Antimicrobial administration may dramatically reduce blood culture sensitivity in septic patients

1. In this prospective multicenter observational trial among adult patients with severe manifestations of sepsis, administration of antimicrobial treatment prior to collection of blood cultures resulted in significantly diminished sensitivity (52.9%).

2. Study findings demonstrated the importance of obtaining blood cultures prior to proceeding with antimicrobial therapy, strengthening the current recommendations of the Surviving Sepsis Campaign. 

Evidence level: 2 (Good)

Study Rundown: Sepsis is a life-threatening condition with short-term mortality rates approaching 20%. Prompt antimicrobial therapy is essential in combating severe symptoms, but accurate microbiological information is equally important in guiding subsequent treatment and deescalation. Current best-practice guidelines heavily emphasize the value of the latter, designating a therapy delay of 45 minutes to be acceptable in pursuit of accurate test results. However, at present, no studies have offered compelling evidence either in favor of or against this advice. In this single-group diagnostic trial of adult patients with severe manifestations of sepsis, sensitivity of blood cultures from all anatomical sites was found to significantly decrease following initiation of empirical antimicrobial therapy, offering strong evidence promoting adherence to existing guidelines propounded by the Surviving Sepsis Campaign. The main strength of the study lied in its repeated measure design which aided in minimizing the number of false-negative results, thereby bolstering the sample size and increasing power. Because of its broad inclusion criteria, these results can likely be generalized to larger, more diverse populations, but an important consideration is that ~20% of previously eligible patients were excluded from per protocol analysis due to delays in blood drawing and assessment, highlighting the difficulty of obtaining blood cultures in a timely manner.

Click to read the study in Annals of Internal Medicine

Click to read an accompanying editorial in Annals of Internal Medicine

Relevant Reading: Emerging Technologies for Molecular Diagnosis of Sepsis

In-Depth [prospective cohort]: 264 adult participants presenting with severe manifestations of sepsis to 7 urban emergency departments in North America were tracked longitudinally for the detectable presence of pathogens within the bloodstream.  Two sets of blood cultures were obtained prior to initiating antimicrobial therapy and additional sets were drawn within two hours of empirical administration.  Inclusion criteria were evidence of a severe systemic inflammatory response syndrome (<90 mmHg systolic blood pressure or serum lactate level >4 mmol/L) as well as a presumed or confirmed source of infection.  Exclusion criteria were clinically significant bleeding disorders, a platelet count of <20,000 × 10⁹ cells/L, or an international normalized ratio >6. The primary outcome was to determine the sensitivity of blood cultures within 120 minutes of administration of antimicrobial therapy, and the main secondary outcome was to evaluate the sensitivity of cultures from varying anatomical sites.  In the per protocol population, preantimicrobial blood cultures were positive for 1 or more pathogens in 80 patients, and postantimicrobial cultures were positive in 52 patients, yielding an absolute difference of 10.6% ([CI, 3.3% to 17.9%]; P < 0.001) and a sensitivity of 56.3% (CI, 44.7% to 67.3%).  Upon pooling the results of cultures from all anatomical sites, sensitivity increased to 68.8% ([CI, 57.4% to 78.7%]).  However, in all analyses, antimicrobial administration significantly increased the time required for blood cultures to appear positive.

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