Molecules Against Microbes

We are witnessing a time of rapid change in the world of microbial testing. In recent years, molecular diagnostic tools have emerged from their previous niche use to become the gold standard for more and more conditions. Our need for the particular advantages molecular assays bring – which include fast results, and high sensitivity and specificity – is more pressing than ever, as we strive to overcome a range of diagnostic challenges. And most pressing of all is the growing crisis of antibiotic resistance.

Several developments are underway that will shape microbial testing for years to come. From determining targets to performing tests in the lab or at the patient’s bedside, the entire process of microbial assays is undergoing a shift that should dramatically enhance care and outcomes for patients.

Antimicrobial stewardship programs are working to identify resistance markers in microbes to guide drug selection for the best chance of success. Improvements in molecular testing for microbes will help doctors ensure that the right treatment gets to the right patient at the right time, and inappropriate treatments are never prescribed – which benefits both individual patients, and public health. If this can be achieved, it would be a major step towards addressing antibiotic resistance. But how close are we? Here, we take a look at some of the most important trends affecting microbial testing today.

Rapid testing

Molecular diagnostics offer a significant benefit to clinical labs and the physicians they serve: a much shorter turnaround time to generate results. Molecular assays can shave many hours or even whole days off of the timeline compared to more traditional diagnostic processes, such as culture-based tests. Typical process for culture is that the specimen is received and inoculated onto a variety of culture media based on the typical pathogens that would be expected for that specimen and infection type. Then the inoculated media are incubated and checked visually on daily intervals to see if there is any growth.

For a molecular test, the specimen is either directly placed into the test device and the results are available in minutes to hours, or the specimen may be processed to extract and purify any nucleic acids present first and then the extracted nucleic acid placed into the molecular test, with results available within a few hours.

Several recent studies show the clinical results of getting answers more quickly (1)(2)(3). In general, these analyses demonstrate that rapid tests allow patients to be treated more quickly with the right therapy, which in turn leads to shorter hospital stays and reduced readmission rates. They also provide evidence that this approach lowers overall healthcare costs for these patients and the institutions serving them.

Superior target selection

Some molecular tests are designed to detect a single microbe, but an increasing number can identify several species in a single assay. These panel-based tests allow clinical labs to look for some likely culprits in parallel, avoiding the time-consuming sequential testing of individual microbes as each diagnostic comes back with negative results. Physicians can now choose syndromic molecular tests to look broadly across several candidates multiplexed into a single test, which in many cases makes it more straightforward to diagnose the source of an infection.

For certain situations, however, pre-selected target panels may be too broad. For instance, during flu season, it would likely not make sense to start with more than flu and respiratory syncytial virus testing for an otherwise healthy patient presenting with respiratory symptoms. If an immunocompromised patient came into the hospital with the same symptoms, physicians might decide to use a much broader range of targets to cover all the bases.

A testing method known as masking allows clinical labs to implement either approach without changing assays. In this protocol, the lab runs the same multiplexed test for each sample, choosing which targets to report, and the masked targets report no results. If the first round of testing yields no useful answers, additional targets from the panel can be unmasked and viewed. In a new variation of this known as flexible testing, the lab only pays the manufacturer for the targets it chooses to be reported. Such approaches help labs keep costs in check while delivering as much or as little testing as requested by the ordering physician.

Sample to answer

As molecular testing becomes more mainstream, developers are improving automation to allow clinical lab teams to run tests with minimal hands-on time. These so-called “sample to answer” platforms essentially allow users to load the patient’s sample, choose the test, and walk away. The instruments handle everything else, from adding reagents at the right time to managing complex thermal cycling profiles. Results can often be monitored at a central command station, rather than instrument by instrument.

Although convenience is a major factor here – these machines allow technicians to run more tests at once – another important element is the reduced risk of error. Every manual intervention carries a small opportunity for mistakes; eliminating such opportunities increases the accuracy of results. In the coming years, lab teams can expect that even more elements of microbial testing will become automated for a truly streamlined workflow.

Centralization and decentralization

The trends on where testing is performed are also shifting. Many types of tests that were traditionally performed in a central or reference lab, such as Clostridium difficile, MRSA, and flu, are moving toward the point of care, perhaps in a small regional lab, or even close to the bedside. At the same time, new high-complexity testing, such as sequencing-based testing of oncology markers, is shifting to modern centralized labs that have the capacity and sophistication to manage them. Where any individual test occurs can depend on the size of the healthcare system, geography, patient demographics, test type, and more. Medical professionals have more flexibility than ever to decide whether they need a very simple test that can be performed near the patient, or a more complicated diagnostic that is handled by a central lab facility. This allows lab teams to respond more nimbly to shifting needs for speed versus complexity.

At the point of impact

Following the decentralization trend, point-of-care testing has enabled a number of advantages for treating patients, such as responding more quickly to hospital-associated infections. Getting rapid results from onsite labs has also been essential for understanding antimicrobial resistance profiles, allowing hospital staff to choose more targeted treatments, and quickly quarantine patients when necessary.

The same information feeds into antimicrobial stewardship programs, making a real difference in how patients are treated for MRSA, C. diff, norovirus, and many other infectious diseases. Antibiotic resistance has become a major public health threat, with some experts estimating that 700,000 people die each year from drug-resistant infections (4).

In light of this trend, it is no longer enough to identify the microbial source of an infection –already a tall order in some cases. Now, labs must also quickly detect markers of resistance to support therapy selection for optimal outcomes and reduce the misuse of antibiotics (5)(6)(7)(8)(9).

Looking Ahead

Though we cannot anticipate every change that will affect microbial testing in the next few years, we can safely predict that most advances will be developed to support recognized needs in clinical labs today: streamlined workflows and information systems, cost-effective and accurate tests, rapid generation of results, and ultimately, better outcomes.

In the near future, many of the developments explored above will continue to gain traction. Increasing flexibility for clinical lab teams – whether in assay design, platform capacity, cost options, or other areas – will serve as a driving force for innovation. Particularly for microbial testing, where demand changes dramatically by geographic region, season, and more, labs need as much versatility as possible to meet the needs of their patient populations.

Advances in microbial testing have already had a noticeable positive influence on patient care and outcomes. As newer, more flexible technologies are developed, molecular methods hold tremendous potential to improve human health.

Sherry Dunbar has a background in clinical and public health microbiology and is Senior Director of Global Scientific Affairs for Luminex Corporation.

Gunjot Rana is the Product Manager for Gastrointestinal and Hospital Acquired Infections at Luminex Corporation.