Trends in Invasive Methicillin-Resistant Staphylococcus aureus Infections

Martha Iwamoto, Yi Mu, Ruth Lynfield, Sandra N. Bulens, Joelle Nadle, Deborah
Aragon, Susan Petit, Susan M. Ray, Lee H. Harrison, Ghinwa Dumyati, John M.
Townes, William Schaffner, Rachel J. Gorwitz and Fernanda C. Lessa
Pediatrics; originally published online September 23, 2013;
DOI: 10.1542/peds.2013-1112

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Trends in Invasive Methicillin-Resistant Staphylococcus aureus Infections

Martha Iwamoto, Yi Mu, Ruth Lynfield, Sandra N. Bulens, Joelle Nadle, Deborah
Aragon, Susan Petit, Susan M. Ray, Lee H. Harrison, Ghinwa Dumyati, John M.
Townes, William Schaffner, Rachel J. Gorwitz and Fernanda C. Lessa
Pediatrics; originally published online September 23, 2013;
DOI: 10.1542/peds.2013-1112
Updated Information &
Services

including high resolution figures, can be found at:

http://pediatrics.aappublications.org/content/early/2013/09/18
/peds.2013-1112

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PEDIATRICS is the official journal of the American Academy of Pediatrics. A monthly

publication, it has been published continuously since 1948. PEDIATRICS is owned, published,
and trademarked by the American Academy of Pediatrics, 141 Northwest Point Boulevard, Elk
Grove Village, Illinois, 60007. Copyright 2013 by the American Academy of Pediatrics. All
rights reserved. Print ISSN: 0031-4005. Online ISSN: 1098-4275.

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ARTICLE

Trends in Invasive Methicillin-Resistant

Staphylococcus aureus Infections
AUTHORS: Martha Iwamoto, MD, MPH,a Yi Mu, PhD,a Ruth
Lyneld, MD,b Sandra N. Bulens, MPH,a Joelle Nadle, MPH,c
Deborah Aragon, MSPH,d Susan Petit, MPH,e Susan M. Ray,
MD,f,g Lee H. Harrison, MD,h,i Ghinwa Dumyati, MD,j John M.
Townes, MD,k William Schaffner, MD,l Rachel J. Gorwitz,
MD, MPH,a and Fernanda C. Lessa, MD, MPHa
aCenters

for Disease Control and Prevention, Atlanta, Georgia;

Department of Health, St Paul, Minnesota; cCalifornia
Emerging Infections Program, Oakland, California; dColorado
Department of Public Health and Environment, Denver, Colorado;
eConnecticut Department of Health, Hartford, Connecticut;
fGeorgia Emerging Infections Program, Atlanta, Georgia; gDivision
of Infectious Diseases, Department of Medicine, Emory University
School of Medicine, Atlanta, Georgia; hMaryland Emerging
Infections Program, Baltimore, Maryland; iDepartment of
International Health, Johns Hopkins Bloomberg School of Public
Health, Baltimore, Maryland; jDepartment of Medicine, Infectious
Diseases, University of Rochester, Rochester, New York; kDivision
of Infectious Diseases, Oregon Health and Science University,
Portland, Oregon; and lDepartment of Preventive Medicine,
Vanderbilt University School of Medicine, Nashville, Tennessee
bMinnesota

KEY WORDS
Staphylococcus aureus infection, methicillin resistance, children,
infants, epidemiology
ABBREVIATIONS
ABCsActive Bacterial Core Surveillance
BSIbloodstream infection
CAcommunity-associated
CDCCenters for Disease Control and Prevention
CIcondence interval
CLABSIcentral lineassociated bloodstream infection
HACOhealth careassociated community-onset
HOhospital-onset
MRSAmethicillin-resistant Staphylococcus aureus
PFGEpulsed-eld gel electrophoresis
Dr Iwamoto conceptualized and designed the study and drafted
the initial manuscript; Dr Mu carried out the statistical analyses
and reviewed and revised the manuscript; Drs Lyneld and
Townes critically interpreted the data, supervised data
collection at one of the study sites, and reviewed and revised the
manuscript; Ms Bulens coordinated and supervised data
collection and reviewed and revised the manuscript; Ms Nadle,
Ms Aragon, Ms Petit, and Drs Ray, Harrison, Dumyati, and
Schaffner supervised data collection at one of the study sites
and reviewed and revised the manuscript; Dr Gorwitz critically
interpreted the data and reviewed and revised the manuscript;
Dr Lessa conceptualized and designed the study and critically
reviewed and revised the manuscript; and all authors approved
the nal manuscript as submitted.
The ndings and conclusions in this report are those of the
authors and do not necessarily represent the ofcial position of
the Centers for Disease Control and Prevention.
(Continued on last page)

