Top Infectious Disease News of the Week— December 16, 2018

#5: Sepsis Treatment Trial Evaluates Vitamin C, Thiamine, and Steroid Combination

In the United States, at least 1.7 million adults suffer from sepsis each year and about 270,000 die as a result. The current standard-of-care for sepsis includes early appropriate antibiotics, aggressive fluid resuscitation, and blood pressure support with vasopressors to prevent septic shock, which can lead to respiratory and organ failure and death. Because of the deleterious consequences of the condition and a lack of tried-and-true therapies to decrease mortality, investigators are examining treatments that a have good track record with sepsis and further studying their effects.

“Despite many years of clinical trials and elucidation of sepsis pathophysiology, there are no proven ancillary therapies to decrease sepsis mortality and no gold standard test for its diagnosis,” Katherine Nugent, MD, an emergency medicine physician at Emory University Hospital and an investigator on the trial, told Contagion® in a recent interview.

Previous research has demonstrated success in treating sepsis using intravenous vitamin C, thiamine, and hydrocortisone. Inspired by this success, Dr. Nugent and her colleagues from Emory launched The VItamin C, Thiamine And Steroids in Sepsis (VICTAS) clinical trial in August 2018 to investigate the use of the combination therapy to reduce the duration of cardiovascular and respiratory organ dysfunction and to reduce 30-day mortality in critically ill patients with sepsis.

Read about the VICTAS clinical trial.

#4: Study Outlines Machine-Based Model for Identifying Drug-Resistant Bacteria

With food recalls making headlines—and people sick—across the country, clinicians desperately need new approaches for identifying pathogens and diagnosing related illnesses.

A recent study suggests a solution to this challenge may be on the horizon.

In a collaboration between computer scientists, engineers, and infectious disease specialists (among others), models using whole genome sequence data to predict minimum inhibitory concentrations (MICs) for nontyphoidal Salmonella in strains collected and sequenced via the National Antimicrobial Resistance Monitoring System between 2002 and 2016 have emerged. The team published their findingsthis fall in the Journal of Clinical Microbiology (JCM). And, importantly, they believe their whole genome sequence-based models “can be readily applied to other important human pathogens” and thereby “guide responses to outbreaks and inform antibiotic stewardship decisions.”

Investigators could not be reached for comment on deadline; however, in their concluding remarks, they noted, “In this study, we have built machine learning-based MIC prediction models for nontyphoidal Salmonella genomes using XGBoost that achieve overall accuracies of 95% to 96%... To our knowledge, this is one of the largest and most accurate MIC prediction models to be published to date. Importantly, it provides a model strategy for performing MIC prediction directly from genome sequence data that could be applied to other human or veterinary pathogens.”

Read about the machine-based model to identify drug-resistant bacteria.

#3: A Look Into the Antimicrobial Stewardship Collaborative of South Carolina

Antimicrobial resistance is an urgent public health threat. State and local health departments can play a critical role in promoting appropriate antimicrobial use and implement prevention strategies to help slow the development of antimicrobial resistance. The Antimicrobial Stewardship Collaborative of South Carolina (ASC-SC) was established in 2016 through a grant from the US Centers for Disease Control and Prevention.

The South Carolina Department of Health and Environmental Control was the lead organization on the grant application, partnering with the University of South Carolina School of Medicine and College of Pharmacy.

The goals of the collaborative are to coordinate and improve antimicrobial steward­ship across South Carolina and to improve surveillance to drive public health action. ASC-SC currently partners with 44 acute care hospitals and 12 long-term care facil­ities (LTCFs) to improve antimicrobial stewardship efforts in South Carolina.

Read about ASC-SC’s antimicrobial stewardship collaborative.

#2: Seven Days of Antibiotics Enough for Uncomplicated Bacteremia

even days of antibiotic treatment is sufficient for patients with uncomplicated gram-negative bacteremia, according to the results of a new study publishedonline December 11 in the journal Clinical Infectious Diseases.

“Shortening antibiotic duration is important for antimicrobial stewardship,” Dafna Yahav, MD, from the Sackler Faculty of Medicine, Tel Aviv University, Ramat Aviv, Israel, and colleagues reported. “Current treatment guidelines recommend a range of treatment duration from 7 to 14 days for bacteremia.”

Because gram-negative bacteremia is a significant cause of morbidity and mortality in hospitalized patients, clinicians need evidence-based guidance about the appropriate duration of use of antibiotics to manage these cases.

With this in mind, Dr. Yahav and colleagues conducted a randomized controlled trial to investigate whether a shorter course of antibiotics is appropriate for patients who have gram-negative bacteremia.

Read about a 7-day course of antibiotics for uncomplicated bacteremia.

#1: De-Escalation in Under 48 Hours Reduces 90-Day C difficile Infection Incidence 3-Fold

A novel study from Seddon and colleagues adds to the body of evidence that supports what antimicrobial stewardship programs are so often challenged to do, early de-escalation.¹ The study’s investigators looked at the independent risk factors of empiric antipseudomonal β-lactam (APBL) therapy for patients with Enterobacteriaceae bloodstream infections who received more than 48 hours of therapy compared with those who received less and found a 3-fold lower incidence of Clostridium difficile infection in patients who received less than 48 hours of APBL therapy.

With each hour that passes after receiving noneffective therapy, patients with sepsis are at increased risk of mortality.^2,3 As a result, empiric treatment for the condition often includes APBL therapy. With the increased threat of antimicrobial resistance, however, clinicians are growing concerned over the development of difficult-to-treat gram-negative bacteremia, and so the initial selection of the appropriate, targeted antibiotic is imperative.^4,5 Furthermore, excessive antimicrobial coverage brings additional risks, such as C difficile infection.

Seddon and colleagues challenged the practice of broad-spectrum antipseudomonal coverage up front for those patients without risk factors, referencing another recent study completed at their center. The results from that study demonstrated only 1% prevalence of Pseudomonas aeruginosabloodstream infections in community-onset, immunocompetent patients who have not received prior antimicrobial use within 3 months.⁶ In addition, the investigators assessed the risk of antimicrobial exposure and early de-escalation of APBL therapy at 48 hours on the rate of C difficile infection.^7,8

The retrospective cohort study included 951 adult patients with gram-negative bloodstream infections. Data were collected for 54 months. Not all non-Enterobacteriaceae bloodstream cases (n = 78) were included, as the authors stated they lacked the possibility of de-escalation. Those patients who were discharged, transferred, or died were also excluded from the results (n = 56). Additionally, the investigators excluded those patients with recent (within a year) or concurrent C difficile infection (developed within 24 hours of blood culture collection).

Read about de-escalation and reducing of C difficile infection incidence.