Analytic methods such as mass spectrometry (MS) and PCR are "challenging what we know as the gold standard" for identifying microbial pathogens, says Donna Wolk of the University of Arizona in Tucson, who spoke during the symposium, "Is the Era of Bacterial Culture Ending?" held as part of the 50th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC), in Boston, Mass., last September.  These approaches, while costly and still under development, could prove critical for addressing diagnostic challenges such as sepsis or endocarditis that can so quickly become life-threatening, she and other symposium participants point out.

"It is frustrating to wait for blood culture and susceptibility testing from severely ill patients, especially those with sepsis," says Jacques Schrenzel of Geneva University Hospital in Geneva, Switzerland. Molecular analytic methods can reduce the time to yield results, but come with other drawbacks, including high cost. "Another major limit is sample preparation," he says. "It should be automated and capable of handling large volumes." Whether PCR or MS will prevail as diagnostic methods, he cannot predict. For now, he says, "Keep each method for what it will do well; we could well end up with a combination of new and old methods."

One advantage of MS is that it has the capacity to detect already characterized antibiotic resistance markers, Wolk says. "But the sensitivity might not be there. We're trying to develop algorithms for the most common pathogens and drug resistance determinants. At this point, however, it's not a one-stop shop."

However, PCR has its advantages, too, including the fact that clinical microbiologists tend to be more familiar with its uses than with those involving MS, Wolk says. Technology choices can depend, in part, on "an individual's training and experiences," she says. "It will take a village to assess MS. Not one lab can do that, but we will have to evaluate these methods at multiple sites, and I'm calling out to microbiologists to form alliances to do this."

Although MS looks to be a very costly procedure for diagnosing bloodborne infections, its accuracy reaches as high as 98.7% in some cases, and it sometimes outperforms blood cultures in identifying pathogens, according to Wolk. MS, other molecular methods, and traditional blood culture procedures all have difficulties when dealing with mixed infections, she points out. "Faster-growing pathogens may mask slower pathogens in culture, and of 229 mixed infections, about half were not picked up using blood cultures."

"Commercial methods fail to detect simple pathogens in patients with endocarditis," says another symposium participant, Patricia Munoz of the Hospital University Gregorio Maranon in Madrid, Spain. Whether newer molecular detection methods can be adapted to this purpose is uncertain. However, with endocarditis on the rise, there is a need for improvements in diagnostic capabilities. For instance, mortality rates run as high as 20% in part because diagnosis, which continues to rely on blood cultures, performs poorly, yielding a rate of false-negative tests of about 15%, she says. Having a molecular method that could provide a reliable and faster readout would be "a great advance."

Jeffrey L. Fox