The impact of incorrect MRSA diagnoses

Introduction

The probability of acquiring an infection in a healthcare setting is relatively high, and the risk of death is not negligible. Data from the Centers for Disease Control and Prevention (CDC) and U.S. Department of Health and Human Services (HHS) indicate that more than one million healthcare-associated infections (HAIs) occur in the United States annually, causing approximately 90,000 deaths. According to a study published by the “Global Patient Safety Challenge: Clean Care Is Safer Care” more than 1.4 million people worldwide suffer from an HAI at any given time. In the U.S., dedicated professionals, tasked with reducing HAIs to the lowest possible levels, seek leading-edge tools to detect, control and prevent the spread of deadly pathogens.

Among these, S. aureus (SA) and Methicillin-resistant S. aureus (MRSA) are formidable and growing subsets of HAIs. They are opportunistic pathogens that are carried as commensal organisms on the skin and nares and that cause a broad spectrum of diseases resulting in substantial morbidity and mortality. The incidence rate for S. aureus in the general population is approximately 30%. Incidence rates for MRSA in the general population range from 2% to 6%, and many who are infected are asymptomatic. For inpatient populations, incidence rates of 5% to 10% have been observed, creating a significant public health issue;¹ in the U.S. approximately 20,000 deaths annually are directly attributable to resistant strains of S. aureus. These observations, coupled with the emergence of community-associated MRSA infections (CA-MRSA), have led many healthcare providers to establish active surveillance programs for patient admissions to hospitals, long-term, and complex care facilities.²

In addition to the serious clinical implications, S. aureus and MRSA create significant economic challenges for healthcare providers due to the impact they have on patient safety, quality of care, and overall healthcare costs.³ In the U.S. these incremental costs can range from $10,000 to $35,000 per event and typically are not reimbursed by third-party payers. These unsustainable costs have fuelled debate over the merits of MRSA screening and surveillance strategies and the possible benefit of such efforts to the institutional bottom-line.^4-6

Commercial molecular-based methods that determine the presence or absence of MRSA/SA DNA are playing an increasingly important clinical role.^4,7 Among the most popular are real-time polymerase chain reaction methods (RT-PCR) that are highly sensitive and offer rapid turn-around times compared to traditional culture methods. But it is important to understand the limitations of some of the current RT-PCR methods.

Misdiagnoses of MRSA and S. aureas

That misdiagnoses of MRSA and S. aureus may lead to improper management and delivery of patient care is well documented, as is the fact that misdiagnoses can result in serious primary and secondary complications, including death.^{8, 9} Accurate—or inaccurate—diagnoses of MRSA/SA are influenced by many factors; clinical presentation/symptomology, laboratory test methods (culture, molecular tests or agglutination tests), and the relative strengths and weaknesses of the tests employed. Real-Time PCR is generally faster and more accurate than traditional methods such as culture and is increasingly the tool of choice to help clinicians understand MRSA and S. aureus infections and to guide patient care. Sensitivity and specificity of RT-PCR methods are critical to overall assay performance. However, false negative and false positive rates are sometimes overlooked when evaluating competing RT-PCR methods. A clear performance issue with competing, commercially available technologies for MRSA is the unacceptably high number of MRSA false negative results—ranging from 6% to 30%—and false positive rates as high as 20%.^10-14

False negatives: a clear and present danger

A false negative MRSA diagnosis can have serious or fatal consequences. In the case of a false negative MRSA RT-PCR result, a patient may be diagnosed as infected with a non-resistant strain of S. aureus or none at all when in fact he or she may be infected with a methicillin-resistant strain of S. aureus. This may lead to inappropriate delivery of care in the following ways.¹⁴

• The MRSA infected patient may be allowed to remain in the general population and may infect other patients or staff.
• The patient may be administered antibiotics that have no effect and may not resolve the MRSA infection.
• Left untreated, the MRSA infection may progress, resulting in more serious disease.
• Depending on co-morbidities, the MRSA infection may cause more serious complications related to the patient’s primary condition, further complicating treatment and recovery.

MRSA infection may progress rapidly. Failing to correctly identify MRSA-infected patients in the early stages of disease progression may result in a more protracted and costly treatment and convalescence than if the infection had been properly diagnosed in its early stages.⁶ Accurate and early identification of true MRSA positive patient specimens has significant clinical and financial value to healthcare providers.^15,16 Depending on the size of the hospital, yearly admission rates, and incidence in the population, the potential incremental costs associated with MRSA false negative results can exceed hundreds of thousands of dollars per year per hospital.

False positives: lost time and lost resources

While generally less serious, false positive MRSA diagnoses still have undesirable consequences. In the case of a false positive MRSA RT-PCR result, a patient may be diagnosed as infected with methicillin-resistant S. aureus when he or she may in fact be infected with a non-resistant form of S. aureus, or have no infection at all. This can lead to inappropriate delivery of care in the following ways:¹⁷

• The patient may be placed in isolation to protect staff and the general patient population, leading to fewer “touches” with staff and lower patient satisfaction with the quality of care delivered.
• The patient may be administered more expensive and unnecessary antibiotics.
• Healthcare providers may recommend unnecessary decolonization protocols.

Antibiotic stewardship: effect of drug shortages on MRSA care

Drug shortages are a reality that is an often overlooked component of managing and delivering appropriate care. It has been estimated that on average 96% of all hospitals in the U.S. experience between two and four shortages of critical drugs and antibiotics per year.^18,19

Effective, appropriate, and timely utilization of antibiotic therapies for MRSA and S. aureus infected patients is critical to positive patient outcomes. A critical unmet need for guiding MRSA care is a diagnostic tool that accurately differentiates MRSA/SA from other pathogens and has a negligible rate of false negative/false positive results. A diagnostic tool with these features would enable healthcare providers to more effectively and appropriately manage valuable and sometimes limited therapeutic resources. The moniker “antibiotic stewardship” has become an important metric in evaluating products that help providers better manage and administer the sometimes limited availability of antimicrobials used to treat MRSA and S. aureus.¹⁹

Conclusion

MRSA and S. aureus are associated with increases in mortality, morbidity, and overall cost to deliver care. To guide patient care, clinicians desire accurate, rapid and cost-effective tools that enable them to effectively detect, control, and prevent MRSA/SA in the clinical setting while managing limited resources. RT-PCR is playing an increasingly important role in infection control strategies and the clinical management of HAIs, enabling healthcare providers to make better medical decisions, improve patient outcomes, and deliver a superior level of service and care.

David DeBonville is the Product Marketing Manager for ELITech Molecular Diagnostics, NA. He has more than 25 years of IVD experience, both as a scientist/product developer and marketing manager. He has written extensively on molecular diagnostics and its role in laboratory testing, clinical endpoint analysis and the advancement of personalized healthcare.

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