ORIGINAL CONTRIBUTION

Invasive Methicillin-Resistant
Staphylococcus aureus Infections
in the United States
R. Monina Klevens, DDS, MPH
Melissa A. Morrison, MPH
Joelle Nadle, MPH
Susan Petit, MPH
Ken Gershman, MD, MPH
Susan Ray, MD
Lee H. Harrison, MD
Ruth Lynfield, MD
Ghinwa Dumyati, MD
John M. Townes, MD
Allen S. Craig, MD
Elizabeth R. Zell, MSTAT
Gregory E. Fosheim, MPH
Linda K. McDougal, MS
Roberta B. Carey, PhD
Scott K. Fridkin, MD
for the Active Bacterial Core
surveillance (ABCs) MRSA
Investigators

A

FTER BEING INITIALLY RE ported among injecting drug
users in Detroit in 19811 and
then associated with the deaths
of 4 children in Minnesota and North Dakota in 1997,2 community-associated
methicillin-resistant Staphylococcus aureus (MRSA) has become the most frequent cause of skin and soft tissue infections presenting to emergency
departments in the United States.3 Although community outbreaks of MRSA
in diverse populations, including American Indian and Alaska Natives,4 sports

See also p 1803 and Patient Page.

Context As the epidemiology of infections with methicillin-resistant Staphylococcus aureus (MRSA) changes, accurate information on the scope and magnitude of MRSA
infections in the US population is needed.
Objectives To describe the incidence and distribution of invasive MRSA disease in
9 US communities and to estimate the burden of invasive MRSA infections in the United
States in 2005.
Design and Setting Active, population-based surveillance for invasive MRSA in 9
sites participating in the Active Bacterial Core surveillance (ABCs)/Emerging Infections Program Network from July 2004 through December 2005. Reports of MRSA
were investigated and classified as either health care–associated (either hospitalonset or community-onset) or community-associated (patients without established health
care risk factors for MRSA).
Main Outcome Measures Incidence rates and estimated number of invasive MRSA
infections and in-hospital deaths among patients with MRSA in the United States in
2005; interval estimates of incidence excluding 1 site that appeared to be an outlier
with the highest incidence; molecular characterization of infecting strains.
Results There were 8987 observed cases of invasive MRSA reported during the surveillance period. Most MRSA infections were health care–associated: 5250 (58.4%)
were community-onset infections, 2389 (26.6%) were hospital-onset infections; 1234
(13.7%) were community-associated infections, and 114 (1.3%) could not be classified. In 2005, the standardized incidence rate of invasive MRSA was 31.8 per 100 000
(interval estimate, 24.4-35.2). Incidence rates were highest among persons 65 years
and older (127.7 per 100 000; interval estimate, 92.6-156.9), blacks (66.5 per 100 000;
interval estimate, 43.5-63.1), and males (37.5 per 100 000; interval estimate, 26.839.5). There were 1598 in-hospital deaths among patients with MRSA infection during the surveillance period. In 2005, the standardized mortality rate was 6.3 per 100 000
(interval estimate, 3.3-7.5). Molecular testing identified strains historically associated
with community-associated disease outbreaks recovered from cultures in both hospitalonset and community-onset health care–associated infections in all surveillance areas.
Conclusions Invasive MRSA infection affects certain populations disproportionately. It is a major public health problem primarily related to health care but no longer
confined to intensive care units, acute care hospitals, or any health care institution.
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JAMA. 2007;298(15):1763-1771

Author Affiliations: Centers for Disease Control and
Prevention, Atlanta, Georgia (Drs Klevens, Carey, and
Fridkin and Mss Morrison, Zell, and McDougal and
Mr Fosheim); California Emerging Infections Program, Oakland (Ms Nadle); Connecticut Department of Health, Hartford (Ms Petit); Colorado Emerging Infections Program, Denver (Dr Gershman); Grady
Memorial Hospital, Atlanta (Dr Ray); Maryland Emerging Infections Program and Johns Hopkins Bloomberg
School of Public Health, Baltimore (Dr Harrison); Minnesota Department of Health, Minneapolis (Dr

©2007 American Medical Association. All rights reserved.

Lynfield); University of Rochester, Rochester General
Hospital, Rochester, New York (Dr Dumyati); Oregon Health & Science University, Portland (Dr
Townes); and Tennessee Department of Health, Nashville (Dr Craig).
The ABCs MRSA Investigators are listed at the end
of this article.
Corresponding Author: R. Monina Klevens, DDS, MPH,
Division of Healthcare Quality Promotion, Centers for
Disease Control and Prevention, 1600 Clifton Rd (A24), Atlanta, GA 30333 (rmk2@cdc.gov).

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INVASIVE MRSA INFECTIONS IN THE UNITED STATES

teams,5,6 prison inmates,7 and child care
attendees,8 usually involved skin disease, MRSA also can cause severe, sometimes fatal invasive disease.9-13
Studies of the emergence of community-associated MRSA disease over the
past decade determined that isolates
causing community-associated and
health care–associated MRSA infections were distinct.10 Isolates from the
community were susceptible to most
non–␤-lactam antimicrobial agents,10
carried staphylococcal cassette chromosome type IV,14 and frequently encoded the dermonecrotic cytotoxin
known as Panton-Valentine leukocidin.15 The strain most often isolated in
community outbreaks was pulsedfield type USA300.16 Other strains of
community origin include USA400,
USA1000, and USA1100. 17 In contrast, strains most frequently associated with MRSA infections in health
care settings were USA100, USA200,
and less often, USA50018; these traditionally have been multidrugresistant and have carried staphylococcal cassette chromosome type II.10
In hospitalized patients, MRSA has
been a problem since the 1960s19; approximately 20% of bloodstream infections in the hospital setting have been
caused by S aureus.20 The proportion of
hospital-onset S aureus infections that
were methicillin-resistant reached
64.4% in US intensive care units in
2003.21 In the hospital, MRSA infections are associated with greater lengths
of stay, higher mortality, 22 and increased costs.23,24 Although more recently there has been increased surveillance activity for invasive MRSA
infections in the community, surveillance for MRSA bloodstream infections in the United States traditionally
has been limited to hospital-onset (ie,
nosocomial) disease.20,21
As the epidemiology of MRSA disease changes, including both community- and health care–associated disease, accurate information on the scope
and magnitude of the burden of MRSA
disease in the US population is needed
to set priorities for prevention and control. In this report we describe the in-

