Prevalence of Antibiotic-Resistant Organisms among
Adults Hospitalized in Canadian Hospitals – A Follow-up Survey, 2016
Background
The emergence of antibiotic-resistant organisms is a major public health concern,
particularly in hospitals and other healthcare settings (1-3). Antibiotic-resistant
organisms appear to be biologically fit, and are capable of causing severe, lifethreatening infections that may be more difficult to manage because treatment options
are limited. The Centers for disease Control and Prevention (CDC) estimates that each
year, in the United States, 2 millions illnesses and 23,000 deaths are caused by drugresistant bacteria (4). Antimicrobial resistance may emerge in bacteria as a response to
selective antibiotic pressure (5, 6), or a resistant organism may be spread from personto-person within or between healthcare facilities (7-10).
Methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant
enterococci (VRE), extended spectrum B-lactamase (ESBL) producing
Enterobacteriaceae, carbapenem-resistant Enterobacteriaceae (CREs) and Clostridium
difficile represent antibiotic-resistant organisms that currently are of great clinical
significance in hospitalized patients in Canada. Infections caused by each of these
pathogens have been associated with excess morbidity and mortality (11-15). A high
prevalence of antibiotic-resistant pathogens may lead to increased lengths of hospital
stay and bed-blocking in healthcare facilities. This, in turn, exacerbates hospital
overcrowding, leading to a vicious cycle characterized by impeded access to care,
diminished quality of care, and greater risk of infection prevention and control failures
(16).
The treatment and prevention of these infections are associated with substantial
increased direct and indirect costs to Canadian hospitals and society at-large. In the
United States, cost estimates for managing antimicrobial resistance were estimated to
be between $4 billion and $10 billion per year (US Office Technology, 1998). A report
commissioned by the Canadian Coordinating Committee on Antimicrobial Resistance
noted that significant gaps existed in data addressing the issue of financial costs of
antibiotic resistance, but estimated that infections caused by antibiotic-resistant
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organisms increased direct hospital costs in Canada by $15-25 million annually (17).
These estimates do not take into account indirect costs, or costs associated with
infection prevention and control measures. An American study found the treatment costs
associated with antimicrobial-resistant infections to be about $6,000 to $30,000 more
per patient compared with the treatment costs of antimicrobial-susceptible infections
(18). Ironically, this increase in the incidence of drug-resistant pathogens is occurring at
a time when the discovery and development of new anti-infective agents is decreasing
(2).
Despite the concern about antimicrobial resistance, remarkably little is known
about the epidemiology or burden of disease caused by antibiotic resistant organisms in
Canada. The only national surveillance system, with linked epidemiologic and
microbiologic data, tracking antimicrobial resistance in hospitalized patients is the
Canadian Nosocomial Infection Surveillance Program (CNISP), currently involving 54
sentinel hospitals across the country working in collaboration with the Public Health
Agency of Canada (19-25). Although the CNISP has provided valuable information, the
surveillance involves a relatively small number of healthcare facilities, primarily tertiarycare teaching hospitals. Moreover, CNISP surveillance has provided important
incidence data, but has not done any prevalence surveys directed at antibiotic-resistant
organisms. Several provinces have now mandated public reporting of infections caused
by these organisms, but these data are also limited in terms of the scope of infections
reported, and by the small amount of information that is collected. An example is the
province of Ontario where the only index reported for “MRSA infection” is the rate of
MRSA bacteremia. This fails to capture the rates of other infections and colonization that
are also associated with morbidity and mortality.
The Need for Prevalence Data in Canada
The prevalence rate of an antibiotic resistant organism may be defined as the
total number of patients with the organism (associated with either infection or
colonization) in a specific population during a specified period of time. It may be
possible to determine the prevalence per 100 patients admitted to hospital during the
specified time period, or to determine a prevalence density to account for length of
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patient stay in the hospital (for prevalence density, the denominator would be the
number of patient-days). Prevalence surveys have been used for a variety of
evaluations including monitoring of infection control, trends in nosocomial infection rates,
device utilization, patient acuity and costs of hospital infections (26-30). Despite lacking
the accuracy of prospective data, prevalence surveys can provide baseline information
and help establish priorities for efficient changes (19). Antimicrobial resistance
surveillance that provides accurate prevalence data is critical for the development of
strategies that may be used to limit the emergence and spread of antimicrobial resistant
organisms. Determining the prevalence of antibiotic resistance organisms has been
recognized as an important metric for assessing the burden of disease associated with
antimicrobial resistance, for identifying vulnerable patient populations, and for monitoring
the effectiveness of various interventions (31).
