December 2, 2019

Background: Recently there have been some observed trends in decreasing susceptibility among Strep pneumoniae isolates to antimicrobials used to treat community acquired pneumonia (CAP) (Resistance to oral penicillin and macrolides for Strep pneumoniae & macrolides and fluoroquinolones for Staph aureus).  New antibacterials are therefore needed to treat CAP because of growing antibacterial resistance. Lefamulin is the first pleuromutilin antibiotic approved for intravenous and oral use in humans. Both the intravenous and oral formulations were approved in August 2019 by the US Food and Drug Administration (FDA) to treat CAP.  It is active against the most common CAP-causing pathogens, including bacteria resistant to other antimicrobial classes. Lefamulin Evaluation Against Pneumonia 1 (LEAP 1) [1] looked at IV Lefamulin vs IV Moxifloxacin in adult patients with moderate to severe CAP and demonstrated noninferiority in that trial.   Given those results, LEAP 2 was performed to compare oral Lefamulin to oral Moxifloxacin in adult patients with moderate to severe CAP.

November 25, 2019

Background: In 2016, Paul Marik published a study in Chest [2] demonstrating a decrease in hospital mortality of 32% for sepsis patients treated with vitamin C, thiamine and hydrocortisone.  The Marik protocol(as it has come to be known), entails IV vitamin C 1.5g q6hr for 4d + IV hydrocortisone 50mg q6hr for 7d + IV thiamine 200mg q12hr x4d. The authors’ hypothesis was that vitamin C, hydrocortisone, and thiamine have synergistic effects that reverse vasoplegic shock and potentially limit the duration of vasopressor treatment resulting in a reduction in organ and limb ischemia from vasopressors themselves.  Although the results of the study are promising, it is important to remember that this was only a hypothesis generating study.  We have been waiting for a randomized clinical trial to recreate the results of this study and finally we have our first of many… CITRIS-ALI. This randomized trial looks to see if high-dose vitamin C could reduce organ failure and biomarkers of inflammation and vascular injury in patients with sepsis and ARDS.

November 14, 2019

Background: Septic shock is the most severe form of sepsis. It is characterized by vasodilation and increased capillary permeability leading to hypotension and tissue hypoxia.  The initial treatment of septic shock includes early identification, intravenous fluids when necessary, appropriate broad-spectrum antibiotics, source control and organ support. Vasopressor therapy is often required to maintain adequate perfusion to support end organs.  Norepinephrine is the accepted first-line vasopressor for patients in septic shock, but it is not always effective in patients with extreme vasoplegia due to sepsis. Selepressin, a selective vasopressin V1a receptor agonist, is a non-catecholaminergic vasopressor that may assist in these patients.  It works by mitigating vasodilatation, vascular leakage, and tissue edema, but without V1b- or V2-mediated effects seen with vasopressin, which result in increased procoagulant factors, salt/water retention, nitric oxide release, and corticosteroid stimulation.

November 7, 2019

Background: Despite minimal high-quality supporting evidence (Seymour 2017, Liu 2017, Ferrer 2014, Sterling 2015), regulatory bodies have pushed for benchmark times for administration of antibiotics in patients with sepsis. While most clinicians would agree that in patients with septic shock antibiotics should be given as quickly as possible, the same does not hold true for those patients with less severe infections. In the US, the Centers for Medicare and Medicaid Services (CMS) currently mandates that antibiotics be started in patients within 3 hours of onset of new organ dysfunction in patients with systemic inflammatory response syndrome and documented infection. The Surviving Sepsis Campaign (SSC) has even more extreme recommendations stating that antibiotics should be started within 1 hour from triage in septic patients (Levy 2018). Based on prior experience with arbitrary time to antibiotic administration (see community acquired pneumonia), such draconian recommendations are likely to increase inappropriate use of antibiotics, distract clinicians from more important tasks and have minimal effect on patient outcomes. This is likely why the Infectious Disease Society of America (IDSA) declined endorsement of the SSC guidelines. The ridiculous nature of these recommendations has been discussed elsewhere.

Even if the recommendation had some merit, it’s important to ask whether it’s even possible to implement. None of those on the SSC committee work in emergency departments and their understanding of the logistical challenges of such a policy is limited.

August 22, 2019

Background: Unwarranted use of antibiotics has several deleterious effects which include, antimicrobial resistance, wasted resources, adverse effects, negative affect on the microbiome of patients, and distracts from potentially more effective interventions. There has recently been a huge push for tests such as procalcitonin to help in curtailing the use of antibiotics when it is not warranted.  Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines recommend only prescribing antibiotics in moderately or severely ill patients with acute COPD exacerbations, increased cough, and/or sputum purulence [2]. The authors of this trial wanted to test another such marker, point of care CRP in patients with acute COPD exacerbations.  Along with bronchodilators and steroids, antibiotic prescriptions seem to be a common treatment modality as well. CRP is an acute-phase protein that is readily available and can be measured quickly with point of care testing.  The authors of this trial hypothesized that the results of POC CRP may help inform prescribing decisions for acute COPD exacerbations, however RCTs regarding clinical effectiveness of this test are lacking.
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