cidence and distribution of invasive
MRSA disease in 9 US communities and
use these results to estimate the burden of invasive MRSA infections in the
United States.
METHODS
Surveillance Methodology
and Definitions

The Active Bacterial Core surveillance
system (ABCs) is an ongoing, population-based, active laboratory surveillance system and is a component of the
Emerging Infections Program (EIP) of
the US Centers for Disease Control and
Prevention (CDC). From July 2004
through December 2005, 9 EIP sites conducted surveillance for invasive MRSA
infections. A site number was assigned
in descending order of population size:
site 1, the state of Connecticut (estimated population, 3.5 million); site 2,
the Atlanta, Georgia, metropolitan area
(8 counties; estimated population, 3.5
million); site 3, the San Francisco, California, Bay Area (3 counties; estimated
population, 3.2 million); site 4, the Denver, Colorado, metropolitan area (5
counties; estimated population, 2.3 million); site 5, the Portland, Oregon, metropolitan area (3 counties; estimated
population, 1.5 million); site 6, Monroe County, New York (estimated population, 733 000); site 7, Baltimore City,
Maryland (estimated population,
636 000); site 8, Davidson County, Tennessee (estimated population, 575 000);
and site 9, Ramsey County (St Paul area),
Minnesota (estimated population,
495 000). The total population under
surveillance in 2005 was an estimated
16.5 million, or approximately 5.6% of
the US population. Surveillance sites
were similar to the US population in the
distribution by male sex (49.2% and
49.3%, respectively); however, surveillance sites had a lower frequency of
whites (72.7% and 81.0%, respectively) and of persons 65 years and older
(10.8% and 12.4%, respectively).
ABCs case finding was both active
and laboratory-based. Clinical microbiology laboratories in acute care hospitals and all reference laboratories processing sterile site specimens for

1764 JAMA, October 17, 2007—Vol 298, No. 15 (Reprinted)

residents of the surveillance area were
contacted regularly for case identification. In hospitals without computerized microbiology data, surveillance
personnel telephoned designated microbiology laboratory contacts regularly to identify new cases and request
isolate submission. Where microbiology data were computerized, electronic line listings of all MRSA isolated from normally sterile sites were
received on a monthly basis by surveillance staff, which investigated each potential case to confirm residency status, presence of infection, demographic
characteristics, and underlying illness. The burden of disease can be estimated by this surveillance method
using census data and the surveillance
site–specific incidence rates and age-,
race-, and sex-adjusted incidence rates
pooled across all surveillance sites. This
infrastructure is the same as that used
for estimated incidence and disease burden for bacterial meningitis25 and invasive infections with Streptococcus
pneumoniae.26,27
Case reporting and isolate collection were determined to be surveillance activities at the CDC; in addition, each of the 9 participating
surveillance sites evaluated the protocol and either deemed it a surveillance
activity (eg, that involving a reportable disease) or obtained institutional
review board approval with a waiver of
informed consent.
A case of invasive MRSA infection
was defined by the isolation of MRSA
from a normally sterile body site in a
resident of the surveillance area, including residents institutionalized in
long-term care facilities, prisons, etc.
Normally sterile sites included blood,
cerebrospinal fluid, pleural fluid, pericardial fluid, peritoneal fluid, joint/
synovial fluid, bone, internal body site
(lymph node, brain, heart, liver, spleen,
vitreous fluid, kidney, pancreas, or
ovary), or other normally sterile sites.
Cultures designated as “fluid” were investigated as potentially sterile culture sites; cultures designated as “tissue” with no specification of original
source were not investigated.

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INVASIVE MRSA INFECTIONS IN THE UNITED STATES

Personnel in each EIP site abstracted
data from medical records from hospital and clinic visits using a standard case
report form. Information on the following health care risk factors for MRSA was
collected: culture obtained more than 48
hours after admission; presence of an invasive device (eg, vascular catheter, gastric feeding tube) at time of admission
or evaluation; and a history of MRSA infection or colonization, surgery, hospitalization, dialysis, or residence in a longterm care facility in the 12 months
preceding the culture. Cases could have
more than 1 health care risk factor. For
this analysis, we used health care risk factor information to classify cases into mutually exclusive groups (those with health
care–associated and communityassociated infections) justified previously28 and consistent with other studies (T A B L E 1). 2 9 , 3 0 Health care–
associated infections, in turn, were
classified as either community-onset
(cases with a health care risk factor but
with a culture obtained Յ48 hours after hospital admission) and hospitalonset (cases with culture obtained Ͼ48
hours after admission, regardless of
whether they also had other health care
risk factors). Community-associated
cases were those without documented
health care risk factors.
Surveillance personnel also collected demographic (including race),
clinical, and outcome (hospital death or
discharge) information on each case
from the initial hospitalization. Mortality was collected from the patient record and represented crude, in-hospital
deaths only. Race was collected from information available in the medical record. Cases were considered to have a diagnosis of bacteremia, pneumonia,
cellulitis, osteomyelitis, endocarditis,
septic shock, or other infection, if there
was documentation of such a diagnosis
in the medical record, regardless of the
source of the isolate. Cases could have
more than 1 clinical diagnosis. Bacteremias included those classified as primary, secondary, and not specified. Use
of up to 4 antimicrobial agents was recorded, but all such agents reflected only
initial empirical therapy and did not in-

