Determinants of mortality in cancer patients with unscheduled admission to the Intensive Care Unit: A prospective multicenter study.

OBJECTIVES: To analyze clinical features associated to mortality in oncological patients with unplanned admission to the Intensive Care Unit (ICU), and to determine whether such risk factors differ between patients with solid tumors and those with hematological malignancies. DESIGN: An observational study was carried out. SETTING: A total of 123 Intensive Care Units across Spain. PATIENTS: All cancer patients with unscheduled admission due to acute illness related to the background oncological disease. INTERVENTIONS: None. MAIN VARIABLES: Demographic parameters, severity scores and clinical condition were assessed, and mortality was analyzed. Multivariate binary logistic regression analysis was performed. RESULTS: A total of 482 patients were included: solid cancer (n=311) and hematological malignancy (n=171). Multivariate regression analysis showed the factors independently associated to ICU mortality to be the APACHE II score (OR 1.102; 95% CI 1.064-1.143), medical admission (OR 3.587; 95% CI 1.327-9.701), lung cancer (OR 2.98; 95% CI 1.48-5.99) and mechanical ventilation after the first 24h of ICU stay (OR 2.27; 95% CI 1.09-4.73), whereas no need for mechanical ventilation was identified as a protective factor (OR 0.15; 95% CI 0.09-0.28). In solid cancer patients, the APACHE II score, medical admission, antibiotics in the previous 48h and lung cancer were identified as independent mortality indicators, while no need for mechanical ventilation was identified as a protective factor. In the multivariate analysis, the APACHE II score and mechanical ventilation after 24h of ICU stay were independently associated to mortality in hematological cancer patients, while no need for mechanical ventilation was identified as a protective factor. Neutropenia was not identified as an independent mortality predictor in either the total cohort or in the two subgroups. CONCLUSIONS: The risk factors associated to mortality did not differ significantly between patients with solid cancers and those with hematological malignancies. Delayed intubation in patients requiring mechanical ventilation might be associated to ICU mortality.

[Infections related to invasive devices in COVID-19 patients admitted to critical care units]. / Infecciones relacionadas con dispositivos invasivos en pacientes COVID-19 ingresados en unidades de críticos.

Introduction: COVID-19 patients admitted to critical care units present an intense inflammatory response and the need to replace organs or systems for long periods of time, which facilitates the presence of infectious complications. Objectives: To present the national rates of infections related to invasive devices (IRDI) in COVID-19 patients, as well as the rates of multi-resistant bacteria (MBR) acquired during their stay in critical care units. Method: Retrospective analysis of COVID-19 patients included during the first, second and fourth waves of the pandemic in a national observational and multicenter database (ENVIN-HELICS). Pneumonias related to mechanical ventilation (N-MV), urinary tract infections related to urethral catheter (UTI-SU) and primary bacteremia related to central venous catheters (BP-CVC) were recorded, whose rates are presented as incidence density (ID). The BMRs acquired during the stay in the critical care units were recorded and presented as cumulative incidence (CI). Results: Seven thousand seven hundred seventy-eight patients were included, 1,525 (19.6%) in the first wave of the pandemic, 3,484 (44.8%) in the second, and 2,769 (35.6%) in the fourth. ICU stay of 21 days in the first and second waves and 19.7 days in the fourth. Intra-ICU mortality in the first wave, decreasing from 31% to 26.3% in the second and 18.9% in the fourth. N-MV rates of 14.31, 13.56, and 19.99 episodes per 1,000 days of MV in each wave. UTI-SU rates of 6.54, 5.63 and 7.97 episodes per 1000 days of SU. BP-CVC rates of 12.42, 7.95, and 8.13 per 1,000 CVC days. The BMR rate was 22.9, 15.3, and 15.3 BMR per 100 admitted patients. Conclusions: High rates of the different IRDI in COVID patients that are maintained in the three waves analyzed. High rates of BMR acquired during the stay in critical care units with a tendency to decrease in the fourth wave.

