E D I T O R I A L C O M M E N TA R Y
Two Studies Feed the Debate on Active Surveillance
for Methicillin-Resistant Staphylococcus aureus
and Vancomycin-Resistant Enterococci Carriage:
To Screen or Not to Screen?
Thomas R. Talbot
Departments of Medicine and Preventive Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee
(See the articles by Huang et al., on pages 330–8 and 339–46.)
The upsurge in bacteria that are resistant
to many commonly used antimicrobials
has led to growing concern among infectious disease specialists [1]. The increasing
worldwide incidence of multidrug-resistant tuberculosis [2, 3], the emergence of
quinolone-resistant strains of Neisseria
gonorrhoeae [4], and reports of panresistant Acinetobacter baumannii infections
requiring treatment with older antibiotics
once set aside because of their toxicities
[5] are but a few examples. Two of the
more prominent antibiotic-resistant pathogens are methicillin-resistant Staphylococcus aureus (MRSA) and vancomycinresistant enterococci (VRE). According to
a recent report from the National Nosocomial Infections Surveillance system of
the US Centers for Disease Control and
Prevention (CDC), MRSA accounted for
nearly 60% of all nosocomial S. aureus
infections in intensive care units (ICUs),
Received 5 October 2006; accepted 16 October 2006;
electronically published 27 December 2006.
Potential conflicts of interest: none reported.
Financial support: Nabi Pharmaceuticals; GlaxoSmithKline.
Reprints or correspondence: Dr. Thomas R. Talbot, A-2200 Medical Center N., 1161 21st Ave. S., Vanderbilt University Medical
Center, Nashville, TN 37232 (tom.talbot@vanderbilt.edu).
The Journal of Infectious Diseases 2007; 195:314–7
2006 by the Infectious Diseases Society of America. All
rights reserved.
0022-1899/2007/19503-0002$15.00
whereas 29% of enterococcal infections in
this population were caused by vancomycin-resistant species [6].
Infection with either pathogen leads to
substantial morbidity and mortality, even
compared with infection with their antibiotic-sensitive counterparts. MRSA infections have been associated with more prolonged hospitalizations, higher costs, and
higher mortality than methicillin-sensitive
S. aureus infections [7–10]. VRE, which is
sometimes wrongly considered to be a minor pathogen, can also cause substantial
morbidity. Bacteremia caused by VRE, after adjustment for severity of illness, is associated with higher recurrence, mortality,
and excess costs than vancomycin-sensitive enterococcal infection [11–13].
Individuals can become colonized with
the organisms in pathogen-specific niches:
MRSA primarily in the nares and VRE in
the intestinal mucosa. Although colonization precedes infection, not all colonized
persons will develop MRSA or VRE infection. Persons colonized with either organism, however, can serve as a nidus for
secondary transmission. The incidence of
MRSA colonization, assisted in no small
part by the epidemic of community-acquired MRSA, has markedly increased in
many communities. In Nashville, for
example, MRSA nasal carriage increased
314 • JID 2007:195 (1 February) • EDITORIAL COMMENTARY
110-fold in healthy children from 2001 to
2004 [14].
The increasing burden of colonization
and disease caused by both pathogens has
led to an increased emphasis on preventive
strategies to reduce their transmission. In
2003, the Society for Healthcare Epidemiology of America (SHEA) released its
guideline for preventing the nosocomial
transmission of MRSA and VRE [15]. This
document outlined a comprehensive set
of strategies with 3 main foci. First, the
guideline recommends the identification
of hospitalized patients colonized with
MRSA and VRE via active microbiologic
screening of patients at high risk for carriage of either organism and the tracking
of previously colonized or infected patients at readmission. Second, prevention
of secondary transmission of these organisms via the use of contact precautions,
patient cohorting, and emphasis on hand
hygiene is suggested. Finally, the guideline
includes the need to reduce factors responsible for the selection of these resistant pathogens by antibiotic stewardship.
Once released, these recommendations
caused consternation among some clinicians and led to a division among the traditionally tightly knit group of infection
control professionals [16–18].
Although most infection control spe-
cialists endorse a majority of recommendations in the SHEA guideline, the role
played by active culture surveillance of
patients for colonization with VRE and
MRSA is at the heart of the disagreement.
Opponents of the SHEA guideline endorse
the draft guideline of the CDC’s Healthcare Infection Control Practices Advisory
Committee (HICPAC), which is, after
some delay, scheduled for release in 2007
[19]. The HICPAC guideline offers a tiered
approach toward preventing the transmission of multidrug-resistant organisms
with intensified measures, including active
surveillance, recommended only when or
if baseline infection control measures fail
to decrease pathogen transmission. The
SHEA and HICPAC guidelines are often
positioned as polar opposites [16–18]. In
reality, they mirror each other in most
recommendations. One key exception is
the active culture screening of patients for
MRSA and VRE.
