Acute Mastoiditis in the Pneumococcal Conjugate Vaccine Era

Sharon Ovnat Tamir,a Yehudah Roth,a Ilan Dalal,b Abraham Goldfarb,a Tal Maroma
Department of Otolaryngology-Head and Neck Surgery, Edith Wolfson Medical Center, Tel Aviv University Sackler School of Medicine, Holon, Israela; Pediatric Allergy/
Immunology Unit, Edith Wolfson Medical Center, Tel Aviv University Sackler School of Medicine, Holon, Israelb

Following the introduction of the 7- and 13-valent pneumococcal conjugate vaccines, we observed an inverse relationship be-
tween the increasing rate of immunized children and the proportion of middle ear fluid cultures collected during acute mastoid-
itis episodes that tested positive for Streptococcus pneumoniae among a subset of children 0 to 6 years old who had initially pre-
sented with severe acute otitis media and had bacterial cultures collected during tympanocentesis or from spontaneous otorrhea.

A cute mastoiditis (AM) is a suppurative complication of acute Statistical analysis was performed per AM episode (not per

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otitis media (AOM), which often requires hospitalization and
intravenous antibiotics and sometimes requires surgery. The most
common otopathogen in AM is Streptococcus pneumoniae (1). In
an attempt to control the impact of pneumococcal diseases, pneu-
mococcal conjugate vaccines (PCVs) were gradually implemented
in many countries during the past decade. In Israel, PCV7 was
formally introduced into the national immunization program in
July 2009 and was replaced by PCV13 in November 2010 (2). Both
vaccines were or are, respectively, given at 2, 4, and 12 months of
age. This change in the vaccination regimen allowed us to study
the dynamics of AM incidence and bacteriology in a subset of
children with AOM throughout a short time frame, from the pre-
PCV7 era to the post-PCV13 era.
This study was approved by the Edith Wolfson Medical Cen-
ters ethics review board. We retrospectively identified children 0
to 6 years of age who presented to the pediatric emergency room
from 1 January 2008 through 31 December 2013 with severe
AOM, defined as an AOM episode which either required tympa-
nocentesis, due to a lack of clinical improvement after 48 h of
antibiotic therapy, or presented with spontaneous otorrhea. In
these children, we identified AM episodes (International Classifi-
cation of Diseases code 383.0X). The AM diagnosis was based on
clinical findings (postauricular tenderness, erythema or swelling,
protruding auricle, palpable/fluctuating mass) and systemic signs
(fever, lethargy, irritability, poor feeding, diarrhea). Children with
previous ear surgery, immune deficiencies, and congenital mal-
formations of the ear, nasopharynx, or palate were excluded from
the study. In all eligible children, middle ear fluid (MEF) cultures
were collected either during tympanocentesis with the use of a
sterile flocked swab or from spontaneous otorrhea, from which
pus was collected by swabbing the external ear meatus. Samples
were processed for conventional cultures at the Edith Wolfson
Medical Centers microbiology laboratory. MEF cultures that
tested positive for external ear canal saprophytes were excluded.
The PCV status for each AM episode was obtained from re-
cords at the Mother and Child Health Clinics, where all childhood
vaccines are given in Israel. Each child was categorized according
to his or her vaccination status at his or her AM presentation as
either unimmunized if no dose of PCV immunization had been
given or any PCV7/PCV13 immunized if 1 dose of PCV7/
PCV13 had been given. Any child who had received both the
PCV7 and the PCV13 immunizations during the transition period
between these 2 vaccines was categorized as any PCV13 immu-
nized, due to the broader coverage of the newer PCV13.
patient) using SPSS 17.0 software. Contingency table analysis for
comparing rates between unmatched samples was performed us-
ing the chi-square test or Fishers exact test, as appropriate.
A total of 279 children 0 to 6 years of age contributed 295 severe
AOM episodes (16 children contributed 2 AOM episodes each).
Of these children, 57 presented with 58 AM episodes (1 boy con-
tributed 2 AM episodes), which resulted in an incidence rate of 1
AM episode/5 severe AOM episodes in our study population.
Table 1 displays the demographic and bacterial data of AM
episodes in our study years. Boys and children 2 years of age
insignificantly contributed more AM episodes (37 [64%] and 38
[66%]; P 0.4 and 0.9, respectively). AM developed despite ade-
quate antibiotic therapy in 29 (50%) episodes. In these instances,
oral antibiotics (mostly amoxicillin) and a combination of oral
antibiotics and otic antibiotic solution treatments were adminis-
tered for 24 (85%) and 4 (15%) episodes, respectively. The rest of
the AM episodes (27 [50%]) presented in an abrupt, sudden man-
ner, and no antibiotics had been given prior to admission. All of
the patients were hospitalized and treated with intravenous anti-
biotic therapy for 7 to 10 days. The most common systemic anti-
biotics were cefuroxime and ceftriaxone, administered for 32
(55%) and 23 (40%) episodes, respectively.
In 3 (5%) AM episodes, advanced complications included in-
ternal jugular vein thrombosis (n 1), epidural abscess (n 1),
and sepsis (n 1). Of the 55 (95%) blood cultures which were
collected during hospitalization of the patients, only one culture
grew S. pneumoniae, which also grew in the MEF culture from that
child. All 3 (5%) cerebrospinal fluid cultures were negative. Sur-
gical interventions were performed for 6 (10%) AM episodes; ven-
tilating tubes were inserted during all of these episodes, and mas-
toidectomy was performed during 5 episodes.
In all of the AM episodes, MEF cultures were obtained; 21
(36%) were positive. When comparing data from 2008 to 2011
with those from 2012 to 2013, there were fewer negative MEF
cultures, and there was a lower rate of AM patients previously
Received 5 May 2014 Accepted 29 May 2014
Published ahead of print 11 June 2014
Editor: H. F. Staats
Address correspondence to Tal Marom, maromtal@orange.net.il.
Copyright 2014, American Society for Microbiology. All Rights Reserved.
doi:10.1128/CVI.00289-14

