Spanish hospitals. PATIENTS: Adult patients (≥ 18 yr) with an episode of Candida bloodstream infection during ICU admission from January 2011 to April 2016. INTERVENTIONS: Patient characteristics, infection-related variables, therapeutic interventions, and metastatic complications were reviewed. A propensity score-adjusted multivariable analysis was performed to identify the risk factors significantly associated with 30-day and 90-day mortality. MEASUREMENTS AND MAIN RESULTS: A total of 294 patients were diagnosed of candidemia in the participant ICUs. Sixty patients were excluded (other antifungals in the primary therapy or the patient died without empirical antifungal therapy). The study group comprised 115 patients who received fluconazole (30-day mortality, 37.4%) and 119 patients treated empirically with an echinocandin (30-day mortality, 31.9%). The use of an echinocandin in the empirical therapy was a protective factor for 30-day (odds ratio, 0.32; 95% CI, 0.16-0.66; p = 0.002) and 90-day mortality (odds ratio, 0.50; 95% CI, 0.27-0.93; p = 0.014) in the propensity score- adjusted multivariable analysis. Deescalation of the empirical echinocandin to fluconazole was not associated with a higher mortality or the occurrence of long-term complications. CONCLUSIONS: Empirical use of an echinocandin in critically ill patients with documented candidemia reduces mortality at 30 and 90 days significantly. Deescalation of the empirical echinocandin to fluconazole is safe and effective in fluconazole-susceptible infections.

Overproduction of Outer Membrane Protein A by Acinetobacter baumannii as a Risk Factor for Nosocomial Pneumonia, Bacteremia, and Mortality Rate Increase.

Background: Outer membrane protein A (OmpA) is a porin involved in Acinetobacter baumannii pathogenesis. However, OmpA clinical implication in hospital-acquired infections remains unknown. We aimed to determine whether OmpA overproduction was a risk factor associated with pneumonia, bacteremia, and mortality. Methods: We analyzed demographic, microbiological, and clinical data from 100 patients included in a unicenter cohort and 246 included in a unicenter cohort and a multicenter cohort. Representative isolates were classified into 2 groups: (1) isolates from patients colonized by A. baumannii (16 from the unicenter and 20 from the multicenter cohort) and (2) isolates from bacteremic or nonbacteremic patients with pneumonia (PP) caused by A. baumannii (13 from the unicenter and 23 from the multicenter cohort) Expression of ompA was determined with quantitative reverse-transcription polymerase chain reaction. Results: Isolates from PP overexpressed more ompA than those from colonized patients from the unicenter (ratio, 1.76 vs 0.36; P < .001) and the multicenter (1.36 vs 0.91; P = .03) cohorts. Among isolates from PP, those from bacteremic patients overexpressed nonsignificantly more ompA than those from nonbacteremic patients in the unicenter (ratio, 2.37 vs 1.43; P = .06) and the multicenter (2.03 vs 0.91; P = .14) cohorts. Multivariate analysis in both cohorts together showed ompA overexpression as independent risk factor for pneumonia (P < .001), bacteremia (P = .005), and death (P = .049). Conclusions: These data suggest that ompA overexpression is an associated factor for pneumonia, bacteremia, and death due to A. baumannii.

Long-Term Impact of an Educational Antimicrobial Stewardship Program on Hospital-Acquired Candidemia and Multidrug-Resistant Bloodstream Infections: A Quasi-Experimental Study of Interrupted Time-Series Analysis.

BACKGROUND: The global crisis of bacterial resistance urges the scientific community to implement intervention programs in healthcare facilities to promote an appropriate use of antibiotics. However, the clinical benefits or the impact on resistance of these interventions has not been definitively proved. METHODS: We designed a quasi-experimental intervention study with an interrupted time-series analysis. A multidisciplinary team conducted a multifaceted educational intervention in our tertiary-care hospital over a 5-year period. The main activity of the program consisted of peer-to-peer educational interviews between counselors and prescribers from all departments to reinforce the principles of the proper use of antibiotics. We assessed antibiotic consumption, incidence density of Candida and multidrug-resistant (MDR) bacteria bloodstream infections (BSIs) and their crude death rate per 1000 occupied bed days (OBDs). RESULTS: A quick and intense reduction in antibiotic consumption occurred 6 months after the implementation of the intervention (change in level, -216.8 defined daily doses per 1000 OBDs; 95% confidence interval, -347.5 to -86.1), and was sustained during subsequent years (average reduction, -19,9%). In addition, the increasing trend observed in the preintervention period for the incidence density of candidemia and MDR BSI (+0.018 cases per 1000 OBDs per quarter; 95% confidence interval, -.003 to .039) reverted toward a decreasing trend of -0.130 per quarter (change in slope, -0.029; -.051 to -.008), and so did the mortality rate (change in slope, -0.015; -.021 to -.008). CONCLUSIONS: This education-based antimicrobial stewardship program was effective in decreasing the incidence and mortality rate of hospital-acquired candidemia and MDR BSI through sustained reduction in antibiotic use.

Epidemiology and prognosis of candidaemia in elderly patients.

The aim of the study was to analyse the epidemiology and prognosis of candidaemia in elderly patients. We performed a comparison of clinical presentation of candidaemia according to age and a study of hazard factors within a prospective programme performed in 29 hospitals. One hundred and seventy-six episodes occurred in elderly patients (>75 years), 227 episodes in middle-aged patients (61-75 years) and 232 episodes in younger patients (16-60 years). Central venous catheter, parenteral nutrition, neutropenia, immunosuppressive therapy and candidaemia caused by Candida parapsilosis were less frequent in elderly patients. These patients received inadequate antifungal therapy (57.3%) more frequently than middle-aged and younger patients (40.5% P < .001). Mortality during the first week (20%) and 30 days (42%) was higher in elderly patients. The variables independently associated with mortality in elderly patients during the first 7 days were acute renal failure (OR: 2.64), Pitt score (OR: 1.57) and appropriate antifungal therapy (OR: 0.132). Primary candidaemia (OR: 2.93), acute renal failure (OR: 3.68), Pitt score (OR: 1.38), appropriate antifungal therapy (OR: 0.3) and early removal of the central catheter (OR: 0.47) were independently associated with 30-day mortality.In conclussion, inadequate antifungal treatment is frequently prescribed to elderly patients with candidaemia and is related with early and late mortality.

A Systematic Review of the Definitions, Determinants, and Clinical Outcomes of Antimicrobial De-escalation in the Intensive Care Unit.

Antimicrobial de-escalation (ADE) is a strategy to reduce the spectrum of antimicrobials and aims to prevent the emergence of bacterial resistance. We present a systematic review describing the definitions, determinants and outcomes associated with ADE. We included 2 randomized controlled trials and 12 cohort studies. There was considerable variability in the definition of ADE. It was more frequently performed in patients with broad-spectrum and/or appropriate antimicrobial therapy (P= .05 to .002), when more agents were used (P= .002), and in the absence of multidrug-resistant pathogens (P< .05). Where investigated, lower or improving severity scores were consistently associated with ADE (P= .04 to <.001). The pooled effect of ADE on mortality is protective (relative risk, 0.68; 95% confidence interval, .52-.88). Because the determinants of ADE are markers of clinical improvement and/or of lower risk of treatment failure this effect on mortality cannot be retained as evidence. None of the studies were designed to investigate the effect of ADE on antimicrobial resistance.