Cristóbal León

A bedside scoring system ("Candida score") for early antifungal treatment in nonneutropenic critically ill patients with Candida colonization.

Objective:To obtain a score for deciding early antifungal treatment when candidal infection is suspected in nonneutropenic critically ill patients. Design:Analysis of data collected from the database of the EPCAN project, an ongoing prospective, cohort, observational, multicenter surveillance study of fungal infection and colonization in intensive care unit (ICU) patients. Setting:Seventy-three medical-surgical ICUs of 70 teaching hospitals in Spain. Patients:A total of 1,699 ICU patients aged 18 yrs and older admitted for at least 7 days between May 1998 and January 1999 were studied. Interventions:Surveillance cultures of urine, tracheal, and gastric samples were obtained weekly. Patients were grouped as follows: neither colonized nor infected (n = 719), unifocal or multifocal Candida colonization (n = 883), and proven candidal infection (n = 97). The odds ratio (OR) for each risk factor associated with colonization vs. proven candidal infection was estimated. A logistic regression model was performed to adjust for possible confounders. The “Candida score” was obtained according to the logit method. The discriminatory power was evaluated by the area under the receiver operating characteristics curve. Measurements and main results:In the logit model, surgery (OR = 2.71, 95% confidence interval [CI], 1.45–5.06); multifocal colonization (OR = 3.04, 95% CI, 1.45–6.39); total parenteral nutrition (OR = 2.48, 95% CI, 1.16–5.31); and severe sepsis (OR = 7.68, 95% CI, 4.14–14.22) were predictors of proven candidal infection. The “Candida score” for a cut-off value of 2.5 (sensitivity 81%, specificity 74%) was as follows: parenteral nutrition, +0.908; surgery, +0.997; multifocal colonization, +1.112; and severe sepsis, +2.038. Central venous catheters were not a significant risk factor for proven candidal infection (p = .292). Conclusions:In a large cohort of nonneutropenic critically ill patients in whom Candida colonization was prospectively assessed, a “Candida score” >2.5 accurately selected patients who would benefit from early antifungal treatment.

Usefulness of the "Candida score" for discriminating between Candida colonization and invasive candidiasis in non-neutropenic critically ill patients: a prospective multicenter study.

Objective:To assess the usefulness of the “Candida score” (CS) for discriminating between Candida species colonization and invasive candidiasis (IC) in non-neutropenic critically ill patients. A rate of IC <5% in patients with CS <3 was the primary end point. Design:Prospective, cohort, observational study. Setting:Thirty-six medical-surgical intensive care units of Spain, Argentina, and France. Patients:A total of 1,107 non-neutropenic adult intensive care unit patients admitted for at least 7 days between April 2006 and June 2007. Measurements and Main Results:Clinical data, surveillance cultures for fungal growth, and serum levels of (1–3)-beta-d-glucan and anti-Candida antibodies (in a subset of patients) were recorded. The CS was calculated as follows (variables coded as absent = 0, present = 1): total parenteral nutrition ×1, plus surgery ×1, plus multifocal Candida colonization ×1, plus severe sepsis ×2. A CS ≥3 accurately selected patients at high risk for IC. The colonization index was registered if ≥0.5. The rate of IC was 2.3% (95% confidence interval [CI] 1.06–3.54) among patients with CS <3, with a linear association between increasing values of CS and IC rate (p ≤ 0.001). The area under the receiver operating characteristic curve for CS was 0.774 (95% CI 0.715–0.832) compared with 0.633 (95% CI 0.557–0.709) for CI. (1–3)-Beta-d-glucan was also an independent predictor of IC (odds ratio 1.004, 95% CI 1.0–1.007). The relative risk for developing IC in colonized patients without antifungal treatment was 6.83 (95% CI 3.81–12.45). Conclusions:In this cohort of colonized patients staying >7 days, with a CS <3 and not receiving antifungal treatment, the rate of IC was <5%. Therefore, IC is highly improbable if a Candida-colonized non-neutropenic critically ill patient has a CS <3.

