Roger Damoiseaux

Antibiotics for acute otitis media: a meta-analysis with individual patient data

BACKGROUND Individual trials to test effectiveness of antibiotics in children with acute otitis media have been too small for valid subgroup analyses. We aimed to identify subgroups of children who would and would not benefit more than others from treatment with antibiotics. METHODS We did a meta-analysis of data from six randomised trials of the effects of antibiotics in children with acute otitis media. Individual patient data from 1643 children aged from 6 months to 12 years were validated and re-analysed. We defined the primary outcome as an extended course of acute otitis media, consisting of pain, fever, or both at 3-7 days. FINDINGS Significant effect modifications were noted for otorrhoea, and for age and bilateral acute otitis media. In children younger than 2 years of age with bilateral acute otitis media, 55% of controls and 30% on antibiotics still had pain, fever, or both at 3-7 days, with a rate difference between these groups of -25% (95% CI -36% to -14%), resulting in a number-needed-to-treat (NNT) of four children. We identified no significant differences for age alone. In children with otorrhoea the rate difference and NNT, respectively, were -36% (-53% to -19%) and three, whereas in children without otorrhoea the equivalent values were -14% (-23% to -5%) and eight. INTERPRETATION Antibiotics seem to be most beneficial in children younger than 2 years of age with bilateral acute otitis media, and in children with both acute otitis media and otorrhoea. For most other children with mild disease an observational policy seems justified.

Primary care based randomised, double blind trial of amoxicillin versus placebo for acute otitis media in children aged under 2 years

Abstract Objective: To determine the effect of antibiotic treatment for acute otitis media in children between 6 months and 2 years of age. Design: Practice based, double blind, randomised, placebo controlled trial. Setting: 53 general practices in the Netherlands. Subjects: 240 children aged 6 months to 2 years with the diagnosis of acute otitis media. Intervention: Amoxicillin 40 mg/kg/day in three doses. Main outcome measures: Persistent symptoms at day four and duration of fever and pain or crying, or both. Otoscopy at days four and 11, tympanometry at six weeks, and use of analgesic. Results: Persistent symptoms at day four were less common in the amoxicillin group (risk difference 13%; 95% confidence interval 1% to 25%). The median duration of fever was two days in the amoxicillin group versus three in the placebo group (P=0.004). No significant difference was observed in duration of pain or crying, but analgesic consumption was higher in the placebo group during the first 10 days (4.1 v 2.3 doses, P=0.004). In addition, no otoscopic differences were observed at days four and 11, and tympanometric findings at six weeks were similar in both groups. Conclusions: Seven to eight children aged 6 to 24 months with acute otitis media needed to be treated with antibiotics to improve symptomatic outcome at day four in one child. This modest effect does not justify prescription of antibiotics at the first visit, provided close surveillance can be guaranteed.

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

OBJECTIVE. The goal was to determine the predictors of a prolonged course for children with acute otitis media. METHODS. A meta-analysis of data with the observation groups of 6 randomized, controlled trials was performed. Participants were 824 children, 6 months to 12 years of age, with acute otitis media. The primary outcome was a prolonged course of acute otitis media, which was defined as fever and/or pain at 3 to 7 days. RESULTS. Of the 824 included children, 303 had pain and/or fever at 3 to 7 days. Independent predictors of a prolonged course were age of <2 years and bilateral acute otitis media. The absolute risk of pain and/or fever at 3 to 7 days for children <2 years of age with bilateral acute otitis media (20% of all children) was 55%, and that for children ≥2 years of age with unilateral acute otitis media (47% of all children) was 25%. CONCLUSIONS. The risk of a prolonged course was 2 times higher for children <2 years of age with bilateral acute otitis media than for children ≥2 years of age with unilateral acute otitis media. Clinicians can use these features (ie, age of <2 years and bilateral acute otitis media) to inform parents more explicitly about the expected course of their childs otitis media and to explain which features should prompt parents to contact their clinician for reexamination of the child.

Recurrence up to 3.5 years after antibiotic treatment of acute otitis media in very young Dutch children: survey of trial participants.

Objective To determine the long term effects of antibiotic treatment for acute otitis media in young children. Design Prospective three year follow-up study within the framework of a primary care based, double blind, randomised, placebo controlled trial. Setting 53 general practices in the Netherlands. Participants 168 children aged 6 months to 2 years with acute otitis media. Interventions Amoxicillin 40 mg/kg/day in three doses compared with placebo. Main outcome measures Recurrence of acute otitis media; referral to secondary care; ear, nose, and throat surgery. Results Acute otitis media recurred in 63% (47/75) of children in the amoxicillin group and in 43% (37/86) of the placebo group (risk difference 20%, 95% confidence interval 5% to 35%); 30% (24/78 amoxicillin; 27/89 placebo) of children in both groups were referred to secondary care, and 21% (16/78) of the amoxicillin group compared with 30% (27/90) of the placebo group had ear, nose, and throat surgery (risk difference −9%, −23% to 4%). Conclusion Recurrent acute otitis media occurred more often in the children originally treated with amoxicillin. This is another argument for judicious use of antibiotics in children with acute otitis media. Trial registration Netherlands Trial Register NTR1426.