Table 1. Definitions Used for Epidemiologic Classification of Invasive Methicillin-Resistant
Staphylococcus aureus (MRSA) Infections
Classification
Health care–associated
Community-onset

Hospital-onset

Community-associated

Definition
Cases with at least 1 of the following health care risk factors: (1)
presence of an invasive device at time of admission; (2) history
of MRSA infection or colonization; (3) history of surgery,
hospitalization, dialysis, or residence in a long-term care facility
in previous 12 mo preceding culture date
Cases with positive culture result from a normally sterile site
obtained Ͼ48 h after hospital admission. These cases might
also have Ն1 of the community-onset risk factors.
Cases with no documented community-onset health care risk factor

clude dose, duration, therapeutic
changes, or procedures (eg, draining,
surgical therapy). Concordant empirical therapy was defined as receipt of any
antimicrobial agent to which the isolate was susceptible by laboratory testing and that was documented in the
medical record. Recurrent invasive
MRSA was defined as a positive culture
result obtained from the same case 30
days or more after the initial culture.

SmaI. PFGE patterns were analyzed
using BioNumerics version 4.01 (Applied Maths, Austin, Texas) and
grouped into pulsed-field types using
Dice coefficients and 80% relatedness,
as previously described.18 PFGE testing was conducted at the CDC and at
the reference centers in Colorado, Connecticut, Georgia, Minnesota, and Oregon. All PFGE patterns were entered
into a single database for analysis.

Isolate Collection and Testing

Statistical Analysis

Laboratories identified by the EIP site
were asked to submit isolates from invasive MRSA infections. Of 123 laboratories serving residents of the surveillance areas, 48 (39%) contributed
isolates. All isolates were sent to the
CDC for identification, selected testing, and storage. In situations in which
more than 1 isolate was available from
a single case, the protocol selected 1 isolate, preferably from a nonblood sterile site. Isolates were prioritized for testing as follows: within each geographic
site, all nonblood isolates and the subsequent submitted blood isolate were
selected; then, among blood isolates,
those from cases with a diagnosis other
than uncomplicated bacteremia were
selected. Testing included confirmation of S aureus identification using
catalase and Staphaurex (Remel Europe Ltd, Dartford, United Kingdom)
agglutination tests and tube coagulase
if necessary, as well as description of
morphology on nonselective blood agar,
confirmation of oxacillin resistance by
the broth microdilution method,18 and
pulsed-field gel electrophoresis (PFGE)
using the restriction endonuclease

We selected cases reported from July
2004 through December 2005 to describe epidemiologic, clinical, and microbiological characteristics. We included only cases reported from January
through December 2005 for the annual 2005 incidence rate calculations.
Recurrent cases were excluded from incidence calculations. We used US Census Bureau bridged-race vintage postcensus population estimates for 2005,
provided by the National Center for
Health Statistics for surveillance area
and national denominator values.
Because the surveillance sites varied in the distribution by age and race,
for national estimates of burden of disease we multiplied the aggregate age-,
race-, and sex-specific rates of disease
in the surveillance areas by the age, race,
and sex distribution of the US population for 2005. Because 1 site (site 7, Baltimore City) reported an excessively
high incidence of infection, we calculated interval estimates for the age-,
race-, and sex-adjusted incidence rates
and estimated burden as well. This was
performed by creating a lower bound
by pooling data from the 3 EIP sites

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INVASIVE MRSA INFECTIONS IN THE UNITED STATES

Table 2. Observed Incidence Rates of Invasive Methicillin-Resistant Staphylococcus aureus (MRSA) by Active Bacterial Core Surveillance Site
and Epidemiologic Classification, United States, 2005 a
Incidence per 100 000
Health Care–Associated
Surveillance Site No.
1 (Connecticut)

(Location) b

No. of Cases
952

Community-Associated
2.7

Community-Onset
15.6

Hospital-Onset
8.4

Total
27.1

2 (Atlanta, GA, metropolitan area)
3 (San Francisco, CA, Bay Area)
4 (Denver, CO, metropolitan area)

1165
936
480

5.1
4.5
2.8

16.7
15.9
12.3

10.3
7.7
6.0

33.0
29.2
21.2

5 (Portland, OR, metropolitan area)
6 (Monroe County, NY)

305
307

4.7
2.7

11.4
22.2

3.6
16.8

19.8
41.9

7 (Baltimore City, MD)
8 (Davidson County, TN)
9 (Ramsey County, MN)

742
305
95

29.7
6.8
1.6

62.9
30.4
11.5

19.7
13.9
6.1

116.7
53.0
19.2

a Epidemiologic classification of disease consisted of health care–associated (either hospital-onset cases with a culture collected Ͼ48 h after hospital admission or community-

onset cases with health care risk factors but a culture collected Յ48 h after hospital admission) and community-associated cases (no health care risk factors).

b Site numbers were assigned in descending order of population size.

