Border patrol: MRSA
  admission screening

October 2005
Cover Story

William Check, PhD

“Guilty until proven innocent.” In the legal system, it’s an unacceptable principle. But when European countries were faced with increasing rates of methicillin-resistant Staphylococcus aureus, or MRSA, infections in their hospitals, some of them set up infection control programs based on this premise. Nasal swabs were taken at admission, then patients were put into isolation until a negative result came back. Having only conventional culture methods, with a two- to three-day turnaround time, this approach made sense.

And it worked. After many years of sticking to this program, “the Dutch, the Danes, and the Swedes have eliminated MRSA from their hospital population,” says Lance R. Peterson, MD, epidemiologist in the Division of Microbiology at Evanston (Ill.) Northwestern Healthcare and professor of pathology and medicine at Northwestern University School of Medicine, Chicago. Other Northern European countries, as well as Canada and Australia, have also greatly reduced rates of nosocomial MRSA infections with rigorous screening (though most have not used preemptive isolation).

Dr. Peterson calls preemptive isolation “too cumbersome” for the U.S. health care system. Nor is it any longer necessary, since a real-time PCR assay for MRSA from Geneohm/IDI, which works directly from nasal swabs and has a turnaround time of a few hours, was approved in the U.S. in late 2004. Molecular testing “gives us a really good opportunity to turn the [European] model upside down,” Dr. Peterson says. He is leading Evanston Northwestern Healthcare’s introduction of MRSA screening at admission for all patients. Identifying carriers with real-time PCR will make it possible to assign them to isolation within a few hours. So far this may be the only hospitalwide MRSA screening program in the U.S., but there is “certainly a lot of interest” in global screening among other hospital epidemiologists, Dr. Peterson has found. Probably the major obstacle remaining is financial, which, he says, can be overcome by showing hospital administrators that screening pays for itself by reducing unrecoverable costs associated with nosocomial MRSA infections.

Leonard Mermel, DO, ScM, medical director of the Department of Infection Control at Rhode Island Hospital and professor of medicine at Brown Medical School in Providence, oversees a program in which all high-risk admissions are screened. “Looking forward,” he says, “the million-dollar question—with the ongoing epidemic of community-acquired MRSA in low-risk groups, might it come to the point of screening everyone coming into the hospital? We in the infection control community need to start thinking and talking about that.” Already there is evidence that community-acquired MRSA is spreading in some hospitals. “If we want to keep community isolates out of our hospitals,” Dr. Mermel says, “screening known risk groups is not a strategy that is particularly designed for that task.”

Tobi B. Karchmer, MD, MS, medical director of the Department of Epidemiology and Infection Control and assistant professor of medicine at Wake Forest University School of Medicine, agrees. “I think it is important that we continue to aggressively control nosocomial MRSA infections and try to limit community MRSA spread in the hospital,” she says. Community-acquired MRSA, she adds, “represents a potentially more virulent infection, which would be disastrous for already compromised hospitalized patients.”

Screening and isolation to control antibiotic-resistant S. aureus is not without precedent. Franklin Cockerill III, MD, has reviewed the history of bacteriology at the Mayo Clinic for the 100th anniversary of the clinic’s Department of Laboratory Medicine and Pathology. He found that, in the late 1950s, 17,000 nasal swabs were taken in an effort to detect and isolate patients with penicillin-resistant S. aureus. “Then the new semi-synthetic penicillins made that unnecessary,” says Dr. Cockerill, who is professor and chair of microbiology and director of bacteriology.

Nor is recognition of the danger of MRSA new. As early as 1991 a group at the University of Iowa School of Medicine recommended “identification of the entire [MRSA-positive] patient reservoir (cases and carriers) for purposes of isolation” (Wenzel RP, et al. Am J Med. 1991;91:221S– 227S). But few, if any, hospitals followed this recommendation. A notable exception was Barry Farr, MD, of the University of Virginia Health Sciences Center, Charlottesville, who set up a program using active surveillance cultures (Jernigan JA, et al. Infect Control Hosp Epidemiol. 1995;16: 686–696).

