The Clinical Impact of Cobas® Eplex Blood Culture Panels for the Diagnosis of Bacteremia and Fungemia

Bloodstream infections (BSIs) impose a considerable burden on patients and healthcare systems due to the need for hospital admission, extended stays, additional diagnostic tests and specific treatments. Receiving inappropriate empirical antibiotic therapy can increase the risk of renal and hepatic toxicity, antibiotic resistance, opportunistic infections and mortality. Therefore, early identification of the causative pathogens and their resistance patterns is of utmost importance.

The gold standard for diagnosis of BSIs is through blood cultures. To detect bacteremia or fungemia, blood from patients is collected and incubated in blood culture bottles. When using conventional culture methods, a positive blood bottle is investigated using direct microscopic investigation, gram-staining, inoculation of selective and non-selective agars, MALDI-TOF identification, rapid antimicrobial susceptibility testing (AST) and standardized AST methods. These methods require several (manual) steps and days of turn-around-time. Following the collection of a blood culture, time to result depends on several factors such as the time needed for transporting the blood bottles and loading in the incubator, the growth rate of bacteria or fungi as well as the time to obtain the identification and AST result.

Rapid diagnostic tests to improve the time to appropriate antimicrobial therapy have been developed. Most tests involve organism identification and genotypic resistance profiles. Rapid molecular diagnostic testing, such as multiplex PCR methods, enable early identification of bacteria or fungi and their antimicrobial resistance genes (results within less than 2 hours after initiation of the test). This helps minimize the time needed to initiate effective antimicrobial therapy. Commercial diagnostic systems to accelerate the identification and detection of antibiotic resistance genes of causative pathogens in BSI have been developed. Examples include Cepheid® GeneXpert, BioFire® FilmArray®TM, and Roche eplex®. The system used in this study, the eplex system, is a random access multiplex PCR platform combining extraction of nucleic acids and rapid RT-PCR. Three Blood Culture Identification (BCID) panels are used to identify the disease-causing organisms: Gram-positive panel, Gram-negative panel and Fungal Pathogen panel. These panels are designed to detect 56 different organisms covering 95% of pathogens commonly associated with BSIs and 10 common antibiotic resistance genes.

The objective of this study is to assess the impact of rapid molecular testing on positive blood cultures with the cobas® eplex system (Roche) on antibiotic therapy and patient outcome.

In this study, we prospectively evaluate the performance of the eplex system for pathogen identification and detection of resistance markers compared to routine SOC for bloodstream infections. The potential impact of the eplex on time to optimization (inititiation, discontinuation, escalation or de-escalation) of antimicrobial therapy and patient outcome will be evaluated.

In summary, Finally, this study will evaluate the potential benefits of implementing CE-IVD registered syndromic diagnostic testing of bloodstream infections.

• Performance of the cobas eplex instrument [Срок оценки: From positive blood culture until eplex (up to a few hours) and SOC culture results (up to two weeks) are available]
• The impact of the eplex result on the time to first antibiotic optimization [Срок оценки: From hospital admission until the time of first optimization of antimicrobial treatment for the bloodstream infection (up to one week after hospital admission))]
• The impact of the eplex result on the hospital and ICU length-of-stay [Срок оценки: From hospital admission until discharge in a single episode of hospitalization, assessed up to one year]
• The impact of the eplex result on 30-day, all cause mortality [Срок оценки: From the start of the BSI episode until 30 days after]
• The impact of the eplex result on antibiotic intensity score at 96 hours after Gram staining [Срок оценки: From hospital admission until 96 hours (day 4) after Gram staining]
• The impact of the eplex result on 30-day readmission [Срок оценки: From hospitalization during the BSI episode until 30 days after discharge]