Table 3. Estimated Incidence Rates of Invasive Methicillin-Resistant Staphylococcus aureus
Infections by Race, Active Bacterial Core Surveillance, United States, 2005
Incidence per 100 000
Age, y
Ͻ1
1
2-4
5-17
18-34
35-49
50-64
Ն65
Total (interval estimates) a

No. of Cases
White
Black
60
14.9
65.9
9
3.7
5.9
18
1.9
6.0
47
0.7
4.8
434
7.3
29.1
1082
16.1
84.9
1327
35.1
127.5
2308
118.0
253.8
5287
27.7 (21.9-32.4) 66.5 (43.5-63.1)

Other
14.2
0
0
0.4
3.2
6.3
15.8
67.0
10.4 (10.7-16.4)

a Interval estimates for the overall incidence by race were calculated for the lower bound by pooling data from the 3

surveillance sites reporting the lowest incidence rates; for the upper bound, by pooling data from the 3 sites reporting the highest rates, excluding data from site 7 (Baltimore City), which reported excessively high rates. These racespecific interval estimates are adjusted by age and sex.

with lowest overall incidence (sites 4,
5, and 9) and an upper bound by pooling data from the 3 EIP sites with highest overall incidence (sites 2, 6, and 8),
excluding site 7. Because data from site
7 were excluded from the interval estimates, there are occasions when the
intervals do not include the overall rate.
Confidence intervals are based on the
properties of a sampling distribution
and cannot be calculated with our data
because our surveillance areas captured all cases, not a sample. We tested
differences in proportions of descriptive characteristics using ␹2. Analyses
were performed using SAS version 9.1.3
(SAS Institute Inc, Cary, North Carolina).

RESULTS
Incidence of Invasive MRSA

There were 8987 observed cases of invasive MRSA reported from July 2004
through December 2005. Most were
health care–associated, with 5250
(58.4%) community-onset infections,
2389 (26.6%) hospital-onset infections, 1234 (13.7%) communityassociated infections, and 114 (1.3%)
that could not be classified.
Unadjusted incidence rates of all types
of invasive MRSA ranged between approximately 20 to 50 per 100 000 in most
ABCs sites but were noticeably higher in
1 site (site 7, Baltimore City) (TABLE 2).
The rate of invasive communityassociated MRSA was less than 3 per

1766 JAMA, October 17, 2007—Vol 298, No. 15 (Reprinted)

100 000 in 4 sites and approximately 5
per 100 000 in 3 sites. Incidence rates
were consistently higher among blacks
compared with whites in the various age
groups (TABLE 3). Adjusting for age, race,
and sex, the standardized incidence rate
of invasive MRSA for calendar year 2005
was 31.8 per 100 000 persons (TABLE 4).
The overall interval estimate after exclusion of the outlier site (site 7) was 24.4
to 35.2 per 100 000.
The rate of health care–associated,
community-onset infections (17.6 per
100 000; interval estimate, 14.7-18.2)
was greater than either health care–
associated, hospital-onset infections (8.9
per 100 000; interval estimate, 6.111.8) or community-associated infections (4.6 per 100 000; interval estimate, 3.6-4.4). Standardized incidence
rates overall were highest among persons 65 years and older (127.7 per
100 000; interval estimate, 92.6-156.9),
blacks (66.5 per 100 000; interval estimate, 43.5-63.1), and males (37.5 per
100 000; interval estimate, 26.8-39.5)
(Table 4). Rates were lowest among persons aged 5 to 17 years (1.4 per 100 000;
interval estimate, 0.8-1.7).
The standardized mortality rate was
6.3 per 100 000 (interval estimate,
3.3-7.5) overall, and was higher
among persons 65 years and older (35.3
per 100 000; interval estimate, 18.444.7), blacks (10.0 per 100 000; interval estimate, 5.7-9.9), and males (7.4

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INVASIVE MRSA INFECTIONS IN THE UNITED STATES

month period from July 2004 through
December 2005. The number of cases
reported per month ranged from 443
in August 2004 to 541 in September
2005. Among all cases reported in the
18-month period, the percentage with
community-associated infections
ranged from 4.2% in April 2005 to 6.6%
in July, August, and October 2005.
When limiting the evaluation to only
the 172 community-associated pneumonia reports, there was no apparent
clustering by season (data not shown).

per 100 000; interval estimate, 3.78.9) (Table 4). Among persons with
MRSA, mortality for health care–
associated, community-onset infections was higher (3.2 per 100 000; interval estimate, 1.7-3.7) than for health
care–associated, hospital-onset infections (2.5 per 100 000; interval estimate, 1.2-3.1) or for communityassociated infections (0.5 per 100 000;
interval estimate, 0.3-0.6).
There were 5287 infections reported in the surveillance areas during 2005; after adjusting for age, race,
and sex to the US population, we estimated that 94 360 (interval estimate,
72 850-104 000) patients had an invasive MRSA infection. There were 988
reported deaths, which we estimated
were 18 650 (interval estimate, 10 03022 070) in-hospital deaths subsequent
to invasive MRSA infections in the
United States (Table 4).
Pooled among all sites, we looked at
the frequency of reports over the 18-

Established MRSA Risk Factors
and Spectrum of Disease

Apart from community-associated cases
which, by definition, had no established health care risk factors for MRSA,
4105 of 5250 (78.2%) cases with health
care–associated, community-onset infections and 1993 of 2389 (83.4%) cases
with health care–associated, hospitalonset infections had more than 1 health
care risk factor for MRSA documented

in medical records. The most common health care risk factors among
cases with community-onset infections and hospital-onset infections were
a history of hospitalization (76.6% and
57.7%, respectively), history of surgery (37.0% and 37.6%), long-term–
care residence (38.5% and 21.9%), and
MRSA infection or colonization (30.3%
and 17.4%).
Of the 8792 cases with complete information, the clinical syndrome associated with invasive MRSA disease included bacteremia (75.2%), pneumonia
(13.3%), cellulitis (9.7%), osteomyelitis (7.5%), endocarditis (6.3%), and septic shock (4.3%). Almost all cases (8304
[92.4%]) were hospitalized, 1598
(17.8%) of all cases died during hospitalization, and 1162 (12.9%) developed recurrent invasive infections.
Cases with endocarditis had a high frequency of recurrent infections (108
[19.3%]). Clinical outcome was recorded for 8849 cases (98%). Crude

