PROSPECTIVE EVALUATION OF THE ETIOLOGY AND
PATHOGENESIS OF ACUTE OTTIS MEDIA WITH
SPONTANEOUS TYMPANIC MEMBRANE PERFORATION
P. Marchisio, S. Esposito, M.Picca, E. Baggi,
A. Orenti, E. Biganzoli, N. Principi
Pediatric Highly Intensive Care Unit,
Department of Pathophysiology and Transplantation,
Fondazione IRCSS Cà Granda Ospedale Maggiore
University of Milan, Milan, Italy
BACKGROUND
• Spontaneous tympanic membrane perforation
(STMP) can occur during an episode of acute otitis
media (AOM) and complicate the clinical course of
the disease.
• Incidence of AOM with STMP varies between 5%
and 30%.
• Several studies have suggested that AOM with
STMP could have some specific characteristics and
be differentiated from uncomplicated AOM.
OBJECTIVES
• To evaluate the microbiology of acute otitis
media with otorrhea due to spontaneous
tympanic membrane perforation in children
living in Italy
• To evaluate pneumococcal serotypes
METHODS (1)
•
•
•
•
prospective, single-center study, Italy
enrollment for 12 months: May 1, 2015 to April 30,
2016
previously healthy children (6 m – 7 yrs)
diagnosis of AOM with spontaneous otorrhea:
(a) middle ear effusion + signs of acute
inflammation of the tympanic membrane + acute
symptoms and (b) otorrhea (within 12 hours of
spontaneous rupture of TM)
METHODS (2)
•
excluded: tubes, midfacial abnormalities, chronic middle ear conditions, including
chronic perforation, immunodeficiency, antibiotics in the previous 2 weeks, topical
treatment
•
purulent fluid removed and MEE collected close to the perforation using an extrathin flexible wire swab (Copan eNAT transport and preservation medium, Brescia,
Italy).
•
bacterial genomic DNA was extracted by clinical specimens by semi-automatic DNA
extraction system. The presence of Streptococcus pneumoniae (S.pn) (and its
serotypes) , Haemophilus influenzae (Hi), Moraxella catarrhalis (M.cat), group A
beta hemolyticus Streptocccus (GABHS) and Staphylococcus aureus was evaluated
by means of real-time PCR using specific oligos-probe sets. S.pn. cases were
serotyped using primers and probes designed on the basis of the GenBank
database sequences (www.ncbi.nlm.nih.gov)
STUDY POPULATION
Sex (males)
Age (group)
< 2 years
2 - 4 years
> 5 years
mean age ± SD (years)
History of rAOM
PCV13 fully vaccinated
Children
N = 177 (%)
103 (58.2)
65 (36.7)
70 (39.6)
42 (23.7)
3.5 ± 2.7
100 (56.5)
162 (91.5)
PATHOGENS DETECTED ALONE OR AS CO-PATHOGENS
50.8%
H. influenzae
35.0%
Axis Title
M. Catarrhalis
27.1%
S. pneumoniae
26.0%
S. pyogenes
11.3%
S. aureus
0.0%
10.0%
20.0%
30.0%
40.0%
50.0%
60.0%
Axis Title
All H.influenzae strains were non typeable
How many children had a positive sample for
one or more pathogens?
30.5
11.3
0
1
2
3
4
4
14.7
39.5
Non typeable H.Influenzae  the most frequent pathogen (70%)
in co-infections (M.catarrhalis  GAS  S.pneumoniae)
COMPARISON BETWEEN TIME AND DETECTION METHODS
51.0%
50.8%
H. influenzae
1.1%
35.0%
M. Catarrhalis
19.4%
27.1%
S. pneumoniae
26.0%
S. pyogenes
17.4%
11.3%
S. aureus
0.0%
10.0%
20.0%
30.0%
10.7%
40.0%
50.0%
60.0%
PCR – Italian data 2015 to 2016
Marchisio P et al., CMI, epub 2017
0.0%
10.0%
20.0%
30.0%
40.0%
50.0%
Culture – Italian data 2001 to 2011
Marchisio P et al., Infection, 2013
60.0%
Streptococcus pneumoniae positive cases:
age distribution
100
80
60
%
40
36,9
20
27,1
20,0
23,8
24-59
months
> 60
months
0
all
children
< 24
months
Streptococcus pneumoniae positive cases:
PCV13 versus non-PCV13 serotypes
100
80
77
60
71
67
70
%
40
20
28
33
29
30
0
all children < 24 m
24-59 m
> 60 m
0
PCV7
PCV13
non PCV13
38
non t
yp
23 B
24 A/
B/ F
33 F/
37
35 B
35 F
21
22 A/
F
23 A
8
11 A/
D
12 A/
B/ F
15 A/
F
16 F
6C/D
6A
7F
19 A
5
3
1
23 F
14
18 C
19 F
4
6B
9V
% positive cases
Streptococcus pneumoniae serotypes
10
8
6
4
2
CONCLUSIONS - 1
• Non typeable H.influenzae , which is the most frequently pathogen
associated with biofilm formation, is predominant in spontaneous otorrhea
• Group A Strep is confirmed to be a main cause of otorrhea, especially in
older children
• M. catharralis seems to be a relevant pathogen
• Co-infections are common , especially in children with recurrent AOM and
especially for NTHi
• The therapeutic approach should be different from that which is usually
reported for uncomplicated AOM, taking into account the possible formation
of biolfim and the presence of betalactamase producers
CONCLUSIONS - 2
• S. pneumoniae is still one of the main pathogens despite full immunization
with PCV13
• most of the pneumococcal cases are associated with serotypes not
included in the vaccine. This finding suggests that a significant
replacement phenomenon has developed, reducing the potential effect of
PCV13 on AOM incidence
• periodical monitoring of pneumococcal ST circulation after introduction of
PCV with a defined number of ST is needed in order to evaluate
replacement phenomenon and the need for new vaccines with greater
protective activity
Thank you for your attention