M A J O R A R T I C L E
Distribution of 13-Valent Pneumococcal
Conjugate Vaccine Streptococcus pneumoniae
Serotypes in US Adults Aged ≥50 Years With
Robert L. Sherwin,1Sharon Gray,2Ronika Alexander,2Paul C. McGovern,2Jay Graepel,2Michael W. Pride,3Jay Purdy,2
Peter Paradiso,2and Thomas M. File Jr4,5
1Sinai Grace Hospital Emergency Department and Sinai Grace Hospital/Detroit Receiving Hospital, Wayne State University School of Medicine, Detroit,
Michigan;2Pfizer Inc, Collegeville, Pennsylvania;3Vaccine Research East and Early Development, Pfizer Research, Pearl River, New York;4Infectious
Disease Section Northeast Ohio Medical University, Rootstown; and5Summa Health System, Akron, Ohio
(See the editorial commentary by Griffin and Grijalva on pages 1734–6.)
(CAP) and healthcare-associated pneumonia (HCAP) in the United States. Limited data are available regarding the
pneumococcal serotypes causing CAP and HCAP.
Methods. Adults aged ≥50 years presenting to participating US hospitals with radiographically confirmed
pneumonia between February 2010 and September 2011 were screened for inclusion. S. pneumoniae was identified
using microbiological cultures, BinaxNOW® S. pneumoniae assay, or urine antigen detection (UAD) assay capable
of detecting 13-valent pneumococcal conjugate vaccine (PCV13)–associated serotypes.
Results.Among 710 subjects enrolled, the median age was 65.4 years; 54.2% of subjects were male, 22.4% of
radiographically confirmed pneumonia cases were considered HCAP, and 96.6% of subjects were hospitalized.
S. pneumoniae was detected in 98 subjects (13.8%) by any test, and PCV13-associated serotype(s) were identified by
UAD in 78 (11.0%). Serotype 19A was most prevalent, followed by 7F/A, 3, and 5. Serotypes associated with 7-
valent pneumococcal conjugate vaccine (PCV7) accounted for 25% of UAD-positive isolates.
Conclusions.Pneumococcal serotypes causing noninvasive pneumonia in adults may differ significantly from
those causing invasive disease, with PCV7-associated serotypes overrepresented. Serotype 5, rarely seen in contem-
porary surveillance of invasive disease in the United States, substantially contributed to the observed cases of
S. pneumoniae–positive CAP or HCAP.
Streptococcus pneumoniae causes a substantial proportion of community-acquired pneumonia
type distribution; community-acquired pneumonia; healthcare-associated pneumonia; urinaryantigen detection assay.
Streptococcus pneumoniae; pneumococcal serotypes; 13-valent pneumococcal conjugate vaccine; sero-
Pneumonia and influenza combined represent the eighth
most common cause of death in the United States and
the leading cause of death from infectious disease .
An estimated 4 million cases of community-acquired
pneumonia (CAP) occur annually in the United States,
resulting in >1 million hospitalizations and substantial
morbidity and mortality, particularly among older
It has been estimated that 17%–41% of CAP and
6%–10% of healthcare-associated pneumonia (HCAP)
cases in the United States are caused by Streptococcus
pneumoniae [3, 4], with the rate of S. pneumoniae isola-
tion increasing when more invasive methods are used for
obtaining specimens .Compared with S. pneumoniae–
negative cases, S. pneumoniae–related CAP is associat-
ed with poorer patient outcomes, including increased
Received 18 February 2013; accepted 24 May 2013; electronically published 2
Presented in part: ID Week 2012, San Diego, California, 17–21 October 2012.
Correspondence: Dr Robert L. Sherwin, MD, Department of Emergency Medicine,
Sinai Grace Hospital, Wayne State University School of Medicine, 6071 West Outer
Dr, Detroit, MI 48235 (email@example.com).
The Journal of Infectious Diseases 2013;208:1813–20
© The Author 2013. Published by Oxford University Press on behalf of the Infectious
Diseases Society of America. All rights reserved. For Permissions, please e-mail:
Pneumococcal Vaccine Serotypes in CAP • JID 2013:208 (1 December) • 1813
at Pfizer Inc. on May 22, 2014
incidence of bacteremia, septic shock, need for mechanical
ventilation, and mortality . Pneumococcal pneumonia can
be subdivided into invasive (bacteremic) and noninvasive (non-
bacteremic) cases, the latter responsible for the majority of
disease. Estimates suggest that approximately 500000 cases of
noninvasive pneumonia occur annually in the United States in
adults aged ≥50 years, causing nearly 20000 deaths [7,8].
