Rafael Zaragoza

Community-acquired respiratory coinfection in critically ill patients with pandemic 2009 influenza A(H1N1) virus.

BACKGROUND Little is known about the impact of community-acquired respiratory coinfection in patients with pandemic 2009 influenza A(H1N1) virus infection. METHODS This was a prospective, observational, multicenter study conducted in 148 Spanish ICUs. RESULTS Severe respiratory syndrome was present in 645 ICU patients. Coinfection occurred in 113 (17.5%) of patients. Streptococcus pneumoniae (in 62 patients [54.8%]) was identified as the most prevalent bacteria. Patients with coinfection at ICU admission were older (47.5±15.7 vs 43.8±14.2 years, P<.05) and presented a higher APACHE (Acute Physiology and Chronic Health Evaluation) II score (16.1±7.3 vs 13.3±7.1, P<.05) and Sequential Organ Failure Assessment (SOFA) score (7.0±3.8 vs 5.2±3.5, P<.05). No differences in comorbidities were observed. Patients who had coinfection required vasopressors (63.7% vs 39.3%, P<.05) and invasive mechanical ventilation (69% vs 58.5%, P<.05) more frequently. ICU length of stay was 3 days longer in patients who had coinfection than in patients who did not (11 [interquartile range, 5-23] vs 8 [interquartile range 4-17], P=.01). Coinfection was associated with increased ICU mortality (26.2% vs 15.5%; OR, 1.94; 95% CI, 1.21-3.09), but Cox regression analysis adjusted by potential confounders did not confirm a significant association between coinfection and ICU mortality. CONCLUSIONS During the 2009 pandemics, the role played by bacterial coinfection in bringing patients to the ICU was not clear, S pneumoniae being the most common pathogen. This work provides clear evidence that bacterial coinfection is a contributor to increased consumption of health resources by critical patients infected with the virus and is the virus that causes critical illness in the vast majority of cases.

Impact of therapeutic strategies on the prognosis of candidemia in the ICU.

Objectives:To determine the epidemiology of Candida bloodstream infections, variables influencing mortality, and antifungal resistance rates in ICUs in Spain. Design:Prospective, observational, multicenter population-based study. Setting:Medical and surgical ICUs in 29 hospitals distributed throughout five metropolitan areas of Spain. Patients:Adult patients (≥ 18 yr) with an episode of Candida bloodstream infection during admission to any surveillance area ICU from May 2010 to April 2011. Interventions:Candida isolates were sent to a reference laboratory for species identification by DNA sequencing and susceptibility testing using the methods and breakpoint criteria promulgated by the European Committee on Antimicrobial Susceptibility Testing. Prognostic factors associated with early (0–7 d) and late (8–30 d) mortality were analyzed using logistic regression modeling. Measurements and Main Results:We detected 773 cases of candidemia, 752 of which were included in the overall cohort. Among these, 168 (22.3%) occurred in adult ICU patients. The rank order of Candida isolates was as follows: Candida albicans (52%), Candida parapsilosis (23.7%), Candida glabrata (12.7%), Candida tropicalis (5.8%), Candida krusei (4%), and others (1.8%). Overall susceptibility to fluconazole was 79.2%. Cumulative mortality at 7 and 30 days after the first episode of candidemia was 16.5% and 47%, respectively. Multivariate analysis showed that early appropriate antifungal treatment and catheter removal (odds ratio, 0.27; 95% CI, 0.08–0.91), Acute Physiology and Chronic Health Evaluation II score (odds ratio, 1.11; 95% CI, 1.04–1.19), and abdominal source (odds ratio, 8.15; 95% CI, 1.75–37.93) were independently associated with early mortality. Determinants of late mortality were age (odds ratio, 1.04; 95% CI, 1.01–1.07), intubation (odds ratio, 7.24; 95% CI, 2.24–23.40), renal replacement therapy (odds ratio, 6.12; 95% CI, 2.24–16.73), and primary source (odds ratio, 2.51; 95% CI, 1.06–5.95). Conclusions:Candidemia in ICU patients is caused by non-albicans species in 48% of cases, C. parapsilosis being the most common among these. Overall mortality remains high and mainly related with host factors. Prompt adequate antifungal treatment and catheter removal could be critical to decrease early mortality.

