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Bacterial reasons of otitis media with spontaneous perforation of the tympanic membrane in the era of 13 valent pneumococcal conjugate vaccine
Bacterial causes of otitis media v spontaneous perforation of the tympanic membrane in the era of 13 valent pneumococcal conjugate vaccine Corinne Levy, Emmanuelle Varon, Naim Ouldali, Alain Wollner, Franck Thollot, François Corrard, Andreas Werner, Stéphane Béchet, Stéphane Bonacorsi, Robert Cohen





After pneumococcal conjugate vaccine (PCV) implementation, the variety of acute otitis media (AOM) episodes has decreased, but AOM tho remains amongst the most usual diagnoses in childhood. Indigenous 2% come 17% of cases of AOM attribute spontaneous perforation that the tympanic membrane (SPTM). The target of this study was to define the bacteriological reasons of SPTM 5 come 8 years years after ~ PCV13 implementation, in 2010. From 2015 to 2018, children with SPTM were prospectively enrolled by 41 pediatricians. Center ear fluid was derived by sampling voluntarily discharge. Amongst the 470 children with SPTM (median period 20.8 months), no otopathogen was isolated because that 251 (53.4% <95% CI 48.8%;58.0%>): 47.1% the infants and toddlers, 68.3% older children (pCreative Commons Attribution License, which permits unrestricted use, distribution, and also reproduction in any kind of medium, provided the original writer and resource are credited.

Data Availability: The protocol the this examine was authorized by the Saint Germain en Laye Hospital values Committee under the stipulation that we do not make our data public. This is since these data contain perceptible patient records. Because that this reason, we have the right to only provide aggregated data. Interested researchers may send requests because that the aggregated data come the association Clinique et Thérapeutique Infantile du Val de Marne (ACTIV) in ~ the complying with email address: activ


Acute otitis media (AOM) remains a major public health trouble in childhood worldwide; that is the top bacterial infection in children and the first cause that antibiotics prescription in youngsters in plenty of countries <1, 2>. After ~ pneumococcal conjugate vaccine (PCV) implementation, the number of pneumococcal and non-pneumococcal AOM episodes reduced <3, 4>. However, AOM still remains amongst the most typical diagnoses in childhood <4>.

To determine the bacteriological reasons of AOM, the detection the bacterial varieties in middle ear fluid (MEF) derived by tympanocentesis is the gold standard method <5, 6>. However, in countless countries, mainly because the procedure is painful, tympanocentesis is not recommended or performed on regular basis for first-line AOM <7>. Indeed, to strategy the bacter etiology of AOM, two types of samples can be quickly obtained: nasopharyngeal (NP) samples and also MEF v an existing perforation <7–10>. NP carriage studies have several famous limitations, yet they have epidemiological value for surveillance serotypes and also antibiotic resistance changes after PCV implementation <10, 11>.

MEF samples acquired through an currently perforation might be contaminated by the external auditory canal flora throughout MEF collection <12, 13>. Indeed, the causative duty of Staphylococcus aureus, Pseudomonas aeruginosa or Turicella otitidis in AOM is doubtful due to the fact that these are normal citizens of the external auditory canal <13>. Therefore, just otopathogens such as Streptococcus pneumoniae (Sp), non-typable Haemophilus influenzae (NTHi), Moraxella catharalis and also group A Streptococcus (GAS) should be taken into consideration if they thrive in otorrhea samples <7, 9, 13, 14>.

