Bench-to-bedside review: The promise of rapid infection diagnosis during sepsis using polymerase chain reaction-based pathogen detection

Paul M Dark,Geoffrey Warhurst,Paul Dean

doi:10.1186/cc7886

Abstract

Early infection diagnosis as the cause of a patient's systemic inflammatory syndrome is an important facet of sepsis care bundles aimed at saving lives. Microbiological culture provides the main route for infection diagnosis but by its nature cannot provide time-critical results that can impact on early management. Consequently, broad-spectrum and high-potency antibiotics are essential during the immediate management of suspected sepsis in critical care but are associated with the development of drug-resistant organisms and superinfections. Established molecular laboratory techniques based on polymerase chain reaction (PCR) technology can detect pathogen DNA rapidly and have been developed for translation into a clinical diagnostic setting. In the setting of sepsis in critical care, emerging commercial systems are now available for the analysis of whole blood within hours, with the presumed aim of adoption into the current care bundles. In this review, we consider the importance of early infection diagnosis in sepsis, how this is limited by culture approaches and how the emerging PCR methods are showing promise in early clinical observational studies. The strengths and weaknesses of culture and PCR pathogen detection in whole-blood samples will be highlighted and recommendations made for urgent appropriately powered diagnostic validation studies in advance of clinical effectiveness trials before these emerging PCR pathogen detection techniques can be considered for adoption in clinical practice.

Highlights

Importance of rapid infection diagnosis in surviving sepsisSepsis is the clinical syndrome resulting from a host’s systemic inflammatory response to infection and is a major international health care problem
The consensus definitions of infection in critical care require microbiological evidence of pathogens to make a probable diagnosis or culture to confirm the diagnosis [2]
Current opinion in critical care favours the early use of antibiotics, guided by local pathogen surveillance, usually of a broad spectrum and high potency, that is applicable to all clinical settings in patients with suspected severe sepsis [1]

Summary

Importance of rapid infection diagnosis in surviving sepsis

Sepsis is the clinical syndrome resulting from a host’s systemic inflammatory response to infection and is a major international health care problem. Current opinion in critical care favours the early use of antibiotics, guided by local pathogen surveillance, usually of a broad spectrum and high potency, that is applicable to all clinical settings in patients with suspected severe sepsis [1]. There is evidence showing that the correct initial choice of antibiotic saves more lives than virtually any other intensive care unit intervention [1,3,4,5]. This may require broad-spectrum cover in the face of as-yet-unidentified infection because delaying antibiotic therapy in sepsis has been shown to increase mortality and morbidity [6,7].

Use and limitations of blood culture in sepsis diagnosis

Polymerase chain reaction approaches to the diagnosis of pathogenaemia

Findings

Conclusions