By Gary Tufel
In the past few years, new rapid diagnostic microbiology tests have become a “game changer” for healthcare providers who manage patients with infections, says Debra Goff, PharmD, a clinical associate professor and infectious disease specialist at Ohio State University’s Wexner Medical Center. “Historically, when a physician suspected a patient was clinically infected with bacteria, he/she would draw a blood culture, send it to the microbiology laboratory, start an antibiotic, and then wait for the culture results.
“The culture tells the physician whether the antibiotic is active against the bacteria. But obtaining a final culture result can take up to 3 to 4 days,” Goff says. “Potentially, the patient can be on an antibiotic that is not active against the bacteria for all that time.”
But, she notes, newer diagnostic tests have been shown to improve patient care when the results are communicated from the microbiologist to the clinician in a meaningful time frame. Not only do these new tests identify bacteria faster, some of them can also identify antibiotic-resistant bacteria. “Instead of waiting 3 to 4 days for test results, microbiologists can have results in 20 minutes to 2 hours—truly game-changing,” she says.
While microbiologists across the United States want to implement this new technology, Goff says, there are some barriers. The cost of the instruments can be as high as $250,000, and some of the instruments have large physical space requirements that can present a challenge for small labs. Although many of the instruments are user-friendly, the complexity of some tests may be an issue for low-volume labs. And finally, the development of rapid tests has outpaced clinical awareness, so education is critical for ensuring uptake of new tests.
According to Goff, this is? where antimicrobial stewardship ?programs (ASPs) can help. ASPs? include a collaborative team of?infectious disease physicians, pharmacists, microbiologists, and infection-control practitioners who work together to provide care to patients with infections. “ASPs can help educate and justify the costs of these new expensive diagnostic instruments,” Goff says. “Numerous studies—including a landmark study from the ASP team at Ohio State’s Wexner Medical Center—have demonstrated that rapid diagnostic tests can have a significant impact on improving patient care through rapid optimization of antibiotics, decreased hospital length of stay, and cost savings in the treatment of infections such as methicillin-resistant Staphylococcus aureus (MRSA).
In a recent typical ASP case at OSU, Goff says, “the microbiologist not only communicated the rapid test result to the physician, he/she also phoned the ASP infectious disease clinical pharmacist. This process ensured that the patient received the most effective antibiotic in a timely matter.
“Several others have published similar studies, and the results have been consistent: rapid diagnostic tests with timely communication of results improves patient outcomes,” Goff says. “But the most important point to remember is that the fast, new diagnostic test is of little value if no one reacts to the results.”
Mayo Advances Molecular Testing
An enormous volume of molecular testing is taking place in clinical microbiology at the Mayo Clinic, Rochester, Minn. One of the largest academic clinical microbiology laboratories in the United States, the Mayo facility is in the vanguard of research and development that has revolutionized the field. And according to Robin Patel, MD, professor of medicine and microbiology and chair of the division of clinical microbiology at the Mayo Clinic College of Medicine, the field is continuing to evolve in ways that profoundly benefit patients. But change is not coming in great leaps and bounds, she says. Rather, it’s gradual and incremental.
A major initial driver of these changes, she says, was the development of polymerase chain reaction (PCR), which was followed by an explosion of other nucleic acid amplification techniques. “PCR was invented in 1983 and began to be adopted as a routine clinical microbiology diagnostic in the 1990s. Nucleic acid amplification techniques enabled diagnoses to be made that were difficult to make without them. Prior to the advent of PCR, for example, a brain biopsy was often required to diagnose herpes encephalitis. But since the 1990s, this diagnosis has been more easily made by per- forming a herpes simplex virus-specific PCR assay on spinal fluid.
“Nucleic acid amplification techniques have also played a key role in the successful management of some of the ‘newer’ infectious agents—including HIV and hepatitis C virus,” Patel says. “Today, there are standardized, commercially available nucleic acid amplification platforms for a wide range of infectious agents. And molecular diagnostics have become the standard in the field for the diagnosis of a number of infectious diseases.”
