A Randomized, Multicenter, Double Blind, Double Dummy Trial of Single Dose Azithromycin Versus High Dose Amoxicillin for Treatment of Uncomplicated Acute Otitis Media

WHAT'S KNOWN ON THIS SUBJECT: Many pediatric acute respiratory tract infections (ARTI) are viral and do not require antimicrobial treatment. Recent estimates of antimicrobial overprescribing for these infections, defined based on the published bacterial disease prevalence among all ARTI, are not available. WHAT THIS STUDY ADDS:Based on the published bacterial prevalence rates for pediatric ARTI, antimicrobial agents are prescribed almost twice as often as expected to outpatients nationally, amounting to an estimated 11.4 million potentially preventable antimicrobial prescriptions annually. abstract BACKGROUND AND OBJECTIVES: Antimicrobials are frequently prescribed for acute respiratory tract infections (ARTI), although many are viral. We aimed to determine bacterial prevalence rates for 5 common childhood ARTI -acute otitis media (AOM), sinusitis, bronchitis, upper respiratory tract infection, and pharyngitis-and to compare these rates to nationally representative antimicrobial prescription rates for these ARTI. METHODS:We performed (1) a meta-analysis of English language pediatric studies published between 2000 and 2011 in Medline, Embase, and the Cochrane library to determine ARTI bacterial prevalence rates; and (2) a retrospective cohort analysis of children age ,18 years evaluated in ambulatory clinics sampled by the 2000-2010 National Ambulatory Medical Care Survey (NAMCS) to determine estimated US ARTI antimicrobial prescribing rates. RESULTS:From the meta-analysis, the AOM bacterial prevalence was 64.7% (95% confidence interval [CI], 50.5%-77.7%); Streptococcus pyogenes prevalence during pharyngitis was 20.2% (95% CI, 15.9%-25.2%). No URI or bronchitis studies met inclusion criteria, and 1 sinusitis study met inclusion criteria, identifying bacteria in 78% of subjects. Based on these condition-specific bacterial prevalence rates, the expected antimicrobial rescribing rate for ARTI overall was 27.4% (95% CI, 26.5%-28.3%). However, antimicrobial agents were prescribed in NAMCS during 56.9% (95% CI, 50.8%-63.1%) of ARTI encounters, representing an estimated 11.4 million potentially preventable antimicrobial prescriptions annually.

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“…We reviewed 71 fulltext articles, of which 12 were included (Supplemental Fig 3). 12,18,21,30,[35][36][37][38]41,[43][44] …”

Section: Aommentioning

confidence: 99%

Bacterial Prevalence and Antimicrobial Prescribing Trends for Acute Respiratory Tract Infections

Kronman¹,

2014

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“…Previous studies of children aged 6 to 30 months with AOM who were treated with amoxicillin (but not clavulanate) have described rates of diarrhea ranging from 10% to 17.5%, depending on the duration of treatment at the time of the report (10,11). In one of the studies, the rate in children receiving only placebo ranged from 8% to 10% (10).…”

Section: Discussionmentioning

confidence: 99%

“…Most recently, in children under age 2 years with initially observed episodes of AOM who were randomized to receive A/C for either 10 days or 5 days, protocol-defined diarrhea (PDD) occurred in 70 (27%) of 257 children assigned to the 10-day treatment group (9). Although diarrhea may be caused also by the amoxicillin component (10,11), evidence points to the clavulanate component as mainly responsible. A reduction in the total effective dose of clavulanate and in the number of daily doses has been associated with reduced rates of diarrhea (5).…”

mentioning

confidence: 99%

Reduced-Concentration Clavulanate for Young Children with Acute Otitis Media

Hoberman

Paradise

Rockette

et al. 2017

Antimicrob Agents Chemother

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Amoxicillin-clavulanate (A/C) is currently the most effective oral antimicrobial in treating children with acute otitis media (AOM), but the standard dosage of 90 mg amoxicillin/6.4 mg clavulanate/kg of body weight/day commonly causes diarrhea. We examined whether an A/C formulation containing lower concentrations of clavulanate would result in less diarrhea while maintaining plasma levels of amoxicillin and clavulanate adequate to eradicate middle-ear pathogens and to achieve clinical success. We conducted an open-label study in children with AOM who were 6 to 23 months of age. In phase 1, we treated 40 children with a reduced-clavulanate A/C formulation providing 90 mg amoxicillin/3.2 mg clavulanate/kg/day for 10 days. In phase 2, we treated 72 children with the same formulation at a dosage of 80 mg amoxicillin/2.85 mg clavulanate/kg/day for 10 days. We compared the rates of protocoldefined diarrhea (PDD), diaper dermatitis, and AOM clinical response in these children with rates we had reported in children who received the standard A/C regimen, and we obtained plasma levels of amoxicillin and clavulanate at various time points. Outcomes in phase 1 children and in children who had received the standard regimen did not differ significantly. Rates of PDD in children receiving phase 2 and standard regimens were 17% and 26%, respectively (P ϭ 0.10). The corresponding rates of diaper dermatitis were 21% and 33% (P ϭ 0.04) and of AOM treatment failure were 12% and 16% (P ϭ 0.44). Symptomatic responses did not differ significantly between regimens; both gave clavulanate levels sufficient to inhibit ␤-lactamase activity. In young children with AOM, clavulanate dosages lower than those currently used may be associated with fewer side effects without reducing clinical efficacy. (This study has been registered at ClinicalTrials.gov under registration no. NCT02630992.) KEYWORDS acute otitis media, amoxicillin-clavulanate, antimicrobial treatment N ext to the common cold, acute otitis media (AOM) is the most frequently diagnosed illness in children in the United States (1) and the most commonly cited indication for antimicrobial treatment (2). Findings of two recent placebo-controlled trials support routine antimicrobial treatment of AOM in very young children. In those trials, affected children under 3 years of age who received antimicrobial treatment for 7 or 10 days experienced more-favorable outcomes than those who received placebo (3, 4). In both studies, amoxicillin-clavulanate was used as the active treatment-albeit in different dosing regimens-because it had been previously shown to have the highest rates of eradication of AOM pathogens, with high resultant rates of clinical cure. The efficacy of A/C is attributable in part to inactivation, by the clavulanate