Passions for and against each guideline
run quite deep. Proponents of the SHEA
guideline seemingly contend that the omission of active screening is tantamount to
malpractice [18, 20]. Opponents argue
that, despite the presence of numerous
published observational and quasi experimental studies, the practice of active surveillance has not been satisfactorily demonstrated in itself to reduce MRSA
colonization and infection in a nonoutbreak or non–academic center setting
[18]. Even a multicenter, randomized trial
designed to rigorously examine the issues
surrounding active surveillance has not
been spared, with critique of the trial occurring in print even before the data
have been analyzed, presented, or peer
reviewed [18, 21].
Now groups outside of the infection
control profession have latched onto the
issue of active surveillance. Earlier this
year, legislation was introduced mandating
the active screening of all hospitalized patients for MRSA carriage in Illinois and
for MRSA and VRE carriage in Maryland
[22, 23]. In addition, the Consumer’s
Union, which recently championed the is-
sue of mandatory public reporting of
hospital infection rates, has now placed
MRSA legislation front and center, providing a template letter that citizens can
send to their state legislators that asks for
hospital-specific MRSA prevention plans
and advocates “universal surveillance” for
MRSA carriage [24]. Of concern with each
of these initiatives is the morphing of the
recommendation in the SHEA guidelines
for active screening of high-risk patients
into a one-size-fits-all universal screening
strategy for all hospitalized patients. Thus,
active screening of patients for carriage
with MRSA and VRE is a hot-button issue
that will probably intensify in the near
future.
In this issue of the Journal of Infectious
Diseases, Huang et al., from the CDC’s
Epicenters Program, provide important
data about the impact of active surveillance for MRSA and VRE in high-risk patients on assessing the burden of colonization [25, 26]. In 2 separate studies
purposefully similar in design, the Epicenter investigators have insightfully examined the role played by active screening
in MRSA surveillance in 12 ICUs and in
VRE surveillance in 14 patient-care units.
By a retrospective examination of 1 year’s
worth of data, measurements of monthly
prevalence, admission prevalence, prevalence density, incidence, and incidence
density were assessed both with and without the inclusion of data obtained via active surveillance (i.e., only using data from
cultures obtained during clinical care).
Predictors of increased admission prevalence and incidence, the impact of active
surveillance on the total number of days
patients were placed in contact precautions, and the persistence of MRSA and
VRE carriage were also determined.
In the first study, which examined the
impact of active screening of ICU patients
for MRSA nasal colonization, data were
collected from 5 academic medical centers
encompassing 12 adult ICUs, 18000 admitted patients, and nearly 50,000 ICU
patient-days [25]. The active surveillance
policies differed slightly among ICUs:
most collected screening nares cultures at
the time of admission to the ICU and each
week thereafter and did not place patients
on contact precautions empirically while
awaiting screening culture results. All
ICUs collected screening cultures from patients already on contact precautions or
known to have been previously infected or colonized with MRSA. Compliance
with admission screening was 170% in
most units, with 5 ICUs having ⭓90%
compliance.
For the second study, the impact of active screening of hospitalized patients for
rectal colonization by VRE was evaluated
in 14 patient-care units from 4 academic
medical centers [26]. The units included
10 ICUs (including medical, surgical,
burn, and cardiac) and 4 units that cared
for immunocompromised hematologyoncology and transplant patients. The
study population included 18266 admitted patients and nearly 61,000 hospital
patient-days. Unit characteristics were
similar, with the exception of a bone marrow–transplant unit, which had a longer
median length of stay and lower total admissions. Again, active surveillance policies differed mildly among the units. Rectal screening cultures were collected at the
time of admission in most areas, with follow-up cultures collected weekly during
the hospitalization. One institution performed both culture and polymerase chain
reaction testing of rectal specimens, which
likely increased the detection of VRE. Precautions were not instituted empirically
pending screening culture results. Compliance with admission screening was
slightly lower than with MRSA screening,
with most units reporting rates 180%.
Compliance in 2 units was !60%, which
possibly indicates the increased logistical
difficulty ascribed to the collection of rectal-swab specimens.
Use of data from active surveillance resulted in increased prevalence and incidence estimates for both MRSA and VRE.
Interestingly, the use of active surveillance
made a substantially larger impact on the
assessment of VRE colonization than on
EDITORIAL COMMENTARY • JID 2007:195 (1 February) • 315
MRSA carriage. Whether this is because
VRE colonization is less likely to result in
invasive infection or whether VRE infection may occur in sites less often routinely
cultured during the workup of a febrile
hospitalized patient (e.g., abdominal abscess) is mere conjecture. The burden
of MRSA and VRE colonization varied
widely among the study units, which suggests that not all high-risk patient units
may be “high risk” in terms of MRSA or
VRE carriage.
Not unexpectedly, active surveillance
resulted in an 18.4% and 137% increase
in MRSA and VRE contact precaution
days, respectively. The suboptimal utility
of using only clinical cultures to identify
persons colonized with MRSA or VRE was
also reinforced [27], given that only 30%
of MRSA carriers and 13% of VRE carriers
had subsequent positive clinical cultures
during their hospitalization. The use of
active surveillance also prevented the errant misclassification of carriage incidence. Persons who, on the basis of clinical
microbiologic data, would have been considered to be incident carriers were appropriately reclassified as carriers at the
time of admission when active surveillance
data were included. Specifically, active surveillance prevented the misclassification of
nearly 17% of MRSA carriers and 43% of
VRE carriers who would have been identified on the basis of clinical cultures alone.
