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Background Although there has been an improved management of invasive candidiasis in the last decade, controversial issues still remain, especially in the diagnostic and therapeutic approaches. Aims We sought to identify the core clinical knowledge and to achieve high level agreement recommendations required to care for critically ill adult patients with invasive candidiasis. Methods A prospective Spanish survey reaching consensus by the DELPHI technique was made. It was anonymously conducted by electronic mail in a first term to 25 national multidisciplinary experts in invasive fungal infections from five national scientific societies, including intensivists, anesthesiologists, microbiologists, pharmacologists and infectious diseases specialists, who answered to 47 questions prepared by a coordination group after a strict review of the literature in the last five years. The educational objectives spanned five categories, including epidemiology, diagnostic tools, prediction rules, and treatment and de-escalation approaches. The level of agreement achieved among the panel experts in each item should exceed 75% to be selected. In a second term, after extracting recommendations from the selected items, a face to face meeting was performed where more than 80 specialists in a second round were invited to validate the preselected recommendations. Results In the first term, 20 recommendations were preselected (Epidemiology 4, Scores 3, Diagnostic tools 4, Treatment 6 and De-escalation approaches 3). After the second round, the following 12 were validated: (1) Epidemiology (2 recommendations): think about candidiasis in your Intensive Care Unit (ICU) and do not forget that non- Candida albicans – Candida species also exist. (2) Diagnostic tools (4 recommendations): blood cultures should be performed under suspicion every 2–3 days and, if positive, every 3 days until obtaining the first negative result. Obtain sterile fluid and tissue, if possible (direct examination of the sample is important). Use non-culture based methods as microbiological tools, whenever possible. Determination of antifungal susceptibility is mandatory. (3) Scores (1 recommendation): as screening tool, use the Candida Score and determine multicolonization in high risk patients. (4) Treatment (4 recommendations): start early. Choose echinocandins. Withdraw any central venous catheter. Fundoscopy is needed. (5) De-escalation (1 recommendation): only applied when knowing susceptibility determinations and after 3 days of clinical stability. The higher rate of agreement was achieved in the optimization of microbiological tools and the withdrawal of the catheter, whereas the lower rate corresponded to de-escalation therapy and the use of scores. Conclusions The management of invasive candidiasis in ICU patients requires the application of a broad range of knowledge and skills that we summarize in our recommendations. These recommendations may help to identify the potential patients, standardize their global management and improve their outcomes, based on the DELPHI methodology. This article is also published in Spanish in this issue. It can be found in 10.1016/j.riam.2013.05.005

Information regarding liver retransplantation in HIV-infected patients is scant. Data from 14 HIV-infected patients retransplanted between 2002 and 2011 in Spain (6% retransplantation rate) were analyzed and compared with those from 157 matched HIV-negative retransplanted patients. In HIV-infected patients, early (≤30 days) retransplantation was more frequently indicated (57% vs. 29%; p = 0.057), and retransplantation for HCV recurrence was less frequently indicated (7% vs. 37%; p = 0.036). Survival probability after retransplantation in HIV-positive patients was lower than in HIV-negative patients, 42% versus 64% at 3 years, although not significantly (p = 0.160). Among HIV-infected patients, those with undetectable HCV RNA at retransplantation and those with late (>30 days) retransplantation showed better 3-year survival probability (80% and 67%, respectively), similar to that in their respective HIV-negative counterparts (72% and 70%). In HIV-infected and HIV-negative patients, 3-year survival probability in those with positive HCV RNA at retransplantation was 22% versus 65% (p = 0.008); in those with early retransplantation, 3-year survival probability was 25% versus 56% (p = 0.282). HIV infection was controlled with antiretroviral therapy after retransplantation. In conclusion, HIV-infected patients taken as a whole have unsatisfactory survival after liver retransplantation, although patients with undetectable HCV RNA at retransplantation or undergoing late retransplantation show a more favorable outcome.

