original article
The
new england journal
of
medicine
n engl j med
352;5
www.nejm.org february
3, 2005
468
A Clone of Methicillin-Resistant
Staphylococcus aureus
among Professional
Football Players
Sophia V. Kazakova, M.D., M.P.H., Ph.D., Jeffrey C. Hageman, M.H.S.,
Matthew Matava, M.D., Arjun Srinivasan, M.D., Larry Phelan, B.S., B.A.,
Bernard Garfinkel, M.D., Thomas Boo, M.D., Sigrid McAllister, B.S., M.T.(A.S.C.P.),
Jim Anderson, B.S., A.T.C., Bette Jensen, M.M.Sc., Doug Dodson, B.S.,
David Lonsway, M.M.Sc., Linda K. McDougal, M.S., Matthew Arduino, Dr.P.H.,
Victoria J. Fraser, M.D., George Killgore, Dr.P.H., Fred C. Tenover, Ph.D.,
Sara Cody, M.D., and Daniel B. Jernigan, M.D., M.P.H.
From the Division of Healthcare Quality
Promotion, National Center for Infectious
Diseases (S.V.K., J.C.H., A.S., S.M., B.J., D.L.,
L.K.M., M.A., G.K., F.C.T., D.B.J.), and the
Epidemic Intelligence Service, Division of
Applied Public Health Training, Epidemiology
Program Office (S.V.K., T.B.), Centers
for Disease Control and Prevention, Atlanta;
the Departments of Orthopedic Surgery
(M.M.) and Internal Medicine (B.G.) and
the Department of Internal Medicine, Infectious
Diseases Division (V.J.F.), Washington
University School of Medicine, St.
Louis; the Missouri Department of Health
and Senior Services, St. Louis (L.P., D.D.);
the BJC Medical Group, St. Louis (B.G.); the
St. Louis Rams Professional Football Team,
St. Louis (J.A.); and the Office of Disease
Control, Santa Clara County Health Department,
San Jose, Calif. (S.C.). Address reprint
requests to Dr. Kazakova at the Epidemic
Intelligence Service, Division of Healthcare
Quality Promotion, National Center for Infectious
Diseases, CDC, 1600 Clifton Rd,
MS A35, Atlanta, GA 30333, or at srk7@
cdc.gov.
N Engl J Med 2005;352:468-75.
Copyright © 2005 Massachusetts Medical Society.
background
Methicillin-resistant
Staphylococcus aureus
(MRSA) is an emerging cause of infections
outside of health care settings. We investigated an outbreak of abscesses due to MRSA
among members of a professional football team and examined the transmission and
microbiologic characteristics of the outbreak strain.
methods
We conducted a retrospective cohort study and nasal-swab survey of 84 St. Louis Rams
football players and staff members.
S. aureus
recovered from wound, nasal, and environmental
cultures was analyzed by means of pulsed-field gel electrophoresis (PFGE) and
typing for resistance and toxin genes. MRSA from the team was compared with other
community isolates and hospital isolates.
results
During the 2003 football season, eight MRSA infections occurred among 5 of the 58
Rams players (9 percent); all of the infections developed at turf-abrasion sites. MRSA
infection was significantly associated with the lineman or linebacker position and a
higher body-mass index. No MRSA was found in nasal or environmental samples; however,
methicillin-susceptible
S. aureus
was recovered from whirlpools and taping gel
and from 35 of the 84 nasal swabs from players and staff members (42 percent). MRSA
from a competing football team and from other community clusters and sporadic cases
had PFGE patterns that were indistinguishable from those of the Rams’ MRSA; all carried
the gene for Panton–Valentine leukocidin and the gene complex for staphylococcal-
cassette-chromosome
mec
type IVa resistance (clone USA300-0114).
conclusions
We describe a highly conserved, community-associated MRSA clone that caused abscesses
among professional football players and that was indistinguishable from isolates
from various other regions of the United States.
abstract
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n engl j med
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methicillin-resistant
s. aureus
among football players
469
ontact sports such as american
football inevitably lead to skin and soft-tissue
injuries that place players at increased
risk for infection.
1,2
Skin infections, particularly
those caused by
Staphylococcus aureus
, are common
among sports participants. Recent reports have described
an increasing number of community-associated
methicillin-resistant
S. aureus
(MRSA) skin
infections in persons without links to health care institutions.
