Clostridium difficile infection (CDI) is an increasing nosocomial problem in North America and Western Europe, where outbreaks caused by a more virulent, toxin-hyperproducing strain have been recently reported. Clostridium difficile infection is now characterized by a higher incidence, more frequent relapses, and a higher case-fatality ratio. As a consequence, fulminant cases requiring admission to the intensive care unit (ICU) are much more common than previously. In recent years, metronidazole has appeared to lose some of its effectiveness in CDI management and vancomycin is now recognized as the first-line treatment of severe cases. Rapid diagnosis and institution of infection control measures are critical components of CDI management. The current review focuses on recent changes in the epidemiology, diagnostic methods, and treatment of CDI, with special emphasis on complicated cases managed in the ICU.

A 53-year-old man was transferred to our intensive care unit for a generalized exanthem with systemic inflammatory response syndrome. His medical history included a possible disseminated infection of herpes zoster 15 years before the current admission. He had no history of psoriasis, cutaneous drug reaction, immune suppression or heart disease. Before the current incident, he had not been using any prescribed or over-the-counter medications.Seven days before admission, the patient was bitten on his finger by a spider. He reported pain at the site, and there was a necrotic crust. His primary care physician prescribed cefprozil. A few hours after the first dose, a rash developed. The rash was described as a generalized exanthem with nonfollicular superficial pustules and fever. Based on a working diagnosis of recurrent herpes zoster, he was given famciclovir.Two days before admission to our intensive care unit, the patient was admitted to another centre with high fever, fatigue and persistent skin lesions. Because of fever, leukocytosis and pustules, an infectious cause was suspected. Antibiotic coverage was broadened to include piperacillin-tazobactam and moxifloxacin. The results of tests for infectious and immunosupressive diseases were negative. A computerized tomography (CT) scan of the patient's chest showed alveolar opacities with a ground-glass appearance in both upper lungs. A CT scan of the patient's abdomen showed small nonspecific opacities in his liver. The patient was then transferred to our centre.When the patient arrived at our centre, he had a fever (39.9°C) and was tachycardic (130 beats/min) and hypotensive (90/80 mm Hg). His oxygen saturation was 90% on room air. There was no jugular venous distension. The results of a cardiac examination were unremarkable, except for tachycardia. More than 80% of his skin, including his face and scalp, was affected by a generalized erythema with multiple small nonfollicular pustules. An examination of his mucous membranes showed redness of his tongue. He did not have the Nicolsky sign. (The Nikolsky sign is detected by applying pressure to the skin, which causes intraepidermal cleavage that allows the superficial skin to slip free from the deeper layer. It is mainly seen with bullous diseases and toxic epidermal necrolysis.)Important laboratory results are shown in Table 1. An electrocardiogram showed only sinus tachycardia. We suspected a cutaneous drug reaction. The main diagnoses considered at that time were Stevens-Johnson syndrome or toxic epidermal necrolysis and acute generalized exanthematous pustulosis associated with severe systemic inflammatory response syndrome. The results of the CT scan of the patient's chest were suggestive of an acute lung injury. An infectious cause was not likely because all of the cultures were negative. Antibiotics were discontinued, and fluid resuscitation was initiated. A few hours after admission, our patient developed pulmonary edema with acute respiratory failure. Noninvasive positive pressure ventilation and diuretic ...

This study suggests that an explicit blood pressure target accompanies nearly every vasopressor prescription and that patient characteristics have little influence on its value. Identification of a titration strategy that will maximize benefit and minimize harm constitutes a research priority.

IntroductionVasodilatory hypotension is common among intensive care unit (ICU) patients; vasopressors are considered standard of care. However, optimal mean arterial pressure (MAP) targets for vasopressor titration are unknown. The objective of the Optimal VAsopressor TitraTION in patients 65 years and older (OVATION-65) trial is to ascertain the effect of permissive hypotension (vasopressor titration to achieve MAP 60–65 mm Hg) versus usual care on biomarkers of organ injury in hypotensive patients aged ≥65 years.Methods and analysisOVATION-65 is an allocation-concealed randomised trial in 7 Canadian hospitals. Eligible patients are ≥65 years of age, in an ICU with vasodilatory hypotension, receiving vasopressors for ≤12 hours to maintain MAP ≥65 mm Hg during or after adequate fluid resuscitation, and expected to receive vasopressors for ≥6 additional hours. Patients are excluded for any of the following: active treatment for spinal cord or acute brain injury; vasopressors given solely for bleeding, ventricular failure or postcardiopulmonary bypass vasoplegia; withdrawal of life-sustaining treatments expected within 48 hours; death perceived as imminent; previous enrolment in OVATION-65; organ transplant within the last year; receiving extracorporeal life support or lack of physician equipoise. Patients are randomised to permissive hypotension versus usual care for up to 28 days. The primary outcome is high-sensitivity troponin T, a biomarker of cardiac injury, on day 3. Secondary outcomes include biomarkers of injury to other organs (brain, liver, intestine, skeletal muscle); lactate (a biomarker of global tissue dysoxia); resource utilisation; adverse events; mortality (90 days and 6 months) and cognitive function (6 months). Assessors of biomarkers, mortality and cognitive function are blinded to allocation.Ethics and disseminationThis protocol has been approved at all sites. Consent is obtained from the eligible patient, the substitute decision-maker if the patient is incapable, or in a deferred fashion where permitted. End-of-grant dissemination plans include presentations, publications and social media platforms and discussion forums.Trial registration numberNCT03431181.

ObjectivesVasopressors are not recommended by current trauma guidelines, but recent reports indicate that they are commonly used. We aimed to describe the early hemodynamic management of trauma patients outside densely populated urban centers.MethodsWe conducted a single-center retrospective cohort study in a Canadian regional trauma center. All adult patients treated for traumatic injury in 2013 who died within 24 hours of admission or were transferred to the intensive care unit were included. A systolic blood pressure <90 mmHg, a mean arterial pressure <60 mmHg, the use of vasopressors or ≥2 L of intravenous fluids defined hemodynamic instability. Main outcome measures were use of intravenous fluids and vasopressors prior to surgical or endovascular management.ResultsOf 111 eligible patients, 63 met our criteria for hemodynamic instability. Of these, 60 (95%) had sustained blunt injury and 22 (35%) had concomitant severe traumatic brain injury. The subgroup of patients referred from a primary or secondary hospital (20 of 63, 32%) had significantly longer transport times (243 vs. 61 min, p<0.01). Vasopressors, used in 26 patients (41%), were independently associated with severe traumatic brain injury (odds ratio 10.2, 95% CI 2.7–38.5).ConclusionsIn this cohort, most trauma patients had suffered multiple blunt injuries. Patients were likely to receive vasopressors during the early phase of trauma care, particularly if they exhibited signs of neurologic injury. While these results may be context-specific, determining the risk-benefit trade-offs of fluid resuscitation, vasopressors and permissive hypotension in specific patients subgroups constitutes a priority for trauma research going forwards.