Molecular Diagnostics: MDx Applications, Development Continue

Increase in antibiotic-resistant infections underscores the need for greater adoption of molecular diagnostics

By Michael McGarrity

In September, the U.S. Centers for Disease Control and Prevention (CDC) issued a first-ever report on the threat of antibiotic resistance. The statistics were alarming. Two million people contract antibiotic-resistant infections every year, resulting in 23,000 deaths.1 Up to 50 percent of antibiotics prescribed to patients are unnecessary or prescribed inappropriately.1 The total economic cost to manage these illnesses is estimated to be as high as $20 billion in direct healthcare costs.1 And as reported by a high-ranking CDC official on the recent PBS Frontline feature, "Hunting the Nightmare Bacteria," the number of antibiotics with activity against these antibiotic-resistant bacteria is swiftly declining, necessitating careful preservation of available and still effective last line antibiotics.

Among the four core actions identified to combat this antibiotic resistance epidemic, the CDC highlighted improved antibiotic stewardship, or optimization of available therapies, and greater adoption of diagnostic tests to better track illness and resistance. The molecular diagnostics industry, with its highly accurate detection capabilities, is uniquely able to address this call to action and further advance antibiotic stewardship.

Current State of the Industry

Early and accurate diagnosis of antibiotic-resistant bacteria like methicillin-resistant Staphylococcus aureus (MRSA) and carbapenem-resistant Enterobacteriaceae (CRE) - some of the most common and deadly healthcare-acquired infections - is crucial to effectively treating these diseases. However, the high mortality associated with these infections is due, in large part, to a fundamental limitation of available diagnostics: Physicians often do not know what kind of infection they are treating until two to three days after their initial assessment.

Use of molecular diagnostic testing in clinical laboratories is growing and is anticipated to expand considerably as hospitals increasingly require methods that enable faster diagnosis and treatment of patients. According to a 2011 report by Piper Jaffray, a majority of hospital infection control personnel surveyed for the report said the ability to identify and report particularly virulent strains of infections were important and most anticipated MRSA testing to increase in the future.2

In an effort to close this gap, laboratories have employed a number of novel methods to provide clinicians with additional information in a timely manner. Direct biochemical methods like the tube coagulase test can differentiate S. aureus from likely contaminants the same day a blood culture bottle goes positive. Similarly, fluorescent in situ hybridization (FISH) methods can identify S. aureus and several other organisms directly from positive blood culture bottles. However, neither of these methods can determine whether these organisms are resistant to common antibiotics.

To address this disparity, laboratories have utilized real-time polymerase chain reaction (PCR) methods to amplify gene segments associated with particular antibiotic-resistant bacteria, such as MRSA, directly from positive blood culture bottles. However, this method is vulnerable to sample impurities and cross contamination. Other assays rely on overnight growth from plated cultures to identify genes associated with antibiotic resistance. Yet, by the time these methods yield results, the patient has likely spent up to 72 hours on empirically prescribed broad-based, and potentially inappropriate, antibiotics that treat a majority of the possible causes of infection.

With understaffing and tight budgets, clinical laboratories are in need of a simplified sample-to-result technology that will streamline the laboratory process while also providing rapid, accurate and comprehensive results.

The MDX Opportunity

In recent years, the need for faster identification of illness to combat antibiotic resistance has been acknowledged by the medical community. In 2011, the Infectious Diseases Society of America (IDSA) issued a statement recognizing that molecular diagnostic tests can "greatly improve antimicrobial stewardship . reducing the spread and impact of antibiotic resistance."3

Highly targeted and specific molecular diagnostic tests can rapidly and accurately produce bacterial identification and antibiotic resistance results to help ensure the sickest patients in our hospitals receive appropriate therapy as quickly as possible.

This information allows physicians to quickly make accurate diagnoses and build appropriate treatment plans, leading to more effective antimicrobial stewardship, thereby optimizing antibiotic therapy and reducing the spread of antibiotic resistance.

