A Novel Approach to Methicillin-resistant Staphylococcus Aureus (MRSA) Screening of Colonized Patients

Study Overview
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Brief Summary
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Methicillin-resistant Staphylococcus aureus (MRSA) is endemic in hospital settings. Colonization with MRSA puts patients at increased risk for invasive infections, and MRSA infections have been associated with high costs and adverse clinic outcomes. Patients can clear MRSA spontaneously. Improved approaches for identifying patients who are no longer colonized are needed; we hypothesize that more sensitive nucleic acid amplification can be used to improve identification of patients who are no longer colonized.

Detailed Description
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Compared with patients with methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia, patients with MRSA bacteremia remained in the hospital for two more days on average and had a median attributable increment in hospital charges of approximately $7000. MRSA status is a determinant of bed allocation, especially in shared-room settings, which represent the most common organization in the US and globally. Based on guidelines from the Centers for Disease Control and Prevention, once patients are designated as having had a positive MRSA culture (either colonized or from a clinical isolate), they require Contact Precautions. This requirement translates into either cohorting with other patients with similar precautions status (i.e., two patients with MRSA share a room) or placement in a private room in the hospital. Cohorting is not the preferred infection control method, but in shared-room settings, it is the most common scenario, particularly in hospitals with high occupancy. Individuals can clear MRSA colonization spontaneously. In fact, up to 38% of patients with MRSA-positive cultures taken greater than 3 months prior were found to be MRSA-negative during a re-screening program conducted by the Massachusetts General Hospital Infection Control Unit from 2004-2006. Other studies have demonstrated that a majority of patients are likely to clear colonization at various time points from original documentation of MRSA infection or colonization. There is currently no standardized approach or accepted guidelines for addressing screening for clearance of colonization in the growing pool of patients who have previous MRSA colonization/infection. Many organizations do provide guidelines for screening, but these guidelines are not based on rigorous study, have a variety of permutations, and have neither consensus acceptance nor adequate implementation among the medical community. The status quo limits bed availability and delays patient discharge to rehabilitation facilities, adversely affecting quality and efficiency, and resulting in use of additional hospital resources. In addition to problems associated with patient flow for admissions and discharges, precaution status results in additional disruptions of patient care through bed moves to accommodate the use of shared rooms by like patients needing Contact Precautions. A patient's precaution status affects his/her care from admission through discharge. During pre-admission, patients identified as previously having MRSA are affected by bed shortages and delays to admission while in emergency departments. While admitted, under current practices, patients who have in fact cleared MRSA may be cohorted with those who have active infection or persistent colonization, putting them at risk of recolonization and hospital acquired infection (HAI). Finally, patients who are on precautions for MRSA often have delayed discharge to rehabilitation or nursing facilities because of bed constraints similar to those experienced by acute care facilities. We hypothesize that the use of more sensitive Polymerase Chain Reaction (PCR) methods detecting MRSA in nasal swabs can facilitate identification of true negative patients and can reliably do so with a single negative test in a shorter period of time, thereby greatly facilitating the ability to complete testing on a larger proportion of patients.

Official Title
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A Novel Approach to MRSA Screening of Colonized Patients and Impact on Hospital Resource Allocation and Patient Care

Conditions
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MRSA Colonization

Intervention / Treatment
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* Device: nucleic acid amplification of nasal swab; nasal swab culture
* Other: Nasal swab culture


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: age > 18 last positive MRSA culture greater than 3 months old admitted to hospital Exclusion Criteria: age < 18 last positive MRSA culture less than or equal to 3 months old

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Active Screening<br>Patients randomized to active screening will have two nasal swabs collected daily for 3 days, for both nucleic acid amplification and culture (CHROMagar)assays. | Device: nucleic acid amplification of nasal swab; nasal swab culture<br>* Nasal swab is performed and analyzed using nucleic acid amplification to determine the presence or absence of MRSA DNA. One nasal swab is performed each day for three consecutive days during hospitalization.<br>* Other names: BD CHROMagar;|
| Other: Passive Screening<br>Patients randomized to passive screening will not actively be identified for testing but may be tested using culture-based algorithm by care team. | Other: Nasal swab culture<br>* Nasal swabs are obtained if the clinician caring for the patient identifies the patient as eligible to be screened for colonization. An algorithm for screening eligible patients is available electronically as part of the patient's standard medical record to the clinicians providing care.<br>* Other names: BD CHROMagar;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects With Single Negative Polymerase Chain Reaction (PCR) Result and 3 Negative Culture Assays | This outcome is the negative predictive value of a single PCR assay for subjects with a history of prior MRSA infection or colonization. | 1 year | 
| Completion of Screening Protocol in Both Trial Arms | Rate at which subjects in both trial arms complete the 3-swab protocol. | 1 year | 
| Discontinuation of Contact Precautions in Both Trial Arms | Patients known to have MRSA require Contact Precautions based on current recommendations from the Center for Disease Control and Prevention (CDC). Contact Precautions mean that hospitalized patients with a history of MRSA infection or colonization are isolated in a private room or together with patients who have the same Contact Precautions status (i.e. both with MRSA). Healthcare workers caring for such patients must wear protective gowns and gloves during interactions and use of equipment dedicated to that patient is recommended. For this study, Contact Precautions are discontinued refers to the practice of discontinuation of Contact Precautions once subjects meet criteria based on institutional infection control policy: history of MRSA but no positive culture in preceding 90 days and three negative nasal surveillance cultures obtained at least 24 hours apart in the absence of concurrent antibiotic use. | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects With a Single Positive PCR Result and at Least 1 Positive Culture Assay | This outcome is the positive predictive value of a single PCR assay for subjects with a history of prior MRSA infection or colonization who completed the 3 swab protocol. | 1 year | 
| Sensitivity of First PCR Assay | Sensitivity of the first PCR assay for subjects enrolled in active arm of trial. | 1 year | 
| Specificity of First PCR Assay. | Specificity of the first PCR assay for subjects enrolled in active arm of trial. | 1 year | 
| Rate of Recolonization or Documented Infection With MRSA | Prospective review of microbiological data for patients enrolled in the trial to determine rate of recolonization or documented infection. Subjects in the Intervention Arm of the study who had documented clearance of colonization and met criteria for discontinuation of contract precautions, and had CP discontinued by staff (N=69) were included. Subjects who had a visit at MGH through 12/31/2012 during which a microbiology sample was obtained and MRSA was recovered (clinical or surveillance) were included. | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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MRSA, colonization, nucleic acid amplification, chromogenic agar