blood culture in evaluation of pediatric community ...€¦ · blood culture in evaluation of...

REVIEW ARTICLE

324 | VOLUME 5 • ISSUE 6 www.hospitalpediatrics.org

AUTHORSPui-Ying Iroh Tam, MD,1 Ethan Bernstein, BA,2 Xiaoye Ma, MS,3 Patricia Ferrieri, MD1,4

1Department of Pediatrics, Division of Pediatric Infectious Diseases and Immunology, University of Minnesota Masonic Children’s Hospital, Minneapolis, Minnesota;2University of Minnesota Medical School, Minneapolis, Minnesota;3Department of Biostatistics, University of Minnesota School of Public Health, Minneapolis, Minnesota; and 4Department of Laboratory Medicine and Pathology, University of Minnesota Medical Center, Minneapolis, Minnesota

KEY WORDSblood culture, bacteremia, community-acquired pneumonia, pediatric, systematic review, meta-analysis, pneumococcal conjugate vaccine, Haemophilus infl uenzae type b vaccine, Streptococcus pneumoniae

ABBREVIATIONSBC: blood cultureCAP: community-acquired pneumoniaCI: confi dence intervalED: emergency departmentICD-9: International Statistical Classifi cation of

Diseases and Related Health Problems, Ninth Revision

PCV: pneumococcal conjugate vaccinePERCH: Pneumonia Etiology Research for Child

Health

www.hospitalpediatrics.orgdoi:10.1542/hpeds.2014-0138

Address correspondence to Pui-Ying Iroh Tam, MD, 3-210 MTRF, 2001 6th St SE, Minneapolis, MN 55455. E-mail: [email protected]

HOSPITAL PEDIATRICS (ISSN Numbers: Print, 2154 - 1663; Online, 2154 - 1671).

Copyright © 2015 by the American Academy of Pediatrics

abstractBACKGROUND AND OBJECTIVE: Current guidelines strongly recommend collection of blood cultures (BCs) in children requiring hospitalization for presumed moderate to severe bacterial community-acquired pneumonia (CAP). Our objective was to systematically review the international pediatric literature to evaluate how often BCs are positive in hospitalized children with CAP, identify the most commonly isolated pathogens, and determine the impact of positive BCs on clinical management.

METHODS: We identifi ed articles in PubMed and Scopus published from January 1970 through December 2013 that addressed BCs in children with CAP. We extracted total number of BCs collected and prevalence of positive BCs and used meta-regression to evaluate whether subgroups had any impact on prevalence.

RESULTS: Meta-analysis showed that the overall prevalence of positive BCs was 5.14% (95% confi dence interval 3.61–7.28). Studies focusing on severe CAP had a signifi cant effect on prevalence (P = .008), at 9.89% (95% CI 6.79–14.19) compared with 4.17% (95% confi dence interval 2.79–6.18) for studies not focusing on severe CAP. The most commonly isolated organisms were Streptococcus pneumoniae (76.7%) followed by Haemophilus infl uenzae(3.1%) and Staphylococcus aureus (2.1%). Contaminants accounted for 14.7%. Only 3 studies reported on BC-driven change in management, with contrasting fi ndings.

CONCLUSIONS: BCs in pediatric CAP identifi ed organisms in only a small percentage of patients, predominantly S. pneumoniae. False-positive BC rates can be substantial. The 3 studies that examined BC-driven changes in management had confl icting results. This systematic review was limited by heterogeneous case defi nitions, which may overestimate the true prevalence of positive BCs in hospitalized children.

Blood Culture in Evaluation of Pediatric Community-Acquired Pneumonia: A Systematic Review and Meta-analysis

Guidelines from the Infectious Diseases Society of America on management of community-acquired pneumonia (CAP) in children strongly recommend collec-tion of blood cultures (BCs) in those requiring hospitalization for presumed mod-erate to severe bacterial CAP.1 The support for these recommendations, however, is based on low- or moderate-quality evidence. Although management guidelines have demonstrated a decrease in morbidity and mortality in adults with presumed pneumonia,2,3 BCs are generally considered to be of limited utility because they infrequently identify organisms and rarely alter antimicrobial management even when positive.4–7 Other considerations complicating BC collection in children

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are the high prevalence of viral and mixed bacterial and viral respiratory infections in children,8 the concern for potential discomfort and distress to the child, and the possibility of false-positive BCs leading to unnecessary antimicrobial use and hospitalization.

We performed a systematic review of the literature with 2 objectives: to identify how often BCs were positive and which pathogens were most com-monly isolated in hospitalized children with CAP and to determine the impact of positive BCs on antimicrobial man-agement in hospitalized patients.

METHODSData Sources

Pertinent articles were identified using the stepwise approach speci-fi ed in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Statement.9 We searched PubMed and Scopus databases to identify articles published in English from January 1970 through December 2013 that addressed BCs in children with CAP. We conducted keyword searches to identify articles with at least 1 of the following Medical Sub-ject Headings terms in the title or abstract: community-acquired infec-tions, community-acquired pneumo-nia, blood culture, blood/microbiology, infant, child, or adolescent (Table 1). At least 1 of the terms from each category

was needed for inclusion. Additional references were identifi ed by hand-searching the reference lists of included articles and snowballing.

Study Selection

Two reviewers (PI and EB) indepen-dently scored abstracts for relevance to the clinical questions using a validated methodology.10,11 If at least 1 reviewer judged the full text of an article to be clinically relevant, then 2 independent reviewers critically appraised the arti-cle using a structured data collection form based on published guidelines.12,13 These 2 reviewers determined by con-sensus whether the article should be cited in the systematic review. The senior author (PF) assessed the identi-fi ed articles for completeness.

Criteria for inclusion were studies involving patients up to 18 years of age with a diagnosis of CAP who were eval-uated in the emergency department (ED) or hospitalized. CAP was defi ned as a case with clinical, radiographic, and/or microbiologic diagnosis of pneu-monia at time of or within 48 hours of admission to hospital. Studies using an International Statistical Classifi cation of Diseases and Related Health Problems, Ninth Revision (ICD-9) code of pneumo-nia in any position were also accepted. A positive BC was defi ned as a BC with growth of an organism. A false-positive BC was defi ned following the National

Healthcare Safety Network defi nition of skin contaminants.14 To be included in the review, BCs were included only from participants in the study who also met their study’s defi nition of CAP. We included peer-reviewed studies but excluded case reports, guidelines, and reviews if no new data were provided. We excluded studies that were based in the ambulatory setting and those that predominantly included patients with comorbidities (underlying chronic heart and lung conditions, malnutrition, immunodefi ciency, or immunosuppres-sion). We also excluded studies evalu-ating known positive isolates, such as studies evaluating diagnostic methods for detection of Streptococcus pneu-moniae in children with pneumonia or studies focusing on pneumonia or invasive disease caused by particular pathogens.

