REVIEW ARTICLE

MRSA Colonization and Risk of Infection in the

Neonatal and Pediatric ICU: A Meta-analysis
AUTHORS: Fainareti N. Zervou, MD, Ioannis M.
Zacharioudakis, MD, Panayiotis D. Ziakas, MD, PhD, and abstract
Eleftherios Mylonakis, MD, PhD
BACKGROUND AND OBJECTIVE: Methicillin-resistant Staphylococcus
Infectious Diseases Division, Rhode Island Hospital, Providence,
aureus (MRSA) is a significant cause of morbidity and mortality in
Rhode Island; and Warren Alpert Medical School of Brown
University, Providence, Rhode Island NICUs and PICUs. Our objective was to assess the burden of MRSA
KEY WORDS colonization on admission, study the time trends, and examine the
methicillin-resistant Staphylococcus aureus, MRSA, intensive significance of MRSA colonization in this population.
care units, neonatal, pediatric, meta-analysis, infection,
colonization
METHODS: PubMed and Embase databases were consulted. Studies
that reported prevalence of MRSA colonization on ICU admission were
ABBREVIATIONS
CI—confidence interval selected. Two authors independently extracted data on MRSA coloniza-
MRSA—methicillin-resistant Staphylococcus aureus tion and infection.
PCR—polymerase chain reaction
RESULTS: We identified 18 suitable articles and found an overall prev-
Drs Zervou and Zacharioudakis designed the study; performed
the literature search; participated in data collection, extraction,
alence of MRSA colonization of 1.9% (95% confidence interval [CI] 1.3%–
and interpretation; prepared tables and figures; and drafted the 2.6%) on admission to the NICU or PICU, with a stable trend over the
manuscript; Dr Ziakas designed the study, performed the past 12 years. Interestingly, 5.8% (95% CI 1.9%–11.4%) of outborn
statistical analysis and data interpretation, prepared tables and
neonates were colonized with MRSA on admission to NICU, compared
figures, and reviewed and revised the manuscript; Dr Mylonakis
conceptualized and designed the study and reviewed and with just 0.2% (95% CI 0.0%–0.9%) of inborn neonates (P = .01). The
revised the manuscript; and all authors approved the final pooled acquisition rate of MRSA colonization was 4.1% (95% CI 1.2%–
manuscript as submitted. 8.6%) during the NICU and PICU stay and was as high as 6.1% (95% CI
www.pediatrics.org/cgi/doi/10.1542/peds.2013-3413 2.8%–10.6%) when the NICU population was studied alone. There was
doi:10.1542/peds.2013-3413 a relative risk of 24.2 (95% CI 8.9–66.0) for colonized patients to
Accepted for publication Jan 17, 2014 develop a MRSA infection during hospitalization.
Address correspondence to Eleftherios Mylonakis, MD, PhD, CONCLUSIONS: In the NICU and PICU, there are carriers of MRSA on
Infectious Diseases Division, Rhode Island Hospital, 593 Eddy St,
POB, 3rd Floor, Suite 328/330, Providence, RI 02903. E-mail:
admission, and MRSA colonization in the NICU is almost exclusively as-
emylonakis@lifespan.org sociated with outborn neonates. Importantly, despite infection control
PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online, 1098-4275). measures, the acquisition rate is high, and patients colonized with
Copyright © 2014 by the American Academy of Pediatrics MRSA on admission are more likely to suffer a MRSA infection during
FINANCIAL DISCLOSURE: The authors have indicated they have
hospitalization. Pediatrics 2014;133:e1015–e1023
no financial relationships relevant to this article to disclose.
FUNDING: The Brown University Infectious Diseases Program in
Outcomes Research is supported through funding from the
Warren Alpert School of Brown University, the Department of
Medicine, and the Division of Infectious Diseases.
POTENTIAL CONFLICT OF INTEREST: The authors have indicated
they have no potential conflicts of interest to disclose.