Isolation of Aspergillus spp. from the respiratory tract in critically ill patients: risk factors, clinical presentation and outcome

IntroductionOur aims were to assess risk factors, clinical features, management and outcomes in critically ill patients in whom Aspergillus spp. were isolated from respiratory secretions, using a database from a study designed to assess fungal infections.MethodsA multicentre prospective study was conducted over a 9-month period in 73 intensive care units (ICUs) and included patients with an ICU stay longer than 7 days. Tracheal aspirate and urine samples, and oropharyngeal and gastric swabs were collected and cultured each week. On admission to the ICU and at the initiation of antifungal therapy, the severity of illness was evaluated using the Acute Physiology and Chronic Health Evaluation II score. Retrospectively, isolation of Aspergillus spp. was considered to reflect colonization if the patient did not fulfil criteria for pneumonia, and infection if the patient met criteria for pulmonary infection and if the clinician in charge considered the isolation to be clinically valuable. Risk factors, antifungal use and duration of therapy were noted.ResultsOut of a total of 1756 patients, Aspergillus spp. were recovered in 36. Treatment with steroids (odds ratio = 4.5) and chronic obstructive pulmonary disease (odds ratio = 2.9) were significantly associated with Aspergillus spp. isolation in multivariate analysis. In 14 patients isolation of Aspergillus spp. was interpreted as colonization, in 20 it was interpreted as invasive aspergillosis, and two cases were not classified. The mortality rates were 50% in the colonization group and 80% in the invasive infection group. Autopsy was performed in five patients with clinically suspected infection and confirmed the diagnosis in all of these cases.ConclusionIn critically ill patients, treatment should be considered if features of pulmonary infection are present and Aspergillus spp. are isolated from respiratory secretions.

Host adaptive immunity deficiency in severe pandemic influenza

IntroductionPandemic A/H1N1/2009 influenza causes severe lower respiratory complications in rare cases. The association between host immune responses and clinical outcome in severe cases is unknown.MethodsWe utilized gene expression, cytokine profiles and generation of antibody responses following hospitalization in 19 critically ill patients with primary pandemic A/H1N1/2009 influenza pneumonia for identifying host immune responses associated with clinical outcome. Ingenuity pathway analysis 8.5 (IPA) (Ingenuity Systems, Redwood City, CA) was used to select, annotate and visualize genes by function and pathway (gene ontology). IPA analysis identified those canonical pathways differentially expressed (P < 0.05) between comparison groups. Hierarchical clustering of those genes differentially expressed between groups by IPA analysis was performed using BRB-Array Tools v.3.8.1.ResultsThe majority of patients were characterized by the presence of comorbidities and the absence of immunosuppressive conditions. pH1N1 specific antibody production was observed around day 9 from disease onset and defined an early period of innate immune response and a late period of adaptive immune response to the virus. The most severe patients (n = 12) showed persistence of viral secretion. Seven of the most severe patients died. During the late phase, the most severe patient group had impaired expression of a number of genes participating in adaptive immune responses when compared to less severe patients. These genes were involved in antigen presentation, B-cell development, T-helper cell differentiation, CD28, granzyme B signaling, apoptosis and protein ubiquitination. Patients with the poorest outcomes were characterized by proinflammatory hypercytokinemia, along with elevated levels of immunosuppressory cytokines (interleukin (IL)-10 and IL-1ra) in serum.ConclusionsOur findings suggest an impaired development of adaptive immunity in the most severe cases of pandemic influenza, leading to an unremitting cycle of viral replication and innate cytokine-chemokine release. Interruption of this deleterious cycle may improve disease outcome.

Risk factors for candidaemia in critically ill patients : a prospective surveillance study

Candidaemia is frequently a life‐threatening complication in patients admitted to the intensive care unit (ICU). To assess the risk factors for candidaemia in critically ill patients with prolonged ICU stay, a total of 1765 adult patients admitted for at least 7 days to 73 medical–surgical ICUs of 70 tertiary care hospitals in Spain participated in a prospective cohort study. Candidaemia was defined as recovery of Candida spp. from blood culture. Sixty‐eight episodes of candidaemia occurred in 63 patients, representing 35.7 episodes per 1000 ICU patients admitted, with an incidence rate of 1.5 episodes per 1000 days of ICU stay. Causative fungi were C. albicans in 57.1% of cases and non‐albicansCandida spp. in 42.9%. In the multivariate analysis, independent factors significantly associated with candidaemia were Candida colonisation (OR = 4.12, 95% CI: 1.82–9.33), total parenteral nutrition (OR = 3.89, 95% CI: 1.73–8.78), elective surgery (OR = 2.75, 95% CI: 1.17–6.45) and haemofiltration procedures (OR = 1.96, 95% CI: 1.06–3.62). In the ICU setting in Spain and in patients who have stayed in units for >7 days, more than half of cases of candidaemia were caused by C. albicans. Risk factors for candidaemia identified included Candida colonisation, elective surgery, total parenteral nutrition and haemodialysis.