Prognostic factors of mortality in patients with community-acquired bloodstream infection with severe sepsis and septic shock ☆,☆☆

PURPOSE The purpose of the study was to determine the independent risk factors on mortality in patients with community-acquired severe sepsis and septic shock. METHODS A single-site prospective cohort study was carried out in a medical-surgical intensive care unit in an academic tertiary care center. One hundred twelve patients with community-acquired bloodstream infection with severe sepsis and septic shock were identified. Clinical, microbiologic, and laboratory parameters were compared between hospital survivors and hospital deaths. RESULTS One-hundred twelve patients were included. The global mortality rate was 41.9%, 44.5% in septic shock and 34.4% in severe sepsis. One or more comorbidities were present in 66% of patients. The most commonly identified bloodstream pathogens were Escherichia coli (25%) and Staphylococcus aureus (21.4%). The proportion of patients receiving inadequate antimicrobial treatment was 8.9%. By univariate analysis, age, Acute Physiology and Chronic Health Evaluation II score, at least 3 organ dysfunctions, and albumin, but neither microbiologic characteristics nor site of infection, differed significantly between survivors and nonsurvivors. Acute Physiology and Chronic Health Evaluation II (odds ratio, 1.13; 95% confidence interval, 1.06-1.21) and albumin (odds ratio, 0.34; 95% confidence interval, 0.15-0.76) were independent risk factors associated with global mortality in logistic regression analysis. CONCLUSION In addition to the severity of illness, hypoalbuminemia was identified as the most important prognostic factor in community-acquired bloodstream infection with severe sepsis and septic shock.

Ventilatory support in critically ill hematology patients with respiratory failure.

IntroductionHematology patients admitted to the ICU frequently experience respiratory failure and require mechanical ventilation. Noninvasive mechanical ventilation (NIMV) may decrease the risk of intubation, but NIMV failure poses its own risks.MethodsTo establish the impact of ventilatory management and NIMV failure on outcome, data from a prospective, multicenter, observational study were analyzed. All hematology patients admitted to one of the 34 participating ICUs in a 17-month period were followed up. Data on demographics, diagnosis, severity, organ failure, and supportive therapies were recorded. A logistic regression analysis was done to evaluate the risk factors associated with death and NIVM failure.ResultsOf 450 patients, 300 required ventilatory support. A diagnosis of congestive heart failure and the initial use of NIMV significantly improved survival, whereas APACHE II score, allogeneic transplantation, and NIMV failure increased the risk of death. The risk factors associated with NIMV success were age, congestive heart failure, and bacteremia. Patients with NIMV failure experienced a more severe respiratory impairment than did those electively intubated.ConclusionsNIMV improves the outcome of hematology patients with respiratory insufficiency, but NIMV failure may have the opposite effect. A careful selection of patients with rapidly reversible causes of respiratory failure may increase NIMV success.

Initial Use of Echinocandins Does Not Negatively Influence Outcome in Candida parapsilosis Bloodstream Infection: A Propensity Score Analysis