PEDIATRICS Volume 133, Number 4, April 2014 e1015

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Methicillin-resistant Staphylococcus au-
reus (MRSA) infections in the pediatric
population range from skin and soft
tissue to lower respiratory and blood-
stream infections and are associated
with significant morbidity and hospital
costs.1,2 These infections are largely
preceded by colonization with MRSA3;
and colonized children serve as a res-
ervoir for the cross-transmission of
MRSA and are frequently identified as
sources of outbreaks in the NICU and
PICU settings.4
A number of reports indicate that the
trends in MRSA invasive infections in
high-risk adult populations are de-
creasing.5,6 The epidemiology of MRSA
invasive infections among critically ill
neonates and children seems to follow
a distinct course,7–9 with data on MRSA
outbreaks in NICUs increasingly being
published.10–13 In this systematic re-
view and meta-analysis, we estimate
the prevalence of MRSA colonization
among patients upon admission to the
NICU and PICU, review the time trends,
and study the significance of MRSA
colonization in this population.
METHODS
Study Selection
A literature search of the PubMed and
Embase databases was conducted, and
articles potentially relevant to our study
were identified. The search was per-
formed by 2 authors (FNZ, IMZ) inde-
pendently, by using the following terms
as keywords: (MRSA OR (Methicillin AND
resistant AND Staphylococcus)) AND
(Neonatal OR Pediatric). Among the
citations extracted, abstracts were
reviewed in an attempt to retrieve the
clinical studies on MRSA colonization
on admission to the NICU and PICU.
Articles that were relevant, by title and
abstract, were accessed in full text to
determine those that provided suffi-
cient information to be included in our
meta-analysis. Finally, the references
cited by each eligible study were
e1016 ZERVOU et al
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scrutinized to identify additional arti-
cles. We performed our review and
meta-analysis in accordance with the
PRISMA (Preferred Reporting Items for
Systematic reviews and Meta-Analysis)
guidelines.14,15
Inclusion and Exclusion Criteria
Studies were included in our meta-
analysis if they reported extractable
data on the prevalence of MRSA colo-
nization on admission to a NICU or PICU.
A restriction for English literature was
imposed.
Outcomes of Interest
The major outcome of interest was the
prevalence of MRSA colonization on
admission to the NICU or PICU. The prev-
alence was calculated by dividing the
number of cases with positive MRSA
surveillance cultures on admission by
the total number of recruited individ-
uals (ie, those who were screened for
MRSA on admission to the NICU or PICU).
We stratified the results for geographic
location, type of ICU (NICU versus PICU),
screening site(s) (nasal versus nasal
and extranasal), and the MRSA isolation
method (polymerase chain reaction
[PCR] versus culture). As secondary
outcomes of interest, we calculated the
relative risk of ensuing MRSA infection
among colonized on admission com-
pared with noncolonized and the ac-
quisition rate of colonization among
noncolonized patients during their ICU
stay. If the acquisition rate was not
directly reported in the text, we appro-
ximated population at risk by subtract-
ing patients colonized on admission
from the population screened.
Data Extraction
Data from eligible studies were ex-
tracted independently by 2 reviewers
(FNZ, IMZ) and summarized into a
spreadsheet. Discrepancies were re-
solved by consensus. For each of the in-
cluded studies, the following information
was extracted: author names, year of
publication, country of study conduc-
tion, study design (retrospective or
prospective), type and number of ICUs
(NICU or PICU), number of patients
who were screened, time interval from
admission to screening, number of
MRSA-colonized patients, anatomic sites
screened (nasal and extranasal sites),
isolation method (culture or PCR) used,
infection control policies applied to
each ICU, MRSA infection rate among
colonized and noncolonized patients,
and acquisition rate of MRSA during
hospitalization. Also, we extracted the
information on whether the cases were
inborn, outborn, or mixed. The pop-
ulation was considered outborn when
neonates were transferred from out-
side nurseries and inborn when they
were born in the obstetric unit of the
same hospital. To depict the time trends
of MRSA colonization on admission in
the NICU and PICU, we used as an index
year the year that the study was con-
ducted and not the year of publication.
In cases of studies in which the screening
process lasted .1 calendar year, the
midyear was used as the index year.
Quality Assessment
The quality of eligible studies was as-
sessed independently by 2 reviewers
(FNZ, IMZ) using a set of prespecified
criteria regarding the research design
and the quality of data report, as pre-
viously described.16,17 In brief, quality
points were given to studies with pro-
spective design, multicenter trials,
studies that stratified their results by
year, and NICU or PICU setting as well
as studies that provided some details
on the method used to isolate the MRSA
strain. High-quality studies were those
with a quality score greater than the
75th percentile.16–18
Data Analysis
A pooled random effects analysis
was used to calculate the combined
 REVIEW ARTICLE