Early treatment of candidemia in adults: a review

Invasive candidiasis is associated with high mortality, particularly in adults. Retrospective studies show that shorter times to treatment are correlated with a lower risk of death. A number of factors can be used to predict which patients would benefit from antifungal prophylaxis or early (pre-emptive or empirical) therapy. Detection of the fungal cell wall component (1→3)-β-D-glucan (BDG) shows promise as an early biomarker of invasive fungal infection and may be useful in identifying patients who would benefit from early antifungal treatment. To date, no consistent early treatment strategy has evolved. Proof-of-concept studies are needed to assess the role of pre-emptive and empirical therapy in ICU patients and the relevance of BDG as an early marker of infection.

Prospective, randomised, multicentre study of meropenem versus imipenem/cilastatin as empiric monotherapy in severe nosocomial infections

The clinical and bacteriological efficacy and the tolerability of meropenem versus imipenem/cilastatin (both 1 g t.i.d.) in severe nosocomial infections were compared in a multicentre, randomised, nonblinded study. A total of 151 patients were recruited; 133 (66 meropenem, 67 imipenem/cilastatin) were clinically evaluable and 84 (42 meropenem, 42 imipenem/cilastatin) bacteriologically evaluable. Most clinically evaluable patients (90%) were in intensive care units, required mechanical ventilation (72%), and had received previous antibiotic therapy (62%). The mean (±SD) APACHE II score was 15.2 (±6.6) in the meropenem group and 17.8 (±6.8) in the imipenem/cilastatin group. The primary infections were nosocomial lower respiratory tract infections (56% of patients), intra-abdominal infections (15%), septicaemia (21%), skin/skin structure infections (5%), and complicated urinary tract infections (3%); 35% of the patients had two or more infections. There was no significant difference between the meropenem and imipenem/cilastatin groups in the rates of satisfactory clinical (weighted percentage 87% vs. 74%) or bacteriological (weighted percentage 79% vs. 71%) response. There was a slightly higher rate of clinical success with meropenem against primary or secondary lower respiratory tract infection (89% vs. 76%). Drug-related adverse events occurred in 17% and 15% of meropenem and imipenem/cilastatin patients, respectively. Meropenem (1 g t.i.d.) was as efficacious as the same dose of imipenem/cilastatin in this setting, and both drugs were well tolerated.

Antiseptic chamber-containing hub reduces central venous catheter-related infection: a prospective, randomized study.

ObjectiveThe hub connecting the catheter and the infusion equipment is a common portal of entry for bacteria causing catheter-related sepsis. We assessed the efficacy of a new hub model (Segur-Lock) that incorporates an antiseptic chamber filled with 3% iodinated alcohol in preventing endoluminal catheter contamination and catheter-related bloodstream infection arising at the hub. DesignProspective, randomized, multicenter study. SettingSeven medical and surgical adult intensive care units in Spain. PatientsA total of 230 patients aged 18 yrs or older requiring the insertion of a nontunneled central venous catheter for ≥6 days from January 1, 1998, to April 30, 1999. InterventionsPatients were randomized at the time of catheter insertion to receive catheters with standard Luer-lock connector (control group, n = 114) or catheters with the new hub model (n = 116). Measurements and Main ResultsSkin, catheter tip, and hub cultures were performed at the time the catheter was withdrawn because therapy was terminated or due to suspicion of sepsis, in which case peripheral blood and infusate cultures were simultaneously taken. Catheter-related bloodstream infection was diagnosed in 19 (8.3%) patients. Catheters were more often withdrawn because of suspicion of infection in the control group (43.8%) than in the new hub model group (30.1%, p < .035). The prevalence of culture-positive catheter hubs without associated bacteremia (colonization) was higher in the control group (14.4% vs. 4.3%, p < .001). Catheter-related bloodstream infection from the catheter hub also occurred more frequently in controls than in patients assigned to the new hub model (7% vs. 1.7%;p < .049; relative risk, 4.14; 95% confidence interval, 0.8–19). ConclusionsThis new antiseptic chamber–containing hub has proved to be effective in preventing endoluminal bacterial colonization and catheter-related bloodstream infection from hub contamination in intensive care unit patients with central venous catheters inserted for ≥6 days.

Successful treatment of Candida parapsilosis mural endocarditis with combined caspofungin and voriconazole

BackgroundFungal mural endocarditis is a rare entity in which the antemortem diagnosis is seldom made. Seven cases of mural endocarditis caused by Candida spp. have been collected from literature and six of these patients died after treatment with amphotericin B.Case presentationWe report a case of mural endocarditis diagnosed by transesophageal echocardiogram and positive blood cultures to Candida parapsilosis. Because blood cultures continued to yield C. parapsilosis despite caspofungin monotherapy, treatment with voriconazole was added.ConclusionThis is the first description of successful treatment of C. parapsilosis mural endocarditis with caspofungin and voriconazole.

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.