3-6
These infections differ from those due
to health care–associated MRSA in that they are
resistant predominantly to
b
-lactam and macrolide
antimicrobial agents and in that they result in
the formation of skin abscesses. Cases of community-
associated MRSA infection have previously been
reported among football players and other sports
participants; however, little is known about factors
associated with the emergence of communityassociated
MRSA strains that may cause outbreaks
in various geographic regions and community settings.
In September 2003, cases of large skin abscesses
caused by MRSA were first noted among members
of the St. Louis Rams, a professional football team
in Missouri. Additional cases among team members
and subsequent cases in members of an opposing
team suggested that competitive play might
be causing transmission. On November 6, 2003, the
Centers for Disease Control and Prevention (CDC)
was invited to investigate the transmission of MRSA
among the Rams football players, to recommend
prevention and control measures, and to characterize
the staphylococcal isolates.
epidemiologic investigation
We defined a case of MRSA infection as any skin
or soft-tissue infection in a player or staff member
of the St. Louis Rams during the 2003 football season
(August 1 through November 30) from which
MRSA was isolated on culture. To identify potential
activities that might have led to the transmission of
MRSA, we performed an observational study of onfield
and off-field activities and hygiene practices
during competition and training at the Rams facility.
In addition, a retrospective cohort study of
the players was conducted to identify risk factors
for infection. Using a standardized data-collection
form, we collected information about players’ field
positions, demographic characteristics, health care
exposures, antimicrobial use, close contact with
other persons with skin infections, skin-abrasion
management, hygiene practices, and use of saunas,
whirlpools, and training and therapy equipment.
We also evaluated antimicrobial use among the
Rams players by reviewing the team pharmacy log
and calculating the average number of antimicrobial
prescriptions per player per year. We compared
this rate to sex- and age-specific rates in the general
population, as determined by national surveys.
7,8
environmental and laboratory
investigation
To determine whether other Rams players were
colonized with the outbreak MRSA strain, we performed
a nasal-carriage prevalence survey among
all players and staff members and obtained swabs
of uninfected skin abrasions. To identify any environmental
sources of exposure, we sampled surfaces
and shared items in the training facility, including
weight-training equipment, towels, saunas
and steam rooms, and water from whirlpools and
a therapy pool. In addition, we swabbed 0.1-m
2
(1-ft
2
) areas of artificial turf after a game in areas of
the field that were recorded to have the highest number
of tackles. All environmental sampling was performed
after recommended infection-control procedures
and the use of chlorhexidine-containing
soap had been initiated.
After initial screening for oxacillin resistance, all
available MRSA isolates from Rams players’ skin
abscesses and suspected MRSA isolates from skin
abrasions, nasal swabs, and environmental sources
were tested for antimicrobial susceptibility by
means of broth microdilution, according to interpretive
criteria of the Clinical and Laboratory Standards
Institute (formerly the National Committee
for Clinical Laboratory Standards).
9
The antimicrobial
agents tested were ciprofloxacin, clindamycin,
erythromycin, levofloxacin, oxacillin, penicillin,
tetracycline, trimethoprim–sulfamethoxazole, and
vancomycin. In addition, an antimicrobial-susceptibility
disk test to study inducible clindamycin resistance
(i.e., a D-test) was performed.
10,11
All
S. aureus
recovered from skin abscesses, the environment,
nasal swabs, and skin-abrasion specimens
were tested by a polymerase-chain-reaction
assay for the staphylococcal-cassette-chromosome
mec
(SCC
mec
) resistance complex, as described by
Katayama et al.,
12
and for the gene encoding Panton–
Valentine leukocidin cytotoxin.
13,14
After digestion of chromosomal DNA with restriction
endonucleases (
Sma
I for initial digestion
c
methods
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The
new england journal
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470
and
Eag
I,
Sac
II,
Nar
I,
Apa
I, or
Nae
I for subsequent
digestion of subtype USA300-0114), restriction
products were analyzed by pulsed-field gel electrophoresis
(PFGE).
15
The gels were analyzed with
BioNumerics software (Applied Maths) and interpreted
according to criteria published elsewhere.
