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KEY WORDS
pneumonia, pediatric, antibiotics, comparative effectiveness,
hospitalized
ABBREVIATIONS
CAPcommunity-acquired pneumonia
CIcondence interval
IDSAInfectious Diseases Society of America
LOSlength of stay
PHISPediatric Health Information System
PIDSPediatric Infectious Diseases Society
WBCwhite blood cell
Dr Queen conceptualized and designed the study and drafted the
initial manuscript; Dr Myers participated in data collection and
analysis and drafted the initial manuscript; Dr Hall carried out
the initial analyses and reviewed and revised the manuscript; Dr
Shah conceptualized and designed the study and revised the
manuscript; Dr Williams coordinated and supervised data
collection and critically reviewed the manuscript; Drs Auger,
Jerardi, and Statile participated in data collection and analysis
and critically reviewed the manuscript; Dr Tieder conceptualized
and designed the study, provided project oversight, and
critically reviewed the manuscript; and all authors approved the
nal manuscript as submitted.
(Continued on last page)
abstract
BACKGROUND AND OBJECTIVE: Narrow-spectrum antibiotics are
recommended as the rst-line agent for children hospitalized with
community-acquired pneumonia (CAP). There is little scientic evidence
to support that this consensus-based recommendation is as effective as
the more commonly used broad-spectrum antibiotics. The objective was
to compare the effectiveness of empiric treatment with narrowspectrum therapy versus broad-spectrum therapy for children hospitalized with uncomplicated CAP.
METHODS: This multicenter retrospective cohort study using medical
records included children aged 2 months to 18 years at 4 childrens
hospitals in 2010 with a discharge diagnosis of CAP. Patients receiving
either narrow-spectrum or broad-spectrum therapy in the rst 2 days of
hospitalization were eligible. Patients were matched by using propensity
scores that determined each patients likelihood of receiving empiric
narrow or broad coverage. A multivariate logistic regression analysis
evaluated the relationship between antibiotic and hospital length of stay
(LOS), 7-day readmission, standardized daily costs, duration of fever, and
duration of supplemental oxygen.
RESULTS: Among 492 patients, 52% were empirically treated with a narrowspectrum agent and 48% with a broad-spectrum agent. In the adjusted
analysis, the narrow-spectrum group had a 10-hour shorter LOS (P = .04).
There was no signicant difference in duration of oxygen, duration of fever,
or readmission. When modeled for LOS, there was no difference in average
daily standardized cost (P = .62) or average daily standardized pharmacy
cost (P = .26).
CONCLUSIONS: Compared with broad-spectrum agents, narrow-spectrum
antibiotic coverage is associated with similar outcomes. Our ndings support national consensus recommendations for the use of narrow-spectrum
antibiotics in children hospitalized with CAP. Pediatrics 2014;133:e23e29
e23
METHODS
Study Design, Data Source, and
Study Population
Thismulticenter retrospectivestudy was
nested within a cohort of patients from
a study to validate International Classication of Diseases, Ninth Revision,
Clinical Modication, diagnostic codes
for CAP.9 We used the Pediatric Health
Information System (PHIS; Childrens
Hospital Association, Overland Park, KS)
to identify children discharged with
a diagnosis of CAP from 4 freestanding
childrens hospitals (Monroe Carell
Jr Childrens Hospital at Vanderbilt,
Nashville, TN; Childrens Mercy Hospitals
and Clinics, Kansas City, MO; Seattle
Childrens Hospital, Seattle, WA; and
Cincinnati Childrens Hospital Medical
Center, Cincinnati, OH). The institutional
review board at each hospital approved
the study.
Children who were 60 days to 18 years
of age with a discharge diagnosis of
pneumonia at a participating hospital
between January 1, 2010, and December
31, 2010, were eligible for inclusion. A
random subset of discharges was selected formedical record reviewto verify
the diagnosis of CAP as previously described (n = 785).9 The medical records
of children meeting the following denition of CAP were then reviewed to
obtain data on presenting signs and
symptoms, results of laboratory and
radiologic studies, and hospital course:
(1) provider diagnosis of pneumonia
within the rst 48 hours of hospitalization (mention of suspected CAP along
with consistent management strategy),
(2) fever within rst 48 hours of admission or abnormal white blood cell
(WBC) count, (3) evidence of respiratory
illness (eg, cough or increased work of
breathing), and (4) chest radiograph
indicating pneumonia (eg, inltrate or
consolidation).
Children with chronic conditions predisposing to severe, recurrent, or
QUEEN et al
ARTICLE
FIGURE 1
Consort diagram indicating identication of study population and reasons for exclusion.
a
Fluoroquinolone exposure, n = 12; second- and third-generation cephalosporins only, n = 224.
