TOPIC REVIEW AND PERSPECTIVE
The setting of standards and the practice of evidence-based medicine has received much attention in the medical literature. However, in reality, evidence-based medicine is difficult to implement. We believe an example of reluctance to adopt standards can be found in medicine’s response to health care–associated infections. Intense debate has centered on the use of active surveillance testing. The 2003 Society for Healthcare Epidemiology of America guidelines concluded the following: “Active surveillance cultures are essential to identify the reservoir for spread of MRSA (Methicillin-resistant Staphylococcus aureus) and VRE (Vancomycin-resistant Enterococcus) infections and make control possible using the CDC’s long-recommended contact precautions.”1 However, since 2003, medicine has backed away from setting guidelines related to when and when not to use active surveillance testing (AST) and, in the process, has hindered the practice of evidence-based medicine.
Active detection and isolation for patients with hospital infections that can be dangerous to health-care workers (such as active Mycobacterium tuberculosis, smallpox, and severe acute respiratory distress syndrome) has been used for decades and is without question.2 Two types of interventions are important with active surveillance testing: The first is full contact precautions (i.e., hand hygiene, donning gloves and gowns, and preferably, the patient is placed in a private room3), and the second is decolonization. Contact isolation requires that the patient is placed in a private room with health-care workers donning gowns and gloves and performing hand hygiene before entering the room. Contact precautions and isolation are designed to prevent the spread of pathogens from person to person and also prevents spread of pathogens from indirect contact (i.e., from person to object to person).3 Methicillin-resistant Staphylococcus aureus can spread by both direct and indirect contact and can live longer than 51 days on widely used plastics.4 Spread to the environment can be quick with 35% of colonized patients having contaminated their environment within 33 hours after admission.5 Despite the publication of significant reductions of MRSA infections by at least 14 studies using active surveillance testing and isolation/decolonization protocols involving high-risk patients,6,7 patients admitted to the medical intensive care unit (ICU)/neonatal ICU,8–12 surgical wards/patients,9,13–17 or the entire hospital,18,19 active surveillance testing and isolation/decolonization have still not been widely adopted by hospitals. Two of the studies that implemented ICU active surveillance testing protocols even observed a facility-wide reduction of MRSA infections.10,11
The publication in prominent journals of 2 studies, the STAR*ICU Study20 and the MRSA-Swiss Study,21 seems to have had a disproportionate impact on health-care policy, which has stymied the widespread adoption of MRSA active surveillance testing in hospitals. The impact of these studies needs to be questioned because in both studies, the intervention group did not have optimal intervention. One of the most important factors in the success of an active surveillance testing program is the percentage of days that MRSA carriers in hospitals are isolated (e.g., 10 days isolated out of 10 total days in a hospital is optimal at 100% isolation). Peterson22 performed a literature review and estimated that for an active surveillance testing program to be successful, the percentage of MRSA isolation days should be as high as possible, with no actualized benefits (e.g., reduction of MRSA) of the active surveillance testing program if colonized patients are not isolated over 72% of the days they are in the hospital. Robicsek et al.,18 reported that MRSA patient isolation days during the baseline period was only 18% of that observed with universal polymerase chain reaction (PCR) surveillance. Robicsek et al.,18 (2008) also reported a 69.6% decrease in MRSA disease observed with universal active surveillance testing and observed that hospital-wide MRSA patient isolation days increased over five-fold using universal PCR surveillance.
In this area, the STAR*ICU study falls far short. There was a 5-day delay in obtaining the test results,23 resulting in the intervention group being assigned to contact precautions a median of 51% of ICU days.20 Once assigned, the staff’s compliance with protocol was poor, as “gloves were used for a median of 82% of contacts, gowns for 77% of contacts, and hand hygiene after 69% of contacts.”20 Because the purpose of active detection and isolation is also to prevent spread from patient to surface to patient, another limitation of this study must also be noted: 2993 (55%) of the 5434 subjects were excluded because their stay in the ICU was less than 3 days.20 These excluded patients may well have had a similar rate (10.6%) of MRSA colonization as the studied patients and served to further contaminate the facility’s environment. Thus, one could argue that combined with the poor staff compliance with gowning, that effective intervention was less than 40% of the time.
Despite its shortcomings, the STAR*ICU study has had a profound impact on health-care policy in the United States.
- The STAR*ICU Study has been used to support the position that there is not enough evidence to recommend active surveillance testing.24
- The AMA’s American Medical News ran a story on the STAR*ICU study entitled, “Doubt cast on effectiveness of universal MRSA screening,” which stated as a subtitle “Ten states require hospitals to screen all ICU patients for the antibiotic-resistant superbug. New research, however, shows that approach may not work.”23
- The Maine Hospital Association has used the STAR*ICU Study to support a successful repeal of Maine’s mandatory active surveillance testing law by entering into testimony, “Furthermore, the STAR*ICU study that Dr. Pinsky described is the latest and best research to date on the issue. My understanding of its conclusion is that screening (as proposed in LD 267) and contact precautions (also proposed in LD 267) were proven to be no more effective than standard precautions.”25
- The Centers for Disease Control has used the results of the STAR*ICU Study to support a statement on a CDC blog that reads, “The fact that these studies seem to give different answers illustrates the challenge we as scientists face in making recommendations on how best to use limited prevention resources-sometimes the answers aren’t as simple as we would like.”26
The lack of recommendations for the control of MRSA is a significant problem and a focus of a Government Accountability Office report that criticizes the CDC for not prioritizing the almost 1200 recommended practices, including the more than 500 strongly recommended practices, to reduce health care–associated infections.27
The control of MRSA in surgical wards/patients has been found to be effective using active surveillance testing by at least 6 authors.9,13–17 In surgical units, there is heightened concern of spread of MRSA to other patients but also for developing a MRSA postoperative infection in the carrier. Harbarth et al.21 observed that 7.8% of MRSA carriers admitted to surgical units developed an infection.