prevalence and the 95% confidence jected to the meta-analysis. Thirty of 82 performed screening both on admission
intervals (CIs), by using the approach of studies were excluded because they did and weekly thereafter without reporting
DerSimonian and Laird.19 We used not include a screen for MRSA coloni- the admission prevalence and were also
Freeman Tukey arcsine methodology to zationonadmission. Twelve studieswere considered nonextractable. Review of
address stabilizing variances.20 The excluded because they provided non- the reference lists of all the included
standard approach of inverse variance stratified data for all hospitalized pa- articles yielded 1 additional eligible
method to calculate pooled estimates tients, including adults. Nine studies study. Among the 18 eligible studies, 2
and SEs does not perform well in meta- were not considered to have extractable had partially overlapping data,24,25 and
analysis of prevalence. For prevalence data because, although they reported the maximum relevant information was
near 0 or 1 (ie, for studies with small or the number of MRSA carriers on ad- extracted (Fig 1).
large prevalence), the inverse variance mission, they did not report the number The 18 studies that fulfilled our eligi-
method adds disproportionately large of patients screened. Finally, 14 studies bility criteria were published from 2006
weight, variance becomes small, and
the calculated CI may lie outside of
the 0 to 1 range. The double arcsine
methodology corrects both variances
instability and CIs.21 We assessed the
heterogeneity of study results by the
use of t2 metric.19,22 Possible sources
of heterogeneity were explored through
a subgroup and meta-regression tech-
nique. The effect of small studies in
publication bias was explored by the
Egger’s test.23 For time trends, model
coefficients were transformed to rates
and plotted against the index year
along with the observed prevalence
rates.17 In a secondary analysis, re-
stricted to studies providing data on
MRSA infections, we calculated the
relative risk of infection among colo-
nized compared with noncolonized on
admission patients. For our statistical
analysis, we used the Stata v11 software
package (Stata Corporation, College
Station, TX) and MetaXL (EpiGear In-
ternational Ltd, Queensland, Australia).
The significance threshold was set
at .05.

RESULTS
Our electronic database search yielded
2433 nonduplicate abstracts, and the
date of our last search was October 10,
2013. Among these studies, 82 were
initially considered eligible by title and
abstract for our meta-analysis, and their
full text was retrieved and assessed for
study inclusion. Of these, 17 studies met FIGURE 1
our inclusion criteria and were sub- Flowchart of meta-analysis.

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to 2013 and reported data from 1999 to
2011 (Table 1).24–41 The studies provided
screening data on 19 722 neonatal and
pediatric patients. More specifically,
11 studies reported data on 12 284
screened neonates in 12 NICUs, whereas
6 studies reported data on 7107 chil-
dren hospitalized in 6 PICUs. There was
1 study containing nonstratified data on
331 neonatal and pediatric patients.33
In studies that reported data stratified
by year or ICU setting, data sets were
split to discrete strata and considered
separately.24,28,34,35,38 The majority of
the included studies (11 of 18) were
prospective, and the remaining 7 were
retrospective.
The pooled prevalence of MRSA colo-
nization on admission to the NICU and
PICU was 1.9% (95% CI 1.3%–2.6%;
Fig 2). Egger’s test for publication bias
yielded insignificant effects (bias –3.92,
P = .11), suggesting absence of small
study effect. Also, quality score did not
significantly affect colonization esti-
mates (meta-regression coefficient
–0.02, P = .26). Details of the quality
assessment of all the eligible studies
are provided in Supplemental Table 4.
Of the 18 studies, the most common
place of origin was North America
(11 studies; 61.1%), followed by studies
from Asia (5 studies; 29.4%) and Europe
(2 studies; 27.8%). No studies from
South America, Africa, and Australia
were identified. The pooled prevalence
of MRSA colonization from the 11
studies that were conducted in the
United States was 2.3% (95% CI, 1.6%–
3.2%), compared with 1.3% (95% CI
0.3%–2.9%) from studies conducted in
Asian countries; the observed differ-
ence was not statistically significant
(P = .18). The summary prevalence
estimates are presented in Table 2.
Among NICU patients, the prevalence of
MRSA colonization on admission was
1.5% (95% CI 0.9%–2.2%), compared
with 3.0% (95% CI 1.9%–4.5%) among
patients hospitalized in the PICU. The
observed difference was marginally
significant (P = .05). Three of 18 eligible
studies subgrouped their population
into inborn and outborn and reported
stratified data on 2726 inborns and 990
outborns.31,38,41 Interestingly, the prev-
alence of MRSA colonization among
outborn neonates was 5.8% (95% CI
1.9%–11.4%), compared with just 0.2%
(95% CI 0.0%–0.9%) among inborn

