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Study may change guidelines in sepsis management

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Among patients with severe manifestations of sepsis, initiation of empirical antimicrobial therapy significantly reduces the sensitivity of blood cultures drawn shortly after treatment initiation.


The study could end the debate among physicians regarding sepsis management. Seven emergency departments across North America, including Maricopa Integrated Health System, participated in the research.

The study revealed that initiating antibiotics immediately reduces the sensitivity of blood cultures drawn shortly after treatment. That, in turn, reduces the chances of treating and tailoring antibiotics to specific bacterial and fungal sepsis infections. “This is a constant debate in the medical field,” said Dr Murtaza Akhter, an assistant professor in the department of emergency medicine at the University of Arizona College of Medicine – Phoenix and co-author of the study.

“Emergency medicine physicians want to administer antibiotics as soon as possible because it prevents mortality, whereas internal medicine physicians want two sets of blood cultures before antibiotics are administered so they can more reliably diagnose the organism.”

A life-threatening infection that causes the immune system to attack the body, sepsis has a mortality rate of 20%. According to the US Centres for Disease Control and Prevention, at least 1.7m adults in the US develop sepsis each year.

The cornerstone of sepsis management is early administration of an antimicrobial, which kills or inhibits the growth of microorganisms such as bacteria or fungi. However, guidelines recommend two blood cultures be drawn before starting antimicrobial therapy, resulting in significant delays and decreasing the chance of survival.

“It was unknown how quickly blood cultures lose their ability to grow organisms after antibiotic administration,” Akhter said. “Now we know that even if blood cultures are performed very rapidly after antibiotics, they lose a significant amount of their diagnostic ability.”

Akhter, who also is an attending physician at Maricopa Integrated Health System, said the study tells physicians that blood cultures performed after antibiotics are unreliable. “Although administering antibiotics to septic patients is important, it is imperative to get at least one blood culture before providing the treatment.”

Prior to this study, it was unknown how quickly antibiotic sensitivity changes. Some physicians thought that if you administer antibiotics shortly before blood cultures, you could still properly diagnose the “bug.” However, this study revealed that this strategy fails because the cultures are affected rapidly after antibiotic administration.

“We already knew that emergency physicians were correct to not delay antibiotics, but now we know that internal medicine doctors were also correct in that blood cultures after antibiotics are not as reliable,” Akhter said.

Abstract
Background: Administering antimicrobial agents before obtaining blood cultures could potentially decrease time to treatment and improve outcomes, but it is unclear how this strategy affects diagnostic sensitivity.
Objective: To determine the sensitivity of blood cultures obtained shortly after initiation of antimicrobial therapy in patients with severe manifestations of sepsis.
Design: Patient-level, single-group, diagnostic study. (ClinicalTrials.gov: NCT01867905)
Setting: 7 emergency departments in North America.
Participants: Adults with severe manifestations of sepsis, including systolic blood pressure less than 90 mm Hg or a serum lactate level of 4 mmol/L or more.

Intervention: Blood cultures were obtained before and within 120 minutes after initiation of antimicrobial treatment.
Measurements: Sensitivity of blood cultures obtained after initiation of antimicrobial therapy.
Results: Of 3,164 participants screened, 325 were included in the study (mean age, 65.6 years; 62.8% men) and had repeated blood cultures drawn after initiation of antimicrobial therapy (median time, 70 minutes [interquartile range, 50 to 110 minutes]). Pre-antimicrobial blood cultures were positive for 1 or more microbial pathogens in 102 of 325 (31.4%) patients. Post-antimicrobial blood cultures were positive for 1 or more microbial pathogens in 63 of 325 (19.4%) patients. The absolute difference in the proportion of positive blood cultures between pre- and post-antimicrobial testing was 12.0% (95% CI, 5.4% to 18.6%; P < 0.001). Sensitivity of post-antimicrobial culture was 52.9% (CI, 42.8% to 62.9%). When the results of other microbiological cultures were included, microbial pathogens were found in 69 of 102 (67.6% [CI, 57.7% to 76.6%]) patients.
Limitation: Only a proportion of screened patients were recruited.
Conclusion: Among patients with severe manifestations of sepsis, initiation of empirical antimicrobial therapy significantly reduces the sensitivity of blood cultures drawn shortly after treatment initiation.

Authors
Matthew P Cheng, Robert Stenstrom, Katryn Paquette, Sarah N Stabler, Murtaza Akhter, Adam C Davidson, Marko Gavric, Alexander Lawandi, Rehman Jinah, Zahid Saeed, Koray Demir, Kelly Huang, Amirali Mahpour, Chris Shamatutu, Chelsea Caya, Jean-Marc Troquet, Greg Clark, Cedric P Yansouni, David Sweet

University of Arizona Health Sciences material Annals of Internal Medicine abstract

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