Management of infectious complications associated with coronavirus infection in severe patients admitted to ICU.

Infections have become one of the main complications of patients with severe SARS-CoV-2 pneumonia admitted in ICU. Poor immune status, frequent development of organic failure requiring invasive supportive treatments, and prolonged ICU length of stay in saturated structural areas of patients are risk factors for infection development. The Working Group on Infectious Diseases and Sepsis GTEIS of the Spanish Society of Intensive Medicine and Coronary Units SEMICYUC emphasizes the importance of infection prevention measures related to health care, the detection and early treatment of major infections in the patient with SARS-CoV-2 infections. Bacterial co-infection, respiratory infections related to mechanical ventilation, catheter-related bacteremia, device-associated urinary tract infection and opportunistic infections are review in the document.

Active humidification in mechanical ventilation is not associated to an increase in respiratory infectious complications in a quasi-experimental pre-post intervention study.

OBJECTIVE: There is controversy regarding the influence of humidification systems upon the incidence of respiratory infections associated to invasive mechanical ventilation (IMV). An evaluation was made of the differences in the incidence of pneumonia and tracheobronchitis associated to mechanical ventilation (VAP and VAT, respectively) with passive and active humidification. DESIGN: A retrospective pre-post quasi-experimental study was carried out. SETTING: A polyvalent ICU with 14 beds. PATIENTS: All patients connected to IMV for >48h during 2014 and 2016 were included. INTERVENTIONS: During 2014, passive humidification with an hygroscopic heat and moisture exchanger (HME) was used, while during 2016 active humidification with a heated humidifier (HH) and an inspiratory heated wire was used. Identical measures for the prevention of VAP were established (Zero Pneumonia Project). MAIN OUTCOME MEASURES: The incidence of VAP and VAT was estimated for 1000 days of IMV in both groups, and statistically significant differences were assessed using Poisson regression analysis. RESULTS: A total of 287 patients were included (116 with HME and 171 with HH). The incidence density of VAP per 1000 days of IMV was 5.68 in the HME group and 5.80 in the HH group (p=ns). The incidence density of VAT was 3.41 and 3.26 cases per 1000 days of VMI with HME and HH respectively (p=ns). The duration of IMV was identified as a risk factor for VAP. CONCLUSIONS: In our population, active humidification in patients ventilated for >48h was not associated to an increase in respiratory infectious complications.

Management of infectious complications associated with coronavirus infection in severe patients admitted to ICU. / Manejo de las complicaciones infecciosas asociadas con la infección por coronavirus en pacientes graves ingresados en UCI.

Infections have become one of the main complications of patients with severe SARS-CoV-2 pneumonia admitted in ICU. Poor immune status, frequent development of organic failure requiring invasive supportive treatments, and prolonged ICU length of stay in saturated structural areas of patients are risk factors for infection development. The Working Group on Infectious Diseases and Sepsis GTEIS of the Spanish Society of Intensive Medicine and Coronary Units SEMICYUC emphasizes the importance of infection prevention measures related to health care, the detection and early treatment of major infections in the patient with SARS-CoV-2 infections. Bacterial co-infection, respiratory infections related to mechanical ventilation, catheter-related bacteremia, device-associated urinary tract infection and opportunistic infections are review in the document.

Epidemiology and prognosis of patients with a history of cancer admitted to intensive care. A multicenter observational study.