TABLE 1 Characteristics of Eligible Studies

Study Mid-year Location ICU Time Screening Method n % MRSA Colonized Preventive Policies Quality Score
Europe
Gray26 2009 UK PICU OA N C 1282 1.6 Decol 9
PCR 1282 2.9
Thorburn27 2001 UK PICU OA T, R C 1241 1.5 CP, Decola 9
North America
Macnow28 2009 New York NICU II ,48h N, A, G, U C 555 2.0 Pre-CP, Decol 7
2007 New York NICU I ,48h N, A, G, U C 1170 3.5 Pre-CP, Decol 7
Lazenby29 2009 South Carolina NICU OA N, A, D C 212 0.0 CP 9
Milstone24,25 2009 Baltimore PICU OA N C 1930 3.3 NR 7
2008 Baltimore PICU OA N C 1210 5.6 NR 7
Horowitz30 2009 New Jersey PICU OA N C 691 4.5 Pre-CP, Decol 9
Myers31 2008 Chicago NICU OA T, A, G PCR 614 2.1 NR 8
Mongkolrattanothai32 2008 Peoria, IL NICU OA N PCR 228 0.0 CP and Decol 10
Nakamura33 2008 Boston NICU,PICU OA (#24 h) N C 331 2.7 NR 9
T C 331 3.0
Song34 2008 Washington, DC NICU OA N PCR 1361 3.6 Pre-CP, Coh 6
2005 Washington, DC NICU OA N C 1412 1.7 Pre-CP, Coh 6
Murillo35 2006 New Jersey NICU OA N PCR 849 2.1 CP, Coh, Decol 10
2005 New Jersey NICU OA N PCR 317 1.6 CP, Coh, Decol 10
Seybold36 2005 Atlanta NICU OA N C 996 1.2 CP, Coh 9
Asia
Naeem37 2010 Saudi Arabia PICU #3 h N PCR 753 2.7 NR 7
Morioka38 2009 Japan NICU OA T, E, U C 956 0.8 CP, Coh 7
2007 Japan NICU OA T, E, U C 690 0.7 CP, Coh, Pre-CP 7
to outborns
Sakamoto39 2006 Japan NICU OA N, U, E, T C 1229 0.2 CP 8
Al Reyami40 2003 Abu Dhabi NICU OA N, E, R, A, G C 239 0.4 Pre-CP to 8
outborns
Kim41 2003 Korea NICU OA N, G C 1456 4.1 CP, Coh, Decol 9
and Pre-CP
to outborns
Time was from admission to screening, n was the evaluable sample. Data stratified by location (Europe, North America, Asia) and midyear of each study. A, axilla; C, culture; Coh, cohorting of
colonized patients; CP, contact precautions to colonized patients; D, diaper area; Decol, decolonization policies (mupirocin and/or chlorhexidine bathing); E, ear; G, groin; N, nares; NR, not
reported; OA, on admission; P, perineum; Pre-CP, preemptive contact precautions to patients admitted until their colonization status becomes known; R, rectum; T, throat; U, umbilicus.
a Decolonization with enteral vancomycin.

