BMJ Open 2:e000392 doi:10.1136/bmjopen-2011-000392
  • Intensive care
    • Protocol

Accuracy of LightCycler® SeptiFast for the detection and identification of pathogens in the blood of patients with suspected sepsis: a systematic review protocol

  1. Geoffrey Warhurst1,3
  1. 1Infection, Injury and Inflammation Research Group, Biomedical Facility, Clinical Sciences, Manchester Academic Health Sciences Centre, Salford Royal NHS Foundation Trust, Salford, Greater Manchester, UK
  2. 2Intensive Care Unit, Salford Royal NHS Foundation Trust, Manchester Academic Health Sciences Centre, Salford, Greater Manchester, UK
  3. 3School of Translational Medicine, Faculty of Medical and Human Sciences, University of Manchester, UK
  4. 4School of Nursing & Midwifery, Queen's University Belfast, Belfast, UK
  5. 5Centre for Infection and Immunity, Queen's University, Belfast, UK
  6. 6Clinical Trials Unit, Warwick Medical School, University of Warwick, Coventry, UK
  7. 7Department of Medical Microbiology, Royal Victoria Hospital, Belfast, UK
  1. Correspondence to Dr Paul Dark; paul.m.dark{at}
  • Received 14 September 2011
  • Accepted 5 December 2011
  • Published 12 January 2012


Background There is growing interest in the potential utility of molecular diagnostics in improving the detection of life-threatening infection (sepsis). LightCycler® SeptiFast is a multipathogen probe-based real-time PCR system targeting DNA sequences of bacteria and fungi present in blood samples within a few hours. We report here the protocol of the first systematic review of published clinical diagnostic accuracy studies of this technology when compared with blood culture in the setting of suspected sepsis.

Methods/design Data sources: the Cochrane Database of Systematic Reviews, the Database of Abstracts of Reviews of Effects (DARE), the Health Technology Assessment Database (HTA), the NHS Economic Evaluation Database (NHSEED), The Cochrane Library, MEDLINE, EMBASE, ISI Web of Science, BIOSIS Previews, MEDION and the Aggressive Research Intelligence Facility Database (ARIF). Study selection: diagnostic accuracy studies that compare the real-time PCR technology with standard culture results performed on a patient's blood sample during the management of sepsis. Data extraction: three reviewers, working independently, will determine the level of evidence, methodological quality and a standard data set relating to demographics and diagnostic accuracy metrics for each study. Statistical analysis/data synthesis: heterogeneity of studies will be investigated using a coupled forest plot of sensitivity and specificity and a scatter plot in Receiver Operator Characteristic (ROC) space. Bivariate model method will be used to estimate summary sensitivity and specificity. The authors will investigate reporting biases using funnel plots based on effective sample size and regression tests of asymmetry. Subgroup analyses are planned for adults, children and infection setting (hospital vs community) if sufficient data are uncovered.

Dissemination Recommendations will be made to the Department of Health (as part of an open-access HTA report) as to whether the real-time PCR technology has sufficient clinical diagnostic accuracy potential to move forward to efficacy testing during the provision of routine clinical care.

Registration PROSPERO—NIHR Prospective Register of Systematic Reviews (CRD42011001289).


  • To cite: Dark P, Wilson C, Blackwood B, et al. Accuracy of LightCycler® SeptiFast for the detection and identification of pathogens in the blood of patients with suspected sepsis: a systematic review protocol. BMJ Open 2012;2:e000392. doi:10.1136/bmjopen-2011-000392

  • Funding PD and GW are part-funded by the UK Health Technology Assessment (HTA) programme of the National Institute of Health Research grant number NIHR HTA 08/13/16. CW is funded by Greater Manchester Comprehensive Local Research Network in support of this programme of work. DFM and GDP receive funding from The Intensive Care Foundation (UK) in support of their roles as National Research Directors. None of these funding organisations or any commercial organisation have contributed to the study design; collection, management, analysis and interpretation of data; writing of the report or the decision to submit the report for publication. Only the named authors have ultimate authority over each of these activities.

  • Competing interests None.

  • Contributors PD and GW initiated the project, CW and BB worked together on the initial architecture for the review with specialist molecular diagnostic input from GW, critical care and clinical trial input from PD, DM and GDP, microbiological input from RM and statistical input from SG. PD drafted the protocol. All authors critically reviewed the first draft and contributed to the production of the final manuscript and its subsequent revision.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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