A 7-valent pneumococcal conjugate vaccine (PCV7) has
been available in the United States for use in children aged <5
years since 2000, providing protection against S. pneumoniae
serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F. In 2010, a 13-valent
pneumococcal conjugate vaccine (PCV13) replaced PCV7 in
the pediatric immunization program; PCV13 includes all the
serotypes contained in PCV7 plus the additional serotypes 1, 3,
5, 6A, 7F, and 19A. Numerous studies have shown that the in-
clusion of PCV7 in the routine infant immunization schedule
in the United States, has led to major reductions in vaccine
serotype–associated invasive pneumococcal disease (IPD) in
both infants and unvaccinated older populations [9–11].
Similar trends for IPD reduction are also becoming apparent
for the additional serotypes in the more recently introduced
PCV13 vaccine .
Culture methods are of limited value for detecting noninva-
sive pneumococcal disease for several reasons, including the
nature of the infection and the difficulty obtaining sputum
samples of sufficient quality to aid diagnosis. Therefore, the dis-
tribution of the S. pneumoniae serotypes in adults presenting
with noninvasive CAP and HCAP is poorly understood. Binax-
NOW®, a commercially available S. pneumoniae assay, can
detect the C-polysaccharide from S. pneumoniae in the urine of
subjects with a diagnosis of pneumonia. However, this assay is
not serotype specific.
Several investigators [13, 14] have recently reported on sero-
type-specific urine antigen detection (UAD) assays that, for the
first time, allow determination of the serotype distribution in both
invasive and noninvasive pneumonia cases. Bewick et al eval-
uated the S. pneumoniae serotype distribution in patients with
noninvasive CAP within the catchment area of 2 large teaching
hospitals in the United Kingdom (including approximately
600 000 adults), using a urinary immunoassay capable of de-
tecting 14 pneumococcal serotypes, including those associated
with the PCV7 and PCV13 vaccines. PCV7-associated sero-
types were identified in 19.7% of pneumococcal CAP cases, and
PCV13-associated serotypes in 57.4% .
The primary objective of this study was to estimate the pro-
portion of adults aged ≥50 years presenting to participating US
hospitals with radiographically confirmed CAP or HCAP who
had the S. pneumoniae serotypes contained in PCV13. This was
done using a UAD diagnostic assay that can simultaneously
detect PCV13 serotype-specific S. pneumoniae polysaccharides
secreted in human urine . A secondary objective was
to describe the serotype distribution among S. pneumoniae–
This was a prospective, cross-sectional, multicenter study based
on a convenience sample drawn from 13 geographically dis-
persed sites across the United States. Individual sites participated
in the study for 2–20 months and were located in Allentown,
Pennsylvania; Norfolk, Virginia; San Antonio, Texas; Akron,
Ohio; Detroit, Michigan (2 sites); San Diego, California; Worces-
ter, Massachusetts; Mobile, Alabama; Tampa, Florida; Chicago,
Illinois; Springfield, Massachusetts; and Las Vegas, Nevada.
Two protocol amendments during the study added additional
sites, permitted subjects with HCAP into the study, and allowed
imaging other than chest radiography to be used as a diagnostic
tool. This study was conducted in accordance with applicable
laws and regulations, including but not limited to the Interna-
tional Conference on Harmonisation Guideline for Good Clini-
cal Practice and the ethical principles of the Declaration of
Helsinki. All included subjects provided informed consent.
Between February 2010 and September 2011, adults aged ≥50
years presenting at outpatient departments or emergency de-
partments of participating hospitals with signs or symptoms
and radiographic evidence of pneumonia, were screened for in-
clusion in this study. To be included, subjects must have met all
of the following criteria: age ≥50 years; presentation to a study
site with clinically suspected pneumonia; a finding consistent
with pneumonia at chest radiograph, computed tomography,
or other imaging modality; and willingness and ability to
provide a urine sample. Subjects were excluded if they were
transferred to a participating hospital after already having been
hospitalized for ≥48 hours at another inpatient facility (ie, a
community hospital); had
(defined as pneumonia developing 48 hours after hospital ad-
mission); or had been previously enrolled in this study within
the past 30 days.
