Objective. To test whether an educational outreach intervention for families and physicians, based on the Centers for Disease Control and Prevention (CDC) principles of judicious antibiotic use, decreases antimicrobial drug prescribing for children younger than 6 years old. Setting. Twelve practices affiliated with 2 managed care organizations (MCOs) in eastern Massachusetts and northwest Washington State. Patients. All enrolled children younger than 6 years old. Methods. Practices stratified by MCO and size were randomized to intervention or control groups. The intervention included 2 meetings of the practice with a physician peer leader, using CDC-endorsed summaries of judicious prescribing recommendations; feedback on previous prescribing rates were also provided. Parents were mailed a CDC brochure on antibiotic use, and supporting materials were displayed in waiting rooms. Automated enrollment, ambulatory visit, and pharmacy claims were used to determine rates of antibiotic courses dispensed (antibiotics/person-year) during baseline (1996–1997) and intervention (1997–1998) years. The primary analysis (for children 3 to Results. The practices cared for 14 468 and 13 460 children in the 2 study years, respectively; 8815 children contributed data in both years. Sixty-two percent of antibiotic courses were dispensed for otitis media, 6.5% for pharyngitis, 6.3% for sinusitis, and 9.2% for colds and bronchitis. Antibiotic dispensing for children 3 to Conclusions. A limited simultaneous educational outreach intervention for parents and providers reduced antibiotic use among children in primary care practices, even in the setting of substantial secular trends toward decreased prescribing. Future efforts to promote judicious prescribing should continue to build on growing public awareness of antibiotic overuse.

Reducing antibiotic use in children: a randomized trial in 12 practices.

Background
Acute otitis media (AOM) is one of the most common diseases in early infancy and childhood. Antibiotic use for AOM varies from 56% in the Netherlands to 95% in the USA, Canada and Australia. This is an update of a Cochrane review first published in The Cochrane Library in Issue 1, 1997 and previously updated in 1999, 2005, 2009 and 2013.

Objectives
To assess the effects of antibiotics for children with AOM.

Search methods
We searched CENTRAL (2015, Issue 3), MEDLINE (1966 to April week 3, 2015), OLDMEDLINE (1958 to 1965), EMBASE (January 1990 to April 2015), Current Contents (1966 to April 2015), CINAHL (2008 to April 2015) and LILACS (2008 to April 2015).

Selection criteria
Randomised controlled trials (RCTs) comparing 1) antimicrobial drugs with placebo and 2) immediate antibiotic treatment with expectant observation (including delayed antibiotic prescribing) in children with AOM.

Data collection and analysis
Two review authors independently assessed trial quality and extracted data.

Main results
For the review of antibiotics against placebo, 13 RCTs (3401 children and 3938 AOM episodes) from high-income countries were eligible and had generally low risk of bias. The combined results of the trials revealed that by 24 hours from the start of treatment, 60% of the children had recovered whether or not they had placebo or antibiotics. Pain was not reduced by antibiotics at 24 hours (risk ratio (RR) 0.89, 95% confidence interval (CI) 0.78 to 1.01) but almost a third fewer had residual pain at two to three days (RR 0.70, 95% CI 0.57 to 0.86; number needed to treat for an additional beneficial outcome (NNTB) 20). A quarter fewer had pain at four to seven days (RR 0.76, 95% CI 0.63 to 0.91; NNTB 16) and two-thirds fewer had pain at 10 to 12 days (RR 0.33, 95% CI 0.17 to 0.66; NNTB 7) compared with placebo. Antibiotics did reduce the number of children with abnormal tympanometry findings at two to four weeks (RR 0.82, 95% CI 0.74 to 0.90; NNTB 11), at six to eight weeks (RR 0.88, 95% CI 0.78 to 1.00; NNTB 16) and the number of children with tympanic membrane perforations (RR 0.37, 95% CI 0.18 to 0.76; NNTB 33) and halved contralateral otitis episodes (RR 0.49, 95% CI 0.25 to 0.95; NNTB 11) compared with placebo. However, antibiotics neither reduced the number of children with abnormal tympanometry findings at three months (RR 0.97, 95% CI 0.76 to 1.24) nor the number of children with late AOM recurrences (RR 0.93, 95% CI 0.78 to 1.10) when compared with placebo. Severe complications were rare and did not differ between children treated with antibiotics and those treated with placebo. Adverse events (such as vomiting, diarrhoea or rash) occurred more often in children taking antibiotics (RR 1.38, 95% CI 1.19 to 1.59; number needed to treat for an additional harmful outcome (NNTH) 14). Funnel plots do not suggest publication bias. Individual patient data meta-analysis of a subset of included trials found antibiotics to be most beneficial in children aged less than two years with bilateral AOM, or with both AOM and otorrhoea.