PEDIATRICS Volume 132, Number 4, October 2013

WHATS KNOWN ON THIS SUBJECT: Invasive methicillin-resistant

Staphylococcus aureus (MRSA) in children is associated with high
morbidity and mortality. Although reductions in health care
associated MRSA infection among adults are documented, it is
unclear if a similar trend is occurring among children.
WHAT THIS STUDY ADDS: Data from population-based surveillance
were analyzed to assess changes in invasive MRSA infection
incidence over time. This analysis describes the epidemiology and
trends of invasive MRSA infections among children in 9 US
metropolitan areas and estimates national burden.

abstract
OBJECTIVE: To describe trends in the incidence of invasive methicillinresistant Staphylococcus aureus (MRSA) infections in children during
20052010.
METHODS: We evaluated reports of invasive MRSA infections in pediatric
patients identied from population-based surveillance during 20052010.
Cases were dened as isolation of MRSA from a normally sterile site and
classied on the basis of the setting of the positive culture and presence
or absence of health care exposures. Estimated annual changes in incidence were determined by using regression models. National age- and
race-specic incidences for 2010 were estimated by using US census data.
RESULTS: A total of 876 pediatric cases were reported; 340 (39%) were
among infants. Overall, 35% of cases were hospital-onset, 23% were
health careassociated community-onset, and 42% were communityassociated (CA). The incidence of invasive CA-MRSA infection per 100 000
children increased from 1.1 in 2005 to 1.7 in 2010 (modeled yearly
increase: 10.2%; 95% condence interval: 2.7%18.2%). No signicant
trends were observed for health careassociated community-onset and
hospital-onset cases. Nationally, estimated invasive MRSA incidence in
2010 was higher among infants aged ,90 days compared with older
infants and children (43.9 vs 2.0 per 100 000) and among black children
compared with other races (6.7 vs 1.6 per 100 000).
CONCLUSIONS: Invasive MRSA infection in children disproportionately
affects young infants and black children. In contrast to reports of declining
incidence among adults, there were no signicant reductions in health
careassociated MRSA infections in children. Concurrently, the incidence
of CA-MRSA infections has increased, underscoring the need for dening
optimal strategies to prevent MRSA infections among children with and
without health care exposures. Pediatrics 2013;132:e817e824

e817

Methicillin-resistant Staphylococcus
aureus (MRSA) causes a wide spectrum of disease ranging from skin and
soft tissue infections to life-threatening
systemic infections. MRSA is an important cause of infections in health
care and community settings, and its
epidemiology has been changing rapidly.1,2 Recent studies, predominantly
in adult populations, have revealed
reductions in both health care
associated and community-onset
invasive MRSA infections.35 Meanwhile,
the epidemiology of infections among
children is less established and likely
distinct from that in adults. The incidence
of invasive infections is high in infants
and young children.6 Studies in single
centers have shown increases in
invasive and noninvasive communityassociated (CA) MRSA infections in
children, and a national study showed
an increase in the number of hospitalized children with MRSA infection.79
Similarly, numerous outbreaks in
NICUs have been attributed to strains of
both health care and community origins, and increasing trends in lateonset infections in US NICUs caused
by MRSA have been reported.10
The prevention of MRSA infections both
in health care and community settings
remains a priority. Identifying the unique
epidemiologic characteristics, burden,
and trends in incidence of MRSA infections in children is needed to develop
strategies to further decrease risks of
infection. We describe the results of
laboratory-, population-based surveillance for invasive MRSA infections in
children during 20052010.