Table 4. Numbers and Incidence Rates of Invasive Methicillin-Resistant Staphylococcus aureus (MRSA) Infections and Deaths, by Selected
Demographic Characteristics and Epidemiologic Classifications, Active Bacterial Core Surveillance, United States, 2005 a
Invasive MRSA Deaths

Invasive MRSA Infections
Incidence per 100 000

Incidence per 100 000

Health Care–
Associated
Actual
Demographic No.
Sex
Male
3066
Female
2220
Age, y
Ͻ1
1
2-4
5-17
18-34
35-49
50-64
Ն65
Race
White
Black
Other
Total (interval
estimates)

Community- HospitalOnset
Onset

Estimated
No.

Community

54 790
39 360

6.1
3.2

20.6
14.7

60
9
18
47
434

950
160
290
730
7050

3.5
2.9
0.8
0.6
3.2

1082
1327
2308

16 100
22 120
46 970

2716
1794
139
5287

66 590
25 980
1790
94 360
(72 850104 000)

Health Care–
Associated
Community- HospitalOnset
Onset Total

Total

Actual
No.

Estimated
No.

Community

10.1
7.9

37.5
26.3

571
417

10 840
7820

0.8
0.3

3.9
2.6

2.7
2.2

7.4
5.2

4.7
0.0
1.0
0.4
4.2

14.7
1.0
0.6
0.3
2.4

23.1
3.8
2.4
1.4
10.1

5
0
1
3
31

80
0
10
60
460

0
0
0
0
0.1

0.3
0
0
0
0.2

1.6
0
0.1
0.1
0.3

2.0
0
0.1
0.1
0.7

6.3
6.7
8.9

11.9
23.9
78.2

5.3
12.1
39.1

24.3
43.9
127.7

92
224
632

1400
3640
13 000

0.4
0.9
2.1

0.8
3.2
19.7

0.9
2.9
13.4

2.1
7.2
35.3

3.8
10.9
1.6

15.3
37.2
5.4

8.1
16.6
3.3

27.7
66.5
10.4

596
263
38

14 270
3900
480

0.4
0.2
0.1

3.1
4.8
1.3

2.4
3.7
1.2

5.9
10.0
2.8

4.6
(3.64.4)

17.6
(14.718.2)

8.9
(6.111.8)

31.8
(24.435.2)

988

18 650
(10 05022 100)

0.5
(0.30.6)

3.2
(1.73.7)

2.5
(1.23.1)

6.3
(3.37.5)

a Epidemiologic classification of disease consisted of healthcare-associated (either hospital-onset cases with a culture collected Ͼ48 hours after hospital admission or community-onset

cases with healthcare risk factors but a culture collected Յ48 hours after hospital admission) and community-associated cases (those with no healthcare risk factors). There were 638
cases and 91 deaths with unknown race.

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INVASIVE MRSA INFECTIONS IN THE UNITED STATES

mortality varied by MRSA-related diagnosis, with high rates observed
among cases with septic shock (55.6%)
and pneumonia (32.4%), low rates
among those with cellulitis (6.1%), and
moderate rates among those with bacteremia (10.2%) or endocarditis
(19.3%). The proportion of cases presenting with each major clinical condition varied between epidemiologic
classifications (TABLE 5). Compared
with the distribution of syndromes
among cases with communityassociated infections, bacteremia was
more common, and cellulitis and endocarditis were significantly less common, among each of the cases with
health care–associated infections.

Empirical therapy was documented
for 5730 of the 8987 cases (63.8%).
Overall, 4720 cases (82.4%) received
concordant empirical therapy. Differential outcomes based on discordant
therapy were not evaluated, since required data such as dose, duration,
therapy changes, and adjunctive
therapy were not abstracted. Receipt of
concordant therapy was slightly lower
among cases with communityassociated infections compared with
those having health care–associated infections either of community onset
(80.1% vs 82.9%, respectively; P =.03)
or hospital onset (80.1% vs 86.0%,
PϽ.001). Vancomycin was the antimicrobial agent most frequently used for

Table 5. Number and Percentage of Invasive Methicillin-Resistant Staphylococcus aureus
Infections by Clinical Condition and Epidemiologic Classification, Active Bacterial Core
Surveillance, United States, July 2004-December 2005 a
Health Care–Associated,
No. (%)

Condition b

CommunityAssociated
(n = 1226)

CommunityOnset
(n = 5191)

Bacteremia
Pneumonia
Cellulitis
Osteomyelitis
Endocarditis
Septic shock

798 (65.1)
172 (14.0)
278 (22.7)
99 (8.1)
155 (12.6)
46 (3.8)

4019 (77.4) e
616 (11.9) d
456 (8.8) e
415 (8.0)
341 (6.6) e
233 (4.5)

HospitalOnset
(n = 2375)
1794 (75.5) e
383 (16.1)
114 (4.8) e
142 (6.0) d
60 (2.5) d
99 (4.2)

Total, No.
(N = 8792) c
6611
1171
848
656
556
378

a Epidemiologic classification of disease consisted of health care–associated (either hospital-onset cases with a culture

collected Ͼ48 h after hospital admission or community-onset cases with health care risk factors but a culture collected Յ48 h after hospital admission) and community-associated cases (those with no health care risk factors).

b Cases could have Ն1 clinical syndrome.
c Of 8987 observed cases with invasive methicillin-resistant Staphylococcus aureus, 114 (1.3%) could not be classi-

fied and 81 had missing condition.

d P Ͻ .05.
e P Ͻ .01; all comparisons use community-associated as the referent category.