Review of randomized controlled trials on pneumococcal vaccination for prevention of otitis media

Background. Increasing resistance to antibiotics of the pathogens causing acute otitis media (AOM) emphasize the need for effective methods to prevent episodes of otitis media in young children. Objective. To assess the effectiveness of pneumococcal vaccination for prevention of AOM in children age 12 years and younger. Methods. Systematic review of 11 randomized controlled trials including 46 074 children in whom pneumococcal vaccination against AOM was compared with a control treatment. Vaccine effect was estimated as a rate ratio (RR): AOM episodes per child month in pneumococcal vaccination group divided by the AOM episodes per child-month in control group. Results. A moderate effect of pneumococcal polysaccharide vaccination was found in children 24 months of age and older [RR 0.78; 95% confidence interval (CI) 0.63 to 0.97]. Pneumococcal polysaccharide vaccine had little effect on prevention of AOM in children without previous documented episodes before vaccination (RR 0.92; 95% CI 0.85 to 0.99). Better efficacy was seen in those children with documented prior AOM before vaccination (RR 0.81; 95% CI 0.72 to 0.91). Pooled results of pneumococcal conjugate vaccine trials in infants vaccinated as early as 2 months of age and in toddlers attending day care showed only a small effect on prevention of AOM (RR 0.92; 95% CI 0.85 to 0.99). Conclusion. Based on these results, a large scale pneumococcal vaccination program for a primary indication of preventing AOM in infancy is not indicated. The results of ongoing trials should provide more information whether the conjugate vaccine is effective in high risk (otitis-prone) children after 1 year of age.

Antibiotic Therapy to Prevent the Development of Asymptomatic Middle Ear Effusion in Children With Acute Otitis Media A Meta-analysis of Individual Patient Data

OBJECTIVES To determine predictors of the development of asymptomatic middle ear effusion (MEE) in children with acute otitis media (AOM) and to assess the effect of antibiotic therapy in preventing the development of MEE in these children. DATA SOURCES A systematic literature search was performed using PubMed, EMBASE, the Cochrane databases, and the proceedings of international otitis media symposia. STUDY SELECTION A trial was selected if the allocation of participants to treatment was randomized, children aged 0 to 12 years with AOM were included, the comparison was between antibiotic therapy and placebo or no (antibiotic) treatment, and MEE at 1 month was measured. DATA EXTRACTION Data from 5 randomized controlled trials were included in the meta-analysis of individual patient data (1328 children aged 6 months to 12 years). We identified independent predictors of the development of asymptomatic MEE and studied whether these children benefited more from antibiotic therapy than children with a lower risk. The primary outcome was MEE (defined as a type B tympanogram) at 1 month. DATA SYNTHESIS The overall relative risk of antibiotic therapy in preventing the development of asymptomatic MEE after 1 month was 0.9 (95% confidence interval, 0.8-1.0; P =.19). Independent predictors of the development of asymptomatic MEE were age younger than 2 years and recurrent AOM. No statistically significant interaction effects with treatment were found. CONCLUSION Because of a marginal effect of antibiotic therapy on the development of asymptomatic MEE and the known negative effects of prescribing antibiotics, including the development of antibiotic resistance and adverse effects, we do not recommend prescribing antibiotics to prevent MEE.

Impact of early daycare on healthcare resource use related to upper respiratory tract infections during childhood: prospective WHISTLER cohort study