16
To determine the relatedness of the outbreak strain
to other strains, we compared the PFGE patterns of
isolates from the Rams with those of MRSA isolates
from Team A, a professional football team that
competed with the Rams and members of which
subsequently had abscess development. In addition,
we compared the PFGE patterns of both teams’ isolates
with all 3241 isolates of
S. aureus
in the CDC
PulseNet database
17
to identify the clonal complex
to which the isolates belonged. To compare the
patterns, we calculated percentage similarities with
Dice coefficients by the unweighted pair-group
method with arithmetic averages.
17
Multilocus sequence
typing was performed on pulsed-field type
USA300 isolates.
18
statistical analysis
All univariate and bivariate analyses were performed
with SAS software, version 9.0. Chi-square
or Fisher’s exact tests were used to analyze the relationships
between categorical variables, and t-tests
were used to analyze the relationship between categorical
and continuous variables. All reported P values
are two-sided. Multivariate analysis was not performed
because of the small number of cases.
epidemiologic investigation
From September 1 through December 1, 2003,
eight MRSA infections occurred in 5 of the 58 Rams
players (9 percent) (Fig. 1). The infections developed
in offensive and defensive linemen and a linebacker
at sites of skin abrasions (turf burns) on elbows,
forearms, or knees. All the infections rapidly
progressed to large abscesses 5 to 7 cm in diameter
and required surgical intervention with incision
and drainage. The mean age of the players with
MRSA infections was 27 years (range, 23 to 33). Various
antimicrobial agents were administered; two
of the players received intravenous antimicrobial
agents (vancomycin and ceftriaxone) before the initiation
of oral antimicrobial therapy, and all five players
received three oral agents (cephalexin, trimethoprim–
sulfamethoxazole, and rifampin) alone or
in combination. Most of the infections resolved
within 10 days after the initiation of treatment.
Recurrent infections developed in three of the five
players. Although none of the players required hospitalization,
three of them missed 1, 4, and 12 days
of games or practice, respectively, for a total of 17
missed days due to infection.
From our player survey and observational study
of games and practices, we found that skin abrasions
occurred frequently among players. Approximately
two to three turf burns per week were acquired
from sliding on the field during competition
or practice (Fig. 2). Players reported that abrasions
were more frequent and severe when competition
took place on artificial turf than when it took place
on natural grass. Trainers, who provided wound
care, did not have regular access to hand hygiene,
and alcohol-based hand-hygiene products were
not available near areas where wound care or physical
therapy was provided. Towels were frequently
shared on the field during practice and games,
with as many as three players using the same towel.
Players often did not shower before using communal
whirlpools. At the training facility, weighttraining
and therapy equipment was not routinely
cleaned. Manufacturer-recommended guidelines
for the routine cleaning of whirlpools, saunas, and
steam rooms were not available for review.
Evaluation of potential risk factors explored in
a cohort study revealed that being a lineman or a
linebacker, as compared with having a backfield
position, was associated with the highest relative
risk of an MRSA infection (10.6 [95 percent confidence
interval, 1.3 to infinity], P=0.02) (Table 1).
Players with MRSA skin infection had a significantly
higher body-mass index than players in whom infection
did not develop. Use of antimicrobial agents
during the previous year was associated with MRSA
infection; however, the association was not statistically
significant (relative risk, 7.8; 95 percent confidence
interval, 0.5 to infinity).
According to the team pharmacy log for the
2002 football season, maintained at the training
facility, a team player on average received 2.6 antimicrobial-
drug prescriptions per year. This rate was
greater than 10 times the rate among persons of
the same age and sex in the general population (0.5
prescription per year). In their survey responses,
approximately 60 percent of players indicated they
had taken or received antimicrobials during the
2003 football season.
Infection-control measures were instituted at
the Rams training facility during the week of Octoresults
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n engl j med
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methicillin-resistant
s. aureus
among football players
471
ber 26, 2003 (Fig. 1), and included installation of
wall-mounted soap dispensers with chlorhexidinecontaining
soap for routine hand washing by players
and staff members, appropriate local wound
care, antimicrobial therapy targeting MRSA, and
active surveillance for skin infections. After this intervention,
only one additional case of MRSA infection
occurred.
laboratory investigation
Susceptibility testing of the MRSA causing infections
in five Rams players showed that, in all cases,
it was resistant to macrolides and oxacillin but susceptible
to ciprofloxacin, clindamycin, tetracycline,
trimethoprim–sulfamethoxazole, and vancomycin.
