[Respiratory infections caused by Aspergillus spp. in critically ill patients admitted to the intensive care units]. / Infecciones respiratorias por Aspergillus spp. en pacientes críticos ingresados en unidades de cuidados intensivos.

UNLABELLED: The presence of respiratory fungal infection in the critically ill patient is associated with high morbidity and mortality. OBJECTIVES: To assess the incidence of respiratory infection caused by Aspergillus spp. independently of the origin of infection in patients admitted to Spanish ICUs, as well as to describe the rates, characteristics, outcomes and prognostic factors in patients with this type of infection. MATERIAL AND METHODS: An observational, retrospective, open-label and multicenter study was carried out in a cohort of patients with respiratory infection caused by Aspergillus spp. admitted to Spanish ICUs between 2006 and 2012 (months of April, May and June), and included in the ENVIN-HELICS registry (108,244 patients and 825,797 days of ICU stay). Variables independently related to in-hospital mortality were identified by multiple logistic regression analysis. RESULTS: A total of 267 patients from 79 of the 198 participating ICUs were included (2.46 cases per 1000 ICU patients and 3.23 episodes per 10,000 days of ICU stay). From a clinical point of view, infections were classified as ventilator-associated pneumonia in 93 cases (34.8%), pneumonia unrelated to mechanical ventilation in 120 cases (44.9%), and tracheobronchitis in 54 cases (20.2%). The study population included older patients (mean 64.8±17.1 years), with a high severity level (APACHE II score 22.03±7.7), clinical diseases (64.8%) and prolonged hospital stay before the identification of Aspergillus spp. (median 11 days), transferred to the ICU mainly from hospital wards (58.1%) and with high ICU (57.3%) and hospital (59.6%) mortality rates, exhibiting important differences depending on the type of infection involved. Independent mortality risk factors were previous admission to a hospital ward (OR=7.08, 95%CI: 3.18-15.76), a history of immunosuppression (OR=2.52, 95%CI: 1.24-5.13) and severe sepsis or septic shock (OR=8.91, 95%CI: 4.24-18.76). CONCLUSIONS: Respiratory infections caused by Aspergillus spp. in critically ill patients admitted to the ICU in Spain are infrequent, and affect a very selected group of patients, characterized by high mortality and conditioned by non-modifiable risk factors.

Changes of resistance rates in Pseudomonas aeruginosa strains are unrelated to antimicrobial consumption in ICU populations with invasive device-related infection.

OBJECTIVE: To evaluate the relationship between antipseudomonal antibiotic consumption and each individual drug resistance rate in Pseudomonas aeruginosa strains causing ICU acquired invasive device-related infections (IDRI). DESIGN: A post hoc analysis was made of the data collected prospectively from the ENVIN-HELICS registry. SETTING: Intensive Care Units participating in the ENVIN-UCI registry between the years 2007 and 2016 (3-month registry each year). PATIENTS: Patients admitted for over 24h. MAIN VARIABLES: Annual linear and nonlinear trends of resistance rates of P. aeruginosa strains identified in IDRI and days of treatment of each antipseudomonal antibiotic family per 1000 occupied ICU bed days (DOT) were calculated. RESULTS: A total of 15,095 episodes of IDRI were diagnosed in 11,652 patients (6.2% out of a total of 187,100). Pseudomonas aeruginosa was identified in 2095 (13.6%) of 15,432 pathogens causing IDRI. Resistance increased significantly over the study period for piperacillin-tazobactam (P<0.001), imipenem (P=0.016), meropenem (P=0.004), ceftazidime (P=0.005) and cefepime (P=0.015), while variations in resistance rates for amikacin, ciprofloxacin, levofloxacin and colistin proved nonsignificant. A significant DOT decrease was observed for aminoglycosides (P<0.001), cephalosporins (P<0.001), quinolones (P<0.001) and carbapenems (P<0.001). CONCLUSIONS: No significant association was observed between consumption of each antipseudomonal antibiotic family and the respective resistance rates for P. aeruginosa strains identified in IDRI.