For the review of immediate antibiotics against expectant observation, five trials (1149 children) from high-income countries were eligible and had low to moderate risk of bias. Four trials (1007 children) reported outcome data that could be used for this review. From these trials, data from 959 children could be extracted for the meta-analysis of pain at three to seven days. No difference in pain was detectable at three to seven days (RR 0.75, 95% CI 0.50 to 1.12). One trial (247 children) reported data on pain at 11 to 14 days. Immediate antibiotics were not associated with a reduction in the number of children with pain (RR 0.91, 95% CI 0.75 to 1.10) compared with expectant observation. Additionally, no differences in the number of children with abnormal tympanometry findings at four weeks, tympanic membrane perforations and AOM recurrence were observed between groups. No serious complications occurred in either the antibiotic or the expectant observation group. Immediate antibiotics were associated with a substantial increased risk of vomiting, diarrhoea or rash compared with expectant observation (RR 1.71, 95% CI 1.24 to 2.36; NNTH 9).

Results from an individual patient data meta-analysis including data from six high-quality trials (1643 children) that were also included as individual trials in our review showed that antibiotics seem to be most beneficial in children younger than two years of age with bilateral AOM (NNTB 4) and in children with both AOM and otorrhoea (NNTB 3).

Authors' conclusions
This review reveals that antibiotics have no early effect on pain, a slight effect on pain in the days following and only a modest effect on the number of children with tympanic perforations, contralateral otitis episodes and abnormal tympanometry findings at two to four weeks and at six to eight weeks compared with placebo in children with AOM. In high-income countries, most cases of AOM spontaneously remit without complications. The benefits of antibiotics must be weighed against the possible harms: for every 14 children treated with antibiotics one child experienced an adverse event (such as vomiting, diarrhoea or rash) that would not have occurred if antibiotics were withheld. Therefore clinical management should emphasise advice about adequate analgesia and the limited role for antibiotics. Antibiotics are most useful in children under two years of age with bilateral AOM, or with both AOM and otorrhoea. For most other children with mild disease in high-income countries, an expectant observational approach seems justified.

/pdf/antibiotics-for-acute-otitis-media-in-children-2q11kpa2ro.pdf

Antibiotics for acute otitis media in children

Objective: To compare immediate with delayed prescribing of antibiotics for acute otitis media. Design: Open randomised controlled trial. Setting: General practices in south west England. Participants: 315 children aged between 6 months and 10 years presenting with acute otitis media. Interventions: Two treatment strategies, supported by standardised advice sheets—immediate antibiotics or delayed antibiotics (antibiotic prescription to be collected at parents9 discretion after 72 hours if child still not improving). Main outcome measures: Symptom resolution, absence from school or nursery, paracetamol consumption. Results: On average, symptoms resolved after 3 days. Children prescribed antibiotics immediately had shorter illness (−1.1 days (95% confidence interval −0.54 to −1.48)), fewer nights disturbed (−0.72 (−0.30 to −1.13)), and slightly less paracetamol consumption (−0.52 spoons/day (−0.26 to −0.79)). There was no difference in school absence or pain or distress scores since benefits of antibiotics occurred mainly after the first 24 hours—when distress was less severe. Parents of 36/150 of the children given delayed prescriptions used antibiotics, and 77% were very satisfied. Fewer children in the delayed group had diarrhoea (14/150 (9%) v 25/135 (19%), χ2=5.2, P=0.02). Fewer parents in the delayed group believed in the effectiveness of antibiotics and in the need to see the doctor with future episodes. Conclusion: Immediate antibiotic prescription provided symptomatic benefit mainly after first 24 hours, when symptoms were already resolving. For children who are not very unwell systemically, a wait and see approach seems feasible and acceptable to parents and should substantially reduce the use of antibiotics for acute otitis media.

https://www.bmj.com/content/bmj/322/7282/336.full.pdf

Pragmatic randomised controlled trial of two prescribing strategies for childhood acute otitis media.

