Rapid Rule Out of Culture-Negative Bloodstream Infections by Use of a Novel Approach to Universal Detection of Bacteria and Fungi.

BACKGROUND: Currently it can take up to 5 days to rule out bloodstream infection. With the low yield of blood cultures (approximately 10%), a significant number of patients are potentially exposed to inappropriate therapy that can lead to adverse events. More rapid rule out can accelerate deescalation or cessation of antimicrobial therapy, improving patient outcomes. METHODS: A method is described, termed enzymatic template generation and amplification (ETGA), that universally and sensitively detects DNA polymerase activity liberated from viable bacteria and fungi isolated from blood culture samples as a measure of bloodstream infection. ETGA was applied in a diagnostic test format to identify negative blood cultures after an overnight incubation. Performance data for a prototype (Cognitor) and automated (Magnitor) version of the test are presented. RESULTS: The Cognitor manual assay displayed analytical reactivity for a panel of the 20 most prevalent causes of bloodstream infection, with a detection range of 28-9050 CFU/mL. Validation with 1457 clinical blood cultures showed a negative predictive value of 99.0% compared to blood culture incubation for 5 days. Magnitor showed an improved detection range of 1-67 CFU/mL, allowing for detection of bacteria-supplemented blood cultures after 2-8 h incubation, and Candida albicans-supplemented blood cultures at 16-22 h, 5-15 h faster than blood culture. Removing an aliquot from a blood culture bottle and replacing the bottle into the incubator was shown not to result in contaminating organisms being introduced. CONCLUSIONS: The described method displays excellent breadth and detection for microbial cells and demonstrates the capability of confirming negative blood cultures after an overnight incubation in a blood culture instrument.

Can rapid negative exclusion of blood cultures by a molecular method, enzyme template generation and amplification technique (Cognitor® Minus), aid antimicrobial stewardship?

OBJECTIVES: Antimicrobial review is an important part of antimicrobial stewardship. A novel enzyme template generation and amplification technique (ETGA), the Cognitor® Minus (Momentum Bioscience, Long Hanborough, UK) test, has a 99.5% negative predictive value for bacteraemia and fungaemia. This observational study asked two questions: (1) Does a negative ETGA, indicating no bacteraemia or fungaemia, aid antimicrobial review within 48 h of admission; (2) In this real-life clinical setting, does a negative ETGA mean no bacteraemia or fungaemia? METHODS: Consecutive blood cultures in patients with clinical infection were tested by ETGA. Negative results indicating an absence of bacteraemia or fungaemia were reviewed by the clinical infection team. Antibiotics were reviewed in these patients, and the role of the ETGA result in antibiotic change was recorded. Patients were followed up for a week. KEY FINDINGS: A total of 197 of 246 samples gave a negative result by ETGA. This led to a positive stewardship outcome (antimicrobials changed) in 145 (73.6%) and negative stewardship outcome (empirical antimicrobials continued) in 47 (23.9%). Of the positive stewardship outcomes, the ETGA result supported the decision not to start antimicrobials in 21 (10.7%) patients, to stop antimicrobials in 21 (10.7%), to switch from IV to oral antimicrobials in 103 (52.2%) or to discharge or leave the patient at home in 58 cases (29.4%). CONCLUSIONS: Enzyme template generation and amplification supports antimicrobial stewardship decisions and may have cost advantages in reducing unnecessary empirical antibiotics and antifungal agents and in discharging patients from hospital earlier. ETGA result was consistent with blood culture findings and gave an earlier negative result.