OBJECTIVE: To assess the epidemiology and outcome at discharge of cancer patients requiring admission to the Intensive Care Unit (ICU). DESIGN: A descriptive observational study was made of data from the ENVIN-HELICS registry, combined with specifically compiled variables. Comparisons were made between patients with and without neoplastic disease, and groups of cancer patients with a poorer outcome were identified. SETTING: Intensive Care Units participating in ENVIN-HELICS 2018, with voluntary participation in the oncological registry. PATIENTS: Subjects admitted during over 24 h and diagnosed with cancer in the last 5 years. PRIMARY ENDPOINTS: The general epidemiological endpoints of the ENVIN-HELICS registry and cancer-related variables. RESULTS: Of the 92 ICUs with full data, a total of 11,796 patients were selected, of which 1786 (15.1%) were cancer patients. The proportion of cancer patients per Unit proved highly variable (1%-48%). In-ICU mortality was higher among the cancer patients than in the non-oncological subjects (12.3% versus 8.9%; p < .001). Elective postoperative (46.7%) or emergency admission (15.3%) predominated in the cancer patients. Patients with medical disease were in more serious condition, with longer stay and greater mortality (27.5%). The patients admitted to the ICU due to nonsurgical disease related to cancer exhibited the highest mortality rate (31.4%). CONCLUSIONS: Great variability was recorded in the percentage of cancer patients in the different ICUs. A total of 46.7% of the patients were admitted after undergoing scheduled surgery. The highest mortality rate corresponded to patients with medical disease (27.5%), and to those admitted due to cancer-related complications (31.4%).

[Management of infectious complications associated with coronavirus infection in severe patients admitted to ICU]. / Manejo de las complicaciones infecciosas asociadas con la infección por coronavirus en pacientes graves ingresados en UCI.

Infections have become one of the main complications of patients with severe SARS-CoV-2 pneumonia admitted in ICU. Poor immune status, frequent development of organic failure requiring invasive supportive treatments, and prolonged ICU length of stay in saturated structural areas of patients are risk factors for infection development. The Working Group on Infectious Diseases and Sepsis GTEIS of the Spanish Society of Intensive Medicine and Coronary Units SEMICYUC emphasizes the importance of infection prevention measures related to health care, the detection and early treatment of major infections in the patient with SARS-CoV-2 infections. Bacterial co-infection, respiratory infections related to mechanical ventilation, catheter-related bacteremia, device-associated urinary tract infection and opportunistic infections are review in the document.

Dosage Individualization of Linezolid: Precision Dosing of Linezolid To Optimize Efficacy and Minimize Toxicity.

The high interindividual variability in the pharmacokinetics (PK) of linezolid has been described, which results in an unacceptably high proportion of patients with either suboptimal or potentially toxic concentrations following the administration of a fixed regimen. The aim of this study was to develop a population pharmacokinetic model of linezolid and use this to build and validate alogorithms for individualized dosing. A retrospective pharmacokinetic analysis was performed using data from 338 hospitalized patients (65.4% male, 65.5 [±14.6] years) who underwent routine therapeutic drug monitoring for linezolid. Linezolid concentrations were analyzed by using high-performance liquid chromatography. Population pharmacokinetic modeling was performed using a nonparametric methodology with Pmetrics, and Monte Carlo simulations were employed to calculate the 100% time >MIC after the administration of a fixed regimen of 600 mg administered every 12 h (q12h) intravenously (i.v.). The dose of linezolid needed to achieve a PTA ≥ 90% for all susceptible isolates classified according to EUCAST was estimated to be as high as 2,400 mg q12h, which is 4 times higher than the maximum licensed linezolid dose. The final PK model was then used to construct software for dosage individualization, and the performance of the software was assessed using 10 new patients not used to construct the original population PK model. A three-compartment model with an absorptive compartment with zero-order i.v. input and first-order clearance from the central compartment best described the data. The dose optimization software tracked patients with a high degree of accuracy. The software may be a clinically useful tool to adjust linezolid dosages in real time to achieve prespecified drug exposure targets. A further prospective study is needed to examine the potential clinical utility of individualized therapy.

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.

Population Pharmacokinetics of Anidulafungin in Critically Ill Patients.

A two-compartment pharmacokinetic (PK) population model of anidulafungin was fitted to PK data from 23 critically ill patients (age, 65 years [range, 28 to 81 years]; total body weight [TBW], 75 kg [range, 54 to 168 kg]). TBW was associated with clearance and incorporated into a final population PK model. Simulations suggested that patients with higher TBWs had less-extensive MIC coverage. Dosage escalation may be warranted in patients with high TBWs to ensure optimal drug exposures for treatment of Candida albicans and Candida glabrata infections.