August 2014 Volume 21 Number 8 Clinical and Vaccine Immunology p. 1189 1191 cvi.asm.org 1189
Tamir et al.

TABLE 1 Demographic and bacterial data from acute mastoiditis episodes among childrena 0 to 6 years of age, by study year
Data per yr (no. of eligible AOM episodes)
Variable 2008 (67) 2009b (48) 2010c (53) 2011 (49) 2012 (39) 2013 (39) Total
No. of AM episodes (% of 12 (18) 7 (15) 8 (15) 12 (25) 12 (31)d 7 (18) 58
eligible AOM episodes)
Boys (no. [%]) 10 (83) 4 (58) 6 (75) 4 (33) 11 (92) 2 (28) 37 (64)
Age 2 yr (no. [%]) 6 (50) 2 (28) 6 (75) 9 (75) 10 (83) 5 (72) 38 (66)
Previously treated with 4 (33) 4 (58) 4 (50) 5 (42) 8 (75) 4 (58) 29 (50)
antibiotics (no. [%])
Patients undergoing surgical 2 (17) 0 (0) 4 (50) 2 (17) 2 (17) 3 (42) 13 (22)
interventione (no. [%])
a
n 58.
b
Formal PCV7 introduction year.
c
PCV13 introduction year.
d
One patient presented with 2 separate AM episodes.
e
Surgical interventions were ventilating tube insertions and mastoidectomies. A ventilating tube was inserted during all mastoidectomies.