Current concern about MRSA stems from its rising incidence, as well as accumulating evidence that it causes increased morbidity and mortality relative to infections with methicillin-susceptible S. aureus, or MSSA. A study at Brooke Army Medical Center showed that patients colonized with MRSA in their nares had a 13-fold increased risk of developing a MRSA infection relative to patients colonized with MSSA (Davis KA, et al. Clin Infect Dis. 2004;39:776–782). Equally important, colonization with MRSA was found on a general medical/ surgical ward (two percent incidence) in addition to ICUs (three percent to seven percent). “Identifying MRSA colonization at admission could target a high-risk population that may benefit from interventions to decrease the risk for subsequent MRSA infection,” these investigators concluded.

Another group found that 29 percent of hospitalized patients colonized with MRSA developed a MRSA infection over the ensuing 18 months (Huang SS, Platt R. Clin Infect Dis. 2003;36:281–285). MRSA bacteremia was also found to be associated with significantly higher mortality than MSSA bacteremia (Cosgrove S, et al. Clin Infect Dis. 2003;36:53–59). And Belgian clinicians found that attributable mortality due to MRSA infection was 23.4 percent, compared with 1.3 percent for MSSA infection (Blot SI, et al. Arch Intern Med. 2002;162:2229– 2235).

In 2003, alarmed by a lack of progress in the U.S. against antibiotic-resistant infections generally and MRSA specifically (as well as vancomycin-resistant enterococcus, or VRE, often a fellow-traveler with MRSA), the Society for Healthcare Epidemiology of America published an evidence-based guideline on preventing nosocomial transmission of these two path o gens (Muto CA, et al. Infect Control Hosp Epidemiol. 2003; 24: 362– 386). Their first recommendation was “active surveillance at the time of admission for patients at high risk for carriage of MRSA, VRE, or both.” Carriers should be isolated with contact precautions, they wrote.

To buttress the soundness of their recommendations, the society’s task force referred extensively to the success with active screening and isolation programs in Europe and Canada. Dr. Cockerill, who was not a member of the task force, agrees that “the literature from Australia, Europe, and Canada looks very convincing.”

Allison McGeer, MD, director of infection control and microbiologist at Mt. Sinai Hospital in Toronto, is responsible for one such program. She notes the irony of being cited as a model for the United States. “The typical attitude in Canada is that Americans are ahead of us,” Dr. McGeer says. About her MRSA screening program, people ask, Why are we doing this when the Americans are not?

In a reverse way, she says, the American experience was helpful. “MRSA appeared as a problem both in Europe and the U.S. before we had it,” according to Dr. McGeer. In most U.S. teaching hospitals, MRSA became a problem in the late 1980s and 1990s. “Folks in the U.S. put lots of effort into arresting its spread, largely unsuccessfully,” she says. “So by and large people said, We can’t make these programs work, we can’t control it. We’re better off not to waste time on it.”

By the time MRSA appeared in Canada in the mid-1990s, they had the benefit of the European experience, which showed that detecting carriers is necessary for successful control. A Dutch group, for instance, recently documented a very low incidence of MRSA carriers at admission (0.03 percent), due largely to what they called “the Dutch search and destroy policy” (Wer theim HF, et al. J Hosp Infect. 2004; 56: 321–325). What’s critical is that most people who carry and spread MRSA are not infected but colonized, so trying to manage the spread of MRSA by dealing only with people who have positive clinical cultures, as had been done in the U.S., “is doomed to failure,” Dr. McGeer says, “because those folks only compose about a third of the people who carry MRSA.”

The Ontario program is similar to what the task force of the Society for Healthcare Epidemiology of America recommended. Its cornerstone is screening at hospital admission people who are at risk of being colonized with MRSA. “What ‘at risk’ means depends on the particular hospital and region,” Dr. McGeer says. In her urban region it means anybody who comes from a nursing home, who has been in a hospital in the past year, or who is on he mo di al y sis—essentially anyone who has had contact with the health care system. (Dr. McGeer says community-acquired MRSA rates are still low in Toronto.) In some settings, the high-risk strategy turns into a global screening strategy. “On the medical wards, 76 percent to 82 percent of patients meet screening criteria,” Dr. McGeer says. “So on those units we just screen everyone.” Because being in a hospital increases risk of MRSA colonization, they periodically select a medical ward and screen everyone on that ward in one day.

While they do not use preemptive isolation for patients—except those with a history of hospitalization in other countries—they do use contact precautions, which means gown and gloves on entry to the room of patients colonized or infected with MRSA. “Some hospitals also require health care workers to wear masks on room entry to protect themselves from acquiring nasal carriage,” she says. As with all programs to prevent nosocomial spread, hand hygiene is a given, though compliance is not.

