Role of the T2Dx magnetic resonance assay in patients with suspected bloodstream infection: a single-centre real-world experience

Delayed administration of active anti-infective therapy is associated with increased rates of mortality and higher medical costs in patients with severe infections, especially bloodstream infection (BSI) [1, 2]. Despite the recent updates of definitions and clinical criteria [3], early recognition of infection and timely management of patients with sepsis remain challenging, especially in multidrug-resistant microorganism-associated infections and in critical care settings [4].

Antimicrobial-resistant ESKAPE (i.e., Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacter species) microorganisms represent a frequent cause of nosocomial BSI [5, 6], and they can acquire antimicrobial resistance genes, thereby reducing treatment options and increasing death rates because of treatment failure [7]. In addition to bacteria, Candida species represent an important cause of BSI [8‐10], which is often misdiagnosed because of the low sensitivity of conventional methods [11], and they are associated with high lethality rates [8].

Although blood culture (BC) is considered the gold standard for BSI diagnosis and it serves as an indispensable assessment method [12], it is often limited by slow turnaround times or the failure to identify causative pathogens [1, 13]. Moreover, the results of BC may be negative even in cases of severe sepsis, and they can be affected by factors such as concurrent antimicrobial use [14]. Because timely and appropriate antimicrobial treatment has a key role in reducing the risk of poor outcomes [4, 9, 15, 16], the development of minimally invasive, highly sensitive and specific diagnostic tests with a short turnaround time and reasonable cost could significantly improve outcomes in patients with bacterial or fungal BSI [1].

The T2Dx system (T2 Biosystems, Lexington, MA, USA), an automated instrument platform using non-culture T2 magnetic resonance technology to detect nucleic acids and microbial cells directly in whole-blood samples [17], has been approved by the US Food and Drug Administration for the rapid detection of BSI caused by a modified panel of ESKAPE bacterial species (including Escherichia coli instead of Enterobacter spp., i.e. T2Bacteria Panel) [18] or Candida spp. (T2Candida Panel) [19]. T2Dx facilitates the significantly more rapid identification of targeted microbial species causing BSI [18, 19]; however, the clinical impact of T2Dx on the appropriateness of empirical antimicrobial therapy and outcome is unclear [20‐22].

In the present single-centre study, our real-world experience of the use of T2Dx in addition to standard BC is described. Moreover, the possible impact of the T2Dx assay on the appropriateness of empiric antimicrobial therapy and clinical outcome was investigated.

This study described our real-world experience of the use of T2Dx in addition to BC in a third-level university hospital, focusing especially on the clinical impact of T2Dx on the appropriateness of empirical antimicrobial therapy and patient outcome.

In this study, an apparently low rate of concordance between the T2Bacteria Panel and BC compared to previous studies [22] was observed. Differing from previous studies, our study was not focused on the performance of the T2Dx tests; for this reason, the crude concordance rate between T2Dx and standard BC was reported, and the performance parameters of the T2Dx test were not calculated. Of note, in previous studies of the T2Bacteria test, a ‘true-infection criterion’ was used in which discordant T2Bacteria results were considered concordant results when the same microorganism detected only by T2Bacteria grew from a culture obtained within 7 days from a clinical sample other than blood and it was considered the primary source of BSI [18, 23]. No recommendations about the exact interpretation of T2Dx results in clinical practice are available to date.

The reported sensitivity rates of the T2Candida Panel range 89–100%, which are higher than that of standard BC for candidemia (50%) [20, 24, 25]. In line with previous studies, the rate of concordance between T2Dx and standard BC was high in our experience. Only in one case, candidemia was diagnosed exclusively by BC, being T2Candida panel negative for Candida spp.. This result is surprising, in view of the fact that T2Candida panel has been reported to have a high negative predictive value such that a negative result could support early discontinuation of empiric antifungal therapy in ICU patients with suspected candidemia. Therefore, T2Dx should be performed in addition to standard BC, and empirical therapy can be stopped only after a definitive result is obtained for BC if invasive candidemia is suspected [21].

Because a delay in the initiation of appropriate antimicrobial therapy represents a well-recognised risk factor for mortality in patients with bacterial or fungal BSI [9, 15, 16, 26‐28], the primary aim of the present study was to investigate the impact of T2Dx on the prescription of appropriate empirical antimicrobial therapy and outcome. Appropriate empirical antimicrobial therapy was prescribed with a significantly higher frequency among patients with a positive T2Dx result than among matched comparator patients, for whom T2Dx was not performed. Interestingly, among patients who underwent the T2Dx assay, the rate of appropriate empirical antimicrobial therapy was increased. Moreover, T2Dx allowed us to identify a breakthrough severe infection by K. pneumoniae and A. baumannii that resulted in clinical failure in a patient whose concomitant BCs were negative, and a new in vitro active antibiotic (cefiderocol) obtained through the manufacturer’s compassionate use was administered with clinical success [29]. Therefore, it can be speculated that T2Dx could improve the appropriateness of empirical antimicrobial therapy. Conversely, it must be noted that T2Dx was performed outside a clinical trial design in our population. In addition, because T2Dx was mostly performed in more critical patients in our experience, extended-spectrum antibiotic therapy was more frequently prescribed.

This study was affected by some limitations. In particular, the small population size and the retrospective nature of the study reduced the generalisability of the results. Specifically, cases and comparator patients were not matched for disease severity.

In conclusion, T2Dx appeared to be a highly sensitive and specific diagnostic test with a short turnaround time and the potential to improve outcomes in patients with BSI. To our knowledge, this is the first study to demonstrate that T2Dx facilitated a statistically significant increase in the rate of appropriate empiric antibiotic therapy and potentially reduced mortality among patients with BSI. We believe that prospective randomised studies are needed to validate these findings. Meanwhile, because no clear recommendations on its use in real clinical practice have been posed and its clinical utility is uncertain [30], T2Dx should be used as complement to standard BC, especially in patients with more severe prognoses.