Hydrocortisone in Severe Community-Acquired Pneumonia.

BACKGROUND: Whether the antiinflammatory and immunomodulatory effects of glucocorticoids may decrease mortality among patients with severe community-acquired pneumonia is unclear. METHODS: In this phase 3, multicenter, double-blind, randomized, controlled trial, we assigned adults who had been admitted to the intensive care unit (ICU) for severe community-acquired pneumonia to receive intravenous hydrocortisone (200 mg daily for either 4 or 7 days as determined by clinical improvement, followed by tapering for a total of 8 or 14 days) or to receive placebo. All the patients received standard therapy, including antibiotics and supportive care. The primary outcome was death at 28 days. RESULTS: A total of 800 patients had undergone randomization when the trial was stopped after the second planned interim analysis. Data from 795 patients were analyzed. By day 28, death had occurred in 25 of 400 patients (6.2%; 95% confidence interval [CI], 3.9 to 8.6) in the hydrocortisone group and in 47 of 395 patients (11.9%; 95% CI, 8.7 to 15.1) in the placebo group (absolute difference, -5.6 percentage points; 95% CI, -9.6 to -1.7; P = 0.006). Among the patients who were not undergoing mechanical ventilation at baseline, endotracheal intubation was performed in 40 of 222 (18.0%) in the hydrocortisone group and in 65 of 220 (29.5%) in the placebo group (hazard ratio, 0.59; 95% CI, 0.40 to 0.86). Among the patients who were not receiving vasopressors at baseline, such therapy was initiated by day 28 in 55 of 359 (15.3%) of the hydrocortisone group and in 86 of 344 (25.0%) in the placebo group (hazard ratio, 0.59; 95% CI, 0.43 to 0.82). The frequencies of hospital-acquired infections and gastrointestinal bleeding were similar in the two groups; patients in the hydrocortisone group received higher daily doses of insulin during the first week of treatment. CONCLUSIONS: Among patients with severe community-acquired pneumonia being treated in the ICU, those who received hydrocortisone had a lower risk of death by day 28 than those who received placebo. (Funded by the French Ministry of Health; CAPE COD ClinicalTrials.gov number, NCT02517489.).

Prevention of acquired invasive fungal infection with decontamination regimen in mechanically ventilated ICU patients: a pre/post observational study.

BACKGROUND: Invasive fungal infections acquired in the intensive care unit (AFI) are life-threating complications of critical illness. However, there is no consensus on antifungal prophylaxis in this setting. Multiple site decontamination is a well-studied prophylaxis against bacterial and fungal infections. Data on the effect of decontamination regimens on AFI are lacking. We hypothesised that multiple site decontamination could decrease the rate of AFI in mechanically ventilated patients. METHODS: We conducted a pre/post observational study in 2 ICUs, on adult patients who required mechanical ventilation for >24 h. During the study period, multiple-site decontamination was added to standard of care. It consists of amphotericin B four times daily in the oropharynx and the gastric tube along with topical antibiotics, chlorhexidine body wash and nasal mupirocin. RESULTS: In 870 patients, there were 27 AFI in 26 patients. Aspergillosis accounted for 20/143 of ventilator-associated pneumonia and candidemia for 7/75 of ICU-acquired bloodstream infections. There were 3/308 (1%) patients with AFI in the decontamination group and 23/562 (4%) in the standard-care group (p = 0.011). In a propensity-score matched analysis, there were 3/308 (1%) and 16/308 (5%) AFI in the decontamination group and the standard-care group respectively (p = 0.004) (3/308 vs 11/308 ventilator-associated pulmonary aspergillosis, respectively [p = 0.055] and 0/308 vs 6/308 candidemia, respectively [p = 0.037]). CONCLUSION: Acquired fungal infection is a rare event, but accounts for a large proportion of ICU-acquired infections. Our study showed a preventive effect of decontamination against acquired fungal infection, especially candidemia.Take home messageAcquired fungal infection (AFI) incidence is close to 4% in mechanically ventilated patients without antifungal prophylaxis (3% for pulmonary aspergillosis and 1% for candidemia).Aspergillosis accounts for 14% of ventilator-associated pneumonia and candidemia for 9% of acquired bloodstream infections.Immunocompromised patients, those infected with SARS-COV 2 or influenza virus, males and patients admitted during the fall season are at higher risk of AFI.Mechanically ventilated patients receiving multiple site decontamination (MSD) have a lower risk of AFI.

Characteristics and prognosis of bloodstream infection in patients with COVID-19 admitted in the ICU: an ancillary study of the COVID-ICU study.

BACKGROUND: Patients infected with the severe acute respiratory syndrome coronavirus 2 (SARS-COV 2) and requiring intensive care unit (ICU) have a high incidence of hospital-acquired infections; however, data regarding hospital acquired bloodstream infections (BSI) are scarce. We aimed to investigate risk factors and outcome of BSI in critically ill coronavirus infectious disease-19 (COVID-19) patients. PATIENTS AND METHODS: We performed an ancillary analysis of a multicenter prospective international cohort study (COVID-ICU study) that included 4010 COVID-19 ICU patients. For the present analysis, only those with data regarding primary outcome (death within 90 days from admission) or BSI status were included. Risk factors for BSI were analyzed using Fine and Gray competing risk model. Then, for outcome comparison, 537 BSI-patients were matched with 537 controls using propensity score matching. RESULTS: Among 4010 included patients, 780 (19.5%) acquired a total of 1066 BSI (10.3 BSI per 1000 patients days at risk) of whom 92% were acquired in the ICU. Higher SAPS II, male gender, longer time from hospital to ICU admission and antiviral drug before admission were independently associated with an increased risk of BSI, and interestingly, this risk decreased over time. BSI was independently associated with a shorter time to death in the overall population (adjusted hazard ratio (aHR) 1.28, 95% CI 1.05-1.56) and, in the propensity score matched data set, patients with BSI had a higher mortality rate (39% vs 33% p = 0.036). BSI accounted for 3.6% of the death of the overall population. CONCLUSION: COVID-19 ICU patients have a high risk of BSI, especially early after ICU admission, risk that increases with severity but not with corticosteroids use. BSI is associated with an increased mortality rate.