Quality Assessment

The methodologic quality of the included studies was evaluated using a modifi ed version of the Downs and Black critical appraisal tool.15 This vali-dated tool comprises 27 questions, each with a maximum score of 1 or 2 points, that address reporting, external validity, internal validity (bias and con-founding), and power.15,16 Because the majority of studies were not designed to detect a clinically important effect, we removed power in our modifi ed ver-sion. On the basis of the score (assigned by PI), study quality was determined to be excellent (25–27), good (19–24), fair (14–18), or poor (13).

Data Extraction

Data on total number of BCs col-lected and prevalence of positive BCs in patients with a diagnosis of pneu-monia were extracted. Studies with insuffi cient data or data that did not

TABLE 1 Search Strategy

Database Search terms

PubMed (((((children OR child))) AND ((((((pneumonia) AND community acquired infections)) OR community acquired pneumonia)) AND ((((blood culture) OR

blood cultures)) OR blood/microbiology[MeSH Terms])))) OR (((((((pneumonia) AND community acquired infections)) OR community acquired pneumonia)) AND ((((blood culture) OR blood cultures)) OR blood/microbiology[MeSH Terms])) AND (medline[sb] AND (infant[MeSH] OR child[MeSH] OR adolescent[MeSH])))

Scopus (((TITLE-ABS-KEY(pneumonia) AND TITLE-ABS-KEY(community acquired infections))) OR (TITLE-ABS-KEY(community acquired pneumonia))) AND

((TITLE-ABS-KEY(children) OR TITLE-ABS-KEY(child))) AND ((TITLE-ABS-KEY(blood culture) OR TITLE-ABS-KEY(blood cultures)))





suffi ciently differentiate total num-ber of BCs from positive BCs were excluded. Communications were sent to authors if clarifi cations from a study were needed. The primary outcome was the rate of positive BCs. The sec-ondary outcome was whether there was a change in the antimicrobial pre-scribed. Data extraction was recorded in Microsoft Excel (version 14.4.4).

Statistical Analysis

Statistical modeling was performed using the “metafor” package in R sta-tistical software (version 2.14.1).17,18 Logistic transformations were used to calculate the 95% confi dence interval (CI) for study-specifi c prevalence esti-mates to avoid exceeding the 0–1 lim-its.19 Meta-analysis of the prevalence of the positive BCs in patients with CAP was conducted using random

effects models20 to incorporate hetero-geneity across studies. Studies were also grouped by study-level charac-teristics and pooled proportions were calculated within these subgroups using random effects models. We used meta-regression to test differ-ences in the prevalence of positive BCs between particular subgroups, and subgroup meta-analysis was con-ducted for subgroups with signifi cant impact on prevalence. Publication bias was examined and adjusted by the trim and fi ll method.21 The signifi cant level for all tests was set at 5%.

RESULTSThe search identifi ed 220 articles of which 199 were systematically excluded, and 21 were included in this review (Fig 1). The studies included 15 prospective and 6 retrospective studies,

comprising a total of 8621 patients (Table 2). The majority of studies were from Europe (7), followed by Asia (5), United States (5), the Middle East (2), and South America and Africa (1 each). Studies ranged from publication dates in 1989 to 2013. Ten studies focused on the etiology of CAP.22–31 One study was focused on infl uenza A–related CAP.32 Two studies examined radiographic features in CAP,33,34 1 evaluated antimi-crobial use in the treatment of CAP,35 and 1 examined infl ammatory markers in CAP.36 Four studies evaluated bac-teremia in children with CAP,37–40 1 study examined management of CAP,41 and another focused on severe CAP admis-sions to the ICU.42 The majority of stud-ies used observational cohort design, except for 1 study that used a nested case-control design.40

Quality Assessment

The included studies ranged in meth-odologic quality (Table 3). Six stud-ies were assessed as good,36,37,39–42 11 were fair,23,24,26–28,30–32,34,35,38 and 4 were poor.22,25,29,33 Poorly rated studies suf-fered from outcomes that were not clearly described, omission of follow-up of participants, and lack of ade-quate adjustment of confounding in the analyses.

Diagnostic Criteria

The diagnostic criteria for CAP were diverse. Only 2 studies had clinical, laboratory, and radiographic crite-ria for CAP.30,35 One study based the diagnosis on clinical features alone,24 whereas 1 study based the diagnosis on microbiologic data alone25 and 1 on radiographic fi ndings alone.38 Four studies identifi ed pneumonia cases using ICD-9 billing codes for pneu-monia.37,39–41 Five studies did not docu-ment any exclusion criteria.26,30,35,37,42FIGURE 1 Search summary.




327|

TAB

LE 2

Stu

dies

that

add

ress

BC

, mic

robi

olog

y, a

nd/o

r B

C-d

rive

n ch

ange

s in

ant

imic

robi

al m

anag

emen

t in

pedi

atric

CA

P

Stud

yLo

catio

nSt

udy

Des

ign

and

Setti

ngA

ge

(Ran

ge)

Incl

usio

n C

riter

iaEx

clus

ion

Crit

eria

Defi

niti

on

of C

AP

BC

s, n

; TP

BC

s, n

(%

); FP

BC

s, n

(%

)

Bac

teria

Isol

ated

in

TP

BC

s, n

(%

)B

C-D

irect

ed

Cha

nge

in

Man

agem

ent

Uni

ted

Stat

es

Hic

key

et

al

1996

38

USA

Ret

ro, E

DM

edia

n 27

mo

(0–2

1 y)

CX

R d

iagn

osis

of

pne

umon

ia,

infi l

trat

e,

cons

olid

atio

n

CX

R d

iagn

osis

of

bron

chiti

s,

atel

ecta

sis,

or

bron

chio

litis

Not

doc

umen

ted

409;

11

(2.7

%);

33

(8.1

%)

S pn

eum

onia

e 10

(23

%),

H p

arai

nfl u

enza

e 1

(2%

), co

ntam

inan

ts

33 (

75%

)

No

chan

ge

in th

erap

y in

all

case

s

Sa

ndor

a

et a

l 20

0941

USA

Ret

ro c

ohor

t, in

patie

nt18

mo–

18 y

; 56

% <

5 y

18 m

o–18

y,

ICD

-9 c

ode

of p

neum

onia

Imm

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efi c

ienc

y,

chro

nic

med

ical

co

nditi

ons

othe

r th

an

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ma;

infa

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born

<

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k; d

iagn

osis

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bron

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R fi

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clin

ical

feat

ures

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nt n

ot

hosp

italiz

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r lo

ng-t

erm

car

e re

side

nt w

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pr

evio

us 1

4 d

139;

2

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%);