Objective/hypothesis Data from cohort studies and untreated groups in randomized controlled trials can be identified through systematic literature review and synthesized with meta-analysis to estimate natural history of acute otitis media (AOM) and otitis media with effusion (OME). Study design Systematic literature review and meta-analysis. Method Source articles were identified by MEDLINE search through August 2002 plus manual crosschecks of bibliographies and published meta-analyses. Data were abstracted independently by two investigators and combined with random effects meta-analysis to estimate spontaneous resolution, 95% confidence intervals (CI), and heterogeneity. Sensitivity analysis was performed. Results Sixty-three articles met inclusion criteria. AOM symptoms improved within 24 hours without antibiotics in 61% of children (95% CI, 50-72%), rising to 80% by 2 to 3 days (95% CI, 69-90%). Suppurative complications were comparable if antibiotics were withheld (0.12%) or provided (0.24%). Children entered recurrent AOM trials with a mean rate of 5.5 or more annual episodes but averaged only 2.8 annual episodes while on placebo (95% CI, 2.2-3.4). No AOM episodes occurred in 41%, and only 17% remained otitis prone (3 or more episodes). OME after untreated AOM had 59% resolution by 1 month (95% CI, 50-68%) and 74% resolution by 3 months (95% CI, 68-80%). OME of unknown duration had 28% spontaneous resolution by 3 months (95%, CI 14-41%), rising to 42% by 6 months (95% CI, 35-49%). In contrast, chronic OME had only 26% resolution by 6 months and 33% resolution by 1 year. Conclusions The natural history of otitis media is very favorable. Combined estimates of spontaneous resolution provide a benchmark against which to judge new or established interventions. The need for surgery in children with recurrent AOM or chronic OME should be balanced against the likelihood of timely spontaneous resolution and the potential risk of learning, language, or other adverse sequelae from persistent middle ear effusion. Further research is needed to identify prognostic factors that can target children unlikely to improve spontaneously for earlier intervention.

https://www.onlinelibrary.wiley.com/doi/pdf/10.1097/00005537-200310000-00004

Natural history of untreated otitis media.

Clinical efficacy of antimicrobial drugs for acute otitis media: Metaanalysis of 5400 children from thirty-three randomized trials

The incidence of acute otitis media and its response to treatment only with nose drops and analgesics (but without antibiotics or myringotomy) were assessed over three months by 45 doctors in and around Tilburg. In addition, over 17 months 60 general practitioners assessed the effects of this limited treatment in children aged 2 to 12 years and referred all those in whom the condition took an unsatisfactory course (either a severe course--illness continuing beyond three to four days with high temperature or pain, or both--or persistent discharge after 14 days) to an ear, nose, and throat specialist. Those referred because of appreciable illness continuing beyond three or four days were entered into a further study, comparing the effects of myringotomy alone, antibiotics alone, and myringotomy and antibiotics combined. Bacteriology was assessed in all children in whom the course of the condition was unsatisfactory. More than 90% of an estimated 4860 children seen over 17 months (estimation based on incidence of severe course in the three month study) recovered within a few days. The course of the condition was severe in only 126 (2.7%) patients; haemolytic streptococci group A were identified in 30 of these 126 patients but Haemophilus influenzae in only one. One hundred of these patients with a severe course entered the trial of treatment, which showed antimicrobial treatment either alone or in combination to be more effective than myringotomy alone. Whether combined treatment was more effective than antibiotics alone remained unconfirmed. Acute otitis media in children can be treated with nose drops and analgesics alone for the first three to four days. Patients in whom this regimen is not accompanied by satisfactory recovery can be recognised within a short time and treated by the general practitioner.

https://www.bmj.com/content/bmj/290/6474/1033.full.pdf

M A van 't Hof

Papers

Acute otitis media: a new treatment strategy.