Is a project needed to prevent urinary tract infection in patients admitted to spanish ICUs? / ¿Es necesario un proyecto para prevenir las infecciones del tracto urinario en los pacientes ingresados en unidades de cuidados intensivos españolas?

OBJECTIVE: To analyze epidemiological data of catheter-associated urinary tract infection (CAUTI) in critically ill patients admitted to Spanish ICUs in order to assess the need of implementing a nationwide intervention program to reduce these infections. DESIGN: Non-intervention retrospective annual period prevalence analysis. SETTING: Participating ICUs in the ENVIN-UCI multicenter registry between the years 2007-2016. PATIENTS: Critically ill patients admitted to the ICU with catheter-associated urinary tract infection (CAUTI). MAIN VARIABLES: Incidence rates per 1,000 catheter-days; urinary catheter utilization ratio; proportion of CAUTIs in relation to total health care-associated infections (HAIs). RESULTS: A total of 187,100 patients, 137,654 (73.6%) of whom had a urinary catheter in place during 1,215,673 days (84% of days of ICU stay) were included. In 4,539 (3.3%) patients with urinary catheter, 4,977 CAUTIs were diagnosed (3.6 episodes per 100 patients with urinary catheter). The CAUTI incidence rate showed a 19% decrease between 2007 and 2016 (4.69 to 3.8 episodes per 1,000 catheter-days), although a sustained urinary catheter utilization ratio was observed (0.84 [0.82-0.86]). The proportion of CAUTI increased from 23.3% to 31.9% of all HAIs controlled in the ICU. CONCLUSIONS: Although CAUTI rates have declined in recent years, these infections have become proportionally the first HAIs in the ICU. The urinary catheter utilization ratio remains high in Spanish ICUs. There is room for improvement, so that a CAUTI-ZERO project in our country could be useful.

Invasive device-associated infections caused by Pseudomonas aeruginosa in critically ill patients: evolution over 10 years.

Invasive device-associated infections caused by Pseudomonas aeruginosa over 10 years (2007-2016) were assessed based on data from the ENVIN-HELICS registry (200 Spanish intensive care units). P. aeruginosa was the leading pathogen except in the last two years in which there was a slight decrease, with Escherichia coli as the leading aetiology. The rate of infections caused by P. aeruginosa remained between 12.0% and 14.6% throughout the study period. There was a significant increase of isolates resistant to imipenem, meropenem, ceftazidime, cefepime, and piperacillin-tazobactam. Multidrug-resistant and the sum of extensively drug- and pandrug-resistant strains also increased. Resistance to anti-pseudomonal antimicrobials remains a matter of concern.

[Summary of the GEIPC-SEIMC and GTEI-SEMICYUC recommendations for the treatment of infections caused by gram positive cocci in critical patients]. / Resumen de las recomendaciones GEIPC-SEIMC y GTEI-SEMICYUC para el tratamiento antibiótico de infecciones por cocos gram positivos en la paciente crítico

OBJECTIVE: In recent years there has been an increase in infections caused by gram-positive cocci in critical patients, together with a rapid development of resistance to the antibiotics which are normally used to treat them. The objective is to prepare an antibiotic treatment guide for the most common infections caused by gram positive cocci in critical patients. This guide will help in the decision-making process regarding the care of such patients. METHOD: Experts from two scientific societies worked together to prepare a consensus document. They were members of the Study Group on Infections in Critical Patients (GEIPC), which is part of the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC), and the Infectious Diseases Working Group (GTEI), belonging to the Spanish Society of Intensive Care Medicine and Coronary Units (SEMICYUC). There was a systematic review of the literature published up to September 2006 regarding this type of infections and the antibiotic treatments marketed to that date. An evidence grading system was applied according to the strength of the recommendation (categories A, B or C) and the level of evidence (categories I, II or III). Recommendations were given if there was consensus among the experts from both societies. RESULTS: The antibiotic regimens recommended for treating infections caused by gram-positive cocci were presented in the form of tables, showing the recommendation grade. Alternatives were given for allergic patients. The scientific basis supporting the aforementioned recommendations is explained within the text and the references upon which they are based are cited. CONCLUSIONS: A summary of an evidence-based practical guide for the treatment of infections caused by gram-positive cocci in critical patients is presented.