1 (0

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S pn

eum

onia

e 1

(33%

), no

ntyp

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e H

infl u

enza

e 1

(33%

), co

agul

ase-

nega

tive

Stap

hylo

cocc

us 1

(3

3%)

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docu

men

ted

Sh

ah

et

al

2011

40

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Nes

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case

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trol

re

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ED

Med

ian

2 y

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8 y)

≤18

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eval

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d in

ED

and

IC

D-9

cod

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ith C

AP

Req

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d ho

spita

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≤14

d be

fore

dia

gnos

is

of p

neum

onia

; im

mun

ocom

-pr

omis

ing/

chro

nic

med

ical

con

ditio

n

ICD

-9 c

ode

291;

6

(2.1

%);

3 (1

%)

S pn

eum

onia

e 4

(44%

), S

aure

us 1

(11

%),

H in

fl uen

zae

1 (1

1%),

coag

ulas

e-ne

gativ

e St

aphy

loco

ccus

3

(33%

)

17%

had

ap

prop

riate

br

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, 67

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ad

appr

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te

narr

owin

g;

17%

had

pa

thog

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ot

sens

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to

empi

rical

th

erap

y

Hei

ne

et

al

2013

37

USA

Ret

ro,

inpa

tient

Mea

n 4.

9 y

(0–1

8 y)

ICD

-9 c

ode

of

pneu

mon

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ot d

ocum

ente

dIC

D-9

cod

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pn

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155;

5

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S pn

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onia

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coli

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S py

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cont

amin

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5 (

50%

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Not

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men

ted

M

yers

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l 20

1339

USA

Mul

ticen

ter

retr

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ian

3.1

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60 d

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ode

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pneu

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, pos

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and

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ICD

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26

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8 (2

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S pn

eum

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e 19

(5

6%),

H in

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1 (3

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reus

6

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), co

ntam

inan

ts

8 (2

4%)

39%

had

th

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27

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ere

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aacs

1989

25

UK

Pro,

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tient

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ian

53 m

o,

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1 m

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y

with

clin

ical

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nd

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th

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im

mun

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se

Posi

tive

BC

/ple

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fl u

id

57; 2

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S pn

eum

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Not

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men

ted

Ju

ven

et

al

2000

26

Finl

and

Pro,

inpa

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Mea

n 3.

8 y

(0.1

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)

Chi

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n w

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CA

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dFe

ver

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and

/or

res

pira

tory

sy

mpt

oms

and

posi

tive

CX

R

125;

1

(0.8

%)

S pn

eum

onia

e 1

(100

%)

Not

docu

men

ted





Stud

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Crit

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Defi

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Isol

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BC

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agem

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M

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0136

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cePr

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patie

ntM

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C

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and

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pete

nt

Chr

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dis

ease

, an

timic

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befo

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dmis

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, no

t adm

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ital,

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C

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38°C

and

a

posi

tive

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et a

l 20

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UK

Pro,

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ian

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crit

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cou

gh, w

ith

posi

tive

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ical

ex

am/C

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51; 4

(8%

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pneu

mon

iae

3 (7

5%),

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enin

gitid

is 1

(2

5%)

Not

do

cum

ente

d

Ku

rz

et

al

2013

27

Aus

tria

Pro,

inpa

tient

Med

ian

36 m

o (2

mo–

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)

2 m

o–18

y

hosp

italiz

ed

with

di

agno

sis

of C

AP

Pree

xist

ing

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di

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mun

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fi cie

ncy,

imm

uno-

supp

ress

ive

ther

apy

Clin

ical

feat

ures

, po

sitiv

e C

XR

173;

5

(2.9

%);

2 (1

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)

S pn

eum

onia

e 2

(29%

), S

aure

us 1

(14

%),

M c

atar

rhal

is 1

(14

%),

Rot

hia

1 (1

4%),

coag

ulas

e-ne

gativ

e St

aphy

loco

ccus

2

(29%

)

Nar

row

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of

trea

tmen

t ba

sed

on

test

res

ults

Inte

rnat

iona

l

Leib

ovitz

et a

l 19

9035

Isra

elPr

o, in

patie

nt,

outp

atie

ntA

vera

ge

3 y,

7 m

o (5

mo-

14.5

y)

2 m

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y w

ith

diag

nosi

s of

sev

ere

bact

eria

l pn

eum

onia

Not

doc

umen

ted

Clin

ical

feat

ures

, la

bora

tory

fi n

ding

s an

d po

sitiv

e C

XR

147;

16

(10

.9%

); 1

(0.7

%)

S pn

eum

onia

e 13

(76

%),

H in

fl uen

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3 (1

8%),

S vi

ridan

s 1

(6%

)

Not

docu

men

ted

C

hong

et a

l 19

9723

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a-po

rePr

o, in

patie

ntM

ean

0.6

y (1

1 d–

11.8

y)

<12

y w

ith

CA

-LR

TIN

osoc

omia

l pn

eum

onia

, im

mun

o-co

mpr

omis

ed

host

Cou

gh/f

ever

<

2 w

k du

ratio

n,

clin

ical

feat

ures

or

pos

itive

CX

R

121;

4

(3.3

%)

S pn

eum

onia

e 1

(25%

), H

infl u

enza

e 1

(25%

), En

tero

bact

er 1

(2

5%),

S pn

eum

onia

e,

H in

fl uen

zae

1 (2

5%)

Not

docu

men

ted

H

ijazi

et a

l 19

9724

Kuw

ait

Pro,

inpa

tient

Med

ian

14 m

(1

0 d–

12 y

)

CA

-LR

TI, n

ot

prev

ious

ly

adm

itted

or

visi

ted

hosp

ital i

n pr

evio

us 8

wk

Sym

ptom

s >

1 w

k,

chro

nic

dise

ase,

br

onch

ial a

sthm

a,

mal

nutr

ition

Cou

gh a

nd

clin

ical

fe

atur

es

390;

38

(9.

7%)

Not

doc

umen

ted

Not

docu

men

ted

D

elpo

rt

et

al

2002

42

Sout

h A

fric

aPr

o, in

patie

ntM

edia

n 10

wk

(2 w

k–5

y)

Adm

itted

to

PIC

U;

intu

bate

d in

ER

; RR

>80

–90

/min

with

an

ticip

ated

ap

nea;

po

sitiv

e C

XR

Not

doc

umen

ted

Not

doc

umen

ted

23; 4

(17.4

%)

K pn

eum

onia

e 2

(50%

), no

t sp

ecifi

ed 2

Not

docu

men

ted

TAB

LE 2

Con

tinue

d




329|

Stud

yLo

catio

nSt

udy

Des

ign

and

Setti

ngA

ge

(Ran

ge)

Incl

usio

n C

riter

iaEx

clus

ion

Crit

eria

Defi

niti

on

of C

AP

BC

s, n

; TP

BC

s, n

(%

); FP

BC

s, n

(%

)

Bac

teria

Isol

ated

in

TP

BC

s, n

(%

)B

C-D

irect

ed

Cha

nge

in

Man

agem

ent

Ta

jima

et

al

2006

30

Japa

nPr

o, in

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Positive BCs

Of the 6975 total BCs obtained in pedi-atric patients with CAP, 425 were posi-tive (6.1%). The proportion of positive BCs in studies of CAP ranged from 0.8% to 17.4% (Table 4). Studies con-ducted before availability of pneumo-coccal conjugate vaccine (PCV) had a higher positive BC rate of 7.7% (range 0.8%–17.4%), compared with the post-PCV era, which had a rate of 4.0% (range 0.9%–7.8%).

