A significant source of community-acquired infections, methicillin-resistant Staphylococcus aureas (MRSA) is associated with 18,000 deaths each year in the United States (US).1 MRSA infections are increasing, and consequently, so are mortality and morbidity rates, treatment costs, and hospital lengths of stay.
The Ohio State University Medical Center (OSUMC) in Columbus, Ohio, is a large, diverse academic center comprising six hospitals, more than a dozen research centers and institutes, and 20 core laboratories. About 10 years ago, the prevalence of MRSA at OSUMC began to increase steadily. From 1997 through 2007, positive MRSA tests grew from approximately 43% of those tested to more than 70%, consistent with rates at other academic medical centers in the US. In 2008, the Centers for Medicare and Medicaid Services (CMS) reduced reimbursement for certain preventable hospital-acquired infections. That year, OSUMC initiated a formalized antimicrobial stewardship program dedicated to identifying the optimal selection, dose, and duration of antimicrobials that result in the best clinical outcome, with minimal toxicity and with a low likelihood of contributing to resistance. This program comprises a multidisciplinary team of physicians, pharmacists, microbiologists, infection control preventionists, and epidemiologists, all dedicated to the appropriate, optimal use of antimicrobial agents. The containment and management of MRSA, specifically, is of highest priority for this team.
The increase in positive MRSA tests and the lower levels of CMS reimbursement prompted the OSUMC antimicrobial stewardship program members to search for a simple, accurate, rapid test for early detection of MRSA; in 2009, the Xpert MRSA/SA blood culture test (Cepheid) was identified as a possibility. The facility’s clinical microbiologist presented data and literature on its accuracy and speed, recommending its use be adopted hospital-wide. After performing an in-house validation of the data, the Xpert rapid polymerase chain reaction (PCR) test was approved and implemented into the antimicrobial stewardship program.
PCR Assay Improves MRSA Detection
At OSUMC, the implementation of the rapid PCR assay for the detection of S. aureus bacteremia and the differentiation between methicillin-resistant and methicillin-susceptible strains shortened the time it took to begin optimal antimicrobial therapy after a blood culture with methicillin-susceptible S. aureus bacteremia was discovered. In patients with suspected MRSA, blood samples are taken and treatment with vancomycin is initiated while awaiting the results. Before the rapid PCR test was used, the majority of patients infected with methicillin-susceptible strains continued to receive vancomycin when it was not required. Information provided by the rapid assay allowed early differentiation between susceptible and resistant strains, allowing for an earlier switch from vancomycin to more appropriate therapy, including nafcillin or cefazolin.
The benefits realized as a result of implementing use of the rapid PCR assay were substantial for OSUMC. Outcomes were compared from a period before use of the PCR assay (September through December of 2008) to a period when the new assay was in use (March through June of 2009). The average time to optimum therapy for patients with MRSA decreased from 3.6 days to 2 days, overall hospital length of stay decreased by more than six days, and costs per patient after the implementation of the rapid PCR assay averaged $7000 less than before (see Figure 1).2
Pharmacy’s Role in Optimal MRSA Management
After OSUMC began using the improved PCR assay for S. aureus detection, it became clear that a pharmacy intermediary was needed to review data and coordinate treatment goals with physicians. As the specialty practice pharmacist for infectious diseases, I was especially suited to this responsibility. My goals as intermediary are to ensure the application of appropriate treatment as early as possible, which includes not only consulting with the physician to choose the most efficacious antibiotic, but also helping ensure the necessary ancillary treatment is performed. For example, patients with S. aureus may need to be scanned using spine MRI or CT to evaluate whether the pathogen has traveled, and an echocardiogram may be necessary to ensure it has not invaded the heart valves. As intermediary, I work with the other antimicrobial treatment program team members and the treating physicians to ensure these important safety steps occur.
The implementation of the rapid PCR test and the development of the intermediary position also prompted an increased emphasis on education at OSUMC, where our robust program focuses on small group learning and daily rounds. After a number of small group discussions had taken place and staff became comfortable using the new assay, the number of pharmacy interventions decreased. Education is ongoing to reinforce the need for pharmacy to be involved in processes and track and report data on proper use to administrators, staff, and physicians.