Subjects were required to participate for approximately 1
day. Final diagnosis and all-cause mortality data were collected
up to 10 days after enrollment. Demographic information,
history of exposure to healthcare facilities, history of immuniza-
tion with 23-valent pneumococcal polysaccharide vaccine
(PPSV23), and relevant medical history were recorded. Urine
samples were collected noninvasively. If a bladder catheter had
been placed as part of routine medical care, a urine sample
could be collected from the bag providing it had not been in
the bag for >8 hours. Results of blood cultures and respiratory
1814 • JID 2013:208 (1 December) • Sherwin et al
at Pfizer Inc. on May 22, 2014
cultures (including sputum, tracheal aspirate, bronchial wash-
ings, and pleural fluid) performed per site-specific standard of
care were recorded on the case report form.
S. pneumoniae–positive CAP or HCAP was defined as radio-
graphically confirmed pneumonia with ≥1 positive results from
the UAD assay, BinaxNOW® S. pneumoniae assay, or bacterial
(blood or respiratory) culture from any site, which fulfilled the
criterion for CAP or HCAP. HCAP was defined as pneumonia
in a subject with exposure to a healthcare facility including a
dialysis center, chronic treatment clinic, nursing home, long-
term care facility, hospital, assisted-living facility, or other facil-
ity, within 3 months before enrollment.
Two aliquots of the urine sample were frozen and stored for
subsequent shipment to the central laboratory (Pfizer Vaccines
Research East and Early Development) for S. pneumoniae
UAD assay testing as described elsewhere . This assay
detects S. pneumoniae serotypes 1, 3, 4, 5, 6A/C, 6B, 7F/A, 9V/
A, 14, 18 (C/A, B, F), 19A, 19F, and 23F . Urine was tested
locally using the commercially available BinaxNOW® S. pneu-
moniae antigen test (Inverness Medical; now marketed by
Alere North America). S. pneumoniae isolates from cultures
were sent to a second central laboratory for serotyping using
the Quellung reaction (Quest Diagnostics).
Evaluable populations were based on all subjects with a final di-
agnosis consistent with radiographically confirmed pneumonia.
For each of the 3 tests (UAD, BinaxNOW® S. pneumoniae, and
bacterial cultures), the analysis populations included all subjects
who had data for that test. Distribution of PCV13-associated
serotypes was assessed in subjects with determinate UAD assay
or bacterial culture data. Evaluation included the presence of co-
morbid conditions that put the subject at risk for pneumonia
(chronic obstructive pulmonary disease, asthma, congestive
heart failure, coronary artery disease, chronic kidney disease,
and diabetes mellitus) orat high risk (eg, immunocompromised)
human immunodeficiency virus, AIDS, cancer, and organ trans-
plant). Subjects with significant protocol violations or indeter-
minate data for a given assay were not included in the final
All analyses performed in this study were descriptive. For results
reported as proportions of subjects with positive results, corre-
sponding 95% confidence intervals were also reported.
In this study, 788 subjects consented to participate of whom 7
were excluded for protocol violations or screening failures, and
the Radiographically Confirmed Pneumonia Population
Subject Demographics and Clinical Characteristics of
Status, No. (%)a
Median age at enrollment, y
50 to <65 y
65 to <75 y
Black or African
American Indian or Alaska
Native Hawaiian or Pacific
Influenza-like illness within
past 30 d
Congestive heart failure
within past 30 dc
Current alcohol or drug
Hospitalized at this visit
Intermediate or step-down
General hospital ward
0 3 (0.5) 3 (0.4)
healthcare-associated pneumonia; HIV, human immunodeficiency virus; ICU,
intensive care unit admission; PPSV23, 23-valent pneumococcal polysaccha-
aAll values represent No. (%) unless stated otherwise. Denominators for
percentage values are based on numbers of subjects with responses to each
specified domain for the specified status.
bSubjects can be counted in >1 race.
cIncluding systemic corticosteroid use
COPD,chronic obstructive pulmonarydisease;HCAP,
Pneumococcal Vaccine Serotypes in CAP • JID 2013:208 (1 December) • 1815
at Pfizer Inc. on May 22, 2014
781 were enrolled. Of those enrolled, 710 subjects had radio-
graphically confirmed pneumonia. The demographic and clini-
cal characteristics of this population are shown in Table 1.
