Microbiology suffers from ‘prescribe first, test later’

Microbiology represents the market segment paradox of the in vitro diagnostics industry. On one hand, it is among the most mature markets. Because of its slow turnaround time (usually 24 hours), an estimated 70 percent of all microbiology tests are not used to guide therapy. Most physicians prefer to “prescribe (antibiotics) first and test second.” That is one of the main reasons, the $1.5 billion microbiology market experienced a negative growth rate (-3%) in 2000. (Merrill Lynch market analysis Nov. 14, 2000)

On the other hand, if you consider nucleic acid testing (NAT) as a subset or offshoot of microbiology, it is among the most dynamic and fastest growing segments.

Even without nucleic acid testing, there is no shortage of macro issues in any discussion of microbiology’s place in today’s IVD industry marketplace. The daily headlines are replete with microbiology topics — infectious disease, bio-terrorism, antibiotic misuse and bacterial resistance, Mad Cow disease, E. coli outbreaks, vaccine stockpiling and, of course, Europe’s latest, hoof-and-mouth disease. How much does the average citizen understand?

“In general, if the public can’t see it, they don’t believe it,” said Colin Wylie, president of Vista Technology, an Edmonton, Canada-based maker of lab automation products. “Microbiology is the poor cousin of the clinical lab: isolated and seen as a money loser, which results in poor budgets.

“People should remember that our generation is the first to grow up with vaccines and antibiotics. Historically, people died of disease long before they reached old age and had any heart, arthritis, cancer or other age-related problems,” Wylie said.

However, there are groups that understand. With more than 42,000 member scientists and health professionals, the American Society for Microbiology (ASM) is the oldest and largest life science membership organization in the world.

Jim Sliwa, ASM communications manager, said microbiology may be suffering from an identity crisis because, “it has a hand in so many related fields. People forget microbiology is its own industry.”

Indeed, microbiology is the fourth largest diagnostics industry segment in terms of sales volume. Sales are dominated by four manufacturers of systems and reagents: BD (Becton Dickinson), Dade Behring, bioMerieux Vitek and Organon Teknika. Of the four, only BD is a public company; the rest are private.

BD
BD, headquartered in Franklin Lakes, N.J., is comprised of three worldwide business segments, one of which is Clinical Laboratory Solutions. Clinical Laboratory Solutions consists of Vacutainer, BD’s $530 million sample collection business that enjoys a 90 percent market share; its molecular diagnostics systems, which includes the ProbeTec ET System; and BD Diagnostics Systems in Sparks, Md., which holds its microbiology franchise.

BD is the market leader in microbiology and flow cytometry testing and has development collaborations with Millennium Predictive Medicine and The Institute for Genomics Research for molecular diagnostic markers for cancers and infectious disease. It also has formed a joint venture, PreAnalytiX, in nucleic acid sample preparation with Qiagen. Some market analysts say BD’s flow cytometry and labware business units are ripe for a spin off.

BD’s microbiology test equipment includes its newest generation Bactec MGIT 960 System for mycobacteria testing. The system’s 960-tube on board capacity accommodates medium-to-high-volume labs that want to process approximately 8,000 specimens a year. Its Bactec 9000MB Mycobacterial Dectection System, for medium-volume labs, uses a fluorescent testing technology, continuous monitoring and a closed-system design. BD has contracted with several reference laboratories to use the BD ProbeTec ET System to perform DNA amplification for chlamydia and gonorrhea testing on urine samples. Test kits can be ordered by telephone or by Web site and are returned to the reference lab for testing.

Dade Microscan
Dade Behring, the seventh largest IVD company with $1.3 million in 1999 sales, is owned by Aventis (50%), Bain Capital (25%) and Goldman Sachs (11%). Dade plays in eight market segments: cardiac diagnostics, chemistry/immunochemistry, drug monitoring, hemostasis, immunohematology, infectious disease, microbiology and plasma proteins.

Dade’s microbiology division, Microscan, makes its Walk-Away Systems (96, 96 SI and 40 SI models). The WalkAway-96 System automates 90 percent of routine ID/Susceptibility testing and processes 96 panels while the Walk-Away-40 process 40 panels. Accurate identification is provided in as little as two hours. The Walk-Away-96 SI performs the same functions as the WalkAway-96 but it automatically dispenses oil, incubates and adds necessary reagents and interprets results.

Recently, Microscan announced the availability of several new antimicrobial reagents for its panels: levofloxacin, sparfloxacin, meropenem, clarithromycin and azithromycin.

bioMerieux
bioMerieux, the No. 8 player in the worldwide IVD market, focuses on infectious disease but develops manufactures and markets reagents and automated systems for medical analysis and microbiological quality control of products in the agri-business, cosmetic and pharmaceutical industries.

Headquartered in Marcy- l’Etoile, France, bioMerieux achieved more than $440 million in sales in 1999, nearly 75 percent of which came from outside France. It employs about 3,500 people worldwide and has eight production facilities located in France, the United States, Brazil and Italy.

bioMerieux, founded in 1963 by Alain Merieux, acquired API company in 1986 and the Vitek company in 1988. These enabled the company to automate its microbiological diagnostics range and establish itself as a worldwide player. Today the Vitek 2 integrates sample preparation, incubation and optical measurement systems so that identification and susceptibility testing of microorganisms can be done on one instrument.

The company’s Vitek 2 microbial identification and susceptiblity system was launched at the 1998 annual meeting of the American Society of Microbiology. It provides rapid, reliable test results to assist physicians in the diagnosis and management of patients with infection.