Table 6. Number and Percentage of Pulsed-Field Types USA100 and USA300 of
Methicillin-Resistant Staphylococcus aureus Isolates, Active Bacterial Core Surveillance Sites,
United States, 2005 a
Isolates at Each Site, No. (%)
Surveillance Site No.
1 (Connecticut)

(Location) b

2 (Atlanta, GA, metropolitan area)
3 (San Francisco, CA, Bay Area)
4 (Denver, CO, metropolitan area)
5 (Portland, OR, metropolitan area)
6 (Monroe County, NY)
7 (Davidson County, TN)
9 (Ramsey County, MN)
Total

No. of
Cases
1583

Isolates
142 (9.0)

USA100
109 (76.8)

USA300
5 (3.5)

Other
28 (19.7)

1995
1604

134 (6.7)
141 (8.8)

36 (26.8)
66 (46.8)

64 (47.8)
53 (37.6)

34 (25.4)
22 (15.6)

805
562
546
423

85 (10.6)
175 (31.1)
81 (14.8)
40 (9.5)

68 (80.0)
83 (47.4)
61 (75.3)
23 (57.5)

14 (16.5)
77 (44.0)
13 (16.3)
15 (37.5)

3 (3.5)
15 (8.6)
7 (8.6)
2 (5.0)

130
7648

66 (50.8)
864 (11.3)

54 (81.1)
500 (6.5)

11 (16.7)
252 (3.3)

1 (1.5)
112 (1.5)

a Isolates not available from site 7, so total does not include 1339 cases reported from that site.
b Site numbers were assigned in descending order of population size.

1768 JAMA, October 17, 2007—Vol 298, No. 15 (Reprinted)

empirical therapy (75%), followed by
semisynthetic penicillins (28%) and
fluoroquinolones (26%). Similar proportions of cases were prescribed monotherapy (31.3%), therapy with 2 antimicrobials (37.9%), or therapy with
more than 2 antimicrobials (30.9%).
Pulsed-Field Typing

PFGE results were available for 864 of
the 1201 (71.9%) isolates received from
8 of the 9 ABCs sites (isolates were not
available from site 7); these results represent 11.3% of the 7648 cases reported from these 8 sites (TABLE 6). Of
these results, 81.6% were from blood
cultures, 4.7% from bone, 4.8% from
synovial fluid, 1.9% from pleural fluid,
1.5% from peritoneal fluid, and the remaining 5.5% from other normally sterile sites; this culture site distribution is
similar to the distribution of culture
sites reported among all 8987 cases. Isolates tested were associated with all of
the major clinical conditions previously described, including uncomplicated bacteremia (69.8%), pneumonia
(19.3%), cellulitis (11.3%), osteomyelitis (10.4%), endocarditis (8.5%), and
septic shock (5.0%).
USA300 was the strain type identified for 100 of 150 (66.6%) isolates
from community-associated cases
and also was found among 108 of
485 (22.2%) isolates from health
care–associated, community-onset
cases and among 34 of 216 (15.7%)
health care–associated, hospitalonset cases (T ABLE 7). Also, 35 of
150 (23.0%) isolates from
community-associated cases were
USA100. In contrast, other strains of
community origin (USA400,
USA1000) were rare, accounting for
only 3 of 150 (2.0%) isolates from
community-associated cases, perhaps
reflecting that these isolates all come
from normally sterile sites and not
skin abscesses, where these strain
types have often been reported.
USA100 and USA300 were the predominant pulsed-field types in each
surveillance site, with the exception
of site 1 (state of Connecticut)
(Table 6).

©2007 American Medical Association. All rights reserved.

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INVASIVE MRSA INFECTIONS IN THE UNITED STATES

COMMENT
These data represent the first US nationwide estimates of the burden of invasive MRSA disease using populationbased, active case finding. Based on
8987 observed cases of MRSA and 1598
in-hospital deaths among patients with
MRSA, we estimate that 94 360 invasive MRSA infections occurred in the
United States in 2005; these infections
were associated with death in 18 650
cases. The standardized incidence rate
of invasive MRSA for calendar year 2005
was 31.8 per 100 000 persons. The incidence of other important invasive
pathogens in 2005, such as invasive infections with S pneumoniae or Haemophilus influenzae, ranged from 14.0
per 100 000 to less than 1 per 100 000,
largely due to the availability and success of vaccination.31-33
The estimated 94 360 infections is
larger than the estimate from a recent
study using hospital discharge–coded
data; in 2000, the CDC estimated that
there were 31 440 hospitalizations for
MRSA bacteremias (ie, septicemia) in
the United States.34 Some of the discrepancy may relate to a more inclusive definition of invasive disease in our
study and to the limitations inherent in
discharge coded data. Of the estimated 94 360 infections from this study,
75.2% were bacteremias, and 26.6%
were of hospital onset; thus, our estimates would yield approximately
18 900 MRSA, hospital-onset bacteremias. In 2002, the CDC estimated that
there were 248 678 hospital-acquired
bacteremias in the United States,35 of
which approximately 20 390 (8.2%)
could be expected to be MRSA20—a result consistent with our findings.
Regarding community-associated
MRSA, noninvasive infections with
MRSA greatly outnumber invasive
MRSA infections. In fact, when 3 of the
ABCs sites began surveillance in 2000
for all MRSA infections, only 7% represented invasive disease. However,
findings described here further document that invasive MRSA disease does
occur in persons without established
health care risk factors,28 is associated
with strains of both community and

