Identification and characterization of the bacterial etiology of clinically problematic acute otitis media after tympanocentesis or spontaneous otorrhea in German children

Acute Otitis Media (AOM) is one of the most frequently reported childhood diseases and is the primary reason for antibiotic use in children [1]. Globally, the major bacterial pathogens responsible for AOM are Streptococcus pneumoniae, Haemophilus influenzae and to a lesser extent, Moraxella catarrhalis, S. pyogenes and Staphylococcus aureus[2]. Little is known about AOM microbial epidemiology in Germany. Perforation of the tympanic membrane (TM) can occur as a consequence of AOM. This has potentially important long term clinical consequences [1].

Widespread vaccination with 7-valent pneumococcal conjugate vaccine (PCV7) has reduced outpatient visits due to AOM in children <2 years of age in the United States, although the magnitude of the effect on AOM incidence remains unclear [3]. PCV7 vaccination has also been linked to an overall reduction in AOM cases due to vaccine related S. pneumoniae, and a relative increase in cases due to H. influenzae and non-vaccine S. pneumoniae serotypes [4].

PCV7 was introduced to the German market in 2001 and became universally recommended for all infants in 2006. No available data from Germany has examined pathogen distribution in AOM using direct Middle Ear Fluid (MEF) sampling [5, 6]. The aim of this prospective non-interventional study was to assess the bacterial etiology and antimicrobial susceptibility of bacteria causing AOM in 100 German children between 3 months and less than 60 months of age. In Germany, tympanocentesis is only indicated for treatment of complications of AOM, treatment failure and in conditions of imminent TM perforation to avoid spontaneous perforation [7]. In our study, MEF samples were collected from spontaneous TM ruptures by an Ear, Nose and Throat (ENT) specialist as part of routine clinical ENT practice or when tympanocentesis was clinically indicated.

The information from this study is important for development and refinement of AOM treatment guidelines, and for assessing potential benefits of new PCVs.

The study (111640) was conducted in 11 centers in Hamburg, Münster, Berlin, Dresden, München, and Bad Segeberg in Germany. All children between 3 months and less than 60 months of age with ENT specialist–confirmed AOM were assessed for eligibility by the ENT specialist at the study center. Written informed consent to analyze MEF samples was obtained from the parents/guardians of eligible children. The treatment of each child was left to the discretion of the ENT specialist. The study protocol was approved by the local ethics committees: the Ethik-Kommission bei der Ärztekammer Hamburg, Ethik- Kommission der Medizinischen Fakultät der Universität Münster, Ethik-Kommission der Sächsischen Landesärztekammer, Ethik-Kommission der Bayerischen Landesärztekammer, Ethik-Kommission der Ärztekammer Schleswig-Holstein and the Ethik-Kommission der Ärztekammer Berlin. MEF samples were collected by the ENT specialist from spontaneous TM ruptures as part of routine clinical ENT practice or when tympanocentesis was clinically indicated.

In this prospective study of AOM characteristics in Germany, H. Influenzae was the most frequently identified pathogen in children 12 months of age and older, and was also frequently identified in 3–11 month olds, consistent with a growing body of evidence implicating H. Influenzae as a key pathogen in AOM [2, 4], and of a possibly increasing role due to PCV vaccination. S. pyogenes was the second most frequently identified pathogen. These results are consistent with preliminary results from another study conducted in Germany [6], but contrast with other studies suggesting a possibly diminishing role for S. pyogenes in AOM etiology [2]. In a large evaluation of AOM etiology conducted in Israel, S. pyogenes AOM was observed more frequently in older children than in younger children, and was often associated with acute TM perforation [9]. In our study S. pyogenes was only isolated from otorrhea samples (not from tympanocentesis samples), supporting the notion that S. pyogenes infection rapidly leads to TM perforation [9]. The high rate of S.pyogenes isolation in the present study likely reflects the severity of disease in the enrolled population (children with TM perforation or with clinically indicated tympanocentesis according to German clinical guidelines).

In the present cohort at least 74% of children had received at least one PCV7 dose. Although the low number of subjects precludes firm conclusions, the results are generally consistent with larger observational studies showing an increase in AOM due to non-PCV7 S. pneumoniae serotypes in countries where PCV7 uptake is high [4]. New pneumococcal conjugate vaccines targeting H. influenzae by use of Protein D as carrier protein (PHiD-CV) [10], may provide additional benefits in Germany.

In contrast with other countries in Europe, antibiotic susceptibility rates were high in German children. This may be due in part to reduced penicillin consumption in Germany, which is lower than in many other countries in Europe [11].

The potential limitations of the study include the low number of culture-positive samples for which a cause was not able to be identified, although the percentage of positive cultures increased (from 43% to 61%) after changes were made to ensure that sample delivery times and temperature constraints were met. It is also possible that the initial delay between sample collection and processing might have introduced a bias toward a differential recovery of more resilient organisms. For example, S. aureus and S. pyogenes are known to overgrow other bacteria on swabs when processing delay increases, and both S. pneumoniae and NTHi are fastidious organisms more likely to perish after 6 hours and in conditions of freezing.

Because tympanocentesis is not routinely performed for AOM management in Germany, only children with spontaneous perforations in which a specimen was obtained using a procedure avoiding contamination or those in whom tympanocentesis was clinically indicated were eligible. Thus, our population had more severe AOM and the results may not necessarily be able to be extrapolated to all cases of AOM.

In the present study, NTHi, S. pneumoniae and S. pyogenes were implicated as important causes of complicated AOM in children in Germany. NTHi disease appeared prevalent in all ages. The impact of vaccination to prevent both S. pneumoniae and NTHi AOM may be substantial in this population and is worth investigating.