In a modeling study, Dr. McGeer and her colleagues showed that screening all patients for MRSA at admission reduced the transmission rate by 40 percent (Raboud J, et al. Infect Control Hosp Epidemiol. 2005; 26:607–615).

Dr. McGeer’s program uses culture for screening. She doesn’t think they will adopt the new real-time PCR assay for MRSA for some time. “We have worked hard to reduce time and cost for culture-based screening, and we still can’t justify the cost of the direct test,” she says.

Screening programs are difficult to maintain financially and psychologically, Dr. McGeer has found. “It is very hard for people to see that MRSA infec tions are causing problems and costing money,” she says, “whereas a MRSA screening program takes time in infection control and lots of laboratory resources and nursing time. I spend an inordinate amount of time justifying it.”

A similar program is directed in the Ottawa region of Ontario by Virginia Roth, MD, director of the Infection Prevention and Control Department at the Ottawa Hospital. It has been in place since 2000 and screens about 25 percent of all admissions. “We saw an initial drop [in MRSA transmission] that was sustained for two to three years,” Dr. Roth says. In 2003–2004 there were a number of outbreaks, which Dr. Roth attributes to decreased compliance with screening—“People lost their enthusiasm,” she says—and to the long turnaround time with the culture method. “That led to us putting in a business case for PCR,” Dr. Roth says. Now they use the Geneohm/IDI assay.

In Basel, Andreas F. Widmer, MD, MS, professor of medicine and infectious disease and head of infection control at the University of Basel Hospital, has been directing what Dr. Mermel calls a “draconian and successful” MRSA screening program since 1992. His criterion for high risk was any group with a prevalence of MRSA carriage higher than 10 percent, with mandatory isolation of all carriers. As a result, Dr. Widmer says, “We now have in a 1,000-bed hospital between five and 10 nosocomial MRSA cases each year and every five years a cluster with less than 20 patients.” Of all S. aureus identified in the laboratory, less than one percent is MRSA, in contrast to the 40 percent to 50 percent rates typically found in many large U.S. hospitals. Dr. Widmer recently started using a faster culture method, a cefoxitin-containing plate that identifies MRSA within 24 hours. He calls the direct PCR method “quite expensive” and suitable mainly for high-prevalence hospitals.

Now Dr. Widmer tests only patients coming from outside Switzerland and health care workers coming from countries with a high prevalence of MRSA. Recently he picked up the first case in Basel of the community-acquired MRSA clone USA300, in a Swiss physician returning from a fellowship in the United States (Tietz A, et al. N Engl J Med. 2005;353:532–533).

At Evanston Northwestern Healthcare, Dr. Peterson says the introduction of hospitalwide screening for MRSA followed a point prevalence survey in August 2004 that showed that 8.5 percent of people in the hospital were colonized. “At the time it seemed high,” he says, “but it has turned out to be about the same at other teaching hospitals.” He met with hospital administrators and presented figures on unreimbursed costs from nosocomial MRSA infections, which range from $30,000 to $40,000 per event. Administrators agreed to offer the program for free when Dr. Peterson showed that reducing MRSA bloodstream infections by one-half would pay for the program. Bloodstream infections have become the outcome measure.

Dr. Peterson initially presented a program to screen high-risk patients. Analysis of the point prevalence survey suggested that screening all patients who had been hospitalized in the prior two years would detect all MRSA carriers. However, looking at two-year longitudinal data from ICUs showed that that criterion would have missed 17 percent of carriers. At the presentation meeting, community physicians favored screening all admissions, which would save time that nurses would spend asking questions to determine risk status.

It took one year to develop and implement the global screening program. Initially, Dr. Peterson planned to use a PCR assay developed in-house, but screening 100 samples per day with that assay would have been “challenging,” he says. Then in late 2004 the Food and Drug Administration cleared the new PCR kit, which runs on the Cepheid SmartCycler, and they adopted that method. The only modification is to do extraction with a faster in-house method. Now one dedicated technologist runs 100 assays each day on four SmartCyclers. Carriers are isolated, treated with contact precautions, and decolonized with nasal mupirocin twice per day for five days plus chlorhexidine baths, three times in one week.

Screening went live about three months ago, on Aug. 1. In the first month compliance was 80 percent, with a goal of 90 percent; seven percent of admissions were carriers.