METHODS
Surveillance Population
The Active Bacterial Core Surveillance
(ABCs) for invasive MRSA infections is
an active, population-based surveillance system for laboratory-conrmed
MRSA that started in July 2004 in selected counties in 9 geographically

e818

IWAMOTO et al

diverse metropolitan areas with

a population of 4.4 million persons
younger than 18 years, including California (Alameda, Contra Costa, and
San Francisco Counties), the state of
Connecticut, Colorado (Arapahoe County),
Georgia (Clayton, Cobb, DeKalb, Douglas,
Fulton, Gwinnett, Newton, and Rockdale
Counties), Maryland (Baltimore City),
Minnesota (Ramsey County), New York
(Monroe County), Oregon (Clackamas,
Multnomah, and Washington Counties), and Tennessee (Davidson County).
During 20052010, the following
changes occurred in the surveillance
catchment area: in 2007, Colorado
added Adams, Denver, Douglas, and
Jefferson Counties; and in 2008, Maryland and Minnesota added Baltimore
County and Hennepin County, respectively. The ABCs population and
surveillance methods have been described.6,11
Denitions
A case of invasive MRSA infection was
dened by the isolation of MRSA from
a normally sterile body site (eg, blood,
cerebrospinal uid, pleural uid) in
a surveillance area resident younger
than 18 years at least 30 days apart of an
initial invasive MRSA culture. Surveillance personnel routinely receive all
positive MRSA clinical microbiology
reports from laboratories serving
residents of surveillance areas. Demographic characteristics, clinical
characteristics, disease outcomes, and
information on established health care
risk factors (ie, history of hospitalization [not including admission to a level I,
well-newborn nursery], surgery, dialysis, or residence in a long-term care
facility in the previous year; or presence
of a central venous catheter within 2
days before culture) were abstracted
from medical records.
Cases were classied into mutually
exclusive epidemiologic categories on
the basis of health care risk factors and

timing of MRSA culture collection. Cases

were considered hospital-onset (HO) if
the MRSA clinical culture was obtained
on or after the fourth calendar day of
hospitalization, where admission was
hospital day 1; as health careassociated
community-onset (HACO) if the culture
was obtained in an outpatient setting
or before the fourth calendar day of
hospitalization in a patient with an
established health care risk factor;
and as CA if the culture was obtained
in an outpatient setting or before the
fourth calendar day of hospitalization
in a patient without documentation of
a health care risk factor. Among young
infants, cases were categorized as
early-onset infection if MRSA was isolated from infants younger than 3 days
or late-onset infection if infants were
3 to 89 days of age. Early-onset infections and other cases in which health
care exposures could not be determined were not classied into an
epidemiologic category.
Cases were categorized into infection
syndromes on the basis of physicians
diagnoses present in the medical record and source of isolate. All syndromes were associated with the
presence of MRSA in a normally sterile
site. Cases were categorized as bloodstream infections (BSIs) if MRSA was
isolated from blood. Syndromes were
not mutually exclusive; for example,
a case could have pneumonia with
a BSI.
Isolate Collection and Testing
As part of surveillance, a convenience
sample of MRSA isolates is sent to the
Centers for Disease Control and Prevention (CDC) for further testing as
described elsewhere.6,12 Briey, isolates undergo conrmation of S aureus
identication, antimicrobial susceptibility testing, and molecular characterization, including pulsed-eld gel
electrophoresis (PFGE). Beginning in
2008, all submitted isolates were

ARTICLE

characterized either by PFGE or by inference of PFGE patterns on the basis of

microbiological characteristics, including staphylococcal cassette chromosome, presence of Panton-Valentine
leukocidin, and antimicrobial susceptibility results.13
Statistical Analysis
Incidence rates were calculated by
using US Bureau of the Census bridgedrace vintage postcensus population
estimates.1416 For cases in patients
with unknown race, race was imputed
on the basis of the distribution of
known race and gender for each surveillance area. Because there are no
population estimates for infants by
month of age, we estimated that the
population of infants younger than 90
days was approximately one-quarter of
the population of infants younger than
1 year. Annual MRSA infection incidence was determined by pooling
data by year across surveillance areas.
To ensure comparability over time,
analyses comparing incidence over
time were restricted to surveillance
areas that reported continuously during the study period. All other analyses
used all available data during 2005
2010.
Trends in incidence were assessed by
using a Poisson regression model or
negative binomial distribution, if there
was evidence of overdispersion. For
cases in patients aged 3 to 89 days,
annual incidences of all late-onset invasive MRSA infections and of HO
infections were used to calculate
trends. For cases in patients aged 90
days to 17 years, trends in incidences
were calculated by epidemiologic category. The outcome variable was
number of invasive MRSA infections,
and time (year) as a continuous variable was the predictor. All models for
trend analysis were adjusted by age,
gender, and race; and P values ,.05
were considered statistically signicant.

