Implementing a real-time PCR assay for rapid surveillance of MRSA

Feb. 1, 2009

Most healthcare
institutions in the United States have been watching an ominous trend of
escalating proportions of methicillin-resistant
Staphylococcus aureus infections. According to the Centers for
Disease Control and Prevention, more people in the United States die
annually from MRSA (estimated 18,650 deaths) than from AIDS (roughly
16,000 deaths).1

In addition to loss of life, MRSA costs the Amercan
healthcare system over $ 2.5 billion in non-reimbursable costs.2
In terms of the healthcare setting, MRSA infection rates have increased over
the past three decades — in 1974, MRSA accounted for 2% of staph infections;
in 2004 the number rose to 63%.3

In healthcare environments, MRSA is spread from
patients who already have an MRSA infection or who are colonized with the
bacterium but do not have any symptoms. The harmful pathogen is passed to
other patients through hand-to-hand contact or by touching contaminated
surfaces such as bed rails
or telephones.

Many institutions have begun selective testing of
some patients believed to be at higher risk. Several commercial chromogenic
agar plates have been developed to culture nasal swabs for active
surveillance of MRSA. Even with the most rapid culture turnaround time,
however, results from cultures are not available for at least 18 hours after
inoculation of the medium. Such results could reach the unit more than a day
after a colonized patient has been sharing a room with a non-colonized

Moving the non-colonized patient into another room at
this point can be a social and public-relations nightmare for patients,
their families, and hospital administrators. The alternative, instituting
barrier precautions pre-emptively on all patients until their MRSA status is
known, is costly and problematic; despite the success of this strategy in
controlling MRSA in Denmark and the Netherlands, not all healthcare
institutions in the United States have that capacity.

Selective testing of patients based on some risk
assessment has been shown to detect less than 85% of the colonized patients
in a hospital4; and the elaborate admission interview required to
determine who might be at risk is counterproductive, disliked by nursing
staff, and slows down admissions. Even less effective is passive
surveillance, in which MRSA carrying patients are discovered and isolated
only if cultures sent to the clinical laboratory yield MRSA. This approach
fails to identify 70% of truly colonized patients.5

As MRSA outbreaks are widely reported in the news
media, the public’s fears are increasing, putting pressure on policymakers
to address the issue. Already five states have enacted legislation mandating
surveillance of MRSA for high-risk units in a hospital, and 31 states have
reporting requirements.

Many hospitals are now implementing systems that use
fully integrated real-time PCR technology, in most cases for the purpose of
implementing rapid MRSA surveillance as part of their overall
infection-control program. Major advantages of such a system is a MRSA test
available in cartridge form with (1) its ability to process and deliver
results in less than one hour, enabling physicians to take the appropriate
precautions before the pathogen has the opportunity to spread, and (2) its
moderate complexity, allowing a non-clinical laboratory scientist to perform
the test.

The new technology combines on-board sample
preparation with real-time PCR amplification and detection functions for
fully integrated and automated nucleic-acid analysis. Training to use a
moderate complexity test is easy, and less experienced workers can perform
such tests with minimal hands-on time. With a random-access system, a new
sample can be added at any time. In many laboratories, the combination of
ease of use and random access translates into 24/7 access to MRSA results.

Nearly 450 U.S. hospitals (and over 900 worldwide) to
date have chosen to deploy this technology, and laboratory technicians and
technologists have voiced their satisfaction with the simplicity of the
system’s workflow and its proven results.

Leaders at sites that have implemented the MRSA assay
have been able to reduce infection rates and cut healthcare-associated costs
while improving patient care.

How are hospitals using rapid testing technology?

“The patients with the highest risk of MRSA infection
are those who undergo invasive surgeries making it a serious concern for our
orthopedic hospital” says Maureen Spencer, RN, MEd, CIC infection-control
manager at New England Baptist Hospital in Boston. “Following invasive
orthopedic surgical procedures, post-operative surgical wounds are
vulnerable to infection — particularly bone infections which are among the
toughest to treat.

“We were one of the first sites in the United States
to implement a pre-screening program for all surgical patients for MRSA.
When selecting a pre-screening program, time to result is a huge factor. It
is critical that patients know their MRSA status before they leave their
surgical consult in order to initiate a topical decolonization protocol and
allow the surgeon to adjust the surgical antibiotic prophylaxis. Using the
MRSA assay and the system, we proactively screen all surgical patients for
MRSA at least two weeks prior to their procedure. If they are colonized with
staph, doctors place the patients on a five-day decolonization protocol and
conduct a second screening for MRSA before admission to the hospital for
surgery. The goal is to reduce the introduction of MRSA into the hospital by
ensuring patients are MRSA-free before they are admitted.