Information about infections unrelated to acquired immunodeficiency syndrome (AIDS) in human immunodeficiency virus (HIV)-infected liver recipients is scarce. The aims of this study were to describe the prevalence, clinical characteristics, time of onset, and outcomes of bacterial, viral, and fungal infections in HIV/hepatitis C virus (HCV)-coinfected orthotopic liver transplant recipients and to identify risk factors for developing severe infections. We studied 84 consecutive HIV/HCV-coinfected patients who underwent liver transplantation at 17 sites in Spain between 2002 and 2006 and were followed until December 2009. The median age was 42 years, and 76% were men. The median follow-up was 2.6 years (interquartile range = 1.25-3.53 years), and 54 recipients (64%) developed at least 1 infection. Thirty-eight (45%) patients had bacterial infections, 21 (25%) had cytomegalovirus (CMV) infections (2 had CMV disease), 13 (15%) had herpes simplex virus infections, and 16 (19%) had fungal infections (7 cases were invasive). Nine patients (11%) developed 10 opportunistic infections with a 44% mortality rate. Forty-three of 119 infectious episodes (36%) occurred in the first month after transplantation, and 53 (45%) occurred after the sixth month. Thirty-six patients (43%) had severe infections. Overall, 36 patients (43%) died, and the deaths were related to severe infections in 7 cases (19%). Severe infections increased the mortality rate almost 3-fold [hazard ratio (HR) = 2.9, 95% confidence interval (CI) = 1.5-5.8]. Independent factors for severe infections included a pretransplant Model for End-Stage Liver Disease (MELD) score >15 (HR = 3.5, 95% CI = 1.70-7.1), a history of AIDS-defining events before transplantation (HR = 4.0, 95% CI = 1.9-8.6), and non-tacrolimus-based immunosuppression (HR = 2.5, 95% CI = 1.3-4.8). In conclusion, the rates of severe and opportunistic infections are high in HIV/HCV-coinfected liver recipients and especially in those with a history of AIDS, a high MELD score, or non-tacrolimus-based immunosuppression.

The characteristics of pandemic influenza 2009 differ from those of seasonal influenza. In Australia-New Zealand the number of admissions to the intensive care unit (ICU) increased by 15-fold in the southern winter. We compared the characteristics of the Spanish series of the first ICU admissions in July with those of series published in Canada and Australia-New Zealand up to October 2009. Unlike the situation in Spain, only half the admissions in Canada and Australia-New Zealand were due to primary viral pneumonia but bacterial pneumonia was much more frequent. In all series, young people, many of whom had no comborbidities, were the most frequently affected population. The most common comorbidities were obesity, chronic pulmonary disease, pregnancy and heart disease. Diagnosis through reverse-transcriptase polymerase chain reaction can have a false-negative rate of 10%. Shock and acute renal insufficiency were more frequent in the Spanish series. A total of 10-30% of patients required ICU admission and 6 of 10 patients required mechanical ventilation with a high frequency of failure of non-invasive ventilation (75%). Mortality was similar among the series (14-25%) but was higher in patients requiring mechanical ventilation (30%). Early oseltamivir administration (< 48h after symptom onset) has been associated with better outcome. Therefore, early administration of this drug in patients with risk factors or those who, although free from risk factors, show clinical progression, could reduce ICU admissions and mortality.

Background & Aims: The aim of this study was to evaluate the results of treatment with pegylated interferon and ribavirin for the recurrence of hepatitis C after liver transplantation in HCV/ HIV-coinfected patients. Methods: This was a prospective, multicentre cohort study, including 78 HCV/HIV-coinfected liver transplant patients who received treatment for recurrent hepatitis C. For comparison, we included 176 matched HCV-monoinfected patients who underwent liver transplantation during the same period of time at the same centres and were treated for recurrent hepatitis C. Results: Antiviral therapy was discontinued prematurely in 56% and 39% (p = 0.016), mainly because of toxicity (22% and 11%, respectively; p = 0.034). Sustained virological response (SVR) was achieved in 21% of the coinfected patients and in 36% of monoinfected patients (p = 0.013). For genotype 1, SVR rates were 10% and 33% (p = 0.002), respectively; no significant differences were observed for the other genotypes. A multivariate analysis based on the whole series identified HIV-coinfection as an independent predictor of lack of SVR (OR, 0.17; 95% CI, 0.06-0.42). Other predictors of SVR were donor age, pretreatment HCV viral load, HCV genotype, and early virological response. SVR was associated with a significant improvement in survival: 5-year survival after antiviral treatment was 79% for HCV/HIV-coinfected patients with SVR vs. 43% for those without (p = 0.02) and 92% vs. 60% in HCV-monoinfected patients (p < 0.001), respectively. Conclusions: The response to pegylated interferon and ribavirin was poorer in HCV/HIV-coinfected liver recipients, particularly those with genotype 1. However, when SVR was achieved, survival of coinfected patients increased significantly. (C) 2014 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

