The rapid detection of bacteria commonly causing sepsis could allow species-specific therapy to be started early. This would lead to improved clinical outcomes. Blood culture is the current gold standard for identification of bacteria from patients with sepsis. It typically takes one to three days to become positive. An additional one to two days might be required for identification of bacteria and their antibiotic sensitivity patterns. In order to cut this extra one to two day period, new diagnostic tests that can identify bacterial species rapidly and accurately are needed.
New DNA-based microarray platforms now allow rapid detection and species identification of several microbial pathogens. The “Prove-it” sepsis test (Mobidiag, Helsinki, Finland) identifies more than fifty species of gram-positive and gram-negative bacteria that cause the majority of sepsis cases. The assay works through amplification and detection of three genes (gyrB, parE, and mecA) of these bacteria. The authors compared in this study the sensitivity, specificity, and time to identification of this new molecular platform with the gold standard which is conventional culture-based method.
A total of 3,318 blood samples were collected in this observational study, with 2,107 positive blood-cultures. Patients with clinically suspected sepsis were investigated for bacterial species by both conventional culture and the “Prove-it” sepsis assay in two centres in the UK and Finland. The authors found that 1,807 of 2,107 (86 percent) positive blood-culture samples included a pathogen covered by the assay. The assay had a clinical sensitivity of 95 percent. Sensitivity measures the proportion of actual positives which are correctly identified as such (for example the percentage of sick people who are identified as having the condition). The specificity was of 99 percent.
Specificity measures the proportion of negatives which are correctly identified (for example the percentage of healthy people who are identified as not having the condition). Specificity was 100 percent for both measures for meticillin-resistant Staphylococcus aureus bacteraemia. The assay was an average eighteen hours faster than was the conventional culture-based method, which in addition takes an extra one to two working days.
The authors explain: “The Prove-it sepsis assay yielded a high sensitivity and specificity, and identified bacterial species about 18 h before conventional culture methods did, providing practical and realistic delivery of same-day bacterial identification after blood-culture positivity. Clinical sensitivity and specificity of the assay were 100% for MRSA bacteraemia.”
They note: “Our study was not designed to address health-care costs. Although additional costs are associated with this assay, these costs need to be assessed in the context of the effect of early identification on total patient management, which might include savings relating to factors such as targeted investigation, length of stay in hospital, and outcomes for the patient. A study to investigate these factors is being undertaken by some of this study’s authors.”
The authors are also anticipating the potential use of the kit in developing countries. They comment: “Equipment could be modified into a transportable kit run on solar power for use in rural areas of developing countries, and at points of care for broad-range rapid pathogen screening and targeted therapy. Cost will remain an issue but will be inversely related to the number of samples analysed.”
They say in conclusion: “We noted that the early knowledge provided by this new diagnostic platform could be easily integrated into everyday laboratory workflow in primary-care and secondary-care settings. Accordingly, we are prospectively investigating the platform’s potential contribution to clinical outcomes and management pathways, and its implementation for rapid routine diagnosis of a range of pathogens in both developed and developing countries.”
In an associated note, Dr Shin Lin, Stanford University School of Medicine, Stanford, CA, USA, and Dr Samuel Yang, Department of Emergency Medicine, Johns Hopkins School of Medicine, Baltimore, MD, USA inquire: “Will resolving these scenarios 18 h earlier than usual translate into demonstrable clinical benefit commensurate to the cost of undertaking the additional test?”
They say in closing: “Although further study is needed before widespread application, the work by Tissari and co-workers is a major advance. By combining elements of nucleic-acid and standard culture-based methods, the Prove-it sepsis assay represents an approach that encompasses the best of both worlds, bringing molecular methods to the threshold of broad pathogen detection.”
“Accurate and rapid identification of bacterial species from positive blood cultures with a DNA-based microarray platform: an observational study”
Written by Stephanie Brunner (B.A.)
Medical News Today.