Of 382 known BC results, the most commonly isolated organisms were S pneumoniae (76.7%), followed by Haemophilus infl uenzae (3.1%) and Staphylococcus aureus (2.1%; Table 5). In the pre-PCV era, 83.3% of iso-lates were S pneumoniae, compared with 61.7% post-PCV. Contaminants accounted for 14.7% of isolates, which in individual studies ranged from 5.9%–75% of positive BCs.27,28,35,38–41 However, reporting varied across

studies, with contaminants docu-mented in all US studies but reported in only 3 studies conducted outside of the United States.27,28,35

Severity of Disease

Severe disease was part of the inclusion criteria in 4 studies.33,35,36,42 However, only 1 study described parameters of severe disease as admission directly to the PICU or intubation in the ED for anticipated apnea.42 Diagnostic criteria

TABLE 3 Quality Assessment of the Included Studies

Study Modifi ed Downs and Black Criteria14

Reporting (n/11) External Validity (n/3) Internal Validity—bias (n/7)

Internal Validity—Confounding (n/6)

Total Score (n/26) Quality Rating

Heine et al 201337 9 2 6 3 20 GoodKurz et al 201327 7 1 4 2 14 FairLakhani et al 201334 6 1 5 2 14 FairMyers et al 201339 10 2 6 3 21 GoodChen et al 201222 4 1 4 2 11 PoorSur et al 201229 4 1 5 2 12 PoorShah et al 201140 10 1 5 3 19 GoodZhang et al 201131 6 1 5 2 14 FairFerrero et al 201033 5 1 4 2 12 PoorSandora et al 200941 11 2 6 4 23 GoodSecmeer et al 200828 7 2 5 3 17 FairTajima et al 200630 7 1 6 3 17 FairLaundy et al.200332 8 1 6 3 18 FairDelport et al 200242 10 1 5 3 19 GoodMoulin et al 200136 9 1 6 3 19 GoodJuven et al 200026 6 2 5 3 16 FairChong et al 199723 7 1 4 3 15 FairHijazi et al 199724 7 1 3 3 14 FairHickey et al 199638 8 1 5 3 17 FairLeibovitz et al 199035 9 1 3 3 16 FairIsaacs 198925 5 1 3 3 12 Poor

TABLE 4 BC Rates Among Studies

Subgroup No. of Studies Total Patients Estimate (95% CI) I2 Observed Range of Positive BC (%)

All studies22–42 21 8621 5.14 (3.61–7.28) 91.3% 0.8–17.4Studies pre-PCV23–26,33,35,36,38,42 9 4301 8.06 (5.74–11.20) 68.6% 0.8–17.4Studies post-PCV22,27–32,34,37,39–41 12 4320 3.04 (1.46–6.21) 83.0% 0.9–7.8Prospective studies only22–27,29–36,42 15 6035 4.83 (2.98–7.73) 91.2% 0.8–17.4Studies pre-PCV23–26,33,35,36,42 8 3892 6.75 (3.6–9.9) 89.6% 0.8–17.4Studies post-PCV22,27,29–32,34 7 2143 3.22 (1.09–5.34) 88.5% 0.9–7.8US studies37–41 5 2488 6.03 (3.40–10.48) 85.0% 2.2-10.8US and Western Europe studies25–27,32,36–41 10 3217 5.79 (3.83–8.66) 75.2% 0.8–11.4International studies22–24,28–31,33–35,42 11 5404 4.70 (2.62–8.29) 93.5% 0.8-17.4Studies in children ≤5 y32–34,36,42 5 2764 8.35 (6.12–11.28) 29.9% 6.1–17.4Studies that focus on severe CAP33,35,36,42 4 2794 9.89 (6.79–14.19) 61.6% 7.1–17.4Studies that do not focus on severe CAP22–32,34,37–41 17 5827 4.17 (2.79–6.18) 85.4% 0.8–10.8

BC, blood culture; CAP, community-acquired pneumonia; PCV, pneumococcal conjugate vaccine




331|

internationally33,35,42 with the excep-tion of 1 study from France,36 were all before the availability of PCV.

Antimicrobial Therapy

Four studies documented the propor-tion of patients who were treated with antimicrobial agents before hospital-ization. These studies, performed in China, Israel, the United States, and Kuwait, reported preadmission antibi-otic rates of 14%, 27%, 36%, and 50%, respectively.24,31,35,41

Seven studies documented antimicro-bial therapy at admission.26–28,30,36,37,41 However, these studies did not all clearly indicate whether antimicrobial therapy was given before or after BC collection, and only 3 studies docu-mented whether BC results led to antimicrobial narrowing or broaden-ing.38–40 In the fi rst study, children were evaluated in the ED and appropriate changes in antimicrobial manage-ment occurred in all 6 cases of posi-tive BCs.40 In the second, a change in antimicrobial management occurred in more than two-thirds of the posi-tive BCs, as well as in a third of false-positive BCs.39 The third study, which reviewed BCs drawn on 409 pediatric patients in the ED and relied solely on radiographic criteria for the diagnosis of pneumonia, nevertheless found that a positive BC identifi ed in 11 patients did not lead to any changes in their management.38 Overall, combining the data in these 3 studies, BCs led to antimicrobial management changes in 53.5% of the patients for whom BC were positive, and 2.2% of the aggre-gate population who had BCs drawn.