Despite numerous calls for action (10, 32, 33), Canada does not currently have a
comprehensive surveillance program for collecting and integrating accurate and
representative national data on antimicrobial resistance (34). This significantly limits our
ability to respond to the challenges posed to our healthcare system by antimicrobial
resistant organisms. This proposal focuses on the burden of illness associated with five
major antibiotic-resistant pathogens: MRSA, VRE, ESBLs, CREs and C. difficile. These
organisms have been selected because they are of particular concern in Canadian
healthcare facilities, because there continue to be significant gaps in our knowledge of
the epidemiology of these organisms in Canadian hospitals, and because the majority of
Canadian hospitals currently do active surveillance for these organisms, so that relevant
data are likely to be available (35). Such information is essential in order to develop and
evaluate the effectiveness of hospital and public health measures for the prevention of
infections caused by these organisms.
Results of the first two National Prevalence Surveys for MRSA, VRE, and C. difficile
Infection in Canadian Hospitals
We conducted the first two national prevalence surveys of antibiotic-resistant
organisms (MRSA, VRE, and C. difficile infection [CDI]) in Canada in November 2010
and November 2012. The survey performed in 2012 also included data on ESBL and
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CREs. This surveillance was done in partnership with Infection Prevention and Control
Canada (formerly CHICA), and in collaboration with the Public Health Agency of
Canada. These surveys provided us with important information regarding the burden of
disease in Canadian hospitals associated with these antibiotic-resistant organisms.
Results were published in July 2013 (36) and February 2015 (37). Briefly, the results can
be summarized as follows:
A national point-prevalence survey for infection or colonization with methicillin-resistant
Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus (VRE), and for
Clostridium difficile infection (CDI) was done in Canadian hospitals in 2010. A follow-up
survey was done in November 2012 to determine whether there were any changes in
the prevalence of these organisms; we also determined the prevalence of extendedspectrum β-lactamase (ESBL)-producing Enterobacteriaceae, and carbapenemresistant Enterobacteriaceae (CREs). Associations between prevalence and infection
prevention and control policies were evaluated in logistic regression models. A total of
143 (67% of eligible facilities) hospitals with 29 042 adult inpatients participated in the
survey, with representation from all 10 provinces; 132 hospitals participated in 2010 and
2012. There were no significant changes in the median prevalence of MRSA in 2010
(4.3%) compared to 2012 (3.9%), or of CDI in 2010 (0.8%) compared to 2012 (0.9%). A
higher median prevalence of VRE was identified in 2012 (1.3%) compared to 2010
(0.5%) (p 0.04), despite decreased VRE screening in 2012. The median prevalence of
ESBLs was 0.7% and was 0 for CREs; CREs were reported from only 10 hospitals
(7.0%). A policy of routinely caring for patients with MRSA or VRE in a private isolation
room was associated with lower prevalence of these organisms. Targeted screening of
high-risk patients at admission was associated with lower MRSA prevalence; better
hand hygiene compliance was associated with lower VRE prevalence.
Mean and median prevalence of selected antimicrobial-resistant organisms in adult
inpatients of Canadian acute-care hospitals, 2010 and 2012
Organism
MRSA
Colonization
or infection
Infection
VRE
Colonization
or infection
Infection
CDI
2010 Prevalence
(per 100 inpatients)
No.
Median Prevalence per
patients
100 inpatients (range)
2012 Prevalence
(per 100 inpatients)
No.
