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NICE 69: National Institute for Health and Clinical Excellence. Prescribing of antibiotics for self-limiting respiratory tract infections in adults and children in primary care. 2008. (Clinical guideline 69) RATIONALE: Acute Otitis Media: NICE 69 includes 3 trials that use a delayed-antibiotic strategy for treating AOM. Two USA studies used a 2-day-delayed antibiotic and the UK primary care study used a 3-day-delayed antibiotic.

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Little P, Gould C, Williamson I, Moore M, Warner G, Dunleavey J. Pragmatic randomised controlled trial of two prescribing strategies for childhood acute otitis media. BMJ 2001;322:336-42 RATIONALE: This RCT makes two important observations: that parents tend to underestimate the amount of analgesia they've administered and that when recommending a no-antibiotic strategy it is all the more important to optimise analgesia.

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Bertin L, Pons G, d’Athis P, Duhamel JF, Mauelonde C, Lasfargues G, Guillot M, Marsac A, Debregeas B, Olive G. A randomized, doubleblind, multicentre controlled trial of ibuprofen versus acetaminophen and placebo for symptoms of acute otitis media in children. Fundam Clin Pharmacol 1996;10(4):387-92 RATIONALE: This small RCT is probably the best trial evidence we have specifically for analgesia use in AOM. Both Paracetamol and Ibuprofen showed a non significant trend towards effective analgesia compared with placebo. Note that all children were also treated with an antibiotic.

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Sanders S, Glasziou PP, Del Mar C, Rovers MM. Antibiotics for acute otitis media in children. Cochrane Database of Systematic Reviews 2004, Issue 1. Art. No.:CD000219.DOI:10.1002/14651858.CD00021 9pub2. (Content up to date 08.11.08). RATIONALE: Most (66%) of children are better in 24 hours and antibiotics have no effect. 80% of children are better in 2-to-7 days and antibiotics have a small effect (symptoms reduced by 16 hours), (RR 0.72; 95% CI 0.62 to 0.83). Antibiotics did not reduce tympanometry (deafness), perforation or recurrence. Vomiting, diarrhoea or rash was more common in children taking antibiotics (RR 1.37; 95% CI 1.09 to 1.76) with a Number Needed to Harm of 16.

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Rovers MM, Glasziou P, Appleman CL, Burke P, McCormick DP, Damoiseaux RA, Little P, Le Saux N, Hoes AW. Predictors of pain and/or fever at 3 to 7 days for children with acute otitis media not treated initially with antibiotics: a meta-analysis of individual patient data. Pediatrics 2007;119(3):579-85. RATIONALE: The risk of prolonged illness was 2 times higher for children <2years with bilateral AOM than for children with unilateral AOM. For this sub-group parents should be advised that symptoms may persist for up to 7 days, and they should optimise analgesia use. The protective immunity against infections with encapsulated bacteria, such as the species that cause AOM, depends on the ability to produce specific antibodies against bacterial capsular polysaccharides, which is inadequate until 2 years of age. The anatomic features of the eustachian tubes and the nasopharynx also differ with age. Consequently, children under 2 years of age seem to be more susceptible to AOM.

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Hoberman A, Paradise JL, Rockette HE, Shaikh N, Wald ER, Kearney DH, Colborn K, Kurs-Lasky M, Bhatnager S, Haralam MA, Zoffel LM, Jenkins C, Pope MA, Balentine TL, Barbadora KA. Treatment of acute otitis media in children under 2 years of age. NEJM 2011;364:105-115 This study included 291 children 6-23 months with otoscopically confirmed OM and compared co-amoxiclav to placebo. There was no significant difference in initial resolution of symptoms between co-amoxiclav and placebo (p=0.14). Sustained resolution of symptoms, was slightly higher for co amoxiclav 20% by day 2, 41% by day 4, and 67% by day 7, as compared with 14%, 36%, and 53% with placebo (P = 0.04 for the overall comparison). At day 10-12 clinical results were less favourable in children with bilateral AOM (p=0.002), *more** bulging tympanic membrane compared to less (p<0.001), higher symptom scores at entry, ( p=0.004, score >8 for fever, tugging ears, crying more, irritability, difficulty sleeping, less playful, eating less, where O=no symptoms, 1 a little , 2 A lot).*

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Tähtinen PA, Laine MK, Houvinen P, Jalava J, Ruuskanen O, Ruohola A. A placebo-controlled trial of antimicrobial treatment for acute otitis media. NEJM 2011;364:116-26.

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Rovers MM, Glasziou P, Appelman CL, Burke P, McCormick DP, Damoiseaux RA, Gaboury I, Little P, Hoes AW. Antibiotics for acute otitis media: a meta-analysis with individual patient data. Lancet 2006;368:1429-1435 RATIONALE: Note this is sub-analysis of data. In children <2 years old with bilateral AOM, 30% on antibiotics and 55% of controls had pain and/or fever at 3 to 7 days (RD -25%; 95% CI: -36, -14) and the NNT was 4 in children with otorrhoea, 24% on antibiotics and 60% of controls had pain and/or fever at 3 to 7 days (RD-36%; 95% CI: -53, -19) and the NNT was 3.

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Thompson PL, Gilbert RE, Long PF, Saxena S, Sharland M, Wong IC. Effect of antibiotics for otitis media on mastoiditis in children: a retrospective cohort study using the United Kingdom general practice research database. Pediatrics 2009;123(2):424-30 RATIONALE: Antibiotics halved the risk of mastoiditis, but GPs would have to treat 4831 episodes of AOM to prevent one episode of mastoiditis. Although mastoiditis is a serious illness, most children make an uncomplicated recovery after mastoidectomy or IV antibiotics, (Incidence mastoiditis 0.15 per 1000 child years).

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Takata GI, Chan LS, Shekelle P, et al. Evidence assessment of management of acute otitis media: The role of antibiotics in treatment of uncomplicated acute otitis media. Pediatrics 2001;108:239-247 RATIONALE: Pooled analyses did not show any difference in efficacy between comparisons of penicillin, ampicillin, amoxicillin (2 or 3 times daily; standard or high dose), amoxicillin-clavulanate, cefaclor, cefixime, ceftriaxone, azithromycin and trimethoprim.

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Macrolides concentrate intracellularly and so are less active against the extracellular H influenzae.

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Sox CM, Finkelstein JA, Yin R, Kleinman K, Lieu TA. Trends on otitis media treatment failure and relapse. Pediatrics 2008;121(4):674-9. RATIONALE: High-dose amoxicillin treatment did not reduce the risk of individual infections resulting in adverse outcomes.

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Kozyrskyj AL, Hildes Ripstein GF, Longstaffe SE, et al. Short-course antibiotics for acute otitis media. Cochrane Database Syst Rev 2000;(2):CD001095. RATIONALE: This review found that 5 days of antibiotic treatment was as effective as 10 days in otherwise healthy children with uncomplicated AOM.

The POCAST project is funded by the National Institute for Health Research Health Protection Research Unit (NIHR HPRU) in Healthcare Associated Infections and Antimicrobial Resistance at Imperial College London and by the Imperial College Healthcare Charity (Grant Ref No:7006/P36U).