Meta-analysis Results

There was a high level of heterogene-ity across the included studies (P < .001; I 2 = 91.32%).43 Consequently, we

TABLE 5 Summary of Bacteria Isolated in Positive BCs

Positive BC (Sample Size) and Most Commonly Isolated Organisms Percentage (%)

All studies (8621)22,23,25–33,35–42

Streptococcus pneumoniae 76.7 Haemophilus infl uenzae 3.1 Staphylococcus aureus 2.1 Klebsiella pneumoniae 1.6 Streptococcus pyogenes 0.3 Haemophilus parainfl uenzae 0.3 Moraxella catarrhalis 0.3 Escherichia coli 0.3 Neisseria meningitides 0.3 Enterobacter spp 0.3 Stenotrophomonas maltophilia 0.3 Contaminants 14.7 Studies conducted in pre-PCV era (4301)23,25,26,33,35,36,38,42

Streptococcus pneumoniae 83.3 Studies conducted in post-PCV era (4320)22,27–32,37,39–41

Streptococcus pneumoniae 61.7Prospective studies only (6035)22,23,25–27,29–33,35,36,42

Studies conducted in pre-PCV era (3892)23,25,26,33,35,36,42

Streptococcus pneumoniae 81.3 Studies conducted in post-PCV era (2143)22,27,29–32

Streptococcus pneumoniae 57.7US studies (2488)37–41

Streptococcus pneumoniae 29.8 Staphylococcus aureus 5.6 Haemophilus infl uenzae 2.4 Contaminants 50.0US and Western Europe studies (3217)25–27,32,36–41

Streptococcus pneumoniae 44.4 Staphylococcus aureus 6.5 Haemophilus infl uenzae 2.4 Contaminants 42.7International studies (5404)22,23,28–31,33,35,42

Streptococcus pneumoniae 92.2 Haemophilus infl uenzae 3.5 Klebsiella pneumoniae 2.3 Contaminantsa 1.2Studies in children ≤5 y (2764)b32,33,36,42

Streptococcus pneumoniae 98.5 Klebsiella pneumoniae 1.0 Neisseria meningitidis 0.5Studies that focus on severe CAP (2794)33,35,36,42

Streptococcus pneumoniae 97.1 Haemophilus infl uenzae 1.4 Klebsiella pneumoniae 1.0 Contaminantsc 0.5Studies that did not focus on severe CAP (5827)22,23,25–32,37–41

Streptococcus pneumoniae 51.7 Haemophilus infl uenzae 5.2 Staphylococcus aureus 4.7 Contaminants 32.0

Data not available in several studies.24,34 BC, blood culture; CAP, community-acquired pneumonia; PCV, pneumococcal conjugate vaccine.a Only 2 studies reported on contaminants.28,35

b No study reported on contaminants.c Only one study reported on contaminants.35

for CAP in the other studies required clinical, laboratory, and radiographic fi ndings consistent with CAP and did

not include ICU admission or intuba-tion in their criteria for severe disease. These studies, conducted primarily





applied random effects models in our meta-analysis to calculate the preva-lence of positive BCs and 95% CI, for all subgroups (Table 4). Meta-regression of the subgroups showed that the only subgroup indicator that had a signifi cant impact on prevalence of positive BCs was severe CAP (P = .008). Subgrouping also reduced the heterogeneity within the subgroup on severe CAP (I2 = 61.6%), which supports our original analysis that severe CAP has a signifi cant impact on prevalence of positive BC.

The effect of meta-regression on the other subgroups were not signifi cant (P > .05), indicating that the prevalence can be considered the same between subgroups of US and Western Europe studies and international studies, and between subgroups of prospective and retrospective studies. The exception was

the subgroup of studies on children ≤5 years (I2 = 29.9%). Studies not included in this subgroup covered a broader range of ages (from 0 to 21 years), and meta-regression between these 2 groups did not result in a signifi cant P value (P = .06). Hence, there is no statis-tical evidence that studies with children ≤5 years report different prevalence than children of a broader range of ages.

The overall prevalence of positive BCs for all studies was 5.14% (95% CI 3.61–7.28; Fig 2). Studies that focused on severe CAP had a prevalence of 9.89% (95% CI 6.79–14.19), compared with a prevalence of 4.17% (95% CI 2.79–6.18) for studies not focusing on severe CAP.

Funnel plot of the observed studies showed asymmetry and signifi cant publication bias (P = .003; Fig 3). We

then adjusted for publication bias using the trim and fi ll method.21 This method infers the existence of unpublished hid-den studies as determined from a fun-nel plot, and corrects the meta-analysis by ascribing the presence of missing studies to yield an unbiased pooled estimate. With the adjusted analysis, the overall adjusted prevalence was 4.71% (95% CI 3.07–6.34).

DISCUSSIONOn the basis of meta-analysis of these studies, children with CAP had posi-tive BCs in 5.14% of cases. However, because of publication bias, the adjusted prevalence is lower at 4.71%. The most frequently isolated organ-isms from the blood of children with CAP were S pneumoniae, H infl uenzae, and S aureus. These bacteria have been noted to be the predominant causes of severe pneumonia before conjugate vaccines and are similar to the literature in adults.44 Notably, 8 studies in our review were conducted before the licensure of the PCV in 2000,23–26,35,36,38,42 and a ninth study was conducted in South America in which none of the patients had received PCV.33 S pneumoniae remained the predominant pathogen isolated from positive BCs even after introduction of PCV. However, in the post-PCV era, S pneumoniae isolates made up 2.4% of all BC obtained in pediatric CAP compared with 5.6% pre-PCV. This is consistent with other pediatric stud-ies demonstrating effi cacy of PCV in reducing cases of invasive pneumo-coccal disease as well as pneumococcal pneumonia45,46 and suggests that in countries with high PCV uptake, the likelihood of a positive BC is low.

Geographic differences in BC positivity and predominant organisms isolated were evident, although no signifi cant

FIGURE 2 Forest plot demonstrating the pooled prevalence of positive BCs in pediatric CAP. Pooled prevalence was calculated using random effects (RE) models using the DerSimonian-Laird method.




333|

differences were seen on meta-regression. US and Western European studies had a combined BC positivity rate of 5.79% (95% CI 3.83–8.66), with S pneumoniae accounting for 44.4% of isolates followed by S aureus at 6.5% and H infl uenzae at 2.4%. International studies had a combined BC positiv-ity rate of 4.70% (95% CI 2.62–8.29) with 92.2% of isolates identifi ed as S pneumoniae, followed by H infl uenzae at 3.5% and K pneumoniae at 2.3%. We excluded studies that evaluated diagnostic methods for detection of S pneumoniae in children with pneu-monia to reduce selection bias. If we had included other diagnostic meth-ods in addition to culture, such as polymerase chain reaction or antigen

testing,26 rates of S pneumoniae identi-fi cation would have been even higher.

Collection of BCs in all patients with pneumonia has traditionally been considered a marker of high-quality care.47 The American Thoracic Society has recommended this test since the 1990s as part of the initial evaluation of patients with CAP.48 This recommen-dation was based on the belief that BC results facilitate more effective antimi-crobial treatment because bacteremia refl ects more severe disease and a higher risk of mortality.49 In adults, BC in management of pneumonia was adopted as a quality measure after a study showed that BCs obtained within 24 hours of admission were

associated with lower 30-day mortal-ity.50 However, there were concerns about selection bias and confounding by variations in hospital quality.50,51 In addition, the mean age of patients was 79 years, and 58% of the patients had at least 1 comorbid illness,50 features that are generally not applicable to the pediatric population.

