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An analysis of more than 300 patients with severe sepsis corroborates what clinical practice guidelines already recommend: draw a blood culture before starting empirical antibiotic treatment. Researchers detailed their results in the Annals of Internal Medicine.

“It is critical to obtain blood cultures before starting antimicrobial therapy, as the sensitivity of post-antimicrobial blood cultures is significantly decreased and the results of other microbiological tests cannot compensate for this decrease,” Matthew Cheng, MD, a clinical instructor in Brigham and Women’s Hospital’s Division of Infectious Diseases and the study’s corresponding author, told CLN Stat.

The Surviving Sepsis Campaign guidelines recommend that clinicians take a blood culture prior to starting patients on antimicrobial treatment, allowing a 45-minute window for delays. The conundrum with this approach is the urgency of treatment: In patients with severe sepsis, prompt therapy is key to survival. “Death has been associated with delayed antimicrobial therapy after the onset of septic shock. Therefore, it is possible that administering antimicrobial agents before obtaining blood cultures could potentially decrease time to treatment and improve outcomes,” explained Cheng and his co-authors.

Less clear is how prior antibiotic administration affects the sensitivity of blood culture.

To explore this approach’s potential impact on diagnostic results, researchers from the University of British Columbia, McGill University, and Harvard Medical School screened more than 3,100 patients from seven emergency departments in North America that met criteria for severe sepsis: systolic blood pressure <90 mm Hg or a serum lactate level ≥4 mmol/L. Selecting 325 patients averaging age 65, they took repeat blood cultures before and within 2 hours after administering antimicrobial treatment.

Initiating antibiotics prior to culture did reduce test sensitivity significantly. Among the 325 patients, 102 had positive blood cultures for one or more microbial pathogens, compared with 63 patients who yielded positive results after receiving antibiotics. “The absolute difference in the proportion of positive blood cultures between pre- and post-antimicrobial testing was 12.0%,” the researchers reported. Overall, the sensitivity of blood cultures post treatment was just under 53%.

“These findings are important in considering the optimal balance between prompt antimicrobial administration and the need for accurate microbiological data in the care of patients with sepsis," said Cheng in a statement. “Given the global burden of sepsis, deepening our understanding of how best to treat this condition is critically important.”

Clinicians who want to promptly dispense antimicrobials may be uncomfortable with this approach, Cheng acknowledged to CLN Stat. That said, “there are important benefits to pathogen identification for stewardship purposes and patient outcomes. Our results support the current Surviving Sepsis Campaign guidelines and reinforce the need to ensure that emergency departments have the necessary resources, protocols, and infrastructure in place” to rapidly identify and treat potentially septic patients, he said.

From a diagnostics point of view, taking cultures prior to antimicrobial treatment has merit, Jacqueline H. Geer, MD and Mark D. Siegel, MD of Yale School of Medicine wrote in a related editorial. However, “it is crucial to prevent unintentional treatment delays, particularly given the increased risk for death associated with delaying anti-infective treatment,” wrote the editorialists. Although less invasive and more efficient than other methods such as lumbar puncture, there have been reports of delays with blood culture as well, they noted.

Geer and Siegel recommended exploring more expeditious methods for drawing blood in future studies. “In addition, given that up to 50% of patients with sepsis are ultimately found to be ‘culture negative,’ it would be useful to create a practical diagnostic tool to identify patients who can be treated immediately without waiting to obtain blood cultures if they are unlikely to provide useful diagnostic information,” they suggested.

As more sophisticated molecular diagnostics come up the pipeline, “we will likely be prompted to ask again if it is necessary to withhold antibiotics until testing is done,” speculated Geer and Siegel.