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“…Circa l'80% dei casi di sinusite acuta risponde al trattamento antibiotico di prima linea [15,16], nei restanti casi, è stato assunto in base ai dati pubblicati in letteratura che il trattamento di seconda linea abbia una percentuale di successo del 70% [10,17] L'85% dei casi di otite media acuta risponde al trattamento antibiotico di prima linea [18][19][20][21]; nel restante 15% dei casi, si è assunto che la terapia di seconda linea abbia una percentuale di successo del 70% [18].…”

Section: Probabilità Degli Eventi Nel Modellounclassified

Costo/efficacia della prevenzione di infezioni alle prime vie aeree mediante un estratto batterico immunostimolante aspecifico (OM-85)

Zaniolo¹,

Pradelli²,

Eandi

2005

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OBJECTIVES: To estimate the pharmacoeconomical impact of preventing recurrent upper respiratory tract infections (URTIs) with OM-85, a non-specific immunostimulating agent, in at-risk children. METHODS: Implementation of a decisional model. The evaluation of effectiveness (number of prevented URTIs/therapeutic cycle) was based on weighted average of the results of four randomized, double-blind, placebo-controlled trials identified by literature reviewing. The clinical events considered in the model were natural resolution of the infection, onset of complications (acute otitis media, sinusitis, others) and their evolution. Baseline event probabilities were derived by reviewing published data in the literature. URTI-related direct and indirect costs supported by patient, by Italian health system and by community were structured according with the principal guidelines and implemented with current Italian prices and tariffs. The cost/ effectiveness of OM-85 was calculated for five scenarios, differing in the number of therapeutic cycles, grade of patient co-payment and other secondary assumptions. Sensibility analyses were performed to evaluate the model robustness. RESULTS: Immunostimulation with one cycle of OM-85 prevented on average 1,60 URTI/patient in six months (RR = 0,515). In the basic scenario, this preventive action induced savings for 107,42 euro/patient in the perspective of the patient's family, for 48,52 euro/patient in the perspective of Italian health system and for 231,26 in the community perspective. Sensibility analyses confirmed the robustness of basic scenario results. Threshold analyses showed that OM-85 prophylaxis is economically convenient as long as more than 7% of infections are prevented or global cost of one episode of URTI is greater than 10,00 euro. CONCLUSIONS: Non-specific immunotherapy with OM-85 induces a reduction in the incidence of URTIs in atrisk children with a concurrent saving for patient and health system. INTRODUZIONELa rinofaringite acuta, o comune raffreddore, consiste in un'infiammazione delle vie aeree superiori che interessa, in vario grado, il naso, i seni paranasali, la gola, la laringe e, in qualche caso, la trachea e i bronchi.In generale le infezioni delle vie aeree superiori (Upper Respiratory Tract Infection -URTI) sono ad eziologia virale; la comparsa di complicanze è invece solitamente un problema batterico e riguarda principalmente lo sviluppo di otite media acuta e sinusite.La comparsa in infezioni ricorrenti segna l'adattamento del bambino all'ambiente circostante e la conseguente acquisizione delle difese immunitarie. Alcuni bambini però, per motivi non ancora chiariti, acquisiscono tali difese meno rapidamente di altri e presentano una forma ricorrente di URTI; un bambino è ritenuto affetto da URTI ricorrente se presenta almeno tre nuovi episodi in un periodo di 6 mesi.Questa condizione rappresenta un problema rilevante sia da un punto di vista clinico che socio-economico e quindi richiede, nella gran parte di casi, la messa a punto da parte d...

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A Randomized, Multicenter, Double Blind, Double Dummy Trial of Single Dose Azithromycin Versus High Dose Amoxicillin for Treatment of Uncomplicated Acute Otitis Media

Abstract: In this study, single dose azithromycin was as effective as high dose amoxicillin for the treatment of children with AOM, whereas rates of adverse events were lower and compliance improved with the simplified single dose regimen.

Cited by 51 publications

References 31 publications

Bacterial Prevalence and Antimicrobial Prescribing Trends for Acute Respiratory Tract Infections

Bacterial Prevalence and Antimicrobial Prescribing Trends for Acute Respiratory Tract Infections

Reduced-Concentration Clavulanate for Young Children with Acute Otitis Media

Costo/efficacia della prevenzione di infezioni alle prime vie aeree mediante un estratto batterico immunostimolante aspecifico (OM-85)

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