None of the tested isolates exhibited inducible
clindamycin resistance on the D-test. Isolates
from the Rams and from Team A were compared
with 3241
S. aureus
isolate patterns in the CDC staphylococcus
PulseNet database, which revealed that
both teams’ isolates were pulsed-field type USA300
(Fig. 3). After digestion with
Sma
I endonuclease,
the teams’ PFGE patterns were indistinguishable
from one another but also indistinguishable from
patterns associated with various community-associated
MRSA clusters and sporadic cases in the United
States. Both the teams’ isolates and the indistinguishable
community-associated isolates differed
from other community-associated MRSA isolates
(USA400) and known health care–associated isolates
(USA100 and USA200).
To discriminate further among the indistinguishable
PFGE patterns, digestion with five additional
enzymes (
Eag
I,
Sac
II,
Nar
I,
Apa
I, and
Nae
I) was
performed on MRSA isolates: two from the Rams,
eight from Team A, and one representative isolate
from each of nine previously investigated community
clusters and sporadic cases among sports par-
Figure 1. Epidemic-Curve Graph (Top) and Field Position Diagram (Bottom) of Cases of MRSA Infection among St. Louis
Rams Professional Football Players in 2003.
Each box on the epidemic-curve graph and field diagram represents an MRSA infection; different colors designate different
players; boxes of the same color thus represent recurrent infections. On the field diagram, X represents a defensiveplayer
position and O an offensive-player position.
Offense
Defense
No. of Infectionss
2
1
0
3 10 17 24 31 7 14 21 28 5 12 19 26 2 9 16 23 30
August September October
Week of Infection
November
First MRSA
infection
in Team A
Game
against
Team A
Initiation of infectioncontrol
measures
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ticipants, children, prisoners, military recruits, and
men who have sex with men. After each of the five
additional digestions, the isolates again had indistinguishable
patterns. This clonal subtype is now
classified as pulsed-field type USA300-0114. All
USA300-0114 isolates contained the gene for Panton–
Valentine leukocidin as well as the gene complex
for SCC
mec
type IVa resistance. The USA300-
0114 subtype has been determined to fall within
sequence type 8 on multilocus sequence typing.
The nasal-swab survey indicated that 23 of the
58 Rams players (40 percent) and 12 of the 26 staff
members (46 percent) were colonized with methicillin-
susceptible
S. aureus
(MSSA). No MRSA was
identified. No environmental specimens yielded
MRSA; however, MSSA isolates were recovered from
a gel-applicator stick used for taping ankles and
from two samples of whirlpool water collected at
the end of the day. The gel and whirlpool-water isolates
were indistinguishable on PFGE from MSSA
recovered from the nasal swabs.
Examination of one nasal MSSA isolate revealed
a two-band difference from the USA300-0114 pattern.
This isolate also had the gene for Panton–
Valentine leukocidin. Southern blot hybridization
analysis of the outbreak MRSA isolates and the nasal
MSSA isolate demonstrated that the band missing
in the MSSA isolate carried the
mecA
resistance
gene. The absence of the
mecA
gene may indicate either
that the isolate lost the resistance gene or that
this MSSA represents a strain that has not yet acquired
the resistance gene.
Our investigation revealed that a cluster of skin abscesses
among professional football players and
other recent outbreaks of skin infection in the United
States were caused by an emerging MRSA clone.
This community-associated clone differed from
strains of MRSA circulating in health care settings
in that it was susceptible to most antimicrobial
agents other than
b
-lactams and macrolides, it primarily
caused skin infections in otherwise healthy
persons, and it carried both a characteristic gene
complex for methicillin resistance (SCC
mec
type
IVa) and the gene for Panton–Valentine leukocidin,
a cytotoxin that has been associated with severe abscesses
and necrotizing pneumonia.
13
During the
2003 football season, abscesses also occurred in a
competing team after a game with the Rams, suggesting
that transmission of MRSA occurred during
game play.
We used PFGE and five restriction endonucleases
to demonstrate that MRSA isolates from both
teams were indistinguishable. Further comparison
with MRSA from epidemiologically unrelated outbreaks
among sports participants and persons in
other settings revealed that these other isolates were
also indistinguishable from those of the two professional
football teams and represented a clone
now classified as pulsed-field type USA300-0114.