BACKGROUND Concerns have arisen regarding the optimal antifungal regimen for Candida parapsilosis bloodstream infection (BSI) in view of its reduced susceptibility to echinocandins. METHODS The Prospective Population Study on Candidemia in Spain (CANDIPOP) is a prospective multicenter, population-based surveillance program on Candida BSI conducted through a 12-month period in 29 Spanish hospitals. Clinical isolates were identified by DNA sequencing, and antifungal susceptibility testing was performed by the European Committee on Antimicrobial Susceptibility Testing methodology. Predictors for clinical failure (all-cause mortality between days 3 to 30, or persistent candidemia for ≥72 hours after initiation of therapy) in episodes of C. parapsilosis species complex BSI were assessed by logistic regression analysis. We further analyzed the impact of echinocandin-based regimen as the initial antifungal therapy (within the first 72 hours) by using a propensity score approach. RESULTS Among 752 episodes of Candida BSI identified, 200 (26.6%) were due to C. parapsilosis species complex. We finally analyzed 194 episodes occurring in 190 patients. Clinical failure occurred in 58 of 177 (32.8%) of evaluable episodes. Orotracheal intubation (adjusted odds ratio [AOR], 2.81; P = .018) and septic shock (AOR, 2.91; P = .081) emerged as risk factors for clinical failure, whereas early central venous catheter removal was protective (AOR, 0.43; P = .040). Neither univariate nor multivariate analysis revealed that the initial use of an echinocandin-based regimen had any impact on the risk of clinical failure. Incorporation of the propensity score into the model did not change this finding. CONCLUSIONS The initial use of an echinocandin-based regimen does not seem to negatively influence outcome in C. parapsilosis BSI.

Current diagnostic approaches to invasive candidiasis in critical care settings

For the specialist, the management of invasive candidiasis infections, from diagnosis to selection of the therapeutic protocol, is often a challenge. Although early diagnosis and treatment are associated with a better prognosis, apart from cases with positive blood cultures or fluid/tissue biopsy, diagnosis is neither sensitive nor specific, relying on many different factors, clinical and laboratory findings but there is certainly a need for the specific markers in this disease. Recently, new serodiagnostic assays as Candida albicans germ‐tube antibodies or (1,3)‐β‐d‐glucan detection and molecular techniques for the detection of fungal‐specific DNA have been developed with controversial results in critical care setting. One of the main features in diagnosis is the evaluation of risk factor for infection, which will identify patients in need of preemptive or empirical treatment. Clinical scores were built from those risk factors. For these reasons, an approach to the new diagnosis tools in the clinical mycology laboratory and an analysis of the new prediction rules and its application situations has been made. Currently, the combination of prediction rules and non‐culture microbiological tools could be the clue for improving the diagnosis and prognosis of invasive fungal infections in critically ill patients.

Clinical factors associated with a Candida albicans Germ Tube Antibody positive test in Intensive Care Unit patients.

BackgroundPoor outcomes of invasive candidiasis (IC) are associated with the difficulty in establishing the microbiological diagnosis at an early stage. New scores and laboratory tests have been developed in order to make an early therapeutic intervention in an attempt to reduce the high mortality associated with invasive fungal infections. Candida albicans IFA IgG has been recently commercialized for germ tube antibody detection (CAGTA). This test provides a rapid and simple diagnosis of IC (84.4% sensitivity and 94.7% specificity). The aim of this study is to identify the patients who could be benefited by the use of CAGTA test in critical care setting.MethodsA prospective, cohort, observational multicentre study was carried out in six medical/surgical Intensive care units (ICU) of tertiary-care Spanish hospitals. Candida albicans Germ Tube Antibody test was performed twice a week if predetermined risk factors were present, and serologically demonstrated candidiasis was considered if the testing serum dilution was ≥ 1:160 in at least one sample and no other microbiological evidence of invasive candidiasis was found.ResultsFifty-three critically ill non-neutropenic patients (37.7% post surgery) were included. Twenty-two patients (41.5%) had CAGTA-positive results, none of them with positive blood culture for Candida. Neither corrected colonization index nor antifungal treatment had influence on CAGTA results. This finding could corroborate that the CAGTA may be an important biomarker to distinguish between colonization and infection in these patients. The presence of acute renal failure at the beginning of the study was more frequent in CAGTA-negative patients. Previous surgery was statistically more frequent in CAGTA-positive patients.ConclusionsThis study identified previous surgery as the principal clinical factor associated with CAGTA-positive results and emphasises the utility of this promising technique, which was not influenced by high Candida colonization or antifungal treatment. Our results suggest that detection of CAGTA may be important for the diagnosis of invasive candidiasis in surgical patients admitted in ICU.