“Our data is showing that pre-screening surgical
patients for MRSA lowers infection rates, creating a win-win situation for
the hospital and patients. Since implementing the first PCR test in July of
2006 and moving to the MRSA test in early 2007, our hospital saw MRSA
infection rates drop nearly 60%; from 0.46% to 0.18% in 2007 and decreasing
further to 0.11% in 2008. This has helped the hospital decrease its
orthopedic surgery hospital-acquired infection rates to 0.3% which is five
times lower than the average national rate of 1.5%.”

In Wooster, OH, Gail Woosley, manager of Lab Services
for Wooster Community Hospital says, “The goal of our infection-control
program is to lower healthcare-acquired infection rates and improve patient
care by delivering physicians the test results they need as quickly as
possible. In my 33 years in the field, it is not often that I am impressed
by some of the new technology being made available, but this system really
impressed me. Relative to other lab equipment, the new system technology is
affordable, even for a small institution. If you have a device that can save
you money in terms of patient time in the hospital, supplies used during
their hospital stay, and the health of the patient, its value is not

“We find that technology to be very useful in three
patient population groups.

  • The first group includes individuals that are having any type of
    surgery where a foreign body will
    remain within the patient
    such as joint replacement or hernia repairs.
  • Our second and largest group includes those coming to us from
    another healthcare facility.
    These people are screened upon
    admission and then placed in the appropriate room with the
    appropriate precautions. The rapid turnaround time allows us to identify
    which patients are
    colonized, enabling us to place that
    at-risk patient in isolation in order to curb the spread of the
    infection. Traditional turnaround time prevented us from taking
    these measures which were
    necessary because we still have semiprivate rooms in our
  • Our final group includes those individuals that have been admitted
    patients in our facility but
    return for re-admission. If this
    happens within 45 days from discharge, we test upon

In Stockton, CA, Richard Wong, administrative
director of Pathology and Clinical Laboratory for Dameron Hospital, says,
“We have been at the forefront in the San Joaquin Valley with regard to
active surveillance on multidrug-resistant organisms since the 1987
implementation of its first screening program.

“Technology has allowed us to expand and improve on
our infection- control methods as the nationwide threat of hospital-acquired
infections grows. The MRSA test delivers the fastest time to result
available today, making it an ideal technology for our critical initiative,
allowing us to reduce hospital-acquired infection rates and provide the
highest standards of patient safety.

On average, our hospital runs about 480 MRSA tests
per month with plans to increase as we move towards universal screening of
all patients who enter the site. Of importance, we have found the MRSA assay
is 100% sensitive compared to culture-based tests.”

More recently tests approved for the system we use
include a combined test for S aureus (usually methicillin sensitive)
and MRSA in blood cultures from patients with suspected sepsis, and a
similar test for direct detection of both organisms in skin and soft-tissue
infections. Both tests deliver results in less than one hour and their
results can be used in real-time to guide optimal treatment or management
decisions. Other tests in development that are relevant to infection control
include a test for VRE,
Clostridium difficile, and multidrug-resistant tuberculosis. It is
becoming increasingly clear that the medical value of rapidly available,
actionable results provided by the new technology can be an important ally
in the “search-and-destroy” strategy being adopted by more and more

David Persing,
MD, PhD, is the executive VP and chief medical and technology officer
for Cepheid.
Ellen Jo Baron, PhD, is director of Medical Affairs for Cepheid. The
systems and tests for which Cepheid is well-known are its GeneXpert System
and its accompanying MRSA/S Aureus test.


  1. Klevens RM, Morrison MA, Nadle J, et al. Invasive Methicillin-Resistant
    Staphylococcus aureus
    Infections in the United States. JAMA.
  2. The Centers for Disease Control and Prevention.
    . Accessed October, 17, 2007.
  3. The Centers for Disease Control and Prevention.
    . Accessed October 3, 2007.
  4. Robiscek A, Beaumont JL, Paule SM, et al. 2008. Universal
    Surveillance for Methicillin-Resistant Staphylococcus aureus Annals
    Intern Med.
  5. Bootsma MC, Diekmann O, Bonten MJ. Controlling methicillin-resistant
    Staphylococcus aureus: Quantifying the effects of interventions and
    rapid diagnostic testing
    . PNAS. 103:5