Their median age was 65.4 years (range, 50–102 years); 54.2%
were male, and 96.6% were hospitalized at this visit for this
episode of pneumonia, with 10.9% admitted to an intensive
care unit (ICU). Overall, 49.2% of subjects were aged 50 to <65
years, 22.3% 65 to <75 years, and 28.6% ≥75 years. Seven en-
rolled subjects died during the study, for an overall all-cause
mortality rate of 0.9%. Of these 1 subject with confirmed pneu-
mococcal pneumonia died of septic shock secondary to necro-
Results of UAD assay were obtained in 708 subjects with ra-
diographically confirmed pneumonia (99.7%), BinaxNOW®
assay results were obtained in the same 708 (99.7%), and mi-
crobiology results in 634 (89.3%), of whom 615 (97.0%) had
S. pneumoniae–Positive CAP or HCAP Population
Ninety-eight subjects (13.8%) with S. pneumoniae detected by
≥1 test and radiographically confirmed pneumonia were con-
sidered to have S. pneumoniae–positive CAP or HCAP. Overall,
11.0% (78 of 708 subjects) had positive UAD assay results indi-
cating the presence of a PCV13-associated serotype. The pro-
portions of subjects with positive results for S. pneumoniae by
BinaxNOW® and bacterial culture were 4.8% (34 of 708 subjects)
and 2.2% (14 of 634), respectively. Among 615 subjects with
blood cultures performed per site-specific standard of care,
only 12 (2.0%) had positive blood cultures for S. pneumoniae.
Among these blood culture–positive subjects, 11 (91.7%) had
positive UAD results, and 5 (41.7%) had positive BinaxNOW®
results. The single isolate with a negative UAD result was not
serotyped. Overall 19.2% of the UAD-positive subjects (15 of
78) were also positive by BinaxNOW® assay.
Overall, 60.2% of subjects with S. pneumoniae–positive CAP
or HCAP were aged 50 to <65 years. In total, 18.4% of the
S. pneumoniae–positive group had HCAP, and the majority of
healthcare exposure within the prior 3 months occurred in a
hospital. The proportion of subjects who had previously been
vaccinated with PPSV23 was similar in the S. pneumoniae–
positive and S. pneumoniae–negative groups (40.8% and 44.8%,
respectively). Influenza-like illness in the past 30 days, immuno-
deficiency (including human immunodeficiency virus), current
smoker status, and current alcohol or drug abuse were more
common among subjects who were S. pneumoniae positive.
Identification of PCV-Associated Serotypes by UAD
A PCV13-associated serotype was detected in 78 (79.6%) of the
98 subjects with S. pneumoniae–positive CAP or HCAP. Of the
78 UAD-positive subjects, 60 (76.9%) had at least 1 comorbid
condition that put them at risk or at high risk for pneumonia.
The numbers and proportions of subjects at each study site
with positive UAD assay results are shown in Table 2. In total,
84 PCV13-associated serotypes were identified in the 78 sub-
jects by UAD assay; 25.0% were PCV7-associated serotypes,
and 75.0% were among the 6 additional serotypes included in
PCV13 (Figure 1).
A PCV7-associated serotype was present in 21 UAD-positive
subjects (26.9%), and 1 of the 6 additional serotypes associated
with PCV13 was present in 62 UAD-positive subjects (79.5%).
Serotype distribution by age, sex, and CAP or HCAP status are
shown in Table 3.
Serotype 19A was the most prevalent of the additional sero-
types in PCV13. Serotype 14 was the most prevalent among the
PCV7-associated serotypes. Six subjects had 2 PCV13-associated
serotypes in the following combinations: serotypes 5 and 23F
(n=1), 5 and 19A (n=1), 5 and 14 (n=3), and 19A and 14
(n=1). At 2 study sites, 4 subjects were positive for the same se-
rotype within a 60-day window; at site 009 (Alabama) 4 subjects
were positive for serotype 9V/A, and at site 1013 (Las Vegas) 4
were positive for serotype 18.