PEDIATRICS Volume 132, Number 4, October 2013

Point estimates and 95% condence

intervals (CIs) for the yearly percentage change were determined by using
each model. The nal models were
used to determine the adjusted incidence for each year. For national
estimates of cases in 2010, age- and
race-specic incidence of infection
across surveillance sites were applied
to the age and racial distribution of
the US population. CIs were estimated
by using a method based on the
gamma distribution.17

RESULTS
Characteristics of Cases
During 2005 through 2010, 876 cases of
invasive MRSA infections were reported
among 834 pediatric patients. The median age at time of infection was 2.1
years (range: 0 days to 17 years), and
39% of cases occurred among infants
younger than 1 year. Most (799 of 876;
91%) were hospitalized, and there were
53 (6%) fatal cases (Table 1). Males
accounted for 59% (490 of 834) of
patients. Among patients with reported
race (n = 682), 59% were black, 36%
were white, and 5% were children of
other races. Overall, 68% (565 of 834) of
children with invasive MRSA infection
had an underlying medical condition,
including prematurity (19%), dermatologic condition (eg, eczema, abscesses)
(18%), asthma (8%), congenital disorder
(4%), renal disease (2%), and malignancy (2%).
Of the 876 cases, 857 were classied into
an epidemiologic category; 363 (42%)
were CA-MRSA infections, 298 (35%)
were HO-MRSA infections, and 196
(23%) were HACO-MRSA infections. Ten
cases were early-onset neonatal infections, and epidemiologic category
was unknown for 9 cases. Eighty percent (151 of 190) of infections in infants
aged 389 days were HO-MRSA infections, with almost half occurring in
premature infants. The most common
health care risk factors among cases

with HO- and HACO-MRSA infections

were previous hospitalization (35%
and 86%, respectively), presence of
a central venous catheter (32% and
28%, respectively), and history of surgery (22% and 26%, respectively). The
distribution of epidemiologic categories varied with age and with underlying medical condition. More than
80% of HO- and HACO-MRSA cases were
in patients with a reported underlying
medical condition, compared with half
of CA-MRSA cases. The proportion of
CA-MRSA infections was highest in
children aged 5 to 10 years old (92 of
130; 71%).
MRSA was isolated from blood in 692
cases (79%), and 364 cases (41.6%)
were BSIs only without another infection syndrome (Table 1). However, of
these 364 cases, 248 (68%) had a central venous catheter within the 2 days
before the positive MRSA blood culture.
Other common types of invasive infections included bone and joint infections
(179 of 876; 20%), skin and soft tissue
infections (152 of 876; 17%), pneumonia or empyema (129 of 876; 15%), and
meningitis or cerebrospinal uid shunt
infection (35 of 876; 4%). Infection
syndromes varied by epidemiologic
category (Table 1).
Characteristics of Invasive MRSA
Isolates
Among the 876 cases, 257 (29%) had an
MRSA isolate submitted to the CDC.
Isolates were obtained from blood (189
cases; 74%), pleural uid (16 cases;
6%), cerebrospinal uid (11 cases; 4%),
joint (10 cases; 4%), peritoneal uid (6
cases; 2%), bone (5 cases; 2%), and
other sites (20 cases; 8%). Overall, the
predominant strain patterns were
USA300 (184 cases; 72%) and USA100
(47 cases; 18%); other pulsed-eld
types were less common, each accounting for ,2% of isolates. USA300
strains were identied among 107
(84%) isolates from CA-MRSA infections,

e819

TABLE 1 Patient Age at Time of Infection, Infection Syndromes, and Outcomes Associated With
Invasive MRSA Infections Among Children by Epidemiologic Category, 20052010
HO (n = 298) HACO (n = 196) CA (n = 363) Totala (N = 876)
Patient age at time of infection, n (%)
,3 days
389 days
311 months
14 years
510 years
1117 years
Invasive infection,c n (%)
BSI
BSI only
Pneumonia or empyemad
Soft tissue/skin infectiond
Bone or joint infection
Other infectiond
Fatal cases, n (%)
Hospitalization, n (%)
Median stay, d (interquartile range)

e
151 (50.7)
52 (17.4)
43 (14.4)
10 (3.4)
42 (14.1)
252 (84.6)
195 (65.4)
42 (14.1)
27 (9.1)
11 (3.7)
28 (9.4)
43 (14.4)
298 (100)
60 (2495)

