Microbiology

By Jonathan Briggs

Microbiology consists of at least two segments: conventional microbiology and molecular diagnostics which “crosses borders” with infectious disease testing. Primary vendors for these two areas are Roche, Dade Behring, BD, and bioMérieux. These vendors have different approaches to the two microbiology markets: focusing on conventional microbiology, focusing on molecular diagnostics, or a combination of the two. As the market share and sales figures below show, these different approaches can all be successful.

Currently, the majority of microbiology done in most clinical labs is conventional. And although molecular diagnostics has great potential, this technology faces challenges similar to those faced by early PCs – a variety of technologies, systems and products, little or no standardization, the need for highly skilled and knowledgeable users and few large market applications. But recent changes, such as increased antibiotic resistance, pressure to decrease hospital LOS, the increased threat of bioterrorism, the need for monitoring therapies, and the rise of point-of-care testing are increasing the demand, and therefore the potential market, for molecular diagnostics. So, will molecular microbiology replace the laboratory “mainframe,” of conventional microbiology, and if so, when? As Kelly Westfall, Industry Analyst with Frost and Sullivan puts it, “Despite the promise of improvements like increased accuracy and the ability to monitor therapy, molecular diagnostics still must meet the challenges of lateral flow and other conventional technologies in terms of cost, automation, personnel skills, and throughput.” This is why conventional microbiology is still a billion-dollar a year industry.

Dade Behring – focus on conventional
“We don’t want people to start thinking of ‘conventional’ as in ‘conventional microbiology’ as a negative” said Jeff Metcalf, vice president for marketing at Dade Behring of Deerfield, Ill. Since DB did more than a third of a billion dollars in business last year, obviously conventional microbiology isn’t going the way of punch cards. The company is “looking into molecular diagnostics,” but in the meantime, DB is launching several new products this year in support of its popular MicroScan analyzers. For example, DB’s new ESbL plus panel will be available this spring. This new panel allows MicroScan users to follow the new NCCLS recommendations on screening and confirmation for potential ESbL-producing bacteria that may be resistant to common antibiotics.

Next out from DB, in a limited release in June and widely available by August, will be their Alert system. This product, also for MicroScan users, flags atypical results. Flagging atypical results “should improve quality of patient care by better targeting and speeding up treatment of certain infections, and it should also reduce the need for operator supervision,” said Metcalf.

Other new products from DB include the MicroStrep Plus panel for strep susceptibility testing. This product includes new antibiotics and now comes with dried rather than frozen reagents.

BD
BD, an industry leader in conventional microbiology, is also focusing on molecular diagnostics with its ProbeTech system, an FDA-approved real-time amplification platform. The main feature of the ProbeTech system, according to Jennifer Walsh, worldwide marketing manager, molecular diagnostics, is that it is considered the easiest of any system to use. It is a one-hour test inside a closed microwell, and ready to use reagents are supplied. Samples can be left on the priming plate for 20 minutes or up to six hours, so there is flexibility in workflow requirements, and multi-channel pipettes cut down the number of times an operator must transfer a specimen. Importantly, amplification control allows for verification of a negative result.

ProbeTech is currently used for chlamydia and gonorrhea testing, and has the flexibility to process a few to thousands of samples per day.

Molecular is a key growth initiative for BD, and industry analysts expect the company’s income from this testing segment to double in the year 2002. To further this expansion, BD plans both to provide labs with automation, and to add more clinically relevant tests to its molecular testing menu.

The Viper sample processor will be a high volume system launched in several iterations, beginning this spring. This will allow full automation of all the up-front pipetting steps, so that lab techs can put samples on board the system and walk away. The system will be upgradeable through software, including barcode reading, automated sample processing and on-board reading of the wells, for improvements in time as well as precision.

BD plans to develop other infectious disease testing, including for the near future atypical pneumonia tests to be launched on sputum as well as throat swabs. This will address a very real problem faced every day in the microbiology lab: 50 percent of etiologies of pneumonia are unknown, and 15 percent of patients die, so the lab needs tools to rapidly diagnose which kind of pneumonia the atypical pneumonia is, rather than simply treating empirically, risking treatment failure, and worsening antibiotic resistance. While these tests may not be inexpensive, their impact on speeding recovery and reducing length of stay should make them cost effective.

According to Walsh, more and more physician’s offices are also interested in molecular testing, which will undoubtedly migrate over time to the point of care. There are still challenges posed by the number of different enzymes required and the need for careful quality control, but the fact that molecular diagnostics can be fast and specific enough to inform a treatment decision at the point of care makes the use of the technology in POLs inevitable. The key, says Walsh, is in the ability to manage a patient alongside these tests results.

Roche Diagnostics – “PCR Meets ICU”
Roche Diagnostics leads the industry in molecular diagnostics because of the early foothold it got with PCR for viral testing. However, moving this technology to bacterial infectious testing means developing reliable and automated systems that can compete with and improve on conventional technology. “If you want to do something better than conventional microbiology culture,” said Peter Kaspar, Ph.D., senior vice president and head of PCR microbiology “it won’t be based on convenience, it will be based on time. Speed is essential.”

But first, there is a problem to resolve that did not exist with viral testing: even if you kill a bacterial bug, the DNA is still in the background. That’s why NAT for bacteriology didn’t come along as fast as it did for viral testing. “Within the past two to three years, however, confidence in PCR has grown, and

the paradigm has shifted. The market is more ready than ever before,” said Kaspar. And just as the challenges of the AIDS epidemic drove development of viral testing, the challenges of resistant bacteria may be pushing molecular microbiology ahead.

In spite of potential technical hurdles, Roche is pursuing the use of molecular diagnostics in bacterial testing in sepsis, and other areas. Roche is looking at sepsis because of the high number of cases and the high mortality rate. PCR can help physicians select the appropriate antibiotics much faster, both saving lives and reducing the chance for resistance to develop. The sequence of product development at Roche is: bacteriology first on the Light Cycler, then on the Cobas Taqman platform and then to point of care. That’s the long-term goal. “Maybe PCR will never be on a pocket device like a glucose meter, but Roche is in the best position because we have a presence in research, large lab and POC testing allowing us to drive one concept through all platforms,” said Kaspar. As for the first step, detection and differentiation kits for pseudomonas, staphylococcus, enterococcus, and candida on the Roche LightCycler will be available soon.

bioMérieux
Many clinical applications for molecular diagnostics are still in the early stages of their evolution. An important part of that evolution is the “home brew” or in-house validated assay done in many labs. The bioMérieux Nuclisens kit helps labs standardize and simplify these assays. Developing their own assays also allows labs to avoid royalties on proprietary products. “We don’t do a lot to promote the kits. The people who develop them like to share them,” said Lynelle Grosso, clinical marketing manager at bioMérieux. “The basic kit has been very popular with hospital labs, reference labs and departments of health.”

In addition to the basic kit, bioMérieux now offers both qualitative and quantitative HIV-1 kits and a CMV pp67 kit.

The next step for bioMérieux will be to involve the Vidas Probe line, so they can move into the POL area.

Like mainframe computers, conventional microbiology has adapted by getting easier to use and more cost effective. And molecular diagnostic platforms, like early PCs, are also developing more applications and getting easier to use.

Jonathan Briggs is a freelance writer in Tijeras, N.M.