These results indicate that this clone may be widely
distributed in the community and thus that the two
teams may have acquired the same strain independently.
With currently available molecular-typing
methods, it was not possible to differentiate between
community and team isolates, and thus neither
team-to-team transmission nor independent,
community acquisition could be implicated as the
primary source of MRSA among football players.
discussion
Figure 2. Photograph of an Uninfected Skin Abrasion
(Turf Burn) on a St. Louis Rams Professional Football
Player in 2003.
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n engl j med
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methicillin-resistant
s. aureus
among football players
473
Findings from our investigation underscore the
importance of certain factors at the player level
and at the team level that could have facilitated the
spread of the clone in this setting. One important
player-level factor was skin abrasions, or turf burns.
All MRSA skin abscesses developed at sites of turf
burns on areas of skin not covered by a uniform
(e.g., elbows and forearms). These abrasions were
usually left uncovered, and when combined with
frequent skin-to-skin contact throughout the football
season, probably constituted both the source
and the vehicle for transmission. In our investigation,
infection occurred only among linemen and
linebackers, and not among those in backfield positions,
probably because of the frequent contact
among linemen during practice and games. We also
observed a lack of regular access to hand hygiene
(i.e., soap and water or alcohol-based hand gels)
for trainers who provided wound care; skipping of
showers by players before the use of communal
whirlpools; and sharing of towels — all factors
that might facilitate the transmission of infection
in this setting.
We did not detect any MRSA in environmental
or nasal samples; however, environmental sources
yielded MSSA that matched nasal MSSA isolates
— a finding that suggests that the environment
may have had a role in the transmission of MRSA
among team members. Previously reported investigations
have identified potential transmission
from contaminated surfaces and shared items.
23
In addition, recovery of MRSA from colonized persons
during outbreaks has been variable, with some
investigations detecting no nasal colonization with
MRSA,
19,22
as was the case in our study. Treatment
of infected players with antimicrobial drugs (e.g.,
rifampin) in our study may have eliminated the nasal
colonization in these persons. In addition, institution
of infection-control practices and enhancement
of personal hygiene may have minimized
* The data reflect information provided by the players who responded to the survey. CI denotes confidence interval, and NA not
applicable. Percentages and relative risks were calculated on the basis of the total number of responses to each question.
† P values and confidence intervals are based on Fisher’s exact and chi-square analysis for categorical variables and t-testing
for continuous variables.
‡ The mean body-mass index is the weight in kilograms divided by the square of the height in meters.
Table 1. Risk Factors for Skin Abscesses Due to Community-Associated MRSA among 53 St. Louis Rams Football Players,
August 1 through November 30, 2003.*
Risk Factor Risk Factor Present
Relative Risk
(95% CI) P Value†
All
Respondents
MRSA
Infection
No MRSA
Infection
Black race — no. of players (%) 25/53 (47) 3/5 (60) 22/48 (46) 1.7 (0.3–9.3) 0.55
Mean body-mass index‡ NA 35.8 31.1 NA 0.03
Lineman or linebacker position
(vs. backfield position)
— no. of players (%)
27/53 (51) 5/5 (100) 22/48 (46) 10.6 (1.3–
∞
) 0.02
Surgery in past year
— no. of players (%)
16/53 (30) 3/5 (60) 13/48 (27) 3.5 (0.6–18.8) 0.13
Hospitalization in past year
— no. of players (%)
10/53 (19) 0/5 10/48 (21) 0.4 (0–3.6) 0.33
Use of antimicrobials in past year
— no. of players (%)
30/51 (59) 5/5 (100) 25/46 (54) 7.8 (0.5–
∞
) 0.06
Turf burns covered during games
— no. of players (%)
39/50 (78) 3/5 (60) 36/45 (80) 0.4 (0.1–2.2) 0.31
Shaved body other than face
— no. of players (%)
9/51 (18) 1/5 (20) 8/46 (17) 1.2 (0.2–9.2) 0.89
Gloves worn during games
— no. of players (%)
44/52 (85) 5/5 (100) 39/47 (83) 2.2 (0.2–
∞
) 0.41
Gloves used >3 times (vs. 1, 2,
or 3 times) before washing
— no. of players (%)
29/46 (63) 2/5 (40) 27/41 (66) 0.4 (0.1–2.1) 0.26
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colonization and transmission to other players before
our nasal-swab survey.
