The Clinical Benefits of Rapid Sepsis Diagnostics

Hospital Associated Infections (HAI) are a major concern for patient well-being and healthcare finances. Time is of the essence in treating such infections, generating increased pressure on laboratory professionals to provide prompt pathogen identification from blood cultures. Once species diagnosis is obtained, clinicians can then initiate more effective targeted antimicrobial therapy, minimising the use of broad spectrum antibiotics.

To address this need, AdvanDX has developed the patented PNA-FISH technology that quickly and accurately identifies the causative pathogen directly from positive blood cultures. This technology is now available on the QuickFISH platform to enable very fast (20 minutes) identification of pathogen species, without compromising specificity or sensitivity. Since its introduction, this technology has proven to be of great interest to clinical microbiologists and a number of reports have recently appeared in the scientific literature describing its performance and clinical utility, especially in comparison to traditional techniques such as coagulase assays and more modern methods such as MALDI-TOF. Here we provide an overview of the most recent relevant articles.

The QuickFISH platform was made commercially available in 2012 and the publication of a study by Deck et al. (2012)1 coincided with its release. The objective of this study was to determine the robustness and specificity of the QuickFISH assay technique for the identification of Staphylococcus aureus vs Coagulase Negative Staphylococci (CoNS) within routine use in a clinical laboratory setting. Their study of 722 samples found that QuickFISH was both sensitive and specific. They commented that it would “enable a clinical microbiology laboratory to accurately identify S. aureus from CoNS in blood cultures in <30 minutes……enabling physicians to implement targeted antibiotic therapy much more quickly than at present”. They concluded that the method has the potential to revolutionise standard testing and reporting protocols…. and significantly impact individual patient outcomes and overall bloodstream infection treatment costs”.

In early 2013, Caretto et al.2 published a paper comparing QuickFISH performance to the traditional tube coagulase method for the identification of Staphylococci. The data from this three month long study again demonstrate the utility of the QuickFISH platform. The major conclusion was that “the QuickFISH technology appears robust and reliable…..quick and simple to perform”. While these authors acknowledged that the ‘up front’ cost of the tube coagulase test was lower, they also pointed out that its inferior sensitivity and lengthy time to result (when compared to QuickFISH) eroded the actual value that this technique could offer. As a result, the QuickFISH technique has now been adopted by these authors as the standard test used in their laboratory.

The most recent publication discussing the application of the QuickFISH system (Deck et al., 2013)3 concerns its use to detect and identify Enterococcus species directly from positive blood cultures. This work demonstrates that the QuickFISH system maintains the high sensitivity and specificity of the PNA-FISH system, with the additional benefit of further time savings. Interestingly, it was also observed that QuickFISH offered the shortest turnaround time of any comparable test, including biochemical assays, amplified assays and MALDI-TOF. More specifically they observed that “QuickFISH provides results one day earlier than MALDI-TOF performed on an isolate”. As in the previous studies, this work concluded that QuickFISH could be of clinical value in enabling rapid prescription of appropriate antimicrobial therapy.

Calderaro et al. (2013)4 also evaluated PNA-FISH assays, in comparison to MALDI-TOF, for the identification of Staphylococci, Enterococci, Gram negative rods and yeasts from positive blood and cerebrospinal fluid cultures. They tested a total of 956 cultures, with the data indicating that “The PNA-FISH assays allowed identification of bacteria and yeasts 1.3 days before MALDI-TOF and 2 days earlier in the case of polymicrobial infections”. It should also be noted that this study employed the first generation PNA-FISH: use of the QuickFISH technique would be expected to further enhance the observed effects.

Other studies into the potential clinical impact of PNA-FISH have also yielded positive results, exemplified by publications by Parcell and Orange (2013)5 on the treatment of bacteraemia and Stone et al. (2013)6 on the treatment of fungaemia. In both these studies, conducted in UK hospitals, the data indicated that in a number of cases antimicrobial treatment could have been implemented more effectively had PNA-FISH data been available to clinicians. In addition, Parcell and Orange (2013) also concur with Calderaro et al. (2013) in their assessment that PNA-FISH would be an effective economical alternative to tests such as MALDI-TOF and PCR based methods. Once again it would be expected that the use of the new QuickFISH methodology would further magnify the positive effects delivered by the use of PNA-FISH technology.

In consequence, a growing body of evidence is proving that the PNA-FISH technology can deliver tangible benefits in a clinical setting and that these are especially pronounced when the QuickFISH kits are used. The technology matches, or betters, other techniques in terms of sensitivity and specificity, but needs no complex instrumentation and is easy to perform in the laboratory. The use of the QuickFISH technique offers tangible benefits to patients, clinicians, pharmacists and medical laboratory professionals.

References

1. Deck MK, et al. Multicenter evaluation of the Staphylococcus QuickFISH method for simultaneous Identification of Staphylococcus aureus and Coagulase-Negative Staphylococci directly from blood culture bottles in less than 30 minutes. J Clin Microbiol 2012; 50(6):1994–8.

2. Caretto E, et al. Comparison of the Staphylococcus QuickFISH BC test with the tube coagulase test performed on positive blood cultures for evaluation and application in a clinical routine setting. J Clin Microbiol 2013; 51(1):131–5.

3. Deck MK, et al. Rapid detection of Enterococcus spp. Direct from blood cultures using Enterococcus QuickFISH method: a multicentre investigation. Diagn Microbiol Infect Dis. Diagn Microbiol Infect Dis 2013; Article in Press DOI: 10.1016/j.diagmicrobio.2013.12.004

4. Calderaro A, et al. Comparison of PNA-FISH assays with culture based MALDI-TOF for the identification of bacteria and yeasts from blood cultures and yeasts from blood cultures and cerebrospinal fluid cultures. Clin Microbiol Infect; 2013. Article in Press DOI: 10.1111/1469-0691.12490

5. Parcell BJ, Orange GV PNA-FISH assays for early targeted bacteraemia treatment. J Microbiol Methods 2013;95(2):253-5.

6. Stone NR, et al. Evaluation of PNA-FISH yeast traffic light for rapid identification of yeast directly from positive blood cultures and assessment of clinical impact. J Clin Microbiol 2013;51(4):1301-2.