December 26, 2020

Background Information: With rising cases, an increasing death toll, and a significant strain on hospital systems globally, the COVID-19 pandemic seemed to have no end in sight. The aggressive pursuit of a vaccine has led to multiple clinical trials starting before the end of this year. In fact, there are 48 vaccines under clinical evaluation and 11 of these are currently being evaluated in phase 3 clinical efficacy trials.1 Among those includes, the replication-deficient chimpanzee adenoviral vector developed at Oxford University (ChAdOx1). Following the initiation of a phase 1 clinical trial in the UK (COV001), three additional randomized controlled trials were initiated across the UK (COV002), Brazil (COV003) and South Africa (COV005). Upon completion of enrollment, the authors of the following paper sought to perform a combined interim analysis of the four trials to assess ChAdOx1’s efficacy and safety

March 18, 2019

Background: With CMS core measures requiring timely use of antibiotics in patients with fever and suspected sepsis, many patients receive antibiotics up front that may ultimately end up having another non-bacterial etiology as the cause of their fever.  On the one hand overuse of antibiotics can increase bacterial resistance, healthcare costs, and potential side effects. On the other hand, withholding antibiotics from patients with bacterial infections can increase morbidity and mortality. The authors of this trial wanted to determine whether a procalcitonin-guided algorithm could be used to reduce antibiotic regimens in the ED.

March 11, 2019

Background: Based on the Surviving Sepsis Campaign, hemodynamic resuscitation of sepsis patients is done by repeating serum lactic acid levels every 2 – 4 hours until normalization. The issue with this strategy is that there are other things that may elevate lactate levels other than sepsis and hypoperfusion.  Another, potentially useful marker to guide hemodynamic resuscitation could be capillary refill time.  Its easy-to-use, requires no resources, and costs nothing.  To answer this question the ANDROMEDA-SHOCK randomized controlled trial tried to evaluate the use of a peripheral perfusion-targeted resuscitation strategy during septic shock in adults.

February 28, 2019

Background: Standard management of septic shock has included, IV fluids until optimal intravascular volume is achieved, appropriate early antibiotics, and source control.  Typically, only after all these measures have been undertaken is vasopressor infusion initiated if a MAP of ≥65mmHg is not achieved. There have been some animal and human studies that have advocated for early norepinephrine administration in septic shock improving hemodynamics and mortality.  The issue, with these trials is that they were retrospective which means these studies suffer from the limitations of this type of methodology (i.e. convenience sampling, recall bias, confounding, and ultimately cannot determine causation, only association).

February 25, 2019

Introduction: The production and release of new antibiotics is rare and should be celebrated by clinicians. As antibiotic resistance continues to mount, our options narrow and, in turn, our patients suffer. Recently, the NEJM published two articles on a new antibiotic that was recently FDA approved - omadacycline. The articles compared omadacycline to moxifloxacin in the treatment of community acquired pneumonia (CAP) and to linezolid in the treatment of skin and soft tissue infections. Both studies yielded promising results for the new drug which should be cause of excitement. However, significant biases, methodological flaws and poor selection of comparator treatments should temper our excitement.

Both studies tested the new antibiotic in a non-inferiority set up. Non-inferiority studies seem to be increasingly prevalent in the literature and because they serve an important purpose, it’s important for us to understand them and also to understand why this approach is used and why it may not be appropriate.