BackgroundDaycare attendance is an established risk factor for upper respiratory tract infections (URTI) and acute otitis media (AOM). Whether this results in higher use of healthcare resources during childhood remains unknown. We aim to assess the effect of first year daycare attendance on the timing and use of healthcare resources for URTI and AOM episodes during early childhood.MethodsIn the Wheezing-Illnesses-STudy-LEidsche-Rijn birth cohort, 2,217 children were prospectively followed up to age six years. Children were categorized according to first-year daycare attendance (yes versus no) and age at entry when applicable (age 0 to 2 months, 3 to 5 months and 6 to 12 months). Information on general practitioner (GP) diagnosed URTI and AOM, GP consultations, antibiotic prescriptions and specialist referral was collected from medical records. Daycare attendance was recorded by monthly questionnaires during the first year of life.ResultsFirst-year daycare attendees and non-attendees had similar total six-year rates of GP-diagnosed URTI and AOM episodes (59/100 child-years, 95% confidence interval 57 to 61 versus 56/100 child-years, 53 to 59). Daycare attendees had more GP-diagnosed URTI and AOM episodes before the age of one year and fewer beyond the age of four years than non-attendees (Pinteraction <0.001). Daycare attendees had higher total six-year rates for GP consultation (adjusted rate ratio 1.15, 1.00 to 1.31) and higher risk for specialist referrals (hazard ratio: 1.43, 1.01 to 2.03). The number of antibiotic prescriptions in the first six years of life was only significantly increased among children who entered daycare between six to twelve months of age (rate ratio 1.32, 1.04 to 1.67). This subgroup of child-care attendees also had the highest overall URTI and AOM incidence rates, GP consultation rates and risk for specialist referral.ConclusionsChildren who enter daycare in the first year of life, have URTI and AOM at an earlier age, leading to higher use of healthcare resources compared to non-attendees, especially when entering daycare between six to twelve months. These findings emphasize the need for improved prevention strategies in daycare facilities to lower infection rates at the early ages.

Referrals for recurrent respiratory tract infections including otitis media in young children.

OBJECTIVE (a) To establish whether disease-related, child-related, and physician-related factors are independently associated with specialist referral in young children with recurrent RTI, and (b) to evaluate whether general practitioners (GPs) follow current guidelines regarding these referrals. METHODS Electronic GP records of children under 24 month of age, born 2002-2008, were reviewed for RTI episodes using ICPC codes. Child-related factors were extracted from the prospective WHISTLER birth-cohort in which a considerable part of children had been enrolled. To evaluate guideline adherence, referral data were compared to national guideline recommendations. RESULTS Consultations for 2532 RTI episodes (1041 children) were assessed. Seventy-eight children were referred for recurrent RTI (3.1% of RTI episodes; 7.5% of children). Disease factors were the main determinants of referral: number (OR 1.7 [CI 1.7-1.7]) and severity of previous RTI episodes (OR 2.2 [CI 1.6-2.8]), and duration of RTI episode (OR 1.7 [CI 1.7-1.8]). The non-disease factors daycare attendance (OR 1.3 [CI 1.0-1.7]) and 5-10 years working experience as a GP compared with <5 years (OR 0.37 [CI 0.27-0.50]) were also associated. Fifty-seven percent of referrals for recurrent RTI were made in accordance with national guidelines. CONCLUSIONS Referral of children for recurrent RTI was primarily determined by frequency, severity, and duration of RTIs; the influence of non-disease factors was limited. Just over half of referrals were made in accordance with guidelines.

Duration of clinical symptoms in children under two years of age with acute otitis media

Objective: To describe the course of symptoms during the first ten days of episodes of AOM in children under two years of age. Methods: Within the framework of a placebo-controlled, double-blind, randomised trial studying the effect of amoxicillin on acute otitis media in children under two years of age in the Netherlands, symptoms were recorded in diaries by the parents. Durations of symptoms were plotted by means of Kaplan-Meier curves. Possible factors influencing the duration were analysed in a Cox regression. Results: Data from 230 children were used in the analyses. The median duration of fever was two days and the median duration of the combination of earache and/or crying was eight days. The duration of earache and/or crying was not influenced by any factor analysed (including treatment allocation). Conclusion: Fifty per cent of the children under two years with an episode of AOM had symptoms for more than eight days (95% CI: 6.9-9.1). Since antibiotic treatment did not influence this period, persistence of symptoms should not be a reason for changing antibiotic therapy.

Antibiotica bij lageluchtweginfecties, de rol van een model in de praktijk

SamenvattingDamoiseaux R, Cleveringa F. Antibiotica bij lageluchtweginfecties, de rol van een model in de praktijk. Huisarts Wet 2006;49(7):374-7.Diagnostische modellen om bij lageluchtweginfecties beter te kunnen differentiëren wanneer een antibioticum nodig is, tonen aan dat factoren die huisartsen belangrijk achten er mogelijk niet toe doen. Auscultatie, comorbiditeit, leeftijd en verwardheid lijken te hebben afgedaan als factoren die men moet meewegen bij de beslissing om al dan niet antibiotica voor te schrijven. Wij bespreken deze factoren aan de hand van enkele casussen uit de praktijk. In de praktijk blijken de diagnostiek en behandeling van lageluchtweginfecties te complex om in een model te vangen. Het klinische beeld en klinische ervaring met het beloop van luchtweginfecties blijven belangrijk.