Bench-to-bedside review: Rapid molecular diagnostics for bloodstream infection - a new frontier?

Abstract

Among critically ill patients, the diagnosis of bloodstream infection poses a major challenge. Current standard bacterial identification based on blood culture platforms is intrinsically time-consuming and slow. The continuous evolvement of molecular techniques has the potential of providing a faster, more sensitive and direct identification of causative pathogens without prior need for cultivation. This may ultimately impact clinical decision-making and antimicrobial treatment. This review summarises the currently available technologies, their strengths and limitations and the obstacles that have to be overcome in order to develop a satisfactory bedside point-of-care diagnostic tool for detection of bloodstream infection.

Sepsis: the LightCycler SeptiFast Test MGRADE®, SepsiTest™ and IRIDICA BAC BSI assay for rapidly identifying bloodstream bacteria and fungi – a systematic review and economic evaluation

“…25,26 A median time to positivity of approximately 15 hours has been reported, but with a wide range for individual samples. 25,26 When a blood culture bottle has been detected as positive, it is recommended that:…”

Evaluation of Three Rapid Diagnostic Methods for Direct Identification of Microorganisms in Positive Blood Cultures

“…Because traditional microbiological methods do not necessarily provide results in a clinically optimal time frame, a number of technologies have been developed that enable rapid organism identification directly from positive blood cultures. These include both amplification (i.e., PCR)-based and non-amplification-based methodologies (6)(7)(8)(9)(10). Importantly, previous studies have shown that rapid organism identification can positively impact patient care by shortening length of stay, lowering mortality rates, and reducing overall hospital-associated costs (11)(12)(13)(14).…”

Comparison of three different commercial PCR assays for the detection of pathogens in critically ill sepsis patients

“…However, a positive PCR result-particularly in the absence of blood culture confirmation-should always be assessed critically within the individual clinical and microbiological context. Posi tivity in a PCRbased assay may well reflect a real infection, but could also result of external contamination, the presence of the NA of non-viable microorganisms, or even be obtained from freely circulating phagocytised microbial DNA from microorganisms already destroyed [29]. The last three scenarios would result in an unnecessary use of antibiotics.…”

“…Blood cultures are often considered the gold standard, but these have limited validity themselves [29]. In our study, we sought to overcome these problems by distinguishing between false-and true-positive PCR assay results by using all available clinical information, including the results of additional microbiological tests and imaging, as well as the clinical course of the patient (.…”