MRSA: a crisis that touches you: how automated molecular dx will help relieve the time and cost crises facing hospital labs.

If time is money, as the saying goes, then hospital laboratories and the managers that oversee them are in crisis. They face ever-mounting pressure from clinical departments to deliver patient test results faster--and around the clock--in order to shorten time to treatment, improve clinical outcomes, and reduce skyrocketing hospitalization costs. (1)

At the same time, hospital administrators often view laboratories as a cost center ripe for budget slashing. In the face of a national laboratory-workforce shortage, (2) lab managers working with shrinking budgets are finding it difficult to attract and retain personnel trained to carry out the labor-intensive molecular diagnostic tests demanded by today's healthcare system. Adequately staffing a single shift is difficult; having such skilled lab professionals available on all three shifts is unheard of, even with the growing demand for on-demand, round-the-clock test results. Further, high reagent costs coupled with low reimbursement rates result, at best, in razor-thin margins on common tests.

These issues do not create simply headaches for lab managers--they represent a serious and growing systemic problem in healthcare, both nationally and globally. (3) Industry groups have proposed multipronged solutions for attracting young talent to the field, improving reimbursement, and, generally, enhancing the awareness of the laboratory-diagnostics field as essential and invaluable to healthcare. A necessary part of any long-term solution, however, will have to include the simplification and automation of molecular diagnostic testing.

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The evolution of automated molecular diagnostics

The demand for molecular diagnostic tests is growing rapidly, fueled especially by the increasing need for hospitals to track and control (4) the spread of infectious diseases, such as methicillin-resistant Staphylococcus aureus (MRSA), group B streptococcus (GBS), Clostridium difficile, and vancomycin-resistant enterococcus (VRE). The current gold-standard technique in molecular diagnostics is polymerase chain reaction (PCR) with real-time fluorescence-based detection. Although an exquisitely sensitive method for detection of nucleic acids in very low copy numbers, PCR is highly complex and labor intensive, and easily susceptible to cross-contamination as well as inhibition by sample impurities. For these reasons, molecular diagnostic tests generally are rated as "highly complex" by the standards of the Clinical Lab Improvement Amendments. They, therefore, must be performed by technicians with special training and certifications, typically staffed during the day shift at most hospital laboratories, leaving at least 16 hours per day during which these tests cannot be performed.

In recent years, a number of companies have developed small, automated bench-top analyzers with low-cost, disposable cartridges for performing, on demand, certain routine lab tests, such as hematocrit, blood lipid, creatinine and electrolyte levels, blood coagulation times, and others. But these technologies are not yet capable of performing PCR-equivalent molecular diagnostics. Now on the horizon is a new generation of automated laboratory analyzers that will meet the growing demand for moderately complex molecular diagnostic tests. They will be able to reduce the complexity of these tests to the point where they can be run by less experienced laboratorians. Although the first such technologies are being rolled out with a relatively high per-test price, these newer products will finally fulfill the need for simple molecular diagnostics at a cost that allows laboratories to realize a reasonable margin on their efforts.

The ideal automated molecular diagnostics system will offer results that are equivalent or superior in sensitivity to current PCR tests--but at a nominal price and with dramatically reduced need for handling and sample preparation compared to PCR techniques. A laboratory technician should simply be able to load a few microliters of minimally prepared sample (e.g., whole or heparinized blood, buffer-suspended swab, or culture samples, and so on) into an inexpensive, disposable test cartridge, insert the cartridge into the analyzer, push "start," and walk away with the expectation of seeing a clear result in about an hour.

Improved time to results has far-reaching implications

Such a drastic simplification of the molecular testing process will have far-reaching implications for laboratories and the patients, physicians, and hospitals they serve:

Streamline lab processes and reduce labor overhead.

The most immediate and obvious benefit of automated molecular diagnostics will be in relieving the labor squeeze felt by most labs today. While the typical moderately complex molecular diagnostic test is very labor intensive and requires skilled handling, automation at this level enables less experienced lab pros to produce the same results in far less time. The laboratory personnel structure can be reshaped to reflect a small number of specialized clinical laboratory scientists, focused on hands-on, highly complex tests, supported by a base of round-the-clock personnel running the automated molecular diagnostics.