Landmark prediction of nosocomial infection risk to disentangle short- and long-stay patients.

Length of stay is one of the key determinants for the risk of nosocomial infections. The distribution of this at-risk time is heavily skewed and depends on discharge or death. This study applied landmark competing risk prediction models to account for a large proportion of short-stay patients and a small proportion of long-stay patients.

Analysis of Clinical Cohort Data Using Nested Case-control and Case-cohort Sampling Designs. A Powerful and Economical Tool.

BACKGROUND: Sampling from a large cohort in order to derive a subsample that would be sufficient for statistical analysis is a frequently used method for handling large data sets in epidemiological studies with limited resources for exposure measurement. For clinical studies however, when interest is in the influence of a potential risk factor, cohort studies are often the first choice with all individuals entering the analysis. OBJECTIVES: Our aim is to close the gap between epidemiological and clinical studies with respect to design and power considerations. Schoenfeld's formula for the number of events required for a Cox' proportional hazards model is fundamental. Our objective is to compare the power of analyzing the full cohort and the power of a nested case-control and a case-cohort design. METHODS: We compare formulas for power for sampling designs and cohort studies. In our data example we simultaneously apply a nested case-control design with a varying number of controls matched to each case, a case cohort design with varying subcohort size, a random subsample and a full cohort analysis. For each design we calculate the standard error for estimated regression coefficients and the mean number of distinct persons, for whom covariate information is required. RESULTS: The formula for the power of a nested case-control design and the power of a case-cohort design is directly connected to the power of a cohort study using the well known Schoenfeld formula. The loss in precision of parameter estimates is relatively small compared to the saving in resources. CONCLUSIONS: Nested case-control and case-cohort studies, but not random subsamples yield an attractive alternative for analyzing clinical studies in the situation of a low event rate. Power calculations can be conducted straightforwardly to quantify the loss of power compared to the savings in the num-ber of patients using a sampling design instead of analyzing the full cohort.

[Methanol and ethylene glycol poisoning. Study of 18 cases]. / Intoxicación por metanol y etilenglicol. Estudio de 18 observaciones.

BACKGROUND: The present study reviews acute intoxication by methanol and ethylenglycol analyzing its form of presentation, treatment applied and prognosis. METHODS: A retrospective study performed in 5 hospitals from the Barcelona area (Spain) from January 1984 to December 1993 is reported. RESULTS: Eighteen patients, 16 intoxicated by methanol and 2 by ethylenglycol were reviewed. The blood levels of methanol on admission ranged from 350 to 4,600 mg/l (mean = 1,649 +/- 1,220 mg/l). The clinical course was initially characterized by alteration of the level of consciousness (in 61% the index of Glasgow of coma was < or = 7) and development of metabolic acidosis (pH < or = 6.80 in 44% of cases). Eighty-seven percent of patients intoxicated by methanol had visual disorders. Treatment consisted in the administration of ethanol, bicarbonate and extrarenal exchange. Mortality was 44%, being greater among patients with the lowest initial pH (p = 0.0001) and with the lowest concentration of bicarbonates (p < 0.03). The patients with lower pH (r2 = 0.65, p < 0.002) and with a lower value of blood bicarbonate (r2 = 0.87; p < 0.0001) on admission were significantly more severe. Sequelae are present in 55% of the survivors. CONCLUSIONS: Intoxication by methanol and ethylenglycol cause severe metabolic acidosis, with high anion and osmolar gaps which may rapidly lead to death or to sequelae in survivors if diagnosis is delayed and specific treatment is not initiated early.

Interventions to control nosocomial infections: study designs and statistical issues.

