Rapid Pathogen Identification Improving in Critically Ill

There has been improvement in rapid diagnostic techniques for identifying infections in critically ill patients over the last decade, according to a review study published Nov. 28, 2014, in BioMed Central Infectious Diseases. However, there are still pressing improvements needed to expedite diagnosis, especially among drug resistant strains and to widen the spectrum of identifiable pathogens and the sample types tests can be run on.

Given the well-documented findings that infections in ICU patients are often deadly “rapid etiologic microbiological diagnosis is mandatory,” the authors write. The Spanish researchers conducted a systematic literature search of peer-reviewed publications published between 1995 and 2014 to evaluate the evolution of diagnostics for common ICU infections, including bloodstream infection (BSI), and ventilator-associated pneumonia (VAP).

Diagnosis of sepsis remains a “major challenge,” the authors say with no specific marker available to determine a true diagnosis of sepsis. While time-consuming blood cultures are still considered the gold standard for diagnosis, they are currently being used in conjunction with molecular tests. The researchers found that molecular technologies are improving diagnosis and impacting clinical decision-making, with results ideally produced within 6 hours, but still have some notable shortcomings, including the lack of an appropriate gold standard, as well as the need for some expertise.

“Although there are still some unresolved limitations of the use of molecular techniques for a rapid diagnosis of infection in the ICU patient, this approach holds much promise for the future,” writes co-author Almudena Burillo.

Suggested areas of future improvement of molecular tests include the need to improve sensitivity to detect clinically relevant low bacterial loads and fastidious microorganisms and to distinguish between living and dead bacteria. For identification of isolated colonies, matrix assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry can be run directly on positive blood culture broths in under one hour and is now replacing biochemical and gene sequencing methods for organism identification.

For VAP bacterial identification and antibiotic susceptibility testing can still take two days to four days. Molecular techniques are needed, the authors say, that can detect multiple microorganisms or resistance mechanisms directly on clinical samples before cultures are available. By directly subjecting clinical samples to PCR (GeneXpert, Cepheid) the authors have shown “high diagnostic efficiency” and can shorten the time to adequate antibiotic treatment, although the kit has not received regulatory approval for this purpose. A definitive marker for VAP diagnosis is also lacking, although evidence is demonstrating that procalcitonin may be a good prognostic marker, with elevated levels indicating a more severe clinical course.