A systematic review and meta-analysis of antimicrobial resistance in paediatric acute otitis media

https://doi.org/10.1016/j.ijporl.2019.04.041Get rights and content

Highlights

  • Two in three samples from middle ear sampling in AOM grew a bacterial pathogen.

  • Common bacterial causes of AOM include Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis.

  • Antimicrobial resistance to first-line antibiotics is common.

  • Amoxicillin-clavulanate offers a higher chance of bacterial eradication than current first-line agents.

  • A greater understanding of local bacteriology and resistance patterns is needed to enable improved antimicrobial stewardship.

Abstract

Objective of review

Acute otitis media (AOM) is the largest cause of antimicrobial prescriptions amongst children in developed countries. Excessive and inappropriate prescribing is known to drive antimicrobial resistance, but less is known of antimicrobial resistance in AOM-associated bacteria.

Type of review & search strategy

We conducted a systematic review and meta-analysis of bacterial prevalence and antimicrobial resistance in studies of paediatric AOM identified from Ovid Medline, Embase and the Cochrane library.

Results

From 48 unique studies, 15,871 samples were included. Only 0.67 (CI 0.63–0.71) of all ear samples grew a bacterial pathogen. The most common bacterial causes of AOM in children were Streptococcus pneumoniae 0.30 (CI 0.27–0.32), Haemophilus influenza 0.23 (CI 0.20–0.26), and Moraxella catarrhalis 0.05 (CI 0.04–0.06). Resistance patterns varied amongst organisms and antimicrobial agents. The pooled proportion of bacterial culture-positive episodes of AOM that could be effectively treated with amoxicillin was 0.85 (CI 0.76–0.94), erythromycin was 0.64 (0.48–0.78) and amoxicillin-clavulanate was 0.95 (CI 0.85–0.98).

Conclusion

We have demonstrated the bacteriology and antimicrobial resistance patterns of AOM. Of samples which grew bacteria, on average approximately 15% of isolates demonstrated resistance to amoxicillin; a typical first-line agent. Greater understanding of local bacteriology and resistance patterns is needed to enable improved antimicrobial stewardship.

Introduction

Acute otitis media (AOM) is defined as the presence of inflammation in the middle ear associated with an effusion, and accompanied by the rapid onset of signs and symptoms of an ear infection [1]. It is the single largest cause of infections amongst children [2] and is the most common cause for antimicrobial prescriptions for children in economically developed countries [1].

Many national guidelines for AOM recommend either immediate or delayed antimicrobial prescribing (amoxicillin in most circumstances), or observation with close follow-up [[3], [4], [5], [6]]. These guidelines are, in part, based on work which has shown that after two to three days of watchful waiting approximately 80% of children will spontaneously recover [7]. Important exceptions to this include; children younger than 2 years, those with bilateral AOM, and those with AOM and otorrhoea, where antibiotics may be more beneficial [8]. Despite these evidence-based guidelines, large scale studies from North America [[9], [10]], Europe [11], and the UK [12] have demonstrated excessive and inconsistent antimicrobial prescribing in paediatric AOM in general practice and secondary care.

There is a clear association between antimicrobial prescribing and the development of antimicrobial resistance [13], and the World Health Organisation (WHO) calculated that in Europe alone infections due to drug-resistant bacteria cause in excess of 25,000 deaths and cost at least 1.5 billion euros each year in direct healthcare costs and lost productivity [14]. Furthermore, there is also evidence that specifically associates antimicrobial use to the development of antimicrobial resistance in AOM, and demonstrates that this increases the likelihood of treatment failure [15].

Recent studies have sought to identify the pathogens responsible for paediatric acute otitis media [16], and older studies have also investigated the overall effectiveness of antibiotics in children with acute otitis media [8]. We present a comprehensive review and meta-analysis, of both the microbiology and antimicrobial resistance of AOM organisms to commonly used antimicrobial agents, with the aim of informing responsible antimicrobial stewardship.

Section snippets

Systematic review

A comprehensive literature search was performed using Medline, Embase and the Cochrane library up to and including January 2017. A keyword search was undertaken using the search terms ‘otitis media’ AND each of the following search terms: ‘aetiology’, ‘otopathogens’, ‘pathogens’, ‘microbiology’, ‘bacteria’, ‘anti-bacterial agents’, and ‘antibiotic resistance’. Search results were limited to those that were in the English language, human-only studies, and published from 1980 onwards. Duplicated

Results

The literature search yielded 7598 articles following the key-word search. Studies were limited to English language, human only studies, and studies from 1980-present day. Following deduplication this provided 4249 unique articles. Abstracts were screened for relevance to bacteriology or antimicrobial resistance in acute otitis media in children, which identified 204 articles. The full texts and bibliographies were read, and 48 articles [[17], [18], [19], [20], [21], [22], [23], [24], [25], [26]

Discussion

Even when a bacteriological cause for AOM is confirmed, many first-line antimicrobial treatments for AOM demonstrate drug-resistance. Whilst the analysed data indicates a pathogenic bacterial species was isolated in two out of every three cases of AOM, it is possible that the children in the studies analysed are at the more severe end of the AOM spectrum as they have engaged with medical services and had an intervention, such as tympanocentesis.

Of the positive cultures the bacteriology of AOM

Conclusions

Commonly used first-line antimicrobial agents are unlikely to confer any positive effect in many cases of paediatric AOM. Firstly, due to the frequently non-bacterial nature of the condition; and secondly, the evidence of bacterial resistance to commonly used first-line antimicrobial agents.

Author contributions

MM was responsible for the conception and content of the article, the database searches, data interpretation, and preparation of the manuscript. MD performed the statistical analysis, data interpretation, and assisted in manuscript preparation. JDP assisted with microbiological data interpretation and manuscript preparation. SP contributed clinical interpretation of data and manuscript preparation. JW contributed clinical interpretation of data and manuscript preparation. JP was responsible for

Data availability

The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.

Funding source

This work received no specific funding.

Competing financial interests disclosure

The authors have no financial relationships relevant to this article to disclose.

Conflicts of interest

The authors have no conflicts of interest relevant to this article to disclose.

Acknowledgements

Not applicable.

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