There is a wide range of potential study designs for intervention studies to decrease nosocomial infections in hospitals. The analysis is complex due to competing events, clustering, multiple timescales and time-dependent period and intervention variables. This review considers the popular pre-post quasi-experimental design and compares it with randomized designs. Randomization can be done in several ways: randomization of the cluster [intensive care unit (ICU) or hospital] in a parallel design; randomization of the sequence in a cross-over design; and randomization of the time of intervention in a stepped-wedge design. We introduce each design in the context of nosocomial infections and discuss the designs with respect to the following key points: bias, control for non-intervention factors, and generalizability. Statistical issues are discussed. A pre-post-intervention design is often the only choice that will be informative for a retrospective analysis of an outbreak setting. It can be seen as a pilot study with further, more rigorous designs needed to establish causality. To yield internally valid results, randomization is needed. Generally, the first choice in terms of the internal validity should be a parallel cluster randomized trial. However, generalizability might be stronger in a stepped-wedge design because a wider range of ICU clinicians may be convinced to participate, especially if there are pilot studies with promising results. For analysis, the use of extended competing risk models is recommended.

Quality control of the surveillance programme of ICU-acquired infection (ENVIN-HELICS registry) in Spain.

BACKGROUND: Data validation is an essential aspect for the accuracy of a nosocomial infection surveillance registry. AIM: To report the results of the first quality control programme in the national surveillance programme of intensive care unit (ICU)-acquired infection in Spain (ENVIN-HELICS registry). METHOD: During 2008, of 13,824 records included in the database, 1500 (10.8%) registries from 20 ICUs were reviewed. These ICUs were selected at random and stratified according to the number of cases included in the registry. The proportion of infected patients, which was 9.6% [95% confidence interval (CI) 8.09-11.16], was maintained during the selection of cases for review. Two physicians were trained for the purpose of the study and undertook the review. RESULTS: Overall sensitivity, specificity and positive and negative predictive values of the ENVIN-HELICS registry for the identification of patients with any device-related infection acquired during their ICU stay were 86.0% (95% CI 80.0-92.0), 98.7% (95% CI 82.19-93.6), 87.9% (95% CI 82.19-93.6) and 98.5% (95% CI 97.8-99.2), respectively, with a kappa index of 0.85 (95% CI 0.79-0.92). Secondary bloodstream infection had the lowest sensitivity (59.3%), and intubation-associated pneumonia had the highest sensitivity (86.3%). CONCLUSION: There was good correlation between data reported by the registrars and data validated by auditors, confirming the reliability of the ENVIN-HELICS registry.

[Epidemiology of the primary and vascular catheter-related bacteriemias in critical patients admitted to an Intensive Medicine Department]. / Epidemiología de las bacteriemias primarias y relacionadas con catéteres vasculares en pacientes críticos ingresados en servicios de medicina intensiva.

OBJECTIVE: In recent years, changes have occurred in the setting of bacteriemia related with the use of vascular catheters (BVC) and with the appearance of multiresistant gram positive cocci (MR-GPC), knowledge of the limitations regarding the antibiotics used most for their treatment (glycopeptides) and the appearance of new antibiotics active against these pathogens. This article analyzes the evolution of the rates, etiologies and markers of multiresistance of the most common pathogens in the BVC (including the primary bacteriemias) in the Spanish Intensive Medicine Departments (ICU). MATERIAL AND METHODS: A multicenter, prospective, observational study of incidence, with voluntary participation, was conducted. A total of 74, 105, 112 and 121 ICUs belonging to 71, 97, 103 and 112 hospitals, respectively, collaborated including the years 2005-2008. The information included in the ENVIN-HELICS registry was used. RESULTS: The rates of this complication have decreased and are now at about 5 episodes per 1,000 days of central venous catheter (CVC). One third of the episodes occur with significant systemic response (severe sepsis or septic shock). The MR-GPC were the most frequent, however Gram-negative bacilli (GNB) were identified in 30% of the cases and fungi (different species of Candida) in 6%. Staphylococcus epidermidis and coagulase-negative, methicillin-resistant staphylococci (CNS) persist in a proportion greater than 80%, while methicillin-resistance S. aureus have decreased to less than 40%. CONCLUSIONS: The empirical treatment in situations of extreme seriousness should consider coverage of the most frequent pathogens such as the MR-GPC and GNB and in special conditions, the fungi.