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FIGURE 2
Forest plot of included studies. Individual and combined estimates of MRSA colonization.
neonates, and the difference was sta-
tistically significant (P = .01).
Among PICU patients, the nares were
the only anatomic site screened in all
but 1 study.27 Among studies that in-
cluded NICU patients, the most com-
mon screening policy (in 6 of 11
studies) was sampling of extranasal
sites such as umbilicus, axilla, groin,
throat, rectum, and external acoustic
meatus along with sampling of the
nares, whereas in 1 study only extra-
nasal sites were screened.31 In the
NICU, sampling solely the nares yielded
a prevalence of MRSA colonization of
1.7% (95% CI 0.9%–2.7%), which was
not statistically different (P = .72) from
the colonization rates of other screen-
ing policies (1.4%, 95% CI 0.5%–2.5%).
Regarding the microbiological assays
used in the studies included in our
analysis, 12 studies exclusively used
culture to isolate MRSA, 4 exclusively
used PCR, and 2 used both culture and
PCR. Of note is that PCR alone yielded
a prevalence of 2.2% (95% CI 1.5%–
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3.1%), which was not significantly
higher from the 1.9% (95% CI 1.2%–
2.8%) of MRSA colonization detected by
culture methods (P = .80).
To model the course of MRSA coloni-
zation on admission to the NICU and
PICU, we used the index year of the
studies, as described in the Methods
section, and we observed no significant
time-trend (P = .6; Fig 3). Eight studies
provided data on the acquisition of
MRSA during the ICU stay.26,27,29,32,36,38,39,41
The acquisition rate was 4.1% (95% CI
1.2%–8.6%) among the neonatal and
pediatric population, whereas among
the neonatal population alone, 6.1%
(95% CI 2.8%–10.6%) of patients ac-
quired MRSA during the NICU stay. The
pooled acquisition rate for the PICU
population alone was not calculated
because of insufficient data reporting
(2 studies).26,27 The acquisition rate
was lower in studies in which de-
colonization measures were imple-
mented (1.8%; 95% CI 0%–6.7%)
compared with those that did not de-
REVIEW ARTICLE
colonize patients (6.5%; 95% CI 2.0%–
13.2%), but this difference failed to
reach statistical significance (P = .15).
Seven of 18 studies (4 that included NICU
patients and 3 that included PICU
patients)24,26–29,31,35 followed the pa-
tients until their discharge, transfer to
another facility, or death and provided
data on the development of MRSA
infections. The data of each individual
study are summarized in Table 3. Two
studies were not analyzed because 1
did not have any patient colonized on
admission, and 1 did not report any
MRSA infection among both colonized
and noncolonized patients. Across the
5 studies with analyzable data, we
found that the relative risk for MRSA
infections among patients who were
colonized with MRSA on admission was
24.2 (95% CI 8.9–66.0) compared with
the patients who were not colonized
(Fig 4). In clinical terms, this indicates
that colonized neonates are 24.2 times
more likely to develop a MRSA infection
during their hospitalization compared
with noncolonized neonates.
DISCUSSION
Recent multicenter studies have dem-
onstrated a reduction in the rate of
MRSA infection in various vulnerable
populations.5,6 However, this does not
appear to be the trend in the pediatric
population.7 Because colonization is
a major independent risk factor for
infection,3 we conducted this meta-
analysis to estimate the burden of
MRSA colonization on admission to
NICUs and PICUs, study its significance
on MRSA-associated infections, and
model its course over time.
Our results distinguish the epidemiol-
ogy of MRSA colonization among the
pediatric population compared with
adults. The observed burden of MRSA