Median Prevalence per
patients
100 inpatients (range)
pa
1472
4.3 (0-22.1)
1218
3.9 (0-26.8)
0.81
175
0.3 (0-5.9)
170
0.3 (0-4.9)
0.78
557
0.5 (0-13.0)
738
1.3 (0-18.0)
0.04
11
350
0 (0-1.8)
0.8 (0-8.6)
18
386
0 (0-1.5)
0.9 (0-5.5)
0.28
0.29
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ESBL
Not measured
345
Colonization
or infection
Not measured
97
Infection
CRE
Colonization
Not measured
32
or infection
Infection
Not measured
12
a
Comparing median prevalence in 2010 with that in 2012
0.7 (0-13.5)
0 (0-4.0)
0 (0-3.0)
0 (0-1.3)
The point-prevalence survey conducted in 2010 was the first such prevalence
survey done in Canadian hospitals and provided baseline data for specific antibioticresistant organisms. The follow-up survey conducted in 2012 allowed to assess the
trends in the prevalence of AROs. We now propose to do a follow-up point-prevalence
survey in early 2016. These data will assist in further defining the burden of AROs in
Canadian hospitals, and in particular to further determine trends and changes that occur
over time. These results will provide important information regarding the appropriate
prioritization of treatment and infection prevention programs.
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Primary Objectives
 To determine the prevalence of MRSA and VRE colonization and infection among
adults hospitalized in Canadian hospitals
 To determine the prevalence of C. difficile infection among adults hospitalized in
Canadian hospitals
 To determine the prevalence of extended-spectrum β-lactamase (ESBL)producing organisms and carbapenem-resistant Enterobacteriaceae (CREs)
colonization and infection among adults hospitalized in Canadian hospitals
 To compare the results of this survey with those obtained in the previous surveys
done in November 2010 and November 2012
Secondary Objectives
 To describe demographic and select clinical/epidemiologic features of patients
with prevalent MRSA, VRE, C. difficile, ESBL and CREs infection and
colonization in Canadian hospitals
 To describe Canadian hospitals policies on screening and select infection control
measures used to control AROs in Canadian hospitals
Methods
Patient population of interest
All acute-care hospitals in Canada with at least 50 inpatients beds will be approached in
this point-prevalence survey (hospitals identified from the Canadian Hospital Association
(CHA) 2008 database, Volume 15.1). All hospitals that participated in the 2010 and 2012
prevalence survey will also be invited to participate in 2012. A letter inviting healthcare
facilities to participate in the prevalence survey will be sent by e-mail to each facility’s
Infection Prevention & Control professional (ICP). If there has been no response to this
initial communication, the ICP will be contacted a second time by e-mail, and if required,
an attempt will also be made to contact the individual by telephone.
Eligible patients will include adult inpatients (≥ 18 years of age) hospitalized in a
participating hospital on the day of the survey. Long-term care patients in these hospitals
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will be included if the long-term care beds are physically associated with a medical unit
in the acute-care hospital, or if patients are awaiting transfer/placement to a long-term
care facility. Other (free-standing) long-term care facilities, rehabilitation hospitals,
complex care facilities and psychiatric hospitals will not be included. Based on the
participation in the survey in 2010 and 2012, it is anticipated that at least 180 (65%)
hospitals will be willing and able to participate in the 2016 survey.
Surveillance design
A one-day point-prevalence survey will be conducted in participating Canadian
hospitals on a week-day chosen by each participating centre between February 8 and
February 19, 2016. On the selected day, eligible patients will be identified by the hospital
census (usually defined at midnight or at 6:00 AM). Adult patients in hospital at that time
will be included in the prevalence survey. Patients admitted after the census is defined
will not be included. Identification of all patients known to be infected or colonized with
MRSA, VRE, ESBL or CRE, and all those known to have C. difficile infection may be
done at any time in the two weeks following this date. In addition, patients hospitalized
on the day of the survey who have cultures or stool specimens that were collected in the
days prior or on the day of the survey and that are still pending on the moment of data
collection, will also be included if they subsequently yield MRSA, VRE, ESBL, CRE or C.