[Prevention of bacteriema related with ICU catheters by multifactorial intervention: a report of the pilot study]. / Prevención de la bacteriemia relacionada con catéteres en UCI mediante una intervención multifactorial. Informe del estudio piloto.

OBJECTIVE: to assess the applicability on a national level of the interventions proposed by Peter Pronovost et al in Michigan state for the prevention of central vascular catheter-related bacteremia (B-CVC) in patients admitted to the ICU. DESIGN: pilot, prospective and comparative study. SETTING: eighteen ICUs (9 control and 9 intervention) from three autonomous communities in Spain during 3 months in 2007 participated in the study. INTERVENTION: the following activities were included: a) training program for health care personnel, b) introduction of specific measures related to the insertion and care of CVC (catheter insertion checklist, basic recommendations for maintenance of central catheters, dedicated cart for venous accesses, information poster with the five procedures proposed to reduce bacteremias: hands hygiene, use of maximal aseptic barriers during insertion, asepsis of the skin at the insertion point with chlorhexidine, avoidance of the femoral access, and removal of all CVC) and c) measures aiming to promote the culture of safe daily work (daily objectives, learning from mistakes, safety rounds). RESULTS: the rate of B-CVC expressed as mean values has shown a half reduction as compared with historical registers. Different problems in the implementation of specific measures related to catheters and safety tools were identified. CONCLUSIONS: the intervention project assessed in the pilot study may be viable on the national level. It is necessary to modify and adapt to the Spanish reality the interventions proposed.

[Immunosuppressive treatment due to paraquat poisoning]. / Tratamiento inmunosupresor en las intoxicaciones por paraquat.

Paraquat is the most important member of the bipyridyl compound. It is directly caustic in nature and it exerts its herbicidal activity by inhibiting the reduction of NADP to NADPH during photosynthesis, a process in which superoxide, singlet oxygen, hydroxyl, and peroxide radicals are formed. Human tissue toxicity likely results from a similar oxidative mechanism. After oxidative destruction, recruitment of inflammatory cells leads to late onset and irreversible pulmonary fibrosis. Ingestion greater than 20-40 mg/kg of paraquat concentrate should be aggressively managed with the administration of intestinal decontaminants and hemoperfusion. Low-inspired oxygen therapy should be given until it becomes impractical in the face of hypoxemia. Administration of immunodepressive therapy, steroids and cyclophosphamide, should be considered. In addition, there should be intermittent assessment of pulmonary function and of plasma and urinary concentrations of paraquat.

[GEIPC-SEIMC and GTEI-SEMICYUC recommendations for antibiotic treatment of gram positive coccal infections in the critical patient]. / Recomendaciones GEIPC-SEIMC y GTEI-SEMICYUC para el tratamiento antibiótico de infecciones por cocos grampositivos en el paciente crítico.

In recent years, an increment of infections caused by gram-positive cocci has been documented in nosocomial and hospital-acquired infections. In diverse countries, a rapid development of resistance to common antibiotics against gram-positive cocci has been observed. This situation is exceptional in Spain but our country might be affected in the near future. New antimicrobials active against these multi-drug resistant pathogens are nowadays available. It is essential to improve our current knowledge about pharmacokinetic properties of traditional and new antimicrobials to maximize its effectiveness and to minimize toxicity. These issues are even more important in critically ill patients because inadequate empirical therapy is associated with therapeutic failure and a poor outcome. Experts representing two scientific societies (Grupo de estudio de Infecciones en el Paciente Critico de la SEIMC and Grupo de trabajo de Enfermedades Infecciosas de la SEMICYUC) have elaborated a consensus document based on the current scientific evidence to summarize recommendations for the treatment of serious infections caused by gram-positive cocci in critically ill patients.