colonization among pediatric patients
admitted to the NICU and PICU is lower
than that among adults admitted to the
ICU.42 This is not surprising and is
e1019
TABLE 2 Summary Estimates of Included Studies associated with both the shorter ex-
Studies (Arms) At risk (n) Combined Effect (95% CI) t2 P posure to the health care system and
MRSA colonization the smaller number of comorbidities in
All studies 18 (22) 19 722 1.9% (1.3%–2.6%) 0.010 this population.30,43 Even though the
Studies $1000 patients 8 (9) 12 291 2.5% (1.5%–3.8%) 0.012 ref
Studies ,1000 patients 11 (13) 7431 1.5% (1.0%–2.2%) 0.007 .11
estimated burden of MRSA on admis-
NICU 11 (15) 12 284 1.5% (0.9%–2.2%) 0.011 ref sion to NICUs is relatively low, it is
PICU 6 (6) 7107 3.0% (1.9%–4.5%) 0.008 .05 interesting given the young age of
Geographic region
United States 11 (14) 11 876 2.3% (1.6%–3.2%) 0.008 ref
NICU patients and the sterile in utero
Asia 5 (6) 5323 1.3% (0.3%–2.9%) 0.018 .18 environment. Transmission of MRSA
Isolation through breast milk,44,45 the birth ca-
Culture 14 (16) 15 600 1.9% (1.2%–2.8%) 0.012 ref
nal,36,46 and contact with family mem-
PCR 6 (7) 5404 2.2% (1.5%–3.1%) 0.004 .80
Screening site in NICU bers has been described.47,48 However,
Nares only 4 (6) 5163 1.7% (0.9%–2.7%) 0.006 ref it appears that MRSA acquisition in this
Nares plus additional sites 7 (9) 7121 1.4% (0.5%–2.5%) 0.016 .72
population is closely associated to
MRSA acquisition 8 (9) 8003 4.1% (1.2%–8.6%) 0.078
Decolonization 4(4) 3947 1.8% (0%–6.7%) 0.062 ref contact with the health care setting.10,49
No decolonization 4(5) 4056 6.5% (2.0%–13.2%) 0.066 .15 First, stratification of data on inborn
Excluding PICUs (2 studies) 6 (7) 5519 6.1% (2.8%–10.6%) 0.046 and outborn neonates yielded a signifi-
Inborn 3 (4) 2726 0.2% (0.0%–0.9%) 0.008 .01
Outborn 3 (4) 990 5.8% (1.9%–11.4%) 0.039 ref cantly higher colonization rate among
ref, referent subgroup for comparison. outborns. Older age of outborn neo-
nates,28,50 which is translated into more
prolonged contact with the health care
workers during their stay in the pre-
vious hospital and their transportation
to the ICU,4 may explain this impressive
difference. The existing literature can-
not lead to valid conclusions of whether
there is difference in the efficacy of in-
fection control policies between com-
munity hospitals and NICUs that could
also play a role in the observed coloni-
zation rate of outborn neonates. How-
ever, neonates who require transfer
from community hospitals to NICUs
cannot be considered representative of
the population of community nurseries.
Although interhospital transfer of neo-
nates is not included in the list of clinical
FIGURE 3 conditions that require empirical appli-
Time trends of MRSA colonization. Observed and fitted estimates.
cation of transmission-based precau-
tions according to the Centers for
Disease Control and Prevention,51 the
impressive increase in MRSA coloniza-
TABLE 3 Individual Study Data to Calculate the Risk of MRSA Infection
tion on admission could justify the
Id # Study Screening NICU/ PICU Method Infections/ Colonized Infections/ Noncolonized
practice of some centers to isolate their
28
1 Macnow N, A, G, U NICU C 3/52 8/1673
outborn population until their MRSA
2 Lazenby29 N, A, D NICU C 0/0 3/212
3 Myers31 T, A, G NICU PCR 3/13 1/601 status becomes known.38,41
4 Murillo35 N NICU PCR 0/18 0/831 A second finding that highlights the
5 Thorburn27 T, R PICU C 3/19 7/1222
6 Milstone24 N PICU C 3/153 7/2987 importance of contact with the health
7 Gray26 N PICU C 1/20 0/1262 care setting in acquiring MRSA coloni-
A, axilla; C, culture; D, diaper area; G, groin; N, nares; R, rectum; T, throat; U, umbilicus. zation in this population is the high