Table 7. Pulsed-Field Gel Electrophoresis Type of Methicillin-Resistant Staphylococcus aureus
Isolates Cultured From Invasive Sites, by Epidemiologic Case Classification, Active Bacterial
Core Surveillance, July 2004-December 2005 (n = 864) a
No. (%)
Community-Onset
HospitalOnset
160 (74)

Health Care–
Associated
303 (62)

CommunityAssociated
35 (23)

Unknown
2 (15)

Total
500 (58)

USA200
USA300
USA400

5 (2)
34 (16)
1 (Ͻ1)

9 (2)
108 (22)
4 (1)

0
100 (67)
1 (Ͻ1)

0
10 (77)
0

14 (2)
252 (29)
6 (Ͻ1)

USA500
USA600

9 (4)
1 (Ͻ1)

30 (6)
4 (1)

4 (3)
0

0
0

43 (5)
5 (Ͻ1)

USA700
USA800
USA1000
Iberian

0
0
0
4 (2)
2 (1)
216

0
6 (1)
3 (1)
6 (1)
12 (2)
485

1 (Ͻ1)
1 (Ͻ1)
2 (2)
3 (2)
3 (2)
150

0
0
0
1 (8)
0
13

1 (Ͻ1)
7 (1)
5 (Ͻ1)
14 (2)
17 (2)
864

Pulsed-Field
Type
USA100

Not typeable b
Total

a Epidemiologic classification of disease consisted of health care-associated (either hospital-onset cases with a culture

collected Ͼ48 h after hospital admission or community-onset cases with health care risk factors but a culture collected Յ48 h after hospital admission) and community-associated cases (those with no health care risk factors).

b SmaI pulsed-field gel electrophoresis typing was successful in giving these isolates a pattern number, but numbers

were outside of the 80% similarity range.

health care origin,36 and is associated
with significant mortality. Molecular
analysis of isolates in our study provides
evidence supporting other studies36
showing that strains of community origin do now cause some hospital-onset
disease but also that, overall, most invasive MRSA disease is still caused by
MRSA strains of health care origin.
Compared with rates of invasive
MRSA infections in 2 of our sites from
2001-2002, the incidence of invasive
MRSA has increased in 2005 from 19.3
per 100 000 to 33.0 per 100 000 in Atlanta and from 40.4 per 100 000 to
116.7 per 100 000 in Baltimore.13 These
increases were in both community- and
health care–associated disease. However, in the state of Connecticut, the rate
of community-onset MRSA bacteremias has been relatively stable at 2.5 per
100 000 in 199829 and 2.8 per 100 000
in 2005.
We describe striking differences in
rates of invasive MRSA infections by
race among all age groups. Connecticut documented a disparity for community-onset S aureus bacteremias in
1998.29 More recently, surveillance in
Atlanta reported a significantly higher
rate of community-associated MRSA

©2007 American Medical Association. All rights reserved.

among blacks compared with whites13;
however, little progress has been made
in understanding why. It is likely that
the prevalence of underlying conditions,37 at least some of which vary by
race,38 may play a role. The incidence
of invasive pneumococcal disease varies widely by underlying chronic illness, but racial disparities persist for all
conditions evaluated.39 MRSA prevalence has been linked to socioeconomic status,40 and this might confound the association between race and
incidence of MRSA. Future analyses
should focus on understanding reasons for differences in MRSA incidence rates.
The geographic variability in MRSA
rates has been documented in other
studies.3,13 In this study we found that
areas with lower incidence rates of invasive MRSA overall did not always
have lower rates of communityassociated MRSA. For example, site 6
(Monroe County, New York) had a relatively high rate of invasive MRSA overall (41.9 per 100 000) but a low rate of
community-associated MRSA (2.7 per
100 000); site 5 (the Portland, Oregon, metro area) had a relatively low
rate of invasive MRSA overall (19.8 per

(Reprinted) JAMA, October 17, 2007—Vol 298, No. 15

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1769

INVASIVE MRSA INFECTIONS IN THE UNITED STATES

100 000) but a high rate of communityassociated MRSA (4.7 per 100 000). In
addition to factors already mentioned
such as socioeconomic status and underlying conditions, MRSA rates may
be higher in urban areas.29 As with differences in the incidence of invasive
MRSA by race, geographic differences
are probably multifactorial and complex. Improved understanding can help
design and focus prevention messages
as well as increase the timeliness of diagnosis and clinical management of invasive infections.
The majority of invasive MRSA cases
occurred outside of the hospital (58%)
but among persons with established risk
factors for MRSA, such as a history of
hospitalization in the past year. This observation was also made recently in a
study from a single facility.30 Patients
with health care risk factors and community-onset disease likely acquired the
pathogen from their health care contacts, such as those from a recent hospitalization or nursing home residence. Molecular analysis suggests that
most of these infections were caused by
MRSA strains of health care origin. If,
in fact, these infections represent acquisition during transitions of care from
acute care,41 it follows that strategies to
prevent and control MRSA among inpatients,42,43 if properly applied, may
have an impact on these infections as
well as on the traditional hospitalonset infections. Since interventions for
MRSA prevention are inconsistently
implemented in US hospitals,44 correlating the impact on either inpatient or
outpatient disease will be challenging.
Interventions used in the community
to control outbreaks consist of improving hygiene and infection control along
with enhanced surveillance, diagnosis, and appropriate treatment of
infections45-47; however, studies of the
effectiveness of community-based prevention and control interventions are
lacking.
Our estimates have certain limitations. First, we may have underestimated the incidence of invasive MRSA
disease if persons in the surveillance
areas sought health care from facili-

