Table 1. Antimicrobial stewardship impact of positive
T2Bacteria Panel results. Data from 15 patients with T2Bacteria Panel
positive results. Please note that ATB treatment does not have to be
T2Bacteria-species only directed, but it has to take into account also
other microbiological findings and patient’s clinical history (not
reported in the Table). ATB=antibiotic.
4. Discussion
The timely administration of effective antimicrobial therapy is crucial
for the survival of patients with sepsis [1]. Rapid diagnostic
assays have been associated with improvements in time to appropriate
antibiotic therapy by enhancing early identification of causative
organisms for BSI [4, 5]. Such data supports the coupling of rapid
diagnostic technology with antimicrobial stewardship programs to
optimize empirical antibiotic therapy and reduce time to targeted
therapy.
In this study, we report the first interventional experience of the
T2Bacteria Panel in the Czech Republic which identified the ESKAPEc
pathogens directly from whole blood. Despite the limited number of
bacterial species included on the T2Bacteria Panel, we found that 77%
of all identified causes of proven and probable BSI (i.e., excluding
common BC contaminants) were detected by the T2Bacteria Panel. High
sensitivity of the T2Bacteria Panel was demonstrated by detection of 8
pathogens in 7 samples that were missed by BC, representing 36.4% (8 of
22) of the total number of identified causes of BSI. All of these
confirmed true positives were from patients who were previously exposed
to antibiotic therapy which is consistent with previous findings in
patients with sepsis demonstrating that BC sensitivity is reduced by
approximately 50% after the initiation of antimicrobial therapy
[15]. It also suggests the T2Bacteria Panel performance may have
limited interference from empirical antimicrobial treatment, which
continues to be an issue with culture-based diagnostics [16].
The T2Bacterial Panel provided species identification in 6.1 hours on
average, which was 55 hours faster compared to BC. These results are
consistent with a multi-hospital survey demonstrating a median BC time
to identification of 43.4 hours and replicates previous reports of
T2Bacteria Panel’s advantage of faster diagnosis compared to standard BC
diagnostic methods [11, 14, 17, 18]. This allowed for early
antibiotic stewardship interventions in 60% of our patients with
T2Bacteria Panel positive samples.
This evaluation is limited by the small number of bacteremic patients
who were enrolled in our single-center cohort study. We did not assess
the potential role of the T2Bacteria-negative result on early
therapeutic decisions, namely the early de-escalation of unnecessary,
broad spectrum antibiotics. Our study did not assess the effect of the
assay on patient outcomes, but it could be expected that faster time to
effective antibiotic prescription would translate into reductions in
length of stay and mortality based on previous reports that observed
reductions in length of stay and mortality based on findings with
alternative post-culture molecular diagnostic methods [1, 19-22].
Lastly, the pathogen coverage by the T2Bacteria Panel is not inclusive
of all causative organisms for BSI and cannot provide antimicrobial
susceptibility information and is not intended to replace routine
culture and susceptibility methods.
5. Conclusions
In this study, T2Bacteria Panel proved high sensitivity (by detecting 8
BC false-negative causes of BSI) and significant reduction of time to
species identification (55 hours on average). A larger study should be
conducted to determine the exact clinical impact of earlier T2Bacteria
Panel results on length of hospital stay and mortality benefit in
patients with BSI. However, based on our experience with rapid BSI
diagnostics, T2Bacteria Panel represents the most promising currently
available diagnostic tool. Implementation of the T2Bacteria Panel at our
institution led to faster time to reliable detection of selected BSI
pathogens and decreased time to administration of species-directed
antibiotic therapy.
Author Contributions:Conceptualization, Pavel Drevinek, Eliska Bebrova, Jan Berousek, Martin
Soucek, Vendula Martinkova, Veronika Hysperska; methodology, Pavel
Drevinek, Jan Tkadlec, Jakub Hurych; software, Jakub Hurych; validation,
Pavel Drevinek, Eliska Bebrova, ; formal analysis,
Jakub Hurych; investigation, Milena Antuskova, Jakub Hurych; resources,
Jan Berousek, Zuzana Prikrylova, Jiri Bures, Jaromir Vajter, Martin
Soucek, Jan Masopust, Vendula Martinkova, Jaroslava Adamkova, Veronika
Hysperska; data curation, Jakub Hurych, Pavel Drevinek with support of
T2Biosystems analytics; writing—original draft preparation, Pavel
Drevinek; writing—review and editing, Jakub Hurych, Jan Tkadlec;
visualization, Pavel Drevinek with support of T2Biosystems analytics ;
supervision, Eliska Bebrova; project administration, Jakub Hurych;
funding acquisition, Pavel Drevinek. All authors have read and agreed to
the published version of the manuscript.
Funding: This research was funded by the Ministry of Health of
the Czech Republic: grant 15-28157A; conceptual development of research
organization Motol University Hospital.
Acknowledgments: The authors acknowledge the contributions of
T2Biosystems which provided the T2Dx instrument and data analysis
support.
Conflicts of Interest: The authors declare no conflict of
interest. The funders had no role in the design of the study; in the
collection, analyses, or interpretation of data; in the writing of the
manuscript, or in the decision to publish the results.
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