Fourteen subjects (2.2%) were positive for S. pneumoniae by
bacterial culture (11 by blood culture alone, 2 by sputum
culture alone, and 1 by both). Five subjects with invasive
disease for whom serotype data were obtained had a PCV13-
associated serotype (serotype 1 in 2, 19A in 2, and 7F in 1) and
1 subject was positive for the nonvaccine serotype 6C. Samples
from the remaining 8 subjects were not serotyped by the local
Subjects With Positive UAD Assay Results by
Site No. (Location)
Subjects With Positive
UAD Assay Results
% (95% CIb)
001 (Allentown, PA)
002 (Norfolk, VA)
003 (San Antonio, TX)
004 (Akron, OH)
006 (Detroit, MI)
007 (San Diego, CA)
008 (Worcester, MA)
009 (Mobile, AL)
011 (Tampa, FL)
012 (Chicago, IL)
1007 (Detroit, MI)
1009 (Springfield, MA)
1013 (Las Vegas, NV)
All sites combined
. . .
Abbreviations: CI, confidence interval; UAD, urine antigen detection.
aNo. with UAD positive results/No. undergoing UAD at site.
b95% CI with normal approximation to binomial distribution.
1816 • JID 2013:208 (1 December) • Sherwin et al
at Pfizer Inc. on May 22, 2014
This study is the first to utilize a serotype-specific UAD assay to
assess the distribution of S. pneumoniae vaccine serotypes asso-
ciated with adult CAP or HCAP in the United States. The use
of this UAD assay provided increased sensitivity over previous
methods and allowed for better understanding of pneumococ-
cal CAP or HCAP epidemiology and the serotype specificity of
the associated disease.
In this study S. pneumoniae was detected in 13.8% of subjects
the 18%–40% prevalence reported in recent studies, including a
study performed in the Netherlands using the same UAD assay
and a UK study that used a similar serotype-specific S. pneumo-
niae urinary immunoassay [13, 15, 16]. The prevalence was
likely affected by the relative insensitivity of the BinaxNOW®
assay; positive in 19.2% of subjects positive by any other test
and 42% of the blood culture–positive subjects. With correction
for this insensitivity, estimates of pneumococcal contribution in
the present study would be 17%–25%. A true decline in pneu-
mococcal CAP and HCAP prevalence in the United States a
decade after PCV7 introduction may also have contributed to
the lower incidence of pneumococcal disease [10,17].
More important, it has been documented elsewhere that
pneumococcus is less likely to be identified in less-severe CAP
. The S. pneumoniae burden observed in the present study
may reflect differences in study design (eg, convenience or op-
portunistic recruitment strategies and consent procedures)
leading to enrollment of subjects with less-severe disease. In the
study by Bewick et al, 40% of CAP cases were associated with
pneumococcus, but, notably, nearly 60% of subjects had pneu-
monia severity index class IV or V disease [13, 19]. Although
we did not document this index, >80% of subjects were admit-
ted to a general hospital ward, and only 11% had severe enough
disease to require ICU admission. Other studies have reported
the proportion of CAP linked to S. pneumoniae as 6.5% in pa-
tients admitted to general wards (vs 15.2% for ICU patients)
and 11% in hospitalized patients with Pneumonia Outcomes
Research Team risk class III or IV, both more in line with our
The overall mortality rate in our study was also lower than
expected. The relative paucity of data on etiology of noninva-
sive CAP and potential impact of changes in diagnostic coding
or documentation make it difficult to determine whether mor-
tality rates have genuinely changed in recent years . Noting
the previously published relationships between ICU admission,
increased disease severity, and increased mortality, however,
the relatively small proportion of subjects admitted to ICUs
may also explain the low mortality rate we observed, compared
with other studies [13,18,22].
PCV13 vaccine serotypes were identified by the UAD assay in
11% of the radiographically confirmed pneumonia population.
The most surprising finding in the study was the number of
subjects in whom PCV7-associated serotypes were detected.