Two studies, which did not show an effect on surgical patients, were published by Harbarth et al.21,28 The 2008 study (MRSA-Swiss) was the most descriptive and, similar to the STAR*ICU study, may not have had effective intervention in the intervention group.29 The MRSA-Swiss study was published approximately 1 month before an important congressional hearing on health-care–associated infections30 and approximately 1 week before a study from Northwestern University in the Annals of Internal Medicine that showed benefit of active surveillance testing in the control of MRSA.18
In the MRSA-Swiss study, only 43% of patients who were known to be MRSA carriers before surgery received effective preoperative antibiotics against MRSA. In addition, 31% of MRSA carriers undergoing surgery were identified only after the surgery because of the emergent nature of the intervention and time delays. Carriers were also only isolated in “flagged side or single rooms whenever available” and “especially in abdominal surgery, surgeons were reluctant to add vancomycin to the standard prophylactic regimen.”21 The place of MRSA acquisition, in the operating room or on the ward, was not determined in the study. In contradistinction, all of the 26 patients who were identified as MRSA carriers on an outpatient basis underwent decolonization and had adequate MRSA prophylaxis. None of these patients developed an infection.21 Another interesting observation in support of active surveillance testing was that the 5.1% of patients who were colonized with MRSA developed 43% of the MRSA infections.
- The MRSA-Swiss study has also been widely quoted in the literature and has been used as a reason for not setting standards. An accompanying editorial to the MRSA-Swiss study stated the findings supported the CDC’s guidelines and control position statement against the routine or mandated use of MRSA active surveillance cultures.31
- Approximately a month after the publication of the MRSA-Swiss study21 and the Northwestern University Study,18 Rep. Henry Waxman referenced these articles32 and made the following statement during a congressional hearing on health care–associated infections: “Other infection control measures may be promising, but are less well understood. For instance, two articles recently appeared in the top medical journals about screening for the drug resistant bacteria known as MRSA. One concluded that MRSA screening did work. One concluded it did not.”30
- Six months later, these seemingly contradictory studies (MRSA-Swiss21 and the Northwestern University Study18) were used by the Society for Healthcare Epidemiology of America/HICPAC in a position paper as justification for the following statement: “Healthcare facilities may or may not choose to conduct AST; 2 recent studies offer conflicting findings as to whether AST for MRSA, followed by measures to prevent transmission by identified carriers, can significantly reduce MRSA disease burden.”33
- In a discussion regarding screening for MRSA on admission, Medscape34 republished a widely read article by Uckay et al.,35 which stated, “However, the results of several outstanding prospective trials in recent years are inconclusive. While some before–after studies report a benefit, other crossover design trials (Harbarth, 2008; Jeyaratnam 2008) fail to show a reduction in SSI rates (or at least in SSI rates due to MRSA).”
- The Evidence Based Review in Surgery Group published an analysis of preoperative MRSA surveillance testing (Henteleff et al.)36 using the MRSA-Swiss article21 as illustration of conflicting evidence, which prevented adopting a recommended practice.29
There have also been a number of studies, which have compared using cultures to PCR testing.37–40 Three of these studies showed a significant decrease in MRSA with PCR testing. In 1 study, Jeyaratnam et al.40 showed a slight nonsignificant decrease. The Jeyaratnam et al. (2008) study was not facility-wide and was limited to designated wards. In addition, the study was a crossover design and had a duration of 14 months; MRSA can live in the environment for a protracted period,4 leading one to wonder if MRSA residing in the facility environment of the control wards would cause indirect contact transmission and contaminate future patients in the experimental arm.
Research studies have sometimes been found to portray a perception that a nonsignificant result has some significance. Boutron et al.41 identified “spin” in over 40% of surveyed studies with primarily nonsignificant results. We feel that the MRSA-Swiss and STAR*ICU studies fall into another category of “spin,” that of having received undue emphasis as evidence that the studied intervention is not effective.
Northern Europe/Scandinavian nations that incorporate a successful “search and destroy” strategy have a percentage of Methicillin resistance found in Staphylococcus aureus cultures of less than 5%.42,43 In the United States, that number has passed the 50% mark and varies widely.43 Although MRSA has receded in some parts of the country, rates in the East South Central U.S. region are approaching 70% with no sight of decline.43
Some evidence indicates that MRSA may be starting to decline.44 However, there is also wide variation around our country.43 Instances where improvement is observed in some regions but not others are supportive for the setting of standards and the practicing of evidence-based medicine.
In setting standards of care, the question should not be whether someone has performed active surveillance testing with negative results, for almost any protocol if not properly executed will not work. The question that needs to be asked is, “Are there any other protocols with equal or greater effectiveness that do not include active surveillance testing?”
There is no question that surveillance for the control of MRSA is still under debate. To formulate an effective strategy, it is imperative that U.S. policy makers base policy decisions on the preponderance of evidence that support widespread surveillance and not just the findings of a few studies. The strength of existing evidence should guide the setting of standards for control of MRSA.
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