Pb

e
20 (10.2)
42 (21.4)
58 (29.6)
26 (13.3)
50 (25.5)

e
19 (5.2)
46 (12.7)
106 (29.2)
92 (25.3)
100 (27.6)

10 (1.1)
190 (21.7)
141 (16.1)
209 (23.9)
130 (14.8)
196 (22.4)

,.01
.02
,.01
,.01
,.01

147 (75.0)
84 (42.8)
30 (15.3)
31 (15.8)
27 (13.8)
33 (16.8)
4 (2.0)
175 (89.3)
10 (619)

277 (76.3)
76 (20.9)
55 (15.2)
93 (25.6)
138 (38.0)
39 (10.7)
6 (1.7)
311 (85.7)
9 (515)

692 (79.0)
364 (41.6)
129 (14.7)
152 (17.3)
179 (20.4)
104 (11.9)
53 (6.1)
799 (91.2)
15 (743)

.01
,.01
.91
,.01
,.01
.03
,.01
,.01
,.01

a Includes cases occurring in patients younger than 3 days and cases in which epidemiologic classication could not be
determined.
b P values were determined by x 2 statistic and indicated signicant differences in proportion of infections by epidemiologic
category.
c A case could represent .1 infection syndrome.
d Associated with an MRSA culture from a normally sterile site (eg, blood, cerebrospinal uid, pleural uid).
e Infants younger than 3 days are categorized as early-onset infections that are not classied in an epidemiologic category.

36 (54%) from HO-MRSA infections,

and 35 (62%) from HACO-MRSA infections (Table 2). USA100 was most
commonly associated with HO-MRSA
infections (22 of 47 USA100 isolates;
47%). Although 10 (21%) USA100
isolates were from CA-MRSA infections, they represented only 8% of
isolates from CA-MRSA infections
overall.
Invasive MRSA Infection Incidence
and Trends
Overall, 178 late-onset invasive MRSA
infections among infants aged 3 to 89
days were identied in areas conducting continuous surveillance during the
study period. The modeled incidence,
adjusted for race, declined 9.8% per
year (95% CI: 217.5% to 21.4%). When

analysis was restricted to late-onset

HO-MRSA infections, a more pronounced decrease was detected
(modeled yearly change: 211.3%; 95%
CI: 219.6% to 22.0%) (Fig 1). Incidence
among black infants was consistently
higher than incidence among infants of
other races, which was not driven by
any particular surveillance site. Stratied by race, there was no statistically
signicant trend observed in incidence
in black infants (modeled yearly
change: 27.8%; 95% CI: 217.7% to
3.2%), whereas the decline in incidence
among nonblack infants approached
signicance (modeled yearly change:
212.8%; 95% CI: 224.4% to 0.6%).
A total of 617 invasive MRSA infections
were identied among children older
than 3 months. Incidence and trends of

TABLE 2 Epidemiologic Categories of Invasive MRSA Isolates by PFGE Type

Epidemiologic Category

USA100, n (%)

USA300, n (%)

Other PFGE Type, n (%)

Total, n

HO
HACO
CA
Early-onset infection
Unknown epidemiologic category

22 (33.3)
13 (23.2)
10 (7.9)
1 (20.0)
1 (33.3)

36 (54.5)
35 (62.5)
107 (84.3)
4 (80.0)
2 (66.7)

8 (12.1)
8 (14.3)
10 (7.8)
0 (0)
0 (0)

66
56
127
5
3

n = 257.

e820

IWAMOTO et al

invasive infections differed by epidemiologic category (Fig 2). The modeled

incidence of CA-MRSA infections, adjusted for age and race, increased
10.2% per year (95% CI: 2.7%18.3%).
Increases in incidence of CA-MRSA
infections were observed across 7 of
the 9 surveillance sites. Overall, no
sustained change over time was observed in the incidence of HACO-MRSA
infections, nor were signicant
changes observed among HO-MRSA
infections. Across all epidemiologic
categories, black children and children
younger than 5 years were at increased risk of infection, compared
with nonblack children and older children, respectively.
An estimated 1895 invasive MRSA
infections and 140 (7.4%) deaths occurred in the United States among
children younger than 18 years in 2010.
Adjusted national incidence was higher
among infants aged 389 days and
among black children, whereas children aged 11 to 17 years had the lowest
incidence (Table 3).

