There is growing interest in the potential utility of real-time PCR in diagnosing bloodstream infection by detecting pathogen DNA in blood samples within a few hours. SeptiFast is a multipathogen probe-based real-time PCR system targeting ribosomal DNA sequences of bacteria and fungi. It detects and identifies the commonest pathogens causing bloodstream infection and has European regulatory approval. The SeptiFast pathogen panel is suited to identifying healthcare-associated bloodstream infection acquired during complex healthcare, and the authors report here the protocol for the first detailed health-technology assessment of multiplex real-time PCR in this setting.
A Phase III multicentre double-blinded diagnostic study will determine the clinical validity of SeptiFast for the rapid detection of healthcare-associated bloodstream infection, against the current service standard of microbiological culture, in an adequately sized population of critically ill adult patients. Results from SeptiFast and standard microbiological culture procedures in each patient will be compared at study conclusion and the metrics of clinical diagnostic accuracy of SeptiFast determined in this population setting. In addition, this study aims to assess further the preliminary evidence that the detection of pathogen DNA in the bloodstream using SeptiFast may have value in identifying the presence of infection elsewhere in the body. Furthermore, differences in circulating immune-inflammatory markers in patient groups differentiated by the presence/absence of culturable pathogens and pathogen DNA will help elucidate further the patho-physiology of infection developing in the critically ill.
Ethics and dissemination
Ethical approval has been granted by the North West 6 Research Ethics Committee (09/H1003/109). Based on the results of this first non-commercial study, independent recommendations will be made to The Department of Health (open-access health technology assessment report) as to whether SeptiFast has sufficient clinical diagnostic accuracy to move forward to efficacy testing during the provision of routine clinical care.
To highlight the unmet need for accurate and rapid infection diagnostics in the setting of life-threatening infection.
To describe the systematic plans of a clinical diagnostic validity study of a new real-time PCR technology, designed to detect circulating pathogen DNA associated with bloodstream infection.
To describe the clinical standards for sepsis and healthcare-associated infection diagnosis and identify how these standards will be utilised to determine the clinical validity of the new real-time PCR test in critically ill patients.
The study will provide the first independent, systematic, clinical validity study of real-time PCR technologies in the focused setting of suspected life-threatening healthcare-associated infections during the provision of routine emergency critical care.
Based on the results of this study, independent recommendations will be made to the UK's Department of Health as to whether the real-time PCR technology has sufficient clinical diagnostic accuracy to move forward to efficacy testing during the provision of routine clinical care.
Strengths and limitations of this study
The study is focused on a carefully delineated clinical cohort at significant risk of developing life-threatening infection.
The study is non-commercial and has been planned systematically by a multidisciplinary team of experts and patient representatives, working on behalf of the key stakeholders within a nationalised healthcare system.
Current clinical infection diagnosis standards may not have a high diagnostic accuracy in all settings and with all infections.
There is a documented high rate of broad-spectrum antimicrobial therapies delivered to critically ill patients empirically which could confound the comparison between culture methods and pathogen DNA-detection methods.