Over the years since their introduction into clinical practice, molecular diagnostics have progressively improved. Compared to conventional PCR, for example, real-time PCR now makes it possible to perform rapid testing while also providing a decreased risk of false-positive results.
Molecular diagnostics have replaced many historically standard, but slow, culture-based assays, improving patient care, Patel says. And molecular approaches perform as well as older tests, if not better. Using molecular technologies, viruses can be detected in a day—and in some cases, in about an hour—greatly reducing the several days or longer required to obtain results using cell cultures. In some cases, rapid results allow a treatment plan to be made without more testing or hospitalization, enabling healthcare providers to focus on therapy and management of the disease at home. And the new-generation tests can also prevent the unnecessary use of antibiotics, which is important in the current era of antimicrobial resistance, Patel says.
More recent changes in molecular diagnostics for infectious diseases include automation of technology and standardized methodologies. “Some assays today are easy to use, no longer requiring technologists with high degrees of expertise in molecular microbiology to run them,” she says.
There is also greater efficiency, because the technology’s producers are developing molecular diagnostic panels that simultaneously test for multiple organisms, Patel says. For instance, when dealing with diarrheal illnesses, traditional testing on stool samples targeted a single organism or a limited group of organisms, such as in the case of stool culture, where a few bacteria might be detected. Now, it’s possible to detect multiple organisms—including viruses, parasites, and bacteria—with a single test, using molecular panels that target multiple organisms simultaneously. Similar multiple-organism panel assays are performed for respiratory tract infections, Patel says.
In the Lab
“The field is changing because the technology is now easier and faster to use,” Patel says. “Performing a molecular diagnostic assay may no longer require specific molecular diagnostic training. For now, the testing is still being done in the laboratory. But in the future, it might move outside the laboratory to point-of-care locations or even, in the distant future, to patients performing their own tests,” she says.
Molecular technologies continue to improve, and can be applied to almost any infectious agent, including fungi, parasites, viruses, and bacteria. Molecular diagnostic assays can be used to detect microorganisms that are difficult to diagnose using other strategies. And they can also be used to detect microorganisms that can be otherwise detected—by culture, for example—but where the speed and sensitivity of a molecular assay makes it the preferred choice.
Contributing to the continuous change and progress in molecular diagnostics, the research and development group at Mayo Clinic has developed dozens of molecular diagnostic assays for use in clinical practice. Over time, some have been replaced by commercially available assays, but others, typically targeting unusual organisms, continue to be used since there are no commercial assays available for such organisms.
But what about the cost of this technology? “It’s a complicated issue,” Patel says. “If a laboratory wants to offer a molecular assay, it needs to consider the cost of the machine, reagents, quality control processes, and staffing, as well as test ordering and reporting processes.
“But the real question is whether there will be benefit to the patient,” Patel says. “We have to look at molecular diagnostics from the patient’s perspective. The tests are costly, but this must be considered alongside the potential value of improved patient outcomes.”
Patel is currently involved in a clinical trial looking at the value of sophisticated, rapid molecular diagnostics in patient care. “The bottom line is: Does it make a difference to the patient?” she says.
Another complicated issue facing laboratories using molecular technologies is reimbursement and the overall cost of healthcare. “Laboratories need to ensure that they’re performing the right test, for the right patient, at the right time,” Patel says. This can be seen as something of a personalized medicine issue.
Patel says she’s convinced that advances over the past 2 decades have made a huge difference in patient care, enabling healthcare providers to accomplish things they couldn’t before. “We’ve been on this journey at the Mayo Clinic for more than 2 decades. Today, we perform an enormous number of molecular microbiologic diagnostic assays on a routine clinical basis. Using molecular diagnostics, we’ve even been able to identify novel organisms and subsequently offer assays to detect them.
“For example, my colleague, Bobbi Pritt, MD, used a molecular assay that detects certain tick-borne pathogens to discover a new tick-borne illness in Wisconsin and Minnesota. We now routinely use this assay in our clinical practice,” Patel says. “And this is not the only novel organism we have discovered along the way.”
Gary Tufel is a contributing writer for CLP. For more information, contact CLP Chief Editor Steve Halasey via [email protected].