DISCUSSION
Our results distinguish the epidemiology of invasive MRSA infections
among children compared with adults,
emphasizing the need for pediatricspecic prevention strategies. In
contrast to recent published reports
of declines in invasive health care
associated MRSA infections and
community-onset BSIs in study populations composed mostly of adults,35
in children older than 3 months we
observed no signicant trends in HO- or
HACO-invasive MRSA infections and an
increase in rates of invasive CA-MRSA
infections. Additionally, we found that
invasive MRSA infections disproportionally affect young infants and blacks.
Taken together, these ndings reveal
that multiple factors may impact risk
and complicate efforts to control MRSA
transmission and infections in children

ARTICLE

FIGURE 1
Incidence of late-onset, HO invasive MRSA infections in infants aged 3 to 89 days by race, 20052010. The
analysis was restricted to surveillance counties that reported continuously during 20052010.

Controlled for gender and race.

FIGURE 2
Trends in age-, gender-, and race-adjusted incidence of invasive MRSA infections among children aged 3
months to 17 years, by epidemiologic category, 20052010. The analysis was restricted to surveillance
counties that reported continuously during 20052010. Controlled for age, gender, and race.

within and outside of health care settings.

In our pediatric population, CA-MRSA
infections represent the largest proportion of cases, which is different from
what has been reported among adults
in whom 60% of cases are HACO.4,6
Although invasive infections are likely
only a small fraction of all CA-MRSA
infections, the increase in incidence
of CA-MRSA invasive infections we observed nationally supports ndings
from single-center studies where both
invasive and noninvasive CA-MRSA
infections in children were reported
to be increasing.8,9,18,19 Additionally,
ndings from a large national study
PEDIATRICS Volume 132, Number 4, October 2013

examining administrative data from

childrens hospitals found an increase
in MRSA hospitalizations, largely driven
by skin and soft tissue infections in
primarily healthy children.7 However,
a direct comparison cannot be made
with these studies because we report
on invasive infections only. The increase in rates of CA-MRSA in children
is concerning. Current prevention
strategies for CA-MRSA focus on education and behavior change aimed at
improving hygiene, and it is unknown
whether these strategies are effective
or have been widely adopted.
In our sample of isolates, USA300
strains were associated with 54% of

HO-MRSA infections and with 63% of

HACO-MRSA infections, which is much
higher than what has been reported in
adult population (25% and 33%, respectively).20 This nding is consistent
with what was recently reported from
30 hospitals in California where pediatric and adult MRSA strains were
compared.21 USA300 has emerged as
a cause of health careassociated
infections causing NICU outbreaks, and
in at least 1 region of the country
USA300 has been reported as the most
prevalent strain causing health care
associated BSIs.2124 It is still unclear,
however, whether USA300 is adding to
the current disease burden or replacing USA100 as the main cause of MRSA
infections in the children.
We examined our data to describe
infections in pediatric subpopulations,
including infants in the NICU. In our
study, the highest incidence of infection
was among infants younger than 3
months old. Infections seemed to occur
among infants in the NICU; most were HO
BSIs in neonates who were premature
and had been hospitalized since birth.
This nding is not surprising given that
established risk factors for MRSA infection in infants include prematurity,
young gestational age, longer length of
hospitalization, and colonization with
MRSA.2531 Promisingly, our study
showed that the rate of late-onset (ie, 3
to 89 days of age) invasive MRSA infection in hospitalized infants is decreasing. The observed decline is likely
due in part to progress in infection
prevention practices in NICUs, especially improvements in central line insertion and maintenance practices.
This interpretation is supported by
results of studies from NICU collaboratives that have implemented programs designed to improve central line
practices leading to substantial
reductions in central lineassociated
BSIs (CLABSIs) caused by all pathogens.3235
e821