The role of non-invasive ventilation (NIV) in acute respiratory failure caused by viral pneumonia remains controversial. Our objective was to evaluate the use of NIV in a cohort of (H1N1)v pneumonia. Usefulness and success of NIV were assessed in a prospective, observational registry of patients with influenza A (H1N1) virus pneumonia in 148 Spanish intensive care units (ICUs) in 2009–10. Significant variables for NIV success were included in a multivariate analysis. In all, 685 patients with confirmed influenza A (H1N1)v viral pneumonia were admitted to participating ICUs; 489 were ventilated, 177 with NIV. The NIV was successful in 72 patients (40.7%), the rest required intubation. Low Acute Physiology and Chronic Health Evaluation (APACHE) II, low Sequential Organ Failure Assessment (SOFA) and absence of renal failure were associated with NIV success. Success of NIV was independently associated with fewer than two chest X-ray quadrant opacities (OR 3.5) and no vasopressor requirement (OR 8.1). However, among patients with two or more quadrant opacities, a SOFA score ≤7 presented a higher success rate than those with SOFA score >7 (OR 10.7). Patients in whom NIV was successful required shorter ventilation time, shorter ICU stay and hospital stay than NIV failure. In patients in whom NIV failed, the delay in intubation did not increase mortality (26.5% versus 24.2%). Clinicians used NIV in 25.8% of influenza A (H1N1)v viral pneumonia admitted to ICU, and treatment was effective in 40.6% of them. NIV success was associated with shorter hospital stay and mortality similar to non-ventilated patients. NIV failure was associated with a mortality similar to those who were intubated from the start.

Eighty-four HCV/HIV-coinfected and 252-matched HCV-monoinfected liver transplant recipients were included in a prospective multicenter study. Thirty-six (43%) HCV/HIV-coinfected and 75 (30%) HCV-monoinfected patients died, with a survival rate at 5 years of 54% (95% CI, 42-64) and 71% (95% CI, 66 to 77; p = 0.008), respectively. When both groups were considered together, HIV infection was an independent predictor of mortality (HR, 2.202; 95% CI, 1.420-3.413 [p < 0.001]). Multivariate analysis of only the HCV/HIV-coinfected recipients, revealed HCV genotype 1 (HR, 2.98; 95% CI, 1.32-6.76), donor risk index (HR, 9.48; 95% CI, 2.75-32.73) and negative plasma HCV RNA (HR, 0.14; 95% CI, 0.03-0.62) to be associated with mortality. When this analysis was restricted to pretransplant variables, we identified three independent factors (HCV genotype 1, pretransplant MELD score and centers with