The impact of the pediatric PCV7 childhood immunization
program on IPD caused by these serotypes in adults is well doc-
umented [9–11]. Pilishvili et al  reported that by 2007, 8
years after the introduction of PCV7, rates of IPD due to
PCV13, 13-valent pneumococcal conjugate vaccine.
Serotypes identified in the 78 subjects by urine antigen detection assay. Abbreviations: PCV7, 7-valent pneumococcal conjugate vaccine;
Pneumococcal Vaccine Serotypes in CAP • JID 2013:208 (1 December) • 1817
at Pfizer Inc. on May 22, 2014
PCV7-associated serotypes had been reduced by 87% and 92%
in subjects aged 50 to <65 years and ≥65 years, respectively. In
2009, before the start of this study, the proportion of PCV7-
associated serotypes observed in IPD in adults aged >50 years
was <4%, accounting for approximately 8% of PCV13-associated
invasive isolates (including serotype 6C) during that year
(M. Moore, personal communication). Recent publications and
commentaries have discussed how the PCV13 vaccine and its
adoption into the pediatric program might affect invasive and
noninvasive pneumococcal disease in adults [23–26]. However,
despite the reductions in PCV7-associated invasive disease,
PCV7-associated serotypes made up 25% of 84 S. pneumoniae
serotypes identified by UAD assay in the present study. Sero-
type 14 was the greatest contributor (6 of 78 serotype-positive
urine samples), serotypes 9V/A and 23F were each detected in
4 urine samples, and serotype 18 in 5 samples. Overall, 6 of
the 7 PCV7-associated serotypes were represented. The lack of
PCV7-associated serotypes identified from normally sterile sites
may reflect the indirect effect on IPD referenced above .
Despite differences in recruitment methods, duration, and
proportion of pneumococcal disease between this work and the
study by Bewick et al, it is interesting that PCV7-associated sero-
types seem overrepresented in both studies . PCV7 was in-
troduced into the United Kingdom in 2006 and an indirect effect
on IPD caused by all PCV7-associated serotypes was detectable
in 2008–2010 . Nevertheless, 37% of the PCV13-associated
serotype isolates identified by Bewick et al were PCV7-associated
serotypes . Similar to the present findings, serotype 14 was
the greatest contributor despite the dramatic decrease in IPD
linked to this serotype in the United Kingdom at that time (90%
reduction in persons aged 5 to <65 years; 84% reduction in those
aged >65 years) . Serotype 4 was the next most important
PCV7-associated serotype in the UK CAP study .
It has previously been assumed that the serotype distribution
measured by IPD surveillance in specific age groups would also
represent the serotypes causing noninvasive pneumonia in
those same groups . However, our findings and those of
Bewick et al suggest that this may not be the case . The un-
derlying explanation for the differences is unknown; however,
our data suggest that the indirect effect of the childhood
immunization program has reduced the circulation of PCV7-
associated serotypes but not eliminated them. There does not
Table 3.PCV13 Serotype Results in the UAD Analysis Population According to Subject Demographics
No. (%) of Subjects Positive for Serotypea
Age Group, ySex Pneumonia
50 to <65
65 to <75
Serotypes covered by PCV7
Any PCV7 serotypes
Additional serotypes covered by PCV13
Any additional PCV13
Abbreviations: CAP, community-acquired pneumonia; HCAP, healthcare-associated pneumonia; PCV7, 7-valent pneumococcal conjugate vaccine; PCV13, 13-
valent pneumococcal conjugate vaccine; UAD, urine antigen detection.
aSample sizes (denominators) represent numbers of subjects with positive UAD results by subject category.
bSubjects are counted once in the combined rows. Of 6 subjects who had >1 serotype result at UAD, 5 had 1 7-valent and 1 additional 13-valent serotype detected
and were therefore counted in combined rows for both.
1818 • JID 2013:208 (1 December) • Sherwin et al
at Pfizer Inc. on May 22, 2014
seem to be any correlation between the presumed “invasiveness”
of a given serotype as determined by Sleeman et al  and the
prevalence of the mostly noninvasive disease we detected for
A second surprising finding was the prevalence of serotype 5,
which represented nearly 15% of the PCV13-associated sero-
type isolates detected by UAD assay. Again, a similar result was
seen in the study by Bewick et al, in which approximately 10%
of the PCV13-associated serotypes observed were serotype
5. This serotype is rarely found in invasive disease isolates in
the United States and United Kingdom, regardless of age group
[10, 12]. Serotype 5 is rarely carried in children and generally
considered highly invasive .