The studies included in this review all lacked a study design that rigorously evaluated the value of BC in manage-ment of pediatric CAP. There were no randomized controlled studies, and the majority of studies were observational. In the few studies that listed severity of CAP as criteria for inclusion, the study’s diagnostic criteria were not always refl ective of severe disease.33,35,36 None of the studies required collection of BC in all patients admitted with CAP. Because the majority of hospitalized patients with CAP may not have been perceived to have a high probability of bacteremia, this selection bias for BC collection in more ill-appearing patients may have resulted in higher rates of documented bacteremia.

Only 3 studies documented antimicro-bial changes in management based on BC results, and all 3 studies had dif-fering results.38–40 However, the study showing that positive BC did not lead to any change in antimicrobial man-agement was performed almost 2 decades ago and may not refl ect cur-rent management practice. In addition, none of these studies documented poor clinical outcomes for patients with either positive or negative BCs.

This impact of diagnostic testing on clinical outcomes has been an area of increasing scrutiny. Studies in the pedi-atric population have demonstrated that diagnostic testing has been shown to

FIGURE 3 Funnel plot testing for publication bias in studies of positive BCs in pediatric CAP. Solid circles are observed studies. Empty circles are fi lled studies by the trim and fi ll method.





lead to higher hospitalization rates but no signifi cant difference in ED revisit rates,52 nor to signifi cant changes in clinical management.53 Other stud-ies have demonstrated the low yield of positive cultures, the lack of sensitivity in detecting bacterial pneumonia, and the low impact that positive cultures have on altering antimicrobial treatment.4,7,54,55 On the basis of the combined data from the 3 studies that documented antimi-crobial changes in management, ther-apy changes occurred in only slightly more than of the cases. However, this accounted for 2.2% of the total popula-tion in these studies who had BCs drawn.

Our review of the literature did point out situations in which BC collection is likely to be most helpful. The high-est yield of positive BCs in studies were from patients who were manifestly sick,34,42 and severe CAP was the only subgroup that had a signifi cant effect on prevalence in the meta-regression model. However, we were unable to determine the benefi t of BC collection in cases of presumed moderate CAP, as is suggested by the current guidelines, because the majority of studies did not stratify patients by severity of illness.

This is also complicated by the sub-stantial number of false-positive BCs in these studies, ranging from 0.7% to 8.1% of all BCs collected, which cor-relates with fi ndings in adult pneu-monia studies.4,56 Contaminants were reported in all the US studies and overall accounted for half of all posi-tive isolates. These results may have been skewed by the large proportion of contaminants identifi ed in 1 United States study conducted in the 1990s,38 which accounted for 75% of positive BCs. Outside of studies conducted in the United States, only 1 study in

Austria,27 Israel,35 and Turkey,28 respec-tively, reported on contaminants.

Our review was limited not only by the discrepancy in reporting of con-taminants but also by the varied cri-teria used to diagnose pneumonia in children.57 Several studies used World Health Organization criteria that defi nes mild to moderate CAP based on cough and tachypnea.32,34 This defi nition is clearly limited because it is nonspe-cifi c for all types of lower respira-tory tract disease. Other studies did not provide a case defi nition of CAP, although this was implied by their inclu-sion criteria and thus were included in the review.28,38,42 Nonetheless, this may affect the consistency of the included studies. Heterogeneity of case defi ni-tions was a major limitation, which may overestimate the true prevalence of positive BCs in hospitalized children. Although there was variation in results, there was consistency in the direction of effect, and therefore it was reason-able to calculate an average prevalence based on the included studies. We also accounted for this by performing a random effects model on the data as well as the subgroups to incorporate heterogeneity among studies, meta-regression to investigate differences for categorical explanatory variables among subgroups, and regression coef-fi cients to evaluate differences between subgroups. However, comparisons of subgroups where there are overlapping studies may not be meaningful, as these are observational by nature and are not based on randomized comparisons.58 In addition, false-negative and false-positive signifi cance tests increase in likelihood rapidly as more subgroup analyses are performed.58

Next, our review included retrospective studies, and this may lead to sampling

bias, even though when we restricted our analysis to prospective studies, we had similar results, and no difference was determined on meta-regression. We did fi nd evidence of publication bias in the included studies, but adjusted for it in our analyses. Although we excluded studies that predominantly involved patients with comorbidities, some studies did include patients with comorbidities in their analysis, most commonly asthma.31,40–42 The comorbid population accounted for roughly 6% of all hospitalized patients with CAP in our review, not large enough to shift the context of our fi ndings. In addition, since the introduction of conjugate vaccines for H infl uenzae type b and S pneumoniae, rates of associated pneu-monia in children have decreased.45,59 We attempted to account for this in our analysis by stratifying our data into pre- and post-PCV eras, but this review may consequently not refl ect the current epidemiology.

This systematic review furthers our general understanding of the utility of BC in evaluation of pediatric CAP. Given that the heterogeneous study designs and case defi nitions may lead to overestimation of the prevalence of positive BCs, the true prevalence may be <4.71%. Additional data from ongo-ing projects such as the Pneumonia Etiology Research for Child Health (PERCH)57 will assist countries in mak-ing program decisions on health invest-ment priorities, and provide evidence for clinicians to revise their protocols and guidelines for empirical therapy regimens. PERCH can also serve as a model for further studies in pediatric CAP, where research should attempt to quantify the true risk for bacteremia in pediatric patients with CAP, and assess the impact of bacteremia on




335|

clinical outcomes. Studies determining whether BC collection is cost-effective in patients hospitalized with moderate CAP may help inform whether admis-sion to hospital is suffi cient justifi ca-tion for this procedure. Further studies are needed to evaluate whether BCs in moderate to severe CAP in children shorten hospital stay, reduce complica-tions, and decrease mortality.

ACKNOWLEDGMENTSWe thank Jim Beattie for assistance with the database search, and Haitao Chu for assistance with statistical analysis.

REFERENCES

1. Bradley JS, Byington CL, Shah SS, et al.

The management of community-acquired

pneumonia in infants and children older than

3 months of age: clinical practice guidelines

by the Pediatric Infectious Diseases Society

and the Infectious Diseases Society of

America. Clin Infect Dis. 2011;53(7):e25-76.

2. Dean NC, Bateman KA, Donnelly SM, Silver

MP, Snow GL, Hale D. Improved clinical

outcomes with utilization of a community-

acquired pneumonia guideline. Chest.

2006;130(3):794–799.

3. McCabe C, Kirchner C, Zhang H, Daley J,

Fisman DN. Guideline-concordant therapy

and reduced mortality and length of

stay in adults with community-acquired

pneumonia: playing by the rules. Arch

Intern Med. 2009;169(16):1525–1531.

