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
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.
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
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
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
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;
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
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
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
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
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
“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.
Despite less-than-optimal compliance with admission screening and contact
precautions, Dr. Mermel says the number of nosocomial MRSA infections in
2004 was one-third the number of cases in 2003. This rate has remained below
five nosocomial infections per 1,000 discharges since January 2004.
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,”
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,”
William Check is a medical writer in Wilmette, Ill.