Sepsis: testing before starting treatment is essential
Given that timely administration of appropriate antibiotics is essential to prevent death in patients with severe infections, can healthcare teams “skip” drawing blood for bacterial cultures and go straight to administering antibiotics, to accelerate treatment and improve outcomes? “No,” answers a team of researchers from the Research Institute of the McGill University Health Centre (RI-MUHC), the University of British Columbia and Harvard Medical School, who have recently shown that the initiation of antimicrobial therapy significantly reduces the sensitivity of blood cultures drawn shortly after treatment initiation. This diminishes the ability to detect the specific bacteria causing the infection. Their finding, published in Annals of Internal Medicine, strengthens existing recommendations to withhold antibiotic treatment until blood cultures are drawn.
“Treatment [before microbiologic testing] can lead to loss of clinical information in blood cultures, making it more difficult to identify pathogens and provide targeted treatment, therefore putting patients at risk,” says Dr. Matthew Cheng, the first author of the study, who was completing his subspecialty training in Infectious Diseases and Medical Microbiology at McGill University during the study.
This evidence confirms the importance of current clinical practice guidelines for treating septic patients, which recommend obtaining blood cultures before giving antibiotics to maximize the likelihood of identifying a pathogen and providing targeted treatment.
A simple idea leading to a high-impact study
Sepsis and septic shock result from uncontrolled infections that can frequently be identified in the blood. This can lead to organ failure, and sepsis is a common cause of death in hospitals. Delaying effective antimicrobial treatment can increase the probability of mortality by as much as 10 percent per hour. However, identifying the pathogen responsible for the infection, whenever possible, is as important as quickly initiating treatment.
“I performed a literature review and found there was a lack of evidence supporting multiple international sepsis guidelines for obtaining blood cultures before administration of intravenous antibiotics in sepsis and septic shock,” says Dr. Cheng.
Dr. Cheng came up with the idea of conducting a study to determine the sensitivity of blood cultures drawn shortly after initiation of treatment. He discussed it with Dr. Cedric Yansouni, a clinician-scientist in the Infectious Diseases and Immunity in Global Health Program at the RI-MUHC, who immediately saw the potential of this high-impact study.
“Matthew’s idea was simple and brilliant. Since this is an important question with practical implications, we designed a project that was relatively straightforward to implement,” says Dr. Yansouni, who also is an assistant professor in the Department of Medicine at McGill University.
The prospective study was performed in seven health centres across Canada and the United States, mostly in Montreal and Vancouver. The researchers enrolled 325 patients who presented in the emergency department in septic shock or with severe manifestations of sepsis. They modified the standard treatment protocols by adding a post-treatment blood culture, which was obtained within two hours of starting antibiotics. When they compared the results of blood cultures obtained before and after the start of therapy, they noticed that among patients who had positive blood cultures before, close to 50 percent had falsely negative cultures afterwards, which proved that treatment interferes with the results of blood tests.
“Bacterial cultures allow us to identify the causative bacteria and to target treatment; we can then prescribe the right antibiotic and discontinue those that are not needed,” explains Dr. Yansouni. “This is beneficial not only to the patient, but also to the community, because reducing unnecessary antibiotic use is key to controlling antimicrobial resistance.”
Evidence basis for updated sepsis guidelines
In a rare move, the journal allowed the authors’ data to be shared with the Infectious Diseases Society of America (IDSA) Sepsis Task Force prior to publication, when they requested it ahead of upcoming revisions to the National SEP-1 Sepsis Quality Measure.
“This is the first data in humans to robustly show that the timing of antimicrobial administration makes a difference to the yield of blood cultures. It provides a basis for clinical guidelines for the care of patients with sepsis,” says Dr. Yansouni.
“This paper is the result of a residency project that never would have been completed without the support and guidance of Dr. Yansouni,” says Dr. Cheng. “Our results demonstrate that it is critical to obtain blood cultures before starting antimicrobial therapy, as the sensitivity of post-antimicrobial blood cultures is significantly decreased, and that this loss of clinical information can negatively impact patient care.”
About the study
The paper Blood culture results prior to and following antimicrobial administration in patients with severe manifestations of sepsis: A diagnostic study was co-authored by Matthew P. Cheng, MD; Robert Stenstrom, MD PhD; Katryn Paquette MD; Sarah N. Stabler, Pharm D; Murtaza Akhter, MD; Adam C. Davidson, MD;Marko Gavric, BS; Alexander Lawandi, MD; Rehman Jinah BSc; Zahid Saeed, MD; Koray Demir, MD; Kelly Huang, BS; Amirali Mahpour, MD; Chris Shamatutu, BSc; Chelsea Caya, MSc; Jean-Marc Troquet, MD; Greg Clark, MD; Cedric Yansouni, MD and David Sweet, MD. DOI: 10.7326/M19-1696
This work was made possible through funding from the Fonds de recherche du Québec – Santé (FRQS), the Research Institute of the McGill University Health Centre (RI-MUHC) and the University of British Columbia.
About the Research Institute of the MUHC
The Research Institute of the McGill University Health Centre (RI-MUHC) is a world-renowned biomedical and healthcare research centre. The Institute, which is affiliated with the Faculty of Medicine of McGill University, is the research arm of the McGill University Health Centre (MUHC) – an academic health centre located in Montreal, Canada, that has a mandate to focus on complex care within its community. The RI-MUHC supports over 420 researchers and close to 1,200 research trainees devoted to a broad spectrum of fundamental, clinical and health outcomes research at the Glen and the Montreal General Hospital sites of the MUHC. Its research facilities offer a dynamic multidisciplinary environment that fosters collaboration and leverages discovery aimed at improving the health of individual patients across their lifespan. The RI-MUHC is supported in part by the Fonds de recherche du Québec – Santé (FRQS). www.rimuhc.ca
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