Antibiotic Dose Volume and Duration
Technology to manage antibiotic dosing requirements, including vancomycin, has improved and streamlined our dosing process. OSUMC uses an interactive antimicrobial stewardship Web site to educate pharmacy staff on antibiotic dose volume. Simply entering the dose, the levels, and any adjustments to regimens as appropriate ensures the correct drug and dose are ordered. Establishing the duration of therapy, however, can be variable and is somewhat difficult to quantify. The use of hospital MRSA and vancomycin guidelines are useful as a general guide, but because each patient reacts somewhat differently to treatment, quantifying optimum duration of therapy is complex and varies by patient.
One challenge encountered regularly is how to dose vancomycin in morbidly obese patients. The maximum dose described in the guidelines is two grams, and though experience has taught that the majority of these patients will require more, there are currently no definitive calculations to guide practitioners. Treating infection with alternatives to vancomycin, such as daptomycin and linezolid is also a complex task with obese patients. If ancillary testing must be performed—such as scanning or obtaining echocardiograms—size constraints imposed by the physical limits of the technology are oftentimes an issue; scanners have been designed to accommodate average-weight patients. An additional concern is that many obese patients are diabetic, and therefore have a higher risk of harm from MRSA infections than average-weight patients. Currently, an individualized, case-by-case process is used to create treatment plans for obese patients, but the development of dosing guidelines for this population and alternative scanning methods would be highly beneficial improvements.
Track Data and Report Outcomes
As with any successful health care management program, data and outcomes must be tracked regularly and reported to administration. Rates of S. aureus, MRSA, antimicrobial use, readmission rates, and clinical outcomes—such as length of stay, infection-related length of stay, and mortality—should be closely monitored. OSUMC employs a dedicated data manager and a facility-specific information warehouse containing patient data to evaluate outcomes. The ability to query data and generate reports allows antimicrobial stewardship program team members to communicate outcomes regularly and quickly. The ultimate goal of closely tracking data is to ensure patients have positive outcomes, but from an antimicrobial stewardship perspective, verifying that OSUMC is using antibiotics appropriately also is vital. Pharmacy manages processes, leads reduction efforts, tracks data, and reports outcomes daily; information on proper use is always reported back to administrators, fellow pharmacy staff, and physician colleagues.
Manage MRSA in the ER
It is common to receive MRSA-infected patients—usually involving the skin and soft tissue—in the ER for treatment. To accommodate and appropriately treat these patients, OSUMC uses an ER-specific antibiogram to track Staphylococcus rates, including MRSA. After the specific infection has been classified, the most appropriate drug for treatment is identified and tracked on the antibiogram.
Treating MRSA in the ER is challenging, as judgment calls are often required. For instance, if the patient has a MRSA abscess, should it be drained? When does an abscess require antibiotics? If antibiotics are required, an IV to PO switch must be incorporated into the care plan. Depending on the infection, the goal is to switch to PO therapy as soon as possible. However, for a patient who is bacteremic, IV therapy is the preferred treatment for the duration. Other patients—⎯especially patients with MRSA pneumonia, MRSA abscess, and cellulitis⎯—can be safely switched to PO, as long as they are given highly available antibiotics.
It is particularly prudent to employ an antibiogram specific to the ER. Capturing information on ER patients and deciding which antibiotics are best to treat them is vital to improving MRSA management. Accordingly, ER-specific antibiograms are quite useful, and help educate ER physicians in identifying pathogen prevalence and determining which antibiotics are effective.
As MRSA infection rates increase, pharmacy leaders likewise must increase efforts aimed at developing policies to identify, prevent, and treat this pathogen. Implementing rapid PCR assay technology can significantly decrease time to diagnosis, hospital lengths of stay, and costs related to treatment. At OSUMC, the combination of employing the rapid assay with improved vigilance, data tracking, and education has enhanced antimicrobial stewardship efforts, as well as patient safety.
Karri Bauer, PharmD, BCPS, is specialty practice pharmacist—infectious diseases at The Ohio State University Medical Center in Columbus, where she manages the antimicrobial stewardship program. Her professional interests include Staphylococcus aureus infections, multidrug-resistant Gram negative infections, and pharmacodynamics.
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