The prevalence of pneumococcal serotypes would be expect-
ed to vary by age and geographic region, and we observed dif-
ferences among both age groups and sites in this study. Two
participating sites reported that pneumococcal CAP or HCAP
cases were caused predominantly by 1 individual serotype—
serotype 9V/A at 1 site and serotype 18 at the other (both
PCV7-associated serotypes). The pneumococcal CAP or HCAP
cases related to these serotypes appeared within a 60-day time
period at each site. No laboratory errors were identified that
would explain these findings. Unfortunately, no further infor-
mation is available from which to conclude whether these pre-
dominant serotypes result from child-to-adult or adult-to-adult
For adults aged ≥65 years or children and adults aged ≥2
years with chronic illness or other risk factors (ie, immunocom-
promising conditions, smoking, living in particular environ-
ments), PPSV23 has been recommended although controversy
persists over its ability to protect against noninvasive pneumo-
coccal pneumonia [9, 30, 31]. Notably, the vaccination rates in
our study were similar (approximately 40%) in the S. pneumo-
niae–positive and S. pneumoniae–negative CAP or HCAP
groups. On 30 December 2011, the US Food and Drug Admin-
istration approved the use of PCV13 in adults aged ≥50 years
for prevention of pneumonia and invasive disease caused by
S. pneumoniae serotypes contained in the vaccine .The Ad-
visory Committee on Immunization Practices currently recom-
mends providing PCV13, in addition to PPSV23, to adults aged
≥19 years with certain immunocompromising conditions .
In the present study, 36% of the UAD-positive pneumonia
cases occurred in patients considered at high risk for pneumo-
nia (eg, immunocompromised individuals).
This study has several limitations. It was conducted using a
convenience sample, which may have introduced bias into the
screening or recruitment process, thereby limiting the general-
izability of the results. Recruitment was limited to adults aged
≥50 years, and the recruitment period varied considerably
among sites, with coverage of 1 winter season reducing the po-
tential number of CAP or HCAP cases. The UAD assay cannot
detect all S. pneumoniae serotypes. This study was performed
soon after the introduction of PCV13 into the pediatric nation-
al immunization program, and its findings therefore would not
reflect any indirect effects of this vaccine on serotype distribu-
tion in adults.
In conclusion, across the geographically dispersed participat-
ing sites, 11.0% of subjects with radiographically confirmed
pneumonia were positive for PCV13-associated serotypes of
S. pneumoniae. The lower-than-expected rate of S. pneumoniae
identification may partly reflect the protective effects of the
PCV7 and PPSV23 vaccination programs but probably reflects
the reduced disease severity in our population compared with
other studies. Assessing serotype-specific pneumococcal CAP
or HCAP with a UAD assay suggests that the serotypes causing
noninvasive CAP or HCAP in adults may differ significantly
from those causing invasive disease, with an overrepresentation
of serotypes present in the PCV7 vaccine. In addition serotype
5, rarely seen in contemporary surveillance of invasive disease
in the United States, was a major contributor to the noninva-
sive pneumonia cases we observed. Further longitudinal studies
are required to monitor the serotype distribution in subjects
with CAP or HCAP and the impact of the PCV13 vaccination
programs and to investigate the transmission of vaccine sero-
types and mechanisms for noninvasive disease progression.
PhD (Pfizer) for his critical review of this manuscript. Medical writing
support was provided by Rachel Spice, PhD, at Excerpta Medica and was
funded by Pfizer.
This work was supported by Wyeth, which was ac-
quired by Pfizer in October 2009.
Potential conflicts of interest.
R. L. S. and T. M. F. have received re-
search support and consulting fees from Pfizer; P. P. and P. C. M. were em-
ployees of Pfizer at the time of this study; and R. A., S. G., J. G., M. W. P.,
and J. P. are all current Pfizer employees and stockholders.
All authors have submitted the ICMJE Form for Disclosure of Potential
Conflicts of Interest. Conflicts that the editors consider relevant to the
content of the manuscript have been disclosed.
The authors would like to thank Emilio Emini,
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