TABLE 3 Estimated National Incidence Rates and Number of Invasive MRSA Infections: ABCs,
United States, 2010

Age group
,3 daysb
389 days
311 months
14 years
510 years
1117 years
Race
Black
White
Other
Gender
Female
Male
Overall
a
b

Adjusteda National Incidence

per 100 000 Population (95% CI)

Estimated Number of
Infections (95% CI)

43.9 (29.363.9)
11.1 (7.016.9)
3.0 (2.14.3)
1.7 (1.12.5)
0.8 (0.41.3)

433 (289630)
327 (207500)
487 (333694)
421 (275620)
227 (127383)

6.7 (5.38.4)
1.6 (1.22.1)
1.2 (0.42.6)

873 (6891093)
954 (7061258)
68 (25150)

2.1 (1.52.8)
3.0 (2.43.8)
2.6 (2.13.1)

746 (551996)
1149 (9071446)
1895 (15732263)

Adjusted for age, race, and gender.

The number of early-onset neonatal infections was too small to accurately calculate incidence.

Although the declining rate of late-onset

infection among neonates is encouraging, we did not observe decreases in
HO- or HACO-MRSA invasive infections,
mostly BSIs, in children older than 3
months. This nding directly contrasts
with declines in MRSA CLABSI rates
reported in adult ICUs.3 The reasons
for this discrepancy in MRSA trends
among children compared with adults
are unknown. However, there are relatively few studies assessing the preventability of MRSA infections in
children, and evidence-based prevention guidelines are largely based on
adult data. Additionally, some interventions recommended for adults may
not be recommended in children because of the lack of data about risks
versus benets for young children. This
situation has led to heterogeneity of
practices to prevent CLABSIs and MRSA
infections in children, with examples
including variability in screening policies for MRSA, isolation precautions,
MRSA decolonization, and central line
care.36,37
We found differences in incidence of
invasive MRSA infections by race among
all age groups in all epidemiologic
categories. Previous studies have described disparities in invasive MRSA
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IWAMOTO et al

infections between blacks and whites1,6;

however, our understanding of factors
that sustain these disparities remains
poor. The higher rates in black children
may suggest differences in behavioral
or host factors. Socioeconomic factors
may play a role in a health careseeking
behavior and MRSA transmission (eg,
household crowding), and additional
studies are needed to better to understand the reasons for racial disparities.
Our analysis was subject to several
limitations. First, our data represent
surveillance in 9 US metropolitan areas.
Although it is unknown whether incidence rates in the surveillance populations are representative nationally,
they represent one of the largest populations evaluated for changes in incidence. Second, the sample of MRSA
isolates received at the CDC was
a sample of less than one-third of the
pediatric cases reported and should
not be interpreted as representative of
all pediatric cases. Third, the population
denominators used for infants younger
than 90 days were extrapolated from
census estimates; however, no US
census estimates for infants by age-inmonths are available and using a denominator for all infants younger than 1

year would underestimate incidence.

Fourth, we were not able to assess
trends in early-onset MRSA infections
because of the small number of neonates in this category. Last, patient data
were collected by medical record review, which could result in misclassication of epidemiologic category
if health care risk factors were not well
documented.
Despite these limitations, our ndings represent those from a large,
population-based surveillance system
with thorough collection of data on
epidemiologic and clinical characteristics of cases. Our study extends the
existing literature by estimating the
national burden of invasive infections in
children and by showing trends in incidence of invasive MRSA infections
acquired from both health care and
community settings. Evaluating these
trends helps us measure progress toward MRSA prevention, identify populations at risk, and set priorities for
future studies.

CONCLUSIONS
In summary, invasive MRSA infection in
children appears to disproportionately
affect young infants and black children.
In contrast to declining incidence
among adults and NICU patients, there
were no signicant reductions in invasive health careassociated MRSA
infections in children older than 3
months during 20052010. Concurrently, the incidence of invasive CAMRSA infections increased. These
ndings underscore the need for dening optimal strategies to prevent
MRSA infections among children, especially children without health care
risk factors, hospitalized children outside of the ICU, and children with recent
exposure to health care.