At Mayo Clinic, Dr. Cockerill says, high-risk admissions are screened and carriers are isolated and in some cases decolonized. Currently, Mayo pays for the assays. Testing is by standard culture. “We will introduce very soon testing by ChromAgar MRSA plate as a first step before a PCR assay is developed,” Dr. Cockerill says, “which from our studies should provide a result in many, but not all, cases in 24 hours, compared with conventional blood agar testing methods that require 48 hours or more.

“Ultimately we plan to go to screening of all admissions,” he says. For this purpose he is developing an in-house real-time PCR assay (see “One of the most challenging PCR tests to develop,” page 66). “Having done multiple studies in-house using various PCR approaches, we are very close to determining the best way to go,” he says. “So far we have not done the proper study to justify this approach from the perspective of decreasing MRSA or saving money, but we are planning a study with one of our regional hospitals.” All admissions would be screened using a real-time PCR assay, then carriers would be isolated. Over 12 months or so data would be gathered to see if the incidence of MRSA infection decreases in that health care facility. His goal is to reduce the rate of S. aureus cultures that are methicillin resistant to a similar rate (that is, less than five percent) as has been reported in foreign countries that use surveillance protocols.

At Rhode Island Hospital, Dr. Mermel, who is president of the Society for Healthcare Epidemiology of America, directs what he calls a “pretty aggressive” program. In addition to screening high-risk admissions—which he defines as “just about everyone except people coming from home who haven’t been hospitalized in the last six months” —he does surveillance cultures on admission to and discharge from medical and surgical ICUs (he says that even this minimal measure is “not so common”) and weekly point prevalence surveys in ICUs. People at high risk of being carriers are identified during admission: The hospital’s information services group has set up the admission record so that where the patient has come from is a mandatory field. Dr. Mermel is also working with information services staff to see which risk groups yield the largest number of carriers.

Screening has been by culture, but Dr. Mermel’s hospital has started a trial using rapid PCR. Molecular techniques for screening would make it easier to screen all admissions, which he is considering.

Dr. Mermel notes that Rhode Island has a statewide screening program. “It is difficult to control MRSA in a community unless all hospitals are trying to control it,” he says. With the cooperation of the state health department, Dr. Mermel, along with the state’s infection control professionals, formulated a statewide guideline for controlling nosocomial MRSA. Unfortunately, many hospitals in the state don’t have adequate information services support to implement screening and isolation and to determine compliance rates. “You really need a fair amount of IS support to do that,” Dr. Mermel says. “If you don’t have it, it’s fairly difficult to make the process work efficiently and to be able to track how you are doing.”

Dr. Karchmer says that high-risk patients at Wake Forest University School of Medicine have been screened for MRSA since 2002. She started the program after coming to Wake Forest following her training with Dr. Farr at the University of Virginia Health Sciences Center. The program “uses a variety of criteria for high risk,” she says, “which reflect exposure to the health care setting—either our institution or somewhere else.” Screens are done weekly: All patients who are high risk and in the hospital on Monday night are tested. In addition, every patient regardless of risk status is screened upon admission or transfer to the ICU, including pediatric and neonatal ICUs. Preemptive isolation is used only for pediatric patients with skin and soft tissue infections, who have a high rate of community-acquired MRSA.

“When we started, there was no alternative to standard culture for nasal specimens,” Dr. Karchmer says. They culture onto a blood agar plate; if S. aureus grows, it is screened for oxacillin resistance. Their turnaround time is usually two days.

Dr. Karchmer has done in-house evaluation of the rapid real-time PCR assay. “We have been pleased with its sensitivity and specificity,” she says. “Currently we are still working on the logistics of converting. We’d ultimately like to go that route for our screening program because more rapid information would be important—if we can work out the logistics.” Logistics means both money and space.

Dr. Karchmer went to administration with a business model to get funding to start and continue the program. “To take it to the next step of using the rapid PCR diagnostic test, we will create a new business plan,” she says. She will have to show incremental savings relative to the incremental cost of adopting the new test. “It’s somewhat different than if you are starting with no surveillance program,” she notes.

To track the impact of the surveillance program, Dr. Karchmer uses the rate of nosocomial MRSA infections in ICUs. “We had many years of data prior to starting,” she says, “so we were able to document a 10 percent to 15 percent decline in nosocomial MRSA infections in ICUs.” Another measure of efficacy has been the MRSA colonization rate in ICUs, which has also declined.

