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.