Shailesh Bihari

OBJECTIVE: To determine the prevalence of intensive care unit (ICU)-acquired infections and the risk factors for these infections, identify the predominant infecting organisms, and evaluate the relationship between ICU-acquired infection and mortality. DESIGN: A 1-day point-prevalence study. SETTING: Intensive care units in 17 countries in Western Europe, excluding coronary care units and pediatric and special care infant units. PATIENTS: All patients (> 10 years of age) occupying an ICU bed over a 24-hour period. A total of 1417 ICUs provided 10 038 patient case reports. MAIN OUTCOME MEASURES: Rates of ICU-acquired infection, prescription of antimicrobials, resistance patterns of microbiological isolates, and potential risk factors for ICU-acquired infection and death. RESULTS: A total of 4501 patients (44.8%) were infected, and 2064 (20.6%) had ICU-acquired infection. Pneumonia (46.9%), lower respiratory tract infection (17.8%), urinary tract infection (17.6%), and bloodstream infection (12%) were the most frequent types of ICU infection reported. Most frequently reported micro-organisms were Enterobacteriaceae (34.4%), Staphylococcus aureus (30.1%;[60% resistant to methicillin], Pseudomonas aeruginosa (28.7%), coagulase-negative staphylococci (19.1%), and fungi (17.1%). Seven risk factors for ICU-acquired infection were identified: increasing length of ICU stay (> 48 hours), mechanical ventilation, diagnosis of trauma, central venous, pulmonary artery, and urinary catheterization, and stress ulcer prophylaxis. ICU-acquired pneumonia (odds ratio [OR], 1.91; 95% confidence interval[Cl], 1.6 to 2.29), clinical sepsis (OR, 3.50; 95% Cl, 1.71 to 7.18), and bloodstream infection (OR, 1.73; 95% Cl, 1.25 to 2.41) increased the risk of ICU death. CONCLUSIONS: ICU-acquired infection is common and often associated with microbiological isolates of resistant organisms. The potential effects on outcome emphasize the importance of specific measures for infection control in critically ill patients.

BACKGROUND Thrombosis and inflammation may contribute to the risk of death and complications among patients with coronavirus disease 2019 (Covid-19). We hypothesized that therapeutic-dose anticoagulation may improve outcomes in noncritically ill patients who are hospitalized with Covid-19. METHODS In this open-label, adaptive, multiplatform, controlled trial, we randomly assigned patients who were hospitalized with Covid-19 and who were not critically ill (which was defined as an absence of critical care-level organ support at enrollment) to receive pragmatically defined regimens of either therapeutic-dose anticoagulation with heparin or usual-care pharmacologic thromboprophylaxis. The primary outcome was organ support-free days, evaluated on an ordinal scale that combined in-hospital death (assigned a value of -1) and the number of days free of cardiovascular or respiratory organ support up to day 21 among patients who survived to hospital discharge. This outcome was evaluated with the use of a Bayesian statistical model for all patients and according to the baseline d-dimer level. RESULTS The trial was stopped when prespecified criteria for the superiority of therapeutic-dose anticoagulation were met. Among 2219 patients in the final analysis, the probability that therapeutic-dose anticoagulation increased organ support-free days as compared with usual-care thromboprophylaxis was 98.6% (adjusted odds ratio, 1.27; 95% credible interval, 1.03 to 1.58). The adjusted absolute between-group difference in survival until hospital discharge without organ support favoring therapeutic-dose anticoagulation was 4.0 percentage points (95% credible interval, 0.5 to 7.2). The final probability of the superiority of therapeutic-dose anticoagulation over usual-care thromboprophylaxis was 97.3% in the high d-dimer cohort, 92.9% in the low d-dimer cohort, and 97.3% in the unknown d-dimer cohort. Major bleeding occurred in 1.9% of the patients receiving therapeutic-dose anticoagulation and in 0.9% of those receiving thromboprophylaxis. CONCLUSIONS In noncritically ill patients with Covid-19, an initial strategy of therapeutic-dose anticoagulation with heparin increased the probability of survival to hospital discharge with reduced use of cardiovascular or respiratory organ support as compared with usual-care thromboprophylaxis. (ATTACC, ACTIV-4a, and REMAP-CAP ClinicalTrials.gov numbers, NCT04372589, NCT04505774, NCT04359277, and NCT02735707.).

Abstract Rationale Open lung ventilation strategies have been recommended in patients with acute respiratory distress syndrome (ARDS). Objectives To determine whether a maximal lung recruitment strategy reduces ventilator-free days in patients with ARDS. Methods A phase II, multicenter randomized controlled trial in adults with moderate to severe ARDS. Patients received maximal lung recruitment, titrated positive end expiratory pressure and further Vt limitation, or control “protective” ventilation. Measurements and Main Results The primary outcome was ventilator-free days at Day 28. Secondary outcomes included mortality, barotrauma, new use of hypoxemic adjuvant therapies, and ICU and hospital stay. Enrollment halted October 2, 2017, after publication of ART (Alveolar Recruitment for Acute Respiratory Distress Syndrome Trial), when 115 of a planned 340 patients had been randomized (57% male; mean age, 53.6 yr). At 28 days after randomization, there was no difference between the maximal lung recruitment and control ventilation strategies in ventilator-free days (median, 16 d [interquartile range (IQR), 0–21 d], n = 57, vs. 14.5 d [IQR, 0–21.5 d], n = 56; P = 0.95), mortality (24.6% [n = 14/56] vs. 26.8% [n = 15/56]; P = 0.79), or the rate of barotrauma (5.2% [n = 3/57] vs. 10.7% [n = 6/56]; P = 0.32). However, the intervention group showed reduced use of new hypoxemic adjuvant therapies (i.e., inhaled nitric oxide, extracorporeal membrane oxygenation, prone; median change from baseline 0 [IQR, 0–1] vs. 1 [IQR, 0–1]; P = 0.004) and increased rates of new cardiac arrhythmia (n = 17 [29%] vs. n = 7 [13%]; P = 0.03). Conclusions Compared with control ventilation, maximal lung recruitment did not reduce the duration of ventilation-free days or mortality and was associated with increased cardiovascular adverse events but lower use of hypoxemic adjuvant therapies. Clinical trial registered with www.clinicaltrials.gov (NCT01667146).