A current study carry out in number of European countries showed that among AOM cases, approximately 7% featured voluntarily perforation of the tympanic membrane (SPTM) <15>. However, over there were far-ranging differences among countries, varying from 2% of episodes in Italy and also the united kingdom to 17.2% in Sweden. These distinctions may be explained by differences in medical care systems, guidelines and diagnostic criteria of AOM <16>. Before PCV13 implementation, since the start of this century, couple of studies in high-income nations have assessed the pathogens associated in otitis media through SPTM. Us excluded researches from low-income countries since the frequency of otorrhea among otitis media and the clinical features substantially differed <17>. Brook et al. Reported a cohort of 100 patients through otorrhea native 1993 to 2006 in the unified States: the main microorganism was Sp, accounting for 49% the cases, followed by NTHi, 21%, and also GAS, 11%. <18>. In Israel, before PCV7 implementation, Leibovitz et al. Explained a cohort that 822 kids less than 3 year old who had actually AOM through otorrhea from 1996 come 2006: NTHi and Sp to be the most frequent pathogens secluded (about 30% of bacteriologically proven cases), followed by GAS (less 보다 6% the cases) <19>. Stamboulidis et al. Reported a big cohort of 5580 patient (20>: before PCV7 implemention, the very first pathogen isolated was Sp (25%), followed by NTHi (20%) and GAS (12%). After ~ PCV7 implementation, the main otopathogen was NTHi (16%), followed by Sp (13%) and also GAS (12%). In Germany, valve der Linden et al. Reported data native 963 MEF acquired from youngsters 2 months to 5 year of period with SPTM complying with PCV7 implementation <21>. They discovered that GAS to be the main otopathogen secluded (11.7%) (more regularly in kids ≥24 months) complying with by Sp (9.1%) and also NTHi (6.5%) <21>. Finally, Marchisio et al. In Italy explained a cohort the 458 youngsters (median period 28 months) enrolled native 2001 come 2011 (before and after PCV7 implementation) <22>: NTHi was the most frequent microorganism isolated (51% that bacteriologically proven cases), followed by Sp (19%) and GAS (17%). Overall, Sp to be the leading microorganism involved in otitis media through otorrhea before PCV implementation, GAS was much more frequently affiliated in larger children and also NTHi was an ext frequent in younger children and also in polymicrobial otorrhea <18–22>. However, PCVs likewise resulted in shifts to non-vaccine pneumococcal serotypes isolated native carriage or pneumococcal epidemic (invasive and also non-invasive) <23>.

In France, PCV13 was implemented in 2010, with high vaccination coverage (>92%) in the targeted populace <24>. The aim of this study was to explain bacteriological causes of AOM v SPTM, 5 come 8 year after PCV13 implementation.


MEF was observed by Gram staining and inoculated because that bacterial growth. All plates (Columbia blood agar with and also without Colistin-Nalidixic acid, and also Polyvitex agar) to be incubated v 5% CO2. A selective society medium v Colistin-Nalidixic acid mix added was used for this non-sterile specimens because it allows for development of Gram-positive bacteria, also in short quantity, in the visibility of Gram-negative rods (particularly with a high inoculum). Bacterial isolates were identified by standard approaches as defined <7>. Sp serotyping and also antibiotic susceptibility trial and error were performed in ~ the nationwide Reference facility for Pneumococci utilizing the capsular swelling an approach with advertisement antisera (Statens Serum Institut, Copenhagen, Denmark). Susceptibility of Sp isolates to penicillin G was identified by minimal inhibitory concentration (MIC) by the agar-dilution an approach as defined <7, 10>. Isolates were divided into penicillin-susceptible (MIC ≤0.06 mg/L), penicillin-intermediate (MIC >0.06–2.0 mg/L) and also penicillin-resistant (MIC >2 mg/L) according europe Committee on Antimicrobial Susceptibility experimentation breakpoints (Table variation 7.1 accessible at H. influenzae isolates underwent capsular serotyping through the slide agglutination an approach with details antisera (Phadebact, Boule Diagnostic, Hudinge, Sweden). The manufacturing of β-lactamase was assessed through a chromogenic cephalosporin check (Nitrocefin; Cefinase; Biomerieux, Marcy l’Etoile, France). NTHi strains were more classified as ampicillin-susceptible (MIC ≤ 1 mg/L) or -resistant (MIC > 1 mg/L). β-lactamase–negative ampicillin resistance (BLNAR) was established according to the Clinical and Laboratory standards Institute rest points <25>. Strains were considered BLNAR strains if the 2-μg ampicillin diffusion check (Becton Dickinson) gave a zone that inhibition statistical analysis.

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Data were double-entered using 4D software application (v6.4), and analyses were performed with Stata/SE v13.1 (StataCorp, university Station, TX, USA). Quantitative variables were contrasted by student t test and also categorical variables through chi-square check or Fisher exact test. All tests were two sided and also the level of significance was set at p20, 22, 26, 27>. We offered multivariate logistic regression analysis to identify components related to MEF results. The variables age (

Results and also discussion

From October 2015 come January 2018, 470 children with SPTM were enrolled: mean age was 28.8 ± 23.2 months (median 20.8 months) (Table 1). SPTM in youngsters older than 3 years developed mainly as the an initial manifestation the AOM (80.6%, n = 112) with otalgia (89.2%, n = 124). By contrast, for younger kids (infants and toddlers), recurrence (22.1%, n = 73) and also conjunctivitis (12.7%, n = 42) were much more frequent (p = 0.013 for each result).