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FIGURE 4
Forest plot of included studies. Relative risk (RR) estimates of MRSA infection.
acquisition rate during ICU stay. The
observed rate is particularly worri-
some if we consider that all included
ICUs applied policies to prevent MRSA
transmission (Table 1). Also, even
though a higher rate of MRSA coloni-
zation can be observed during out-
breaks,10,52 none of the included
studies reported data during an out-
break. This observed breakthrough
acquisition of MRSA could be explained
by the 48-hour turn-around time of
culture for MRSA isolation, which
results in delays in implementation of
infection control measures.53,54 Sub-
optimal application of such measures
also remains a possibility. Of note is
that because we did not have enough
data to study the time trends of the
acquisition rate, we cannot estimate
the impact of such measures over time.
Also, the time trend of MRSA coloniza-
tion on admission to the NICU and PICU,
which is shown to be stable, does not
reflect possible changes in the imple-
mentation of cross-transmission poli-
cies during the last years because it is
determined before the admission to
the ICU.
Importantly, children and neonates who
are carriers of MRSA on admission to
the PICU or NICU are 24.2 times more
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likely to develop a MRSA-associated
infection during their hospitalization
(compared with noncolonized). Of note
is that the corresponding figure among
adult ICU patients was 8.3 (95% CI 3.6–
19.2).42 These effects highlight the im-
portance of previous colonization in
development of MRSA infections in both
populations. The intrinsic character-
istics of newborn patients such as
the immunologic immaturity, as well as
the complexity of care needed in the
majority of neonates hospitalized in
NICUs,55–57 appear to render this pop-
ulation vulnerable to hospital-acquired
infections and underscore the signifi-
cance of the estimated colonization
rate.
It should be noted again that a limitation
of English literature was posed in our
meta-analysis. Also, our analysis was
limited by the quality of the included
studies and by the fact that a number of
studies that included screening on
admission to their protocol did not
report extractable data on the corre-
sponding prevalence. Additionally, the
acquisition rate could be extrapolated
in less than half of eligible studies, and
therefore pooled data may be un-
derpowered to detect a significant ef-
fect of decolonization. The existing
REVIEW ARTICLE
literature could not be used to depict
the exact geographic distribution of
MRSA colonization in NICU and PICU
patients. Also, there were some meth-
odologic differences between studies.
As detailed earlier, among PICU
patients, the nares were the only ana-
tomic site screened in all but 1 study,
whereas among studies that included
NICU patients, the most common
screening policy (in 6 of 11 studies) was
sampling of extranasal sites. However,
this difference did not affect our results,
and MRSA colonization rate was not
statistically different between studies
that sampled only nares compared with
studies that also sampled extranasal
sites. This finding is not surprising and
is in accordance with the recommen-
dations of the Chicago Area Neonatal
MRSA Working Group that nasal or na-
sopharyngeal sampling alone is con-
sidered sufficiently sensitive to detect
MRSA carriage in neonates (recom-
mendation IA—strongly recommended
for implementation and strongly sup-
ported by well-designed experimental,
clinical, or epidemiologic studies).58
CONCLUSIONS
The acquisition rate of MRSA coloniza-
tion during NICU and PICU stay is dis-
proportionately high, and the 29-fold
higher colonization rate of outborn
compared with inborn neonates high-
lights the need of early detection of
MRSA colonization among interhospital
transfer. Also, the 24.2 relative risk of
subsequent infection among MRSA
carriers, compared with noncarriers,
underscores the importance of re-
ducing the acquisition rate in the NICU
and PICU. The development and imple-
mentation of molecular diagnostic
methods, strict compliance with in-
fection control policies, and establish-
ment of decolonization policies with
favorable results among pediatric
patients seem to be the necessary next
steps in this effort.
e1021
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MRSA Colonization and Risk of Infection in the Neonatal and Pediatric ICU: A
Meta-analysis
Fainareti N. Zervou, Ioannis M. Zacharioudakis, Panayiotis D. Ziakas and Eleftherios
Mylonakis
Pediatrics 2014;133;e1015
DOI: 10.1542/peds.2013-3413 originally published online March 10, 2014;

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Pediatrics is the official journal of the American Academy of Pediatrics. A monthly publication, it
has been published continuously since . Pediatrics is owned, published, and trademarked by the
American Academy of Pediatrics, 141 Northwest Point Boulevard, Elk Grove Village, Illinois,
60007. Copyright © 2014 by the American Academy of Pediatrics. All rights reserved. Print
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MRSA Colonization and Risk of Infection in the Neonatal and Pediatric ICU: A
Meta-analysis
Fainareti N. Zervou, Ioannis M. Zacharioudakis, Panayiotis D. Ziakas and Eleftherios
Mylonakis
Pediatrics 2014;133;e1015
DOI: 10.1542/peds.2013-3413 originally published online March 10, 2014;

The online version of this article, along with updated information and services, is
located on the World Wide Web at:
http://pediatrics.aappublications.org/content/133/4/e1015

Pediatrics is the official journal of the American Academy of Pediatrics. A monthly publication, it
has been published continuously since . Pediatrics is owned, published, and trademarked by the
American Academy of Pediatrics, 141 Northwest Point Boulevard, Elk Grove Village, Illinois,
60007. Copyright © 2014 by the American Academy of Pediatrics. All rights reserved. Print
ISSN: .

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