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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 3164 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]). Preantimicrobial blood cultures were positive for 1 or more microbial pathogens in 102 of 325 (31.4%) patients. Postantimicrobial 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 postantimicrobial testing was 12.0% (95% CI, 5.4% to 18.6%; P < 0.001). Sensitivity of postantimicrobial 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.Primary Funding Source: Vancouver Coastal Health, St. Paul's Hospital Foundation Emergency Department Support Fund, the Fonds de recherche Santé-Québec, and the Maricopa Medical Foundation. [ABSTRACT FROM AUTHOR]

Background Current guidelines recommend obtaining blood cultures prior to antimicrobial therapy in patients with sepsis. Administering antimicrobials immediately without waiting for blood cultures could potentially decrease time to treatment and improve outcomes, but it is unclear the degree to which this strategy impacts diagnostic yield. Methods We performed a patient-level, single-arm, diagnostic trial. Seven urban emergency departments affiliated with academic medical centers across Canada and the United States participated in the study. Adults ≥18 years of age presenting to the emergency department with evidence of severe manifestations of sepsis, including a systolic blood pressure <90 mmHg and/or a serum lactate ≥4 mmol/L were included. Study participants had 2 sets of blood cultures drawn prior to and immediately following antimicrobial administration. The primary outcome was the difference in blood culture pathogen recovery rates before and after administration of antimicrobial therapy. Results Of the 3,164 participants screened, 325 were included in the study (mean age, 65.6 years; 63.0% men) and had repeat blood cultures drawn after the initiation of antimicrobial therapy (median time of 70 minutes, IQR 50 to 110 minutes). Pre-antimicrobial blood cultures were positive for one or more microbial pathogens in 102/325 (31.4%) patients. Fifty-four participants (52.9%) had matching blood culture results after initiation of antimicrobial treatment. The absolute difference in pathogen recovery rates was 14.5% ([95% CI 8.0 to 21.0%]; P < 0.0001) between pre- and post-antimicrobial blood cultures. Results were consistent in an analysis of the per-protocol population (absolute difference, 13.3% [95% CI 6.1 to 20.4%]; P < 0.0001). Including the results of other microbiological cultures done as part of routine care, microbial pathogens were recovered in 69 of 102 (67.7%) participants (absolute difference, 10.2% [95% CI 3.4 to 16.8%]; P < 0.0001). Conclusion Among patients with severe manifestations of sepsis, the administration of empiric antimicrobial therapy significantly reduces the yield of pathogen recovery when blood cultures are drawn shortly after treatment initiation. Disclosures All Authors: No reported Disclosures. [ABSTRACT FROM AUTHOR]