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treated with antibiotics (P 0.04). One single bacterial species
grew in 19 (90%) of the specimens, and multiple bacteria grew in
2 (10%) of the specimens. S. pneumoniae and Haemophilus influ-
enzae were cultured as single organisms in 16 (76%) and 2 (10%)
specimens, respectively. In addition, S. pneumoniae grew in 2
other polymicrobial cultures with other bacteria, whereas H. in-
fluenzae grew in 1 polymicrobial culture. The proportion of S.
pneumoniae in AM cultures declined from 2010. In 2012, only 1
MEF culture, from a 20-month-old boy who was not adequately
immunized with PCV13 and presented with 2 AM episodes which
were not treated with antibiotics prior to his presentation, grew S.
pneumoniae. There was no growth of S. pneumoniae in MEF cul-
tures in 2013.
The PCV status was retrieved for all the children. In 2008, none
of the children was immunized with PCV, whereas in at least 90%
of the AM episodes in 2011 to 2013, the children had been immu-
nized with PCV7/PCV13, as shown in Fig. 1A. The dynamics of
MEF bacteriology from AM episodes, by PCV status, are shown in
Fig. 1B. Any-prior-PCV13-immunized children with AM had a
significantly lower proportion of S. pneumoniae-positive MEF
cultures, compared with unimmunized children or any-PCV7-
immunized children (P 0.03 and 0.04, respectively).
Here, we show that following the introduction of PCV7 and,
more prominently, the introduction of PCV13, the proportion of
S. pneumoniae-positive MEF cultures from AM episodes signifi-
cantly decreased.
To date, data on the effect of PCV13 on AOM and AM are
limited. A recent insurance claim study from the United States
showed that the AM incidence rate had already decreased shortly
before the introduction of PCV13 (3). A steeper decline was ob-
served in 2010 (introduction year) and 2011 (first U.S. postmarket
year), almost in parallel to the similar downward trend in rates of
AOM visits. In a different U.S. study, mastoiditis cases, which have
been especially associated with serotype 19A isolates (covered by
PCV13 but not by PCV7), had the greatest percent decrease in
2011, compared with the 3 years preceding the introduction of
PCV13 (4).
Due to the short interval between the introductions of PCV7

FIG 1 (A) PCV status in the study population, by year. PCV status was determined at acute mastoiditis presentation. Any PCV immunized, children who had
received at least 1 dose of PCV7/PCV13; unimmunized, children who had not been PCV immunized. (B) Otopathogen distribution in MEF cultures from acute
mastoiditis episodes, by PCV status. Mc, Moraxella catarrhalis; NTHi, nontypeable Haemophilus influenzae; Sp, Streptococcus pneumoniae. There was a significant
reduction in positive S. pneumoniae-positive MEF cultures in acute mastoiditis cases in PCV13-immunized children (15%), compared with unimmunized
children (41%) and PCV7-immunized children (50%) (P 0.03 and 0.04, respectively).

1190 cvi.asm.org Clinical and Vaccine Immunology


and PCV13 in Israel (spaced only 14 months), we were not able to
witness any AM time trends after PCV7 introduction, as reported
elsewhere (59). While some studies reported decreased AM rates
after the introduction of PCV7 (7, 10), others found no change or
even an increase (11).
This studys main strengths are in the reporting of MEF cul-
tures, not relying on nasopharyngeal cultures, and knowledge of
the exact PCV status for each child at his or her AM presentation.
Therefore, we believe that our results truly reflect these childrens
tympanomastoid cavity colonization status during their AM epi-
sode(s). Limitations of our study include the small number of
patients and the lack of serotype identification. Although our re-
sults may not be generalizable to all AOM patients, we believe that
they are valid and show for the first time that AM incidence and
bacteriology changed after the introduction of PCV13. Further
studies are warranted to monitor all-cause and pneumococcal AM
in the post-PCV13 era.
ACKNOWLEDGMENTS
The enthusiastic assistance and careful methodological approach of Orna
Schwartz, director of the Edith Wolfson Medical Center Microbiology
Laboratory, are gratefully acknowledged. We also thank our residents
from the Departments of Otolaryngology-Head and Neck Surgery and
Pediatrics for their hard work.
We declare no conflicts of interest.
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