Reduce hospital costs by quickly identifying infectious diseases. The time that elapses between when a patient presents with symptoms and when test results become available can be a significant factor in how treatment decisions are made and, ultimately, in clinical outcomes. A key example of the critical nature of time to results is in the diagnosis and treatment of hospital-acquired infections. Currently, confirmation of suspected MRSA in a patient presenting with fever of non-specific origin takes approximately four days and includes several successive steps: a 48-hour culture from drawn blood; an assay to detect Gram-positive cocci in clusters (GPCC); bacterial-strain identification testing; and finally, culturing to determine an antibiotic-resistance profile. In the meantime, hospitalization costs for the infected patient accumulate. A study of hospital-acquired infections done by the state of Pennsylvania and published in 2006 showed insurers paid an average of $53,915 for hospitalization of an infected patient compared to $8,311 for patients without infection. (1) Increasingly, payers are refusing to reimburse for the added cost of infections acquired during hospital stays, shifting that financial burden to the hospital.

While available, manually performed molecular diagnostic tests for MRSA and many other infectious diseases are prohibitively expensive to run on demand because the controls and other reagents are perishable and extremely costly. They, therefore, must be batched, which is not practical in a time-sensitive situation.

Automated molecular diagnostics are beginning to change this scenario, reducing the time to diagnosis, treatment, and cure, and, potentially, saving thousands of dollars in hospitalization costs. (5) In the MRSA example, an automated molecular diagnostic test could be used to determine the exact strain and antibiotic-resistance profile directly from the patient's GPCC-positive blood culture. The test could be designed such that time to results would be 40 to 60 minutes, with minimal handling by a laboratory technician, at very low cost, and run on demand during any shift, day or night.

Improve treatment decisions and patient outcomes with fast, on-demand test results. Another example of a particularly time-sensitive test that would benefit from automation is that for Streptococcus agalactiae or group B streptococcus. GBS is the leading cause of newborn sepsis and meningitis in the United States, with mortality rates of 5% or higher, (6) and can be transmitted from a colonized, asymptomatic mother to her infant during childbirth. Fortunately, antibiotic intervention immediately pre-partum can substantially reduce the risk to the newborn.

The current test for GBS involves a 48- to 72-hour culture, which makes it impractical for testing a woman in active labor whose GBS status is unknown or uncertain. The result is a high incidence of antibiotic over-prescription, at a time when the medical community is making every effort to reduce unnecessary antibiotic use in order to fight the rise of drug-resistant pathogens. A molecular diagnostic test could potentially improve the time to results; but if it is moderately complex and can only be performed by a day-shift, skilled laboratorian, the same problems apply. A low-cost, automated molecular diagnostic solution could be carried out by technicians at any time, day or night, with results available less than an hour after a woman presents at Labor and Delivery.

The time has come for automated molecular solutions

Although molecular diagnostic tests represent a vast improvement over culturing protocols for identifying infectious-disease organisms and other nucleic-acid-based targets, they can still be time consuming, labor intensive, and expensive, and contribute to the clinical laboratories staffing problems today. With the introduction of automated molecular diagnostic solutions, the time has finally come for lab managers, hospitals, healthcare professionals, and patients to benefit from the molecular discoveries of the past decade. The race against disease is really a race against time, and automation is providing a much-needed head start.

Ryan Ashton is the president and CEO of Great Basin Scientific in Salt Lake City, UT.

References

(1.) Report by the Pennsylvania Health Care Cost Containment Council. Hospital-Acquired Infections in Pennsylvania, 2008. http://www.phc4.org. Accessed January 5, 2009.

(2.) Washington G-2 Reports. Alarm Sounded Again Over Shrinking Supply of Lab Personnel. National Intelligence Report. 2008;29:4-6.

(3.) American Society for Clinical Pathology. Shortage. Critical Values Newsletter, 2008;1(4).

(4.) Berens MJ, Armstrong K. MRSA: Patients revolt against hospital secrecy. Seattle Times. November 18, 2008.

(5.) Cunningham R, Jenks P, Northwood J, et al. Effect on MRSA transmission of rapid PCR testing of patients admitted to critical care. J Hosp Infect. 2007; 65:24-28.

(6.) Bergeron MG, Ke D, Menard C, et al. Rapid detection of group B streptococci in pregnant women at delivery. N Engl J Med. 2000; 343: 175-179.

CONTINUING EDUCATION

To earn CEUs, see current test at www.mol-online.com under the CE Tests tab.

LEARNING OBJECTIVES

Upon completion of this article, the reader will be able to:

1. Describe the evolution of automated molecular diagnostics with regard to the spread of infectious diseases.

2. List three major reasons to improve time-to-results through molecular testing.

3. Recognize the importance of antibiotic stewardship and what it means to patient safety.

4. Describe how effective communication between labs and physicians affects antibiotic stewardship.

5. Discuss new technology and surveillance impacts on MRSA statistics in hospitals.