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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