Organon Teknika
Fourth in the microbiology IVD line up is Organon Teknika of Durham, N.C., a business unit of Akzo Nobel headquartered in Boxtel, the Netherlands. At this writing in mid-April, Akzo, which specializes in systems and products for hospitals, laboratories and blood banks, is considering an offer from bioMerieux for Organon Teknika’s in vitro diagnostics business. The offer was made public in February.

Organon Teknika is an international player in the research, manufacturing and marketing of healthcare products for hospitals, laboratories and blood banks. The company’s products are sold in more than 60 countries, and it employs almost 2,200 people. Its systems integrate hardware, software and reagents for six areas of healthcare: neuromuscular block management, immunotherapy for superficial bladder cancer, immunological testing, coagulation testing, bacteriological testing and nucleic acid testing.

Organon Teknika’s automated microbiology systems use a patented colorimetric sensor. BacT/Alert was the first test system to feature this colorimetric technology. A sensor at the base of each culture bottle changes from dark green to yellow as microorganisms grow. A highly sensitive detector continuously scans the sensors, recognizes slight change in color and reports it immediately.

BacT/View software for the BacT/Alert simplifies operation and reduces error. All operations can be performed from a one computer and handling is reduced to a minimum. The operator loads and unloads bottles when signaled. Pre-processing is not required and specimen volumes can be inoculated directly into the culture bottle.

The MB/BacT, a non-isotopic alternative for the detection of mycobacteria, is compatible with the BacT/Alert and can be run by the same computer. It can provide a safer and more cost-effective method than conventional or radiometric methods. It continuously and non-invasively monitors non-blood specimens, but can also detect mycobacteria in blood when dedicated blood culture bottles are used.

The BacT/Alert 3D is a totally automated test system that combines blood, body fluid and mycobacteria specimen testing in one instrument. It consists of 1-6 incubator modules, each capable of accommodating 240 bottles. It is touch-screen directed.

Public health risks
At Dade Behring MicroScan, Bill Welch, vice president of global marketing, ranks emerging antibiotic resistance, cost pressures and epidemiology and surveillance trends as the most pressing issues for microbiology. He looks forward to the development of antibiotics targeted at a genomic level where mutation is less likely to occur.

“However, for today and the foreseeable future, identification and susceptibility testing are the primary means to measure the effectiveness of antibiotic treatments as well as to monitor trends in resistance,” Welch said.

Bioterrorism, another public health threat, has not escaped the attention of the Centers for Disease Control, which has earmarked $275 million to stockpile smallpox vaccines and other pharmaceuticals, increase lab capacity and networking.

Jo Ann Yatabe, Ph.D., and George Berlin, Ph.D., of Specialty Laboratories in Santa Monica, Calif., see an expanding role for clinical microbiology as new pathogens (Ebola, Boma, and Nipah viruses) arise and old pathogens resurface with new “faces” such as multi-drug resistant TB.

Both believe that the industry must develop technologies that can detect organisms from the site/specimen rather than waiting for them to grow (as in a bacterial culture) or cause cytopathic effect as in a viral culture. Molecular-based technologies will be central.

This is where the outlook for microbiology gets confusing. If molecular diagnostics and NAT are just part of the natural evolution of microbiology testing, then the future looks bright. If, on the other hand, those new technologies are competition, then the road ahead for microbiology looks rather narrow.

But it looks like DNA probes and their decendants are here to stay. Certainly direct detection of M. tuberculosis from specimens and culture are the preferred method. In addition, molecular methodologies for identifying Chlamydia trachomatis/Neisseria gonorrhoeae have led to improved efficiency and turnaround time.

John J. Meduri, MBA, MT (ASCP), director of the Worldwide Strategy Center at BD Diagnostic Systems, believes molecular probes can revolutionize laboratory medicine. “Basic research is uncovering previously unknown relationships between microorganisms and disease processes,” he said.

Meduri wants manufacturers and laboratorians to work together to leverage precious resources. “With the emergence of managed care and its impact on laboratory medicine, a laboratory’s ability to adopt newer, more complex diagnostic assays becomes increasingly challenging,” he said.

Antibiotic Resistance
A recent CDC survey found that 50 million outpatient prescriptions written every year — one-third of the 150 million total — are not needed. Writing in Scientific American, Professor Stuart B. Levy of the Tufts University School of Medicine, said that more than 80 percent of physicians surveyed at one of his seminars admitted to having written antibiotic prescriptions on demand against their better judgment.

More Productive Labs
What about products that enhance lab operation? BD’s recent innovations include the Affirm VPIII Microbial Identification System, the BDProbeTec ET automated molecular diagnostic system (supporting SDA chemistry) and the BBL Crystal AutoReader which automatically reads and interprets test reactions.
Vista’s Wylie sees inertia in the industry. “Surprisingly, while everyone says they want automation, we have found, generally, complete resistance to change in microbiology,” he said.

Vista’s IsoPlater 180 automatic petri dish streaking instrument for specimens is faster, safer and less costly than traditional handling. “Yet microbiologists cling to the manual 100-year-old practices,” Wylie said. Vista has installed 105 IsoPlater machines in the United States, Canada and Australia, even though the systems pay for themselves in less than a year, according to Wylie.

In an era of modernization and mechanization, Specialty’s Yatabe said, microbiology is still a field of “culture and sensitivity.”

Nicholas Borgert is freelance writer based in Charlotte, N.C.