RESULTS
A total of 492 patients with CAP were
included in the study: 256 (52%) received a narrow-spectrum antibiotic
and 236 (48%) received a broadspectrum antibiotic (Table 1). Before
matching, there were no differences
between the 2 groups in age, gender,
race, insurance type, asthma, reactive
airway disease, or viral lower respiratory tract infection. However,
patients in the narrow-spectrum antibiotic group were more likely to be 60
days to 2 years of age (44.1% vs 39.8%;
P = .02) or have an abnormal WBC
(41.0% vs 31.4%; P = .03). Patients in the
broad-spectrum antibiotic group were
more likely to receive antibiotics before hospital arrival (30.5% vs 18.4%;
Age
60 days to 2 years
212 years
1218 years
Male
Race/ethnicity
Non-Hispanic white
Non-Hispanic black
Hispanic
Asian
Other
Clinical characteristics
Fever .38C
Tachypnea
Tachycardiaa
Abnormal WBC
Hypotensiona
Altered mental statusa
Government insurance
Antibiotic therapy before
admission
Macrolide empiric antibiotic
therapy
Diagnosis of asthma or
reactive airway diseaseb
Diagnosis of bronchiolitis
viral infectionc
Blood culture obtained
Positive blood culture
Matched Cohort
Total Population
(N = 492)
Narrow-Spectrum
(n = 256)
Broad-Spectrum
(n = 236)
Cohort
Population
Narrow-Spectrum
Broad-Spectrum
207 (42.1)
275 (55.9)
10 (2.0)
268 (54.5)
113 (44.1)
142 (55.5)
1 (0.4)
141 (55.1)
94 (39.8)
133 (56.4)
9 (3.8)
127 (53.8)
.02
184 (42.8)
239 (55.6)
7 (1.6)
234 (54.4)
94 (43.7)
120 (55.8)
1 (0.5)
117 (54.4)
90 (41.9)
119 (55.3)
6 (2.8)
117 (54.4)
.16
269 (54.7)
80 (16.3)
53 (10.8)
15 (3.0)
75 (15.2)
144 (56.3)
44 (17.2)
23 (9.0)
5 (2.0)
40 (15.6)
125 (53.0)
36 (15.3)
30 (12.7)
10 (4.2)
35 (14.8)
.37
227 (52.8)
71 (16.5)
49 (11.4)
14 (3.3)
117 (54.4)
36 (16.7)
23 (10.7)
5 (2.3)
110 (51.2)
35 (16.3)
26 (12.1)
9 (4.2)
.81
220 (44.7)
108 (22.0)
4 (0.8)
179 (36.4)
4 (0.8)
9 (1.8)
259 (52.6)
119 (24.2)
107 (41.8)
59 (23.0)
1 (0.4)
105 (41.0)
1 (0.4)
6 (2.3)
132 (51.6)
47 (18.4)
113 (47.9)
49 (20.8)
3 (1.3)
74 (31.4)
3 (1.3)
3 (1.3)
127 (53.8)
72 (30.5)
.18
.54
.28
.03
.28
.38
.62
.002
194 (45.1)
93 (21.6)
3 (0.7)
145 (33.7)
4 (0.9)
9 (2.1)
235 (54.7)
109 (25.3)
96 (44.7)
47 (21.9)
1 (0.5)
74 (34.4)
1 (0.5)
6 (2.8)
117 (54.4)
47 (21.9)
98 (45.6)
46 (21.4)
2 (0.9)
71 (33.0)
3 (1.4)
3 (1.4)
118 (54.9)
62 (28.8)
.85
.91
.56
.76
.32
.31
.92
.10
87 (17.7)
26 (10.2)
61 (25.8)
.001
70 (16.3)
26 (12.1)
44 (20.5)
.02
153 (31.1)
89 (34.8)
64 (27.1)
.07
125 (29.1)
64 (29.8)
61 (28.4)
.75
130 (26.4)
70 (27.3)
60 (25.4)
.63
118 (27.4)
62 (28.8)
56 (26.0)
.52
253 (51.4)
14 (2.8)
113 (44.2)
3 (1.2)
140 (59.3)
11 (4.7)
.001
.02
234 (54.4)
11 (2.6)
113 (52.6)
3 (1.4)
121 (56.3)
8 (3.7)
.44
.13
.78
e26
QUEEN et al
.95
ARTICLE
DISCUSSION
We compared empiric narrow-spectrum
therapy to broad-spectrum therapy
for children hospitalized with uncomplicated CAP during the era of
conjugate pneumococcal vaccination.
In this multicenter study, we found that
the narrow-spectrum therapy was not
inferior to broad-spectrum antibiotics
in all measured outcomes including
LOS, duration of oxygen, duration of
fever, daily standardized pharmacy and
overall costs, or readmission rates
within 7 days. The results of this study
support the recently published PIDS/
IDSA guideline, which recommends
the empiric use of aminopenicillins in
CAP of hospitalized pediatric patients.
In our study, only 33% of all patients with
CAP received the recommended therapy
with a narrow-spectrum penicillin or
aminopenicillin. Broad-spectrum cephalosporins were the most commonly
prescribed antibiotics, but they were
used with substantial variability across
the 4 participating hospitals. These
ndings are consistent with previous
studies and indicate that physicians
and some hospitals have yet to reliably
change their practice. In 1 multicenter
study of CAP, rates of ampicillin use at
tertiary care childrens hospitals were
as low as 5.5%.15 In another multicenter
LOS, h
Duration of supplemental oxygen, h
Duration of fever, h
Standardized cost per day, $
Standardized pharmacy cost per day, $
Readmission within 7 daysa
Narrow-Spectrum
(n = 256)
Broad-Spectrum
(n = 236)
43 (3946)
15.6 (1220)
6.5 (59)
2209 (20882338)
170 (153188)
Reference
52.3 (4857)
21.8 (1729)
9.1 (712)
2160 (20422286)
188 (170208)
5.1 (0.383.6)
.04
.18
.23
.62
.26
.25
Data are least-squares means (95% CI) unless otherwise indicated and were adjusted for age, gender, race, government
insurance, concurrent diagnosis of asthma or reactive airway disease, previous antibiotic therapy, atypical antibiotic
therapy, presence of effusion on chest radiograph, diagnosis of viral lower respiratory tract infection, admission to the
ICU, blood culture utilization, presence of a positive blood culture, baseline hospital rates for cephalosporin use, tachypnea,
fever, and abnormal WBC.
a Data are adjusted odds ratios (95% CI) for broad-spectrum/penicillin therapy.
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