Single Dose Azithromycin for the Treatment of Uncomplicated Otitis Media

Adriano Arguedas, MD; Cecilia Loaiza, MD; Carolina Soley, MD


Pediatr Infect Dis J. 2004;23(2s) 

In This Article

Abstract and Introduction

Three clinical trials have examined the efficacy and safety of single dose azithromycin (30 mg/kg) in children with uncomplicated acute otitis media (AOM). In the first trial, a small pilot study, the clinical and microbiologic efficacy of single dose azithromycin was comparable with that of 3-day azithromycin or single dose ceftriaxone. A second, noncomparative trial confirmed the clinical and microbiologic efficacy of the single dose regimen. The third study, a large double blind, double dummy trial, demonstrated comparable clinical success rates between single dose azithromycin and 10-day standard amoxicillin/clavulanate. The incidence of drug-related adverse events in patients treated with single dose azithromycin was low in all three trials and similar to rates that have been reported for other antimicrobial agents used for the treatment of patients with AOM. In the amoxicillin/clavulanate trial, compliance with single dose azithromycin was significantly better than with the amoxicillin/clavulanate regimen (P < 0.001). We conclude that a single dose of azithromycin (30 mg/kg) is safe and effective for the treatment of uncomplicated AOM in children.

Acute otitis media (AOM) is one of the most common infectious diseases of childhood and the most frequent condition for which antibiotics are prescribed for children.[1,2,3,4] Bacterial pathogens are isolated from middle ear fluid in about two-thirds of patients, with Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis and Streptococcus pyogenes being the most common.[1,5,6]

The selection of an antibiotic for the treatment of AOM is based on antibacterial spectrum, safety, compliance and cost.[7,8] In the early 1980s the main criterion for empiric antimicrobial drug selection was the need to provide coverage of beta-lactamase-producing strains of H. influenzae and M. catarrhalis. Now empiric therapy must cover the increasing numbers of S. pneumoniae with penicillin or multidrug resistance (resistant to ≥3 different antibiotic classes). The increasing frequency of resistant pathogens and the geographic variations in resistance patterns have increased the need for appropriate surveillance of antimicrobial resistance. This is especially true for pathogens isolated from the middle ear fluid of children with AOM.[9,10]

Azithromycin is an azalide antibiotic with activity against the pathogens that commonly cause AOM, including S. pneumoniae, H. influenzae, M. catarrhalis and S. pyogenes.[11,12,13] In addition middle ear penetration by azithromycin and its long half-life of ~68 h allow for once daily dosing and shortened courses of therapy.[14,15,16,17] Bacterial eradication by azithromycin has been demonstrated in a number of animal models, including pneumococcal pneumonia and otitis, localized S. pyogenes infection and viridans streptococcal endocarditis.[18] Additionally eradication of H. influenzae in the chinchilla otitis model has been shown to be dose-dependent.[19]

Emerging antimicrobial resistance affects antibiotics of all classes, and the macrolides are no exception. In the case of S. pneumoniae, macrolide resistance rates vary geographically and are higher among penicillin-resistant isolates.[20] Macrolide resistance is most commonly mediated by genes that encode either an efflux pump (mefA) or an enzyme that methylates the macrolide-binding site on the ribosome (ermB). Of these mefA (MIC ≤ 32 µg/ml) is the more common type in the United States, and its prevalence relative to ermB has remained constant at 75% to 25%, respectively, from 1994 to 2000. In contrast ermB (MIC ≥ 64 µg/ml) is more common in Europe.[21,22,23]

Multiple clinical trials in pediatric patients with AOM have demonstrated the clinical efficacy of azithromycin (30 mg/kg) administered as either a 3- or a 5-day regimen.[24,25,26,27,28,29] The prolonged half-life and extensive tissue penetration of azithromycin, as well as its pharmacodynamic properties, provided the rationale for studies in which the same total dosage (30 mg/kg) was used as a single dose.[30] Three clinical trials were undertaken to evaluate the efficacy and safety of single dose azithromycin for the treatment of children with uncomplicated AOM. This review summarizes the results of these three trials, which were published separately elsewhere.[31,32,33]


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