Molecular diagnosis of bloodstream infections caused by non-cultivable bacteria

Bloodstream infections are an important cause of morbidity and mortality in patients. Blood culture is clearly the most important diagnostic procedure for identifying micro-organisms involved in bloodstream infections except when the patient has previously received antibiotics or in the presence of slow-growing or intracellular micro-organisms. Detection of micro-organisms, mainly in blood, using pathogen-specific or broad-range PCR assays is promising. However, it is very important to emphasise that the interpretation of this molecular tool is critical because of the risk of interfering contamination, underlining the necessity to interpret the results obtained with caution. Presently, due to more widely available data and to rapid advances in biotechnology, two significant improvements allow new perspectives for molecular diagnosis. Indeed, the complete sequences of genomes have provided an important source of gene sequences for PCR-based assays. In addition, the development of real-time PCR offers several advantages in comparison to conventional PCR, including speed, simplicity, quantitative capability and low risk of contamination. Herein, we review the usefulness of molecular diagnosis of highly fastidious micro-organisms in the context of three different bloodstream infections: systemic diseases (rickettsiosis, Q fever, bartonellosis, Whipple's disease), blood-culture-negative endocarditis and bioterrorism attack.