difficile toxin. Patient with a positive sample collected after the day of the survey will not
be included. Patients with MRSA, VRE, ESBL and CRE will be defined as those
requiring isolation precautions for any of these four organisms (microbiologicallyconfirmed at some point). Patients with MRSA, VRE, ESBL or CRE infection must meet
CDC/National Healthcare Safety Network (NHSN) criteria (2015) for infection, and must
be on antimicrobial therapy for MRSA, VRE, ESBL or CRE infection on the day of the
survey. Patients with C. difficile infection will be identified as those receiving at least one
dose of treatment for CDI with a C. difficile targeted antibiotic (oral vancomycin,
metronidazole, or fidaxomicin) on the day of the survey for laboratory-confirmed (toxinpositive) C. difficile, or determined to have had pseudomembranous colitis on
endoscopy within the previous 14 days. (Definitions in Appendix I)
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Data to be collected for each patient with MRSA, VRE, ESBL, CRE and CDI
include: (i) age; (ii) sex; (iii) hospital service on the day of the survey (medicine, surgery,
obstetrics/gynecology, intensive care unit, etc); (iv) for MRSA, VRE, ESBL and CRE,
whether the most recent isolate was obtain as a clinical specimen (to determine the
presence of an infection), or as a screening/surveillance specimen (eg. nasal or rectal
swab); (v) whether the patient was thought to be infected (using standard definitions) or
colonized; (vi) the anatomic site of the isolate (nose, skin, surgical site, respiratory,
blood, etc); (vii) whether the organism was initially identified during the current
admission or a previous admission; (viii) whether the organism was thought to have
been acquired during this admission or a previous admission; (ix) whether the organism
was thought to be healthcare-associated (index facility or other healthcare facility); (x)
for C. difficile infection, whether this represented a first episode or recurrence (Appendix
I).
Data will also be obtained to describe each participating hospital: (i) number of
admitted inpatients in the hospital on the survey date (at midnight); (ii) total number of
inpatients beds; (iii) number of ICU beds; (iv) hospital location (city, province, postal
code); (v) type of facility (adults only, mixed adults-pediatrics); (vi) educational category
of facility (teaching vs non-teaching hospital); (vii) scope of services provided (acute
trauma, burns, oncology, stem-cell transplants, solid organ transplants, neurosurgery,
cardiac surgery, dialysis, etc); (viii) number of FTE infection control professionals (ICPs);
(ix) hospital policies on MRSA/VRE/ESBL/CRE screening and some aspects regarding
management of carriers/infected; (x) laboratory methods for detection of AROs; (xi) the
total number of patients on the day of the survey who are on additional precaution in the
hospital for any reason (Appendix II).
All of the data are to be collected by a hospital Infection Control Professional
(ICP) or appropriately trained delegate under the ICP’s supervision. Facilities will not be
asked to obtain any additional cultures for the survey. Only data available in the chart or
in the infection prevention and control program records will be collected; no patient
interviews will be expected or required.
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Data analysis
The primary outcome measures will be the mean and median (with 95%
Confidence Intervals) prevalence rates of MRSA, VRE, ESBL, CREs and C. difficile
infection per 100 inpatients. The prevalence of MRSA, VRE, ESBL and CREs infections
will also be determined. Regional (or provincial) rates will be calculated, and the rates
will also be determined based on: (i) hospital size and (ii) hospital type (teaching vs nonteaching). Patients with AROs will be described by demographic information, and by
hospital service. The rates found in this survey will be compared to the rates found in the
2010 and 2012 surveys to assess any change over time.
Ethics
This point-prevalence survey is observational, without any change in patient care.
Moreover, it will be considered to be within the scope of infection surveillance for many
of the hospital’s Infection Prevention & Control programs. In order to maintain
confidentiality, each hospital will be assigned a numeric code, and each patient will also
be assigned a unique study number for entry into the database. No personal identifying
data will be provided to the study investigators. Consequently, Review Ethics Board
(REB) approval may not be required at all participating hospital sites. However, hospitals
may submit the proposal to their local REB for approval if the wish. To facilitate any
requirements for REB approvals at some sites, REB approval has been obtained at
Sunnybrook Health Sciences Centre (Toronto).
Support
This is an unfunded surveillance initiative. The project has been endorsed by
Infection Prevention and Control (IPAC) Canada.
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