ties using laboratories outside the surveillance area. However, any underestimate is probably minor in light of the
estimates derived from discharge data
on MRSA hospitalizations.34
Second, we may have overestimated
the incidence of community-associated MRSA if health care risk factors
were not well documented in medical
records. During surveillance conducted in 2000-2001, patient interviews were used to elicit undocumented health care risk factors; however,
the effect on reclassification was small.13
Third, our surveillance sites were
largely urban areas; thus, we might be
overestimating the incidence of invasive MRSA.29 Although our surveillance areas comprise a diverse set of
regions and are likely representative of
the United States, it is not known
whether the incidence rates in the
observed populations are actually representative of the distribution of incidence rates in other US cities. Since the
methodology of population-based surveillance produces a single point estimate without confidence intervals (ie,
all cases are identified), we calculated
interval estimates excluding site 7 (Baltimore City) to allow the reader to interpret a range of estimates reflecting different metropolitan areas. Regarding the
high observed incidence rates reported
by site 7, we conducted an evaluation
to determine whether these results were
valid, including a review of casefinding methods, elimination of cases
to include only those with zip codes represented in the denominator, contamination in any laboratory, and other
potential causes for increased rates;
however, none were in error.
Fourth, our measures of deaths represented crude, in-hospital deaths,
rather than attributable mortality. It is
possible that MRSA infection did not
cause or contribute to some deaths.
Fifth, the evaluation of isolates in this
study was meant to describe strain diversity and to shed light on the potential crossover of strains from a community origin into the hospital setting. The
isolate collection was a convenience
sample. Furthermore, we only had test

1770 JAMA, October 17, 2007—Vol 298, No. 15 (Reprinted)

results from isolates of 864 (11.3%) of
the cases reported; extrapolation of the
molecular characterization to the US
population should be avoided.
In conclusion, invasive MRSA disease is a major public health problem
and is primarily related to health care
but no longer confined to acute care.
Although in 2005 the majority of invasive disease was related to health care,
this may change.
Author Contributions: Dr Klevens had full access to
all of the data in the study and takes responsibility for
the integrity of the data and the accuracy of the data
analysis.
Study concept and design: Klevens, Morrison,
Gershman, Lynfield, Townes, Craig, Carey, Fridkin.
Acquisition of data: Klevens, Morrison, Nadle, Petit,
Ray, Harrison, Lynfield, Dumyati, Townes, Craig,
Fosheim.
Analysis and interpretation of data: Klevens, Morrison,
Ray, Lynfield, Zell, Fosheim, McDougal, Fridkin.
Drafting of the manuscript: Klevens, Morrison, Fridkin.
Critical revision of the manuscript for importan intellectual content: Klevens, Morrison, Nadle, Petit,
Gershman, Ray, Harrison, Lynfield, Dumyati, Townes,
Craig, Zell, Fosheim, McDougal, Carey, Fridkin.
Statistical analysis: Morrison, Zell.
Obtained funding: Klevens, Fridkin.
Administrative, technical, or material support: Klevens,
Ray, Harrison, Lynfield, Townes, Craig, Fosheim, Carey,
Fridkin.
Study supervision: Klevens, Gershman, Dumyati,
Townes, Craig, Carey, Fridkin.
Financial Disclosures: None reported.
Active Bacterial Core surveillance (ABCs) MRSA Investigators: William Schaffner, MD, Tennessee Emerging Infections Program (EIP); Jessica Buck, Minnesota EIP; Jim Hadler, MD, Connecticut EIP; Monica M.
Farley, MD, Georgia EIP; Laurie Thompson Sanza,
Maryland EIP; Michael Emerson, Oregon EIP; Brandi
M. Limbago, PhD, Fred C. Tenover, PhD, and Jean B.
Patel, PhD, Division of Healthcare Quality Promotion, Centers for Disease Control and Prevention (CDC).
Funding/Support: This study was funded through the
Emerging Infections Program, National Center for Preparedness, Detection, and Control of Infectious Diseases, Coordinating Center for Infectious Diseases, CDC.
Role of the Sponsor: No commercial entity had any
role in the design and conduct of the study; the collection, management, analysis, and interpretation of
the data; or the preparation, review, or approval of
the manuscript.
Additional Contributions: We thank Elizabeth Partridge, Pam Daily, MPH, and Gretchen Rothrock, California EIP; Steve Burnite, Deborah Aragon, Nicole Comstock, Allison Daniels, and Jonathan Schwartz, Colorado
EIP; Zack Fraser and Nancy L. Barrett, MS, MPH, Connecticut EIP; Wendy Baughman, MSPH, Janine Ladson, MPH, James Howgate, MPH, and Emily
McMahan, RN, BSN, Georgia EIP; Janice Langford and
Kathleen Shutt, Maryland EIP; Dave Doxrud and Selina
Jawahir, Minnesota EIP; Nana Bennett, MD, Anita Gellert, RN, and Paul Malpiedi, New York EIP; Robert
Vega, Janie Tierheimer, Karen Stefonek, Michelle Barber, and Ann Thomas, MD, Oregon EIP; Brenda Barnes,
Terri McMinn, Jane Conners, and Melinda Eady, Tennessee EIP; and Sandra Bulens, MPH, Chris Van
Beneden, MD, MPH, Tami Skoff, MS, Carolyn Wright,
and Emily Weston, CDC, for ongoing surveillance and
case follow-up; Christina Crane, CDC, for microbiological testing of the isolates; John Jernigan, MD, CDC,
for guidance with the design of the surveillance project;

©2007 American Medical Association. All rights reserved.

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INVASIVE MRSA INFECTIONS IN THE UNITED STATES
and Jeff C. Hageman, MHS, CDC, for manuscript review and surveillance guidance. None of these individuals received any compensation from industry related to this study.
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