Journal Article; Multicenter Study; BACKGROUND There is a vast amount of information published regarding the impact of 2009 pandemic Influenza A (pH1N1) virus infection. However, a comparison of risk factors and outcome during the 2010-2011 post-pandemic period has not been described. METHODS A prospective, observational, multi-center study was carried out to evaluate the clinical characteristics and demographics of patients with positive RT-PCR for H1N1 admitted to 148 Spanish intensive care units (ICUs). Data were obtained from the 2009 pandemic and compared to the 2010-2011 post-pandemic period. RESULTS Nine hundred and ninety-seven patients with confirmed An/H1N1 infection were included. Six hundred and forty-eight patients affected by 2009 (pH1N1) virus infection and 349 patients affected by the post-pandemic Influenza (H1N1)v infection period were analyzed. Patients during the post-pandemic period were older, had more chronic comorbid conditions and presented with higher severity scores (Acute Physiology And Chronic Health Evaluation II (APACHE II) and Sequential Organ Failure Assessment (SOFA)) on ICU admission. Patients from the post-pandemic Influenza (H1N1)v infection period received empiric antiviral treatment less frequently and with delayed administration. Mortality was significantly higher in the post-pandemic period. Multivariate analysis confirmed that haematological disease, invasive mechanical ventilation and continuous renal replacement therapy were factors independently associated with worse outcome in the two periods. HIV was the only new variable independently associated with higher ICU mortality during the post-pandemic Influenza (H1N1)v infection period. CONCLUSION Patients from the post-pandemic Influenza (H1N1)v infection period had an unexpectedly higher mortality rate and showed a trend towards affecting a more vulnerable population, in keeping with more typical seasonal viral infection. Yes

Introduction Several aspects of ventilator-associated tracheobronchitis (VAT)—including diagnostic criteria, overlap with ventilator-associated pneumonia (VAP), and appropriate treatment regimens—remain poorly defined. The objectives of this study were to survey reported practices in the clinical and microbiological diagnosis of VAT and to evaluate perceptions of the impact of VAT on patient outcomes. Methods We developed a questionnaire consisting of (a) characteristics of the respondent, the ICU, and hospital; (b) current clinical and microbiological diagnostic approach; (c) empirical antibiotic therapy; and (d) the perception of physicians regarding the clinical impact of VAT and its implications. Results A total of 288 ICUs from 16 different countries answered the survey: 147 (51%) from the Latin American (LA) group and 141 (49%) from Spain, Portugal, and France (SPF group). The majority of respondents (n = 228; 79.2%) reported making the diagnosis of VAT based on clinical and microbiological criteria, and 40 (13.9%) by clinical criteria alone. Approximately half (50.3%) of the respondents agreed that patients should receive antibiotics for the treatment of VAT. Out of all respondents, 269 (93.4%) assume that a VAT episode increases ICU length of stay, and this perception is greater in the LA group (97.3%) than in the SPF group (89.4%, P

Introduction Candidemia in critically ill patients is usually a severe and life-threatening condition with a high crude mortality. Very few studies have focused on the impact of candidemia on ICU patient outcome and attributable mortality still remains controversial. This study was carried out to determine the attributable mortality of ICU-acquired candidemia in critically ill patients using propensity score matching analysis. Methods A prospective observational study was conducted of all consecutive non-neutropenic adult patients admitted for at least seven days to 36 ICUs in Spain, France, and Argentina between April 2006 and June 2007. The probability of developing candidemia was estimated using a multivariate logistic regression model. Each patient with ICU-acquired candidemia was matched with two control patients with the nearest available Mahalanobis metric matching within the calipers defined by the propensity score. Standardized differences tests (SDT) for each variable before and after matching were calculated. Attributable mortality was determined by a modified Poisson regression model adjusted by those variables that still presented certain misalignments defined as a SDT > 10%. Results Thirty-eight candidemias were diagnosed in 1,107 patients (34.3 episodes/1,000 ICU patients). Patients with and without candidemia had an ICU crude mortality of 52.6% versus 20.6% (P < 0.001) and a crude hospital mortality of 55.3% versus 29.6% (P = 0.01), respectively. In the propensity matched analysis, the corresponding figures were 51.4% versus 37.1% (P = 0.222) and 54.3% versus 50% (P = 0.680). After controlling residual confusion by the Poisson regression model, the relative risk (RR) of ICU- and hospital-attributable mortality from candidemia was RR 1.298 (95% confidence interval (CI) 0.88 to 1.98) and RR 1.096 (95% CI 0.68 to 1.69), respectively. Conclusions ICU-acquired candidemia in critically ill patients is not associated with an increase in either ICU or hospital mortality.