MDx Key to Antibiotic Stewardship

Numerous studies have shown the link between rapid and accurate pathogen identification with resistance detection and earlier optimization of antibiotic therapy.

A recent study published in the Journal of Clinical Microbiology showed that following implementation of a rapid molecular diagnostic test for the detection of bloodstream infections caused by Enterococcus bacteria, there was a significant decrease in the average time it took for patients to receive appropriate treatment (23.4 hours) and an even greater reduction in time (31.1 hours) for patients with vancomycin-resistant Enterococcus (VRE) bacteremia - an especially deadly cause of bloodstream infection and sepsis.

Another study evaluating the same molecular diagnostic test showed that 11 out of 15 patients initially started on vancomycin were discontinued based on bacterial identification from the test.4 The study also showed the potential for saving the use of other antibiotics - including Piptazo, Penicillin, Clindamycin and Fluconazole - through molecular testing.4

The data also shows that clinicians are acting on these molecular diagnostic results. A further recent study showed by using the same rapid molecular test, there was a 145 percent increase in physician compliance for more efficacious treatment of methicillin-susceptible Staphylococcus aureus (MSSA).5

Reduction of Healthcare Costs

Molecular diagnostics are poised to play an important role in helping hospitals combat antibiotic resistance and fight deadly infectious diseases through rapid and accurate identification. They offer an opportunity for hospitals to reduce costs while improving patient care. A recent study in the Journal of Clinical Microbiology illustrated cost savings of more than $60,000 and reduced hospital stays of up to 20 days using rapid molecular diagnostic testing.6 Additionally, the study found a reduction in the use of inappropriate antibiotic treatment, which could result in savings of $500-$1,000 per patient.6 These findings are consistent with previous studies on molecular diagnostics and health economics.

The Future of MDx

Bloodstream infection and hospital-acquired infection testing that provides faster results while advancing antimicrobial stewardship is only the tip of the iceberg. Multiplexed molecular diagnostics can be used to help diagnose other major health concerns like respiratory infections, including H1N1 flu virus, cancer, cardiovascular disease and autoimmune disease. However, as an industry we must remain vigilantly focused on providing such diagnostics that enable the optimal clinical benefit at the lowest cost.

Like other technologies, molecular diagnostics will continue to advance as test designers work together with the healthcare industry to identify the needs of the community. Molecular diagnostics are already enabling a faster and more targeted patient care spectrum. As the use of these technologies spreads, and the technology itself evolves, everyone involved will benefit from improved patient care, lower costs and enhanced antimicrobial stewardship.

Michael McGarrity is president and CEO of Nanosphere.


1. Centers for Disease Control and Prevention, U.S. Department of Health and Human Services. Antibiotic Resistance Threats in the United States, 2013. Accessed 2013 November 1.

2. Piper Jaffray. HAI Survey Reinforces Expectations For Robust Market Growth. October 19, 2011.

3. Infection Disease Society of America. An Unmet Medical Need: Rapid Molecular Diagnostics Tests for Respiratory Tract Infections. Clin Infect Dis. (2011) 52 (suppl 4): S384-S395. doi: 10.1093/cid/cir055.

4. Appelgate, DA et al. Evaluation of the Nanosphere Verigene System result times compared to traditional culture. Poster presented at: 16th Annual MAD-ID Meeting; 2013 May 9 - 11; Orlando, FL.

5. Koeneman, BA et al. Rapid identification of methicillin-sensitive Staphylococcus aureus from positive blood cultures using the Verigene System: A system-wide impact on patient treatment and physician compliance. Poster presented at: 113th General Meeting of the American Society for Microbiology; 2013 May 18 - 21; Denver, CO.

6. Sango, A et al. A stewardship approach to optimize antimicrobial therapy through use of a rapid microarray assay on blood cultures positive with Enterococcus species. Published ahead of print 2013 September 25, J. Clin. Microbiol. doi:10.1128/JCM.01951-13.

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