ACKNOWLEDGMENTS
Wethankthefollowingcontributorsfrom
the Emerging Infections Program/ABCs

ARTICLE

MRSA surveillance program: Art Reinold,

MD, California Emerging Infections Program; Ken Gershman, MD, MPH and
Wendy Bamberg, MD, Colorado Emerging
Infections Program; Carmen Marquez,
MPH, Connecticut Emerging Infections
Program; Monica Farley, MD and Janine
Ladson, MPH, Georgia Emerging Infections Program; Joanne Benton, RN,

BSN, MHS, Rosemary Hollick, MSc, Kim

Holmes, RN, MS, and Elisabeth Vaeth,
MPH, Maryland Emerging Infections Program; Lindsey Lesher, MPH, Minnesota
Emerging Infections Program; Anita
Gellert, RN, New York Emerging Infections
Program; Ann Thomas, MD, MPH, Mark
Schmidt, PhD, and Robert Vega, MS,
Oregon Emerging Infections Program;

and Brenda Barnes, RN, CCRP, Karen Leib,

RN, Katie Dyer, MPH, Wendi Welch, CCRP,
Tennessee Emerging Infections Program.
Additional contributors were as follows:
Scott Fridkin, MD, Ruth Belower, MPH,
Brandi Limbago, PhD, Valerie Albrecht,
MPH, Jonathan Edward, MStat, Melissa
Lewis, MPH, and Elizabeth Zell, MStats,
from the CDC.

9. Ochoa TJ, Mohr J, Wanger A, Murphy JR,

Heresi GP. Community-associated methicillinresistant Staphylococcus aureus in pediatric patients. Emerg Infect Dis. 2005;11
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10. Lessa FC, Edwards JR, Fridkin SK, Tenover
FC, Horan TC, Gorwitz RJ. Trends in incidence of late-onset methicillin-resistant
Staphylococcus aureus infection in neonatal intensive care units: data from the
National Nosocomial Infections Surveillance System, 1995-2004. Pediatr Infect Dis
J. 2009;28(7):577581
11. Schuchat A, Hilger T, Zell E, et al; Active
Bacterial Core Surveillance Team of the
Emerging Infections Program Network. Active bacterial core surveillance of the
emerging infections program network.
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Active Bacterial Core Surveillance MRSA
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United States Census 2000 population with
bridged race categories. Vital Health Stat 2.
2003;(135):155
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JA, Heck KE, Madans JH. Bridging between
two standards for collecting information
on race and ethnicity: an application to
Census 2000 and vital rates. Public Health
Rep. 2004;119(2):192205

16. Centers for Disease Control and Prevention. US census populations with
bridged race categories. National Vital
Statistics System. Published 2012. Available
at: www.cdc.gov/nchs/nvss/bridged_race.
htm. Accessed June 18, 2013
17. Fay MP, Feuer EJ. Condence intervals for
directly standardized rates: a method
based on the gamma distribution. Stat
Med. 1997;16(7):791801
18. Purcell K, Fergie J. Epidemic of communityacquired methicillin-resistant Staphylococcus aureus infections: a 14-year study at
Driscoll Childrens Hospital. Arch Pediatr
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19. Fortunov RM, Hulten KG, Hammerman WA,
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survreports/mrsa10.html. Accessed August
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Differences in methicillin-resistant Staphylococcus aureus strains isolated from pediatric and adult patients from hospitals in
a large county in California. J Clin Microbiol. 2012;50(3):573579
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(Continued from rst page)

www.pediatrics.org/cgi/doi/10.1542/peds.2013-1112
doi:10.1542/peds.2013-1112
Accepted for publication Jul 15, 2013
Address correspondence to Martha Iwamoto, MD, MPH, Centers for Disease Control and Prevention, 1600 Clifton Rd NE, Mailstop C-09, Atlanta, GA 30333. E-mail:
miwamoto@cdc.gov
PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online, 1098-4275).
Copyright 2013 by the American Academy of Pediatrics
FINANCIAL DISCLOSURE: The authors have indicated they have no nancial relationships relevant to this article to disclose.
FUNDING: Supported through a cooperative agreement with the Emerging Infections Program of the Centers for Disease Control and Prevention.
POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conicts of interest to disclose.

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