Another important aspect of both these
studies is the emphasis on the exclusion
of persons known to carry MRSA or VRE
in the denominator for determinations of
carriage incidence. That is, when determining the actual incidence of a condition,
it is important to include only those at
risk of acquiring that condition in the
population (to exclude those persons already colonized with MRSA or VRE at
admission). Such methods should be included in the tool kit of facilities examining colonization with either of these 2
important pathogens using an active
screening strategy.
The range of impact of the use of active
surveillance in the study units is rather
striking. Although each assessment of
MRSA colonization burden increased with
the inclusion of carriers detected by active
surveillance, the proportional benefit of
their inclusion was 18.7%–63.5% for average monthly prevalence, 29.8%–135.1%
for average monthly admission prevalence, and 6.7%–156.5% for average
monthly incidence of MRSA carriage.
MRSA precaution days increased from as
low as 10.7% in some ICUs to as high as
91.2% in others. In addition, some ICUs
noted minimal benefit from active surveillance for MRSA. As noted earlier, the
benefit of active surveillance on measurements of the burden of colonization with
VRE was much greater than that for
MRSA. Variability in impact occurred
across the units, with increases in carriage
prevalence of 220%–1350% and in incidence of 330%–1540%.
This marked variability in the effect of
active surveillance is noteworthy. It would
be interesting to know more details about
the units in which active surveillance made
a larger impact. Is there a plateau effect
for the impact of active surveillance for
MRSA, given that those units in which
active surveillance for MRSA had been ongoing before the study period showed no
reduction in the colonization incidence of
MRSA? Or does this show the effectiveness
of early placement of carriers on contact
precautions? In addition, in many units,
although the incidence of MRSA and VRE
colonization decreased during the study
period, the net decrease was mild, at
0.23% and 0.22% per month, respectively.
No mention is made of the trends of VRE
incidence in non-ICU areas.
Although Huang et al. note that no
change in infection control practices and
no other special infection control programs to reduce MRSA and VRE were altered at any institution during the study
period, other interventions not directly
targeted at MRSA and VRE—such as a
standardized central venous catheter insertion program, which was in the final
years of implementation at one study institution [28], and a hand-hygiene cam-
316 • JID 2007:195 (1 February) • EDITORIAL COMMENTARY
paign at the primary author’s institution
that began in July 2002 [29]—may have
also affected the incidence of MRSA and
VRE. Given that thousands of culture
specimens were collected and thousands
of days were spent on contact precautions,
the opponents of active surveillance may
argue whether the juice gained from active
surveillance was truly worth the squeeze.
These studies do have some important
limitations, many of which are inherent in
a retrospective investigation. Persons who
had been identified previously as a carrier
of either pathogen at a health-care facility
outside of each Epicenter’s health system
but not at the time of admission may have
errantly been considered to be incident
cases. Use of only nares culture for MRSA
(as opposed to including cultures from
other colonization sites, such as the axilla)
may have underestimated the true burden
of colonization. In addition, the use of
broth enrichment culture for nares cultures increases the sensitivity of the test
[30]. If these facilities did not include
broth enrichment in their standard nares
culture procedure, this may have led to
an underestimation of the MRSA burden.
Rectal-swab culture for VRE has a sensitivity of only 58%, with lower sensitivities
in patients with a lower density of VRE in
stool [31]. Thus, the true burden of VRE
colonization may have been underestimated. The authors also used colonization
incidence to reflect hospital-associated
transmission. Without molecular typing of
the MRSA and VRE isolates to detect
clonal spread, it is not known whether all
incident cases of new colonization are due
to hospital-acquired transmission. It must
also be emphasized that the impact of active surveillance on health-care–associated
infections caused by these pathogens is not
described.
In short, these studies have something
for both sides of the active surveillance
debate. For proponents, these well-designed studies support the notions that active surveillance allows for a more accurate
assessment of the burden of MRSA and
VRE colonization, reduces the misclassi-
fication of hospital-acquired colonization
or infection, and appropriately increases
contact precaution days. For opponents,
the mild impact on carriage incidence in
only some of the units, coupled with the
logistics of mounting an active surveillance program, argues against routine surveillance. Nonetheless, both sides must
agree that the studies by Huang et al. are
important and scientifically sound additions to the debate.
One other key aspect of these studies
must be noted. These investigations highlight the power of a multicenter collaborative study aimed at examining issues in
the field of infection control—an area that
has traditionally been underfunded in
terms of extramural support. Such continued collaborative and methodologically
sound investigations are essential to tackling the many important questions yet to
be answered about infection control practices, especially as interest in the prevention of health-care–associated infections
increases both within and outside healthcare facilities. One hopes that the divide
among infection control professionals created by the SHEA guideline will resolve,
because the infection control community
has too many challenges in the years ahead
that will require a cohesive approach.
Acknowledgments
I thank Drs. William Schaffner, Titus Daniels,
and H. Keipp Talbot, for their critical review of
the manuscript.
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