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.

Patients with influenza A (H1N1)pdm09 admitted to the ICU. Impact of the recommendations of the SEMICYUC. / Pacientes con gripe por el virus influenza A (H1N1)pdm09 ingresados en la UCI. Impacto de las recomendaciones de la SEMICYUC.

OBJECTIVES: To evaluate the impact of the recommendations of the SEMICYUC (2012) on severe influenza A. DESIGN: A prospective multicenter observational study was carried out. SETTING: ICU. PATIENTS: Patients infected with severe influenza A (H1N1) from the GETGAG/SEMICYUC registry. INTERVENTIONS: Analysis of 2 groups according to the epidemic period of the diagnosis (2009-2011; 2013-2015). VARIABLES: Demographic, temporal, comorbidities, severity, treatments, mortality, late diagnosis and place of acquisition. RESULTS: A total of 2,205 patients were included, 1,337 (60.6%) in the first period and 868 (39.4%) in the second one. Age and severity on admission were significantly greater in the second period, as well as co-infection. With regard to the impact of the recommendations, in the second period the diagnosis was established earlier (70.8 vs. 61.1%, P<.001), without changes in the start of treatment. Patients received less corticosteroid treatment (39.7 vs. 44.9%, P<.05), more NIMV was used (47.4 vs. 33.2%, P<.001) and more vaccination was made (11.1 vs. 1.7%, P<.001), without changes in mortality (24.2 vs. 20.7%). A decrease in nosocomial infection was also noted (9.8 vs. 16%, P<.001). Patients needed less MV with more days of ventilation, more vasopressor drug use and more ventral decubitus. CONCLUSIONS: The management of patients with severe influenza A (H1N1) has changed over the years, though without changes in mortality. The recommendations of the SEMICYUC (2012) have allowed earlier diagnosis and improved corticosteroid use. Pending challenges are the delay in treatment, the vaccination rate and the use of NIMV.

Antibiotic selection in the treatment of acute invasive infections by Pseudomonas aeruginosa: Guidelines by the Spanish Society of Chemotherapy.

Pseudomonas aeruginosa is characterized by a notable intrinsic resistance to antibiotics, mainly mediated by the expression of inducible chromosomic ß-lactamases and the production of constitutive or inducible efflux pumps. Apart from this intrinsic resistance, P. aeruginosa possess an extraordinary ability to develop resistance to nearly all available antimicrobials through selection of mutations. The progressive increase in resistance rates in P. aeruginosa has led to the emergence of strains which, based on their degree of resistance to common antibiotics, have been defined as multidrug resistant, extended-resistant and panresistant strains. These strains are increasingly disseminated worldwide, progressively complicating the treatment of P. aeruginosa infections. In this scenario, the objective of the present guidelines was to review and update published evidence for the treatment of patients with acute, invasive and severe infections caused by P. aeruginosa. To this end, mechanisms of intrinsic resistance, factors favoring development of resistance during antibiotic exposure, prevalence of resistance in Spain, classical and recently appeared new antibiotics active against P. aeruginosa, pharmacodynamic principles predicting efficacy, clinical experience with monotherapy and combination therapy, and principles for antibiotic treatment were reviewed to elaborate recommendations by the panel of experts for empirical and directed treatment of P. aeruginosa invasive infections.

Ceftolozane-tazobactam for the treatment of ventilator-associated infections by colistin-resistant Pseudomonas aeruginosa.

The use of colistin for the treatment of multiresistant bacteria has led to the emergence of colistin-resistant strains of Gram-negative bacilli. Treatment of infections caused by these pan-drug-resistant bacteria is difficult owing to the paucity of effective antibiotics. We report two cases of ventilator-associated respiratory infection caused by pan-drug-resistant, colistin-resistant Pseudomonas aeruginosa that were successfully treated with ceftolozane-tazobactam.

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.