We found the highly conserved USA300-0114
MRSA clone was present in diverse regions of the
United States. This clone and other USA300 and
USA400 strains appear to have caused the majority
of community-associated MRSA cases characterized
to date in the United States.
17
The reasons for
the emergence of the clone are unclear; however,
antimicrobial use in the community may have helped
select bacteria that are resistant to standard empiric
therapy for skin and soft-tissue infections (i.e.,
a first-generation cephalosporin or a penicillinaseresistant
penicillin). The players in our investigation
were receiving 10 times the number of antimicrobial
prescriptions dispensed to the general
public. Increased use of antimicrobial agents, when
combined with other factors such as compromised
skin, close skin-to-skin contact, close person-toperson
proximity, a contaminated environment,
and suboptimal hand and personal hygiene may
provide the right conditions for efficient transmission
among the members of a cohort and thus lead
to clusters of skin infections.
On the basis of the findings of this and other investigations
of outbreaks among sports participants,
several recommendations can be made. First,
clinicians and other personnel involved in the care
of sports participants should be aware of the emergence
in the community of MRSA with distinct
microbiologic and epidemiologic characteristics.
Infections with these organisms predominantly
cause skin abscesses in otherwise healthy persons
who often have no health care exposures. Obtaining
cultures in suspected cases of infection and performing
antimicrobial-susceptibility testing will
facilitate early identification of cases and initiation
of targeted treatment. Clinicians should drain
abscesses and ensure that wounds are covered and
contained with clean, dry dressings. Infected persons
should receive guidance regarding enhanced
hand and personal hygiene to prevent transmission.
Frequently touched surfaces should be cleaned
in accordance with manufacturer-recommended
guidelines. Chlorhexidine-containing soap and nasal
decolonization with mupirocin have been recommended
to control outbreaks
19-23
; however, data
demonstrating the independent benefit of these
agents in controlling MRSA in community clusters
are lacking. Some studies have reported that anti-
Figure 3. Pulsed-Field Gel Electrophoresis Patterns with Percentage Similarities for MRSA Isolates from Competing Football Teams (St. Louis
Rams and Team A) and from Outbreaks in Various Community Settings and Geographic Locations.
The dendrogram presents only one representative MRSA isolate for each setting. All strains are from the staphylococcus PulseNet database
of the Centers for Disease Control and Prevention (CDC).
Similarity (%) Isolate Reference
St. Louis Rams professional football
team, Missouri
Professional football team A
College football team, California CDC19
CDC4
CDC4
CDC20
CDC21
CDC21
Martinez-Aguilar et al.22
CDC19
CDC19
College football team, Pennsylvania
Fencers, Colorado
Prison inmates, Mississippi
Prison inmates, Georgia
Prison inmates, Texas
Children, Tennessee
Children, California
Men who have sex with men, California
Hospital Strain USA100
Hospital Strain USA200
60 80 100
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methicillin-resistant
s. aureus
among football players
475
bacterial soap with 1.5 percent triclocarban is effective
in preventing impetigo and atopic dermatitis.
24
Additional studies are needed to determine
whether the use of antibacterial soap should be routinely
recommended and whether decolonization
and the use of body antiseptics are also needed to
control transmission.
The CDC has initiated a collaboration with the
National Collegiate Athletic Association in developing
guidelines for the prevention and control of
community-associated MRSA among college football
players. The guidelines will include educational
materials targeted to athletic trainers and will
describe infection-control practices and measures
for responding to cases or clusters of infections.
To monitor the prevalence of community-associated
MRSA infections, the CDC has initiated active
population-based surveillance in eight geographic
locations in the United States.
25
These data will
help to characterize the emergence of MRSA in the
community and will guide public health interventions,
including strategies to prevent antimicrobial
resistance.
The use of trade names and commercial sources does not imply
endorsement by the U.S. Department of Health and Human Services
or the CDC.
We are indebted to Laura Rose, Terri Forster, Chesley Richards,
and Linda McCaig (CDC); to Dr. Bao-Ping Zhu (Missouri Department
of Health and Senior Services); and to Dr. William Baine
(Agency for Healthcare Research and Quality, U.S. Department of
Health and Human Services) for their support.
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