Decrease in Mortality in Severe Community-Acquired Pneumococcal Pneumonia: Impact of Improving Antibiotic Strategies (2000-2013)

OBJECTIVE The objective of the present study was to compare antibiotic prescribing practices and survival in the ICU for patients with pneumococcal severe community-acquired pneumonia (SCAP) between 2000 and 2013. METHODS This was a matched case-control study of two prospectively recorded cohorts in Europe. Eighty patients from the Community-Acquired Pneumonia en la Unidad de Cuidados Intensivos (CAPUCI) II study (case group) were matched with 80 patients from CAPUCI I (control group) based on the following: shock at admission, need of mechanical ventilation, COPD, immunosuppression, and age. RESULTS Demographic data were comparable in the two groups. Combined antibiotic therapy increased from 66.2% to 87.5% (P < .01), and the percentage of patients receiving the first dose of antibiotic within 3 h increased from 27.5% to 70.0% (P < .01). ICU mortality was significantly lower (OR, 0.82; 95% CI, 0.68-0.98) in cases, both in the whole population and in the subgroups of patients with shock (OR, 0.67; 95% CI, 0.50-0.89) or receiving mechanical ventilation (OR, 0.73; 95% CI, 0.55-0.96). In the multivariate analysis, ICU mortality increased in patients requiring mechanical ventilation (OR, 5.23; 95% CI, 1.60-17.17) and decreased in patients receiving early antibiotic treatment (OR, 0.36; 95% CI, 0.15-0.87) and combined therapy (OR, 0.19; 95% CI, 0.07-0.51). CONCLUSIONS In pneumococcal SCAP, early antibiotic prescription and use of combination therapy increased. Both were associated with improved survival.

First influenza season after the 2009 pandemic influenza: report of the first 300 ICU admissions in Spain

INTRODUCTION During the 2009 influenza pandemic, several reports were published, nevertheless, data on the clinical profiles of critically ill patients with the new virus infection during this second outbreak are still lacking. MATERIAL METHODS Prospective, observational, multi-center study conducted in 148 Spanish intensive care units (ICU) during epidemiological weeks 50-52 of 2010 and weeks 1 - 4 of 2011. RESULTS Three hundred patients admitted to an intensive care unit (ICU) with confirmed An/H1N1 infection were analyzed. The median age was 49 years [IQR=38-58] and 62% were male. The mean APACHE II score was 16.9 ± 7.5 and the mean SOFA score was 6.3 ± 3.5 on admission. Comorbidities were present in 76% (n=228) of cases and 111 (37.4%) patients were reportedly obese and 59 (20%) were COPD. The main presentation was viral pneumonia with severe hypoxemia in 65.7% (n=197) of the patients whereas co-infection was identified in 54 (18%) patients. All patients received antiviral treatment and initiated empirically in 194 patients (65.3%), however only 53 patients (17.6%) received early antiviral treatment. Vaccination was only administered in 22 (7.3%) patients. Sixty-seven of 200 patients with ICU discharge died. Haematological disease, severity of illness, infiltrates in chest X-ray and need for mechanical ventilation were variables independently associated with ICU mortality. CONCLUSIONS In patients admitted to the ICU in the post-pandemic seasonal influenza outbreak vaccination was poorly implemented and appear to have higher frequency of severe comorbidities, severity of illness, incidence of primary viral pneumonia and increased mortality when compared with those observed in the 2009 pandemic outbreak.

Clinical significance of the detection of Candida albicans germ tube-specific antibodies in critically ill patients

The present study, comprising a prospective multicentre study including 53 non-neutropenic patients from intensive care units (ICU) in six Spanish tertiary-care hospitals, was carried out to determine the clinical significance and influence on mortality of Candida albicans germ tube-specific antibodies (CAGTA). There were 22 patients (41.5%) for whom the CAGTA results were positive, although none of had a blood culture positive for Candida. The intra-ICU mortality rate was significantly lower (p = 0.004) in CAGTA-positive patients (61.2% vs. 22.7%). Multivariate analysis confirmed that a positive CAGTA result was the only protective factor to be independently associated with ICU mortality (beta coefficient = -0.3856; 95% confidence interval = -0.648 to -0.123).