As for going to hospitalwide admission screening, Dr. Karchmer says, “Our criteria are already pretty broad. Almost half of patients get screened at some time during their hospital stay.” They are now reassessing their criteria to make them more sensitive. “From doing prevalence sweeps we knew we were not missing people, but rather overscreening,” she says. However, as community-acquired MRSA rises, new criteria are likely to be necessary. “To accommodate for community-acquired MRSA, we may go to on-admission screening on a larger percentage of patients,” Dr. Karchmer says, “though maybe not everyone.” Substantial clinical and epidemiological differences between health-care-associated MRSA and community-acquired MRSA have been documented (Naimi TS, et al. JAMA. 2003; 290: 2976–2984).

Molecular testing would make on-admission screening easier and enhance existing screening. With a molecular test, people who are carriers would be isolated two days earlier, which Dr. Karchmer believes would reduce transmission even more.

At Washington University School of Medicine, “We decided to try to address the whole issue of the increasing prevalence of MRSA in hospitalized patients over the past few years,” says David K. Warren, MD, MPH, hospital epidemiologist for Barnes-Jewish Hospital and assistant professor of medicine in the Division of Infectious Diseases. They decided to do active surveillance in areas traditionally thought to have high rates of MRSA—medical and surgical ICUs, medical oncology, and bone marrow transplantation. On these units they do cultures on admission, weekly screening, and again at the time of discharge, if possible.

Since they use culture methods, they faced the common dilemma—what to do while waiting for results. They considered following the Dutch policy of preemptive isolation, but decided against it because of logistical problems. “Preemptive isolation is difficult from a hospital administration standpoint when beds are at a premium,” Dr. Warren says. Patients with a history of prior colonization are put into contact precautions before culture results are obtained.

While the program has been in place since December 2002, Dr. Warren says it is “hard to say what the impact has been.” Over the past two to three years, an increasing number of patients colonized with MRSA have come into the surveyed units, but there hasn’t been an increase in the MRSA transmission rate. “So we think active surveillance has prevented some transmission,” he says.

He and his colleagues have discussed broader active screening. “We may still do it,” he says. One barrier is the issue of bed availability—their census is always at high capacity. “People are very reluctant to start the process in a hospital with a large number of semi-private rooms,” Dr. Warren says. He has published data showing that VRE often, but not always, travels with MRSA, which raises an issue with cohorting. “If you cohort, you may put a MRSA-positive/VRE-negative patient in with a MRSA-positive/VRE-positive patient, possibly increasing the spread of VRE,” Dr. Warren says.

One concern when they first started the program was that it would greatly increase the days spent in contact precautions in ICUs. However, an observational study in one ICU showed an overall increase of only nine percent in the number of contact precaution days. “At the same time we identified 61 percent of MRSA carriers we wouldn’t have identified previously,” Dr. Warren says.

Molecular testing would finesse the problems of bed availability, delays in the disposition of emergency department patients, and considerations of preemptive isolation—all of which have to do with slow turnaround time. Dr. Warren says that he was one of the study sites for evaluation of the Geneohm/IDI assay kit. The considerable capital investment it requires is an obstacle to switching to that method, he says.

Dr. Cockerill at Mayo Clinic sees a clear direction for the future. “I think the evidence [for wider screening] is increasing,” he says. “Screening everyone going into an institution intuitively makes sense to me as a microbiologist and an infectious disease specialist.” In his view, if everyone isn’t screened, effective reduction in the rate of MRSA and nosocomial transmission may be difficult to achieve. “Maybe a couple of years ago we could do that with screening of high-risk patients. MRSA clones or strains used to be pretty much limited to the hospital setting; there was not much carriage or spread in the community,” he says. However, in the past two years community-acquired MRSA strains are being seen increasingly in people who are not in typical high-risk groups—people who have not recently been in a hospital or nursing home, who are not on renal dialysis, who are not immunocompromised or transplant recipients.

“With community-acquired MRSA being carried by healthy people,” Dr. Cockerill says, “we now have patients coming into our hospitals carrying MRSA who are not in a high-risk group, maybe coming in for an elective procedure or from trauma such as a car accident.” They don’t fit into risk groups as previously defined, making it hard to assess in a comprehensive way who may be a high-risk patient. “Global screening is the only way you are going to capture all carriers,” he says.

William Check is a medical writer in Wilmette, Ill.