4. Abe T, Tokuda Y, Ishimatsu S, Birrer RB.

Usefulness of initial blood cultures in

patients admitted with pneumonia from an

emergency department in Japan. J Infect

Chemother. 2009;15(3):180–186.

5. Benenson RS, Kepner AM, Pyle DN II,

Cavanaugh S. Selective use of blood cultures

in emergency department pneumonia

patients. J Emerg Med. 2007;33(1):1–8.

6. Campbell SG, Marrie TJ, Anstey R, Ackroyd-

Stolarz S, Dickinson G. Utility of blood

cultures in the management of adults with

community acquired pneumonia discharged

from the emergency department. Emerg

Med J. 2003;20(6):521–523.

7. Ramanujam P, Rathlev NK. Blood cultures

do not change management in hospitalized

patients with community-acquired pneumonia.

Acad Emerg Med. 2006;13(7):740–745.

8. Michelow IC, Olsen K, Lozano J, et al.

Epidemiology and clinical characteristics of

community-acquired pneumonia in hospi tal-

ized children. Pediatrics. 2004;113(4):701–707.

9. Moher D, Liberati A, Tetzlaff J, Altman DG.

Preferred reporting items for systematic re views

and meta-analyses: the PRISMA state ment.

Ann Int Med. 2009;151(4):264–269, W264.

10. Haynes RB, Cotoi C, Holland J, et al; McMaster

Premium Literature Service (PLUS) Project.

Second-order peer review of the medical

literature for clinical practitioners. JAMA.

2006;295(15):1801–1808.

11. Lokker C, McKibbon KA, McKinlay RJ,

Wilczynski NL, Haynes RB. Prediction of

citation counts for clinical articles at two

years using data available within three

weeks of publication: retrospective cohort

study. BMJ. 2008;336(7645):655–657.

12. Jaeschke R, Guyatt G, Sackett DL. Users’

guides to the medical literature. III. How

to use an article about a diagnostic test.

A. Are the results of the study valid?

Evidence-Based Medicine Working Group.

JAMA. 1994;271(5):389–391.

13. Laupacis A, Wells G, Richardson WS,

Tugwell P; Evidence-Based Medicine

Working Group. Users’ guides to the medical

literature. V. How to use an article about

prognosis. JAMA. 1994;272(3):234–237.

14. Centers for Disease Control and Prevention/

National Healthcare Safety Network. CDC/

NHSN Surveillance Defi nitions for Specifi c

Types of Infections 2014. Available at:

http://www.cdc.gov/nhsn/pdfs/pscmanual/

17pscnosinfdef_current.pdf. Accessed March

19, 2015

15. Downs SH, Black N. The feasibility of

creating a checklist for the assessment

of the methodological quality both of

randomised and non-randomised studies

of health care interventions. J Epidemiol

Community Health. 1998;52(6):377–384.

16. Sanderson S, Tatt ID, Higgins JP. Tools for

assessing quality and susceptibility to bias

in observational studies in epidemiology:

a systematic review and annotated bibli-

ography. Int J Epidemiol. 2007;36(3):666–676.

17. R Development Core Team. R: A Language

and Environment for Statistical Computing.

Vienna, Austria: R Foundation for Statistical

Computing; 2011.

18. Viechtbauer W. Conducting meta-analyses

in R with the metafor package. J Stat Softw.

2010;36(3):1–48.

19. Barendregt JJ, Doi SA, Lee YY, Norman RE, Vos

T. Meta-analysis of prevalence. J Epidemiol

Community Health. 2013;67(11):974–978.

20. DerSimonian R, Laird N. Meta-analysis in

clinical trials. Control Clin Trials. 1986;7(3):

177–188.

21. Duval S, Tweedie R. Trim and fi ll: A simple

funnel-plot-based method of testing and

adjusting for publication bias in meta-

analysis. Biometrics. 2000;56(2):455–463.

22. Chen CJ, Lin PY, Tsai MH, et al. Etiology

of community-acquired pneumonia in

hospitalized children in northern Taiwan.

Pediatr Infect Dis J. 2012;31(11):e196–e201.

23. Chong CY, Lim WH, Heng JT, Chay OM. The

changing trend in the pattern of infective

etiologies in childhood acute lower

respiratory tract infection. Acta Paediatr

Jpn. 1997;39(3):317–321.

24. Hijazi Z, Pacsa A, el-Gharbawy F, et al. Acute

lower respiratory tract infections in children in

Kuwait. Ann Trop Paediatr. 1997;17(2):127–134.

25. Isaacs D. Problems in determining the

etiol ogy of community-acquired childhood

pneu monia. Pediatr Infect Dis J. 1989;8(3):

143–148.

26. Juvén T, Mertsola J, Waris M, et al. Etiology

of community-acquired pneumonia in 254

hospitalized children. Pediatr Infect Dis J.

2000;19(4):293–298.

27. Kurz H, Göpfrich H, Huber K, et al. Spectrum

of pathogens of in-patient children

and youths with community acquired

pneumonia: a 3 year survey of a community

hospital in Vienna, Austria. Wien Klin

Wochenschr. 2013;125(21-22):674–679.

28. Seçmeer G, Ciftçi AO, Kanra G, et al.

Community-acquired pneumonia and

parapneumonic effusions in developing

countries. Turk J Pediatr. 2008;50(1):51–57.

29. Sur G, Kudor-Szabadi L, Vidrean V,

Samașca G. Etiology of pneumonia in

children in the absence of pneumococcal

and antihaemophilus vaccines. Roum Arch

Microbiol Immunol. 2012;71(1):48–52.

30. Tajima T, Nakayama E, Kondo Y, et al. Etiology

and clinical study of community-acquired

pneumonia in 157 hospitalized children.

J Infect Chemother. 2006;12(6):372–379.

31. Zhang Q, Guo Z, MacDonald NE. Vaccine

preventable community-acquired pneumonia





in hospitalized children in Northwest China.

Pediatr Infect Dis J. 2011;30(1):7–10.

32. Laundy M, Ajayi-Obe E, Hawrami K, Aitken

C, Breuer J, Booy R. Infl uenza A community-

acquired pneumonia in East London infants

and young children. Pediatr Infect Dis J.

2003;22(suppl 10):S223–S227.

33. Ferrero F, Nascimento-Carvalho CM, Cardoso

MR, et al; CARIBE group. Radiographic

fi ndings among children hospitalized with

severe community-acquired pneumonia.

Pediatr Pulmonol. 2010;45(10):1009–1013.

34. Lakhani D, Muley P. The association of

positive chest radiograph and laboratory

parameters with community acquired

pneumonia in children. J Clin Diagn Res.

2013;7(8):1629–1631.

35. Leibovitz E, Tabachnik E, Fliedel O, et al.

Once-daily intramuscular ceftriaxone in the

outpatient treatment of severe community-

acquired pneumonia in children. Clin

Pediatr (Phila). 1990;29(11):634–639.

36. Moulin F, Raymond J, Lorrot M, et al.

Procalcitonin in children admitted to hospital

with community acquired pneumonia. Arch

Dis Child. 2001;84(4):332–336.

37. Heine D, Cochran C, Moore M, Titus MO,

Andrews AL. The prevalence of bacteremia

in pediatric patients with community-

acquired pneumonia: guidelines to reduce

the frequency of obtaining blood cultures.

Hosp Pediatr. 2013;3(2):92–96.

38. Hickey RW, Bowman MJ, Smith GA. Utility

of blood cultures in pediatric patients found

to have pneumonia in the emergency depart-

ment. Ann Emerg Med. 1996;27(6):721–725.

39. Myers AL, Hall M, Williams DJ, et al.

Prevalence of bacteremia in hospitalized

pediatric patients with community-acquired

pneumonia. Pediatr Infect Dis J. 2013;32(7):

736–740.

40. Shah SS, Dugan MH, Bell LM, et al. Blood

cultures in the emergency department

evaluation of childhood pneumonia. Pediatr

Infect Dis J. 2011;30(6):475–479.

41. Sandora TJ, Desai R, Miko BA, Harper MB.

Assessing quality indicators for pediatric

community-acquired pneumonia. Am J

Med Qual. 2009;24(5):419–427.

42. Delport SD, Brisley T. Aetiology and

outcome of severe community-acquired

pneumonia in children admitted to a

paediatric intensive care unit. S Afr Med J.

2002;92(11):907–911.

43. Higgins JP, Thompson SG, Deeks JJ, Altman

DG. Measuring inconsistency in meta-

analyses. BMJ. 2003;327(7414):557–560.

44. Afshar N, Tabas J, Afshar K, Silbergleit R.

Blood cultures for community-acquired

pneumonia: are they worthy of two quality

measures? A systematic review. J Hosp

Med. 2009;4(2):112–123.

45. Grijalva CG, Nuorti JP, Arbogast PG, Martin

SW, Edwards KM, Griffi n MR. Decline

in pneumonia admissions after routine

childhood immunisation with pneumococcal

conjugate vaccine in the USA: a time-series

analysis. Lancet. 2007;369(9568):1179–1186.

46. Whitney CG, Farley MM, Hadler J, et al;

Active Bacterial Core Surveillance of the

Emerging Infections Program Network. De-

cline in invasive pneumococcal disease after

the introduction of protein-polysaccharide

conjugate vaccine. N Engl J Med. 2003;

348(18):1737–1746.

47. Dedier J, Singer DE, Chang Y, Moore M, Atlas

SJ. Processes of care, illness severity, and

outcomes in the management of community-

acquired pneumonia at academic hospitals.

Arch Intern Med. 2001;161(17):2099–2104.

48. Niederman MS, Bass JB Jr, Campbell GD,

et al; American Thoracic Society. Medical

Section of the American Lung Association.

Guidelines for the initial management of

adults with community-acquired pneumonia:

diagnosis, assessment of severity, and initial

antimicrobial therapy. Am Rev Respir Dis.

1993;148(5):1418–1426.

49. Liapikou A, Ferrer M, Polverino E, et al.

Severe community-acquired pneumonia: vali-

dation of the Infectious Diseases Society of

America/American Thoracic Society guidelines

to predict an intensive care unit admission. Clin

Infect Dis. 2009;48(4):377–385.

50. Meehan TP, Fine MJ, Krumholz HM, et al.

Quality of care, process, and outcomes in

elderly patients with pneumonia. JAMA.

1997;278(23):2080–2084.

51. Fine JM, Fine MJ, Galusha D, Petrillo M,

Meehan TP. Patient and hospital charac-

teristics associated with recommended pro-

cesses of care for elderly patients hospitalized

with pneumonia: results from the medicare

quality indicator system pneumonia module.

Arch Intern Med. 2002;162(7):827–833.

52. Florin TA, French B, Zorc JJ, Alpern ER,

Shah SS. Variation in emergency department

diagnostic testing and disposition outcomes in

pneumonia. Pediatrics. 2013;132(2):237–244.

53. Leonard P, Beattie TF. How do blood

cultures sent from a paediatric accident

and emergency department infl uence

subsequent clinical management? Emerg

Med J. 2003;20(4):347–348.

54. Arbo MD, Snydman DR. Infl uence of blood

culture results on antibiotic choice in the

treatment of bacteremia. Arch Intern Med.

1994;154(23):2641–2645.

55. Requejo HI, Guerra ML, Dos Santos

M, Cocozza AM. Immunodiagnoses of

community-acquired pneumonia in child-

hood. J Trop Pediatr. 1997;43(4):208–212.

56. Zwang O, Albert RK. Analysis of strategies

to improve cost effectiveness of blood

cultures. J Hosp Med. 2006;1(5):272–276.

57. Scott JA, Wonodi C, Moisi JC, et al. The defi ni-

tion of pneumonia, the assessment of severity,

and clinical standardization in the Pneumonia

Etiology Research for Child Health study. Clin

Infect Dis. 2012;54(suppl 2):S109–116.

58. Deeks JJ, Higgins JPT, Altman DG, eds.

Analysing data and undertaking meta-

analyses. In: Higgins JPT, Green S, eds.

Cochrane Handbook for Systematic Reviews

of Interventions Version 5.0.1 [updated

September 2008]. London, UK: The Cochrane

Collaboration; 2008.

59. Madhi SA, Levine OS, Hajjeh R, Mansoor

OD, Cherian T. Vaccines to prevent

pneumonia and improve child survival. Bull

World Health Organ. 2008;86(5):365–372.

FINANCIAL DISCLOSURE: The authors have indicated they have no fi nancial relationships relevant to this article to disclose.

FUNDING: Dr Iroh Tam has received grant support from Pfi zer for an unrelated study. Dr Ma was supported in part by the US Agency for Healthcare Research and Quality grant R03HS020666 and the US National Institute of Allergy and Infectious Diseases grant AI103012.

POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential confl icts of interest to disclose.

(Continued on First page)



DOI: 10.1542/hpeds.2014-01382015;5;324Hospital Pediatrics

Pui-Ying Iroh Tam, Ethan Bernstein, Xiaoye Ma and Patricia FerrieriSystematic Review and Meta-analysis

Blood Culture in Evaluation of Pediatric Community-Acquired Pneumonia: A

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Pui-Ying Iroh Tam, Ethan Bernstein, Xiaoye Ma and Patricia FerrieriSystematic Review and Meta-analysis

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