Acute otitis media: Making sense of recent guidelines on antimicrobial treatment
Several new recommendations could influence treatment choices.
All guidelines recommend oral amoxicillin as first-line therapy in AOM. The AAP/AAFP guideline recommends increasing the dosage used for empiric treatment from 40–45 mg/kg/d to 80–90 mg/kg/d for all children, because the prevalence of penicillin-resistant S pneumoniae has continued to rise and has reached a level in 2004 where standard-dose amoxicillin is no longer considered adequate (see Acute otitis media’s etiologic profile today).
Both penicillin-intermediate S pneumoniae (minimum inhibitory concentration [MIC] 0.12–1.0 μg/mL) and resistant S pneumoniae (penicillin MIC ≥2.0 μg/mL) are common causes of AOM in the United States.10 Further complicating treatment, most resistant strains of S pneumoniae are also resistant to other classes of antimicrobials, such as macrolides, trimethoprim/sulfamethoxazole, and clindamycin.
A steadily increasing number of H influenzae and nearly all M catarrhalis strains are β-lactamase producers.11 These resistant pathogens are most commonly isolated from children in day care, from children younger than 2 years of age, during the winter months, from children recently treated with antimicrobials, and from those who have not responded to treatment.3,12
Extensive and often inappropriate use of antimicrobials has contributed to increased resistance, which complicates treatment of AOM, increases treatment failure, has motivated a search for newer drugs effective against resistant strains.
Differences among the guidelines
After the CDC2 and Clinical Advisory Committee3 guidelines were published, the Agency for Healthcare Research and Quality (AHRQ) report13 was released; it suggested most episodes of AOM resolve without the use of antimicrobials. Therefore, the AAP/AAFP guideline4 included a watchful waiting option in its clinical algorithm.
Disagreement over watchful waiting. The CDC guideline did not comment on spontaneous resolution and watchful waiting as an option, and the Clinical Advisory Committee3 did not agree with the often quoted 70% to 80% spontaneous resolution. The Clinical Advisory Committee and Wald14 expressed concerns that the included studies used poor enrollment criteria and likely misclassified some benign upper respiratory infections and OME as AOM. Wald resigned from the AAP/AAFP writing group in a dispute on this issue. She and the Clinical Advisory Committee favored effective antibiotic therapy because it more rapidly resolves the clinical signs and symptoms of AOM,13 and because children who receive only symptomatic treatment have consistently higher failure rates than those treated with antimicrobials.13
How compliance factors influence treatment outcomes. The CDC guidelines2 did not give weight to the taste of the medication, frequency of dosing, duration of therapy, or adverse side effects (rash, spitting, vomiting, and diarrhea). The Clinical Advisory Committee guideline3 and the AAP/AAFP guideline4 viewed these compliance factors as important in selecting an appropriate antimicrobial for children.3,12,15
Two new antibiotics were licensed following publication of the CDC and Clinical Advisory Committee Guidelines—amoxicillin/clavulanate extra-strength, and the third-generation cephalosporin, cefdinir. Cefdinir was endorsed by the Clinical Advisory Committee and the AAP/AAFP guideline, given the drug’s efficacy and compliance-enhancing features—ie, pleasant taste, once- or twice-per-day dosing, and a 5-day course for AOM treatment.
Which drugs get priority. In the event initial amoxicillin treatment fails, all guidelines recommend high-dose amoxicillin/clavulanate as a preferred second-line agent.
In addition, the CDC and Clinical Advisory Committee guidelines cite one or several of the cephalosporins as preferred second-line agents, including ceftriaxone, cefdinir, cefpodoxime, cefprozil, or cefuroxime.
The AAP/AAFP guideline endorsed cefdinir, cefpodoxime, cefuroxime, and ceftriaxone as alternatives to amoxicillin and amoxicillin/clavulanate for patients with “non-type I allergy.” The addition of cefdinir was based on satisfactory efficacy and high-compliance potential. Designation of the preferred cephalosporins as “alternatives” was not explained.
No guideline recommends trimethoprim/sulfamethoxazole (TMP/SMX) or azithromycin as a preferred second-line choice unless a severe reaction like anaphylaxis due to penicillin allergy is a confounding factor. Other antibiotics are recommended alone or in combination in some but not all guidelines (TABLE 1).
TABLE 1
Consistency of guidelines for acute otitis media
| All recommend as first-line | Amoxicillin, mostly at 80–90 mg/kg/d |
| All recommend as second-line | Amoxicillin/clavulanate, mostly “ES” 80–90 mg/kg/d |
| Some recommend as second-line | Cefdinir 14 mg/kg/d |
| Cefprozil 30 mg/kg/d | |
| Cefuroxime axetil 30 mg/kg/d | |
| Cefpodoxime 10 mg/kg/d | |
| Ceftriaxone 50 mg/kg/d | |
| Not recommended by any guideline Unless pathogen known to be sensitive; patient had severe allergic reaction to penicillin or amoxicillin; or combined with another antibiotic that is effective against additional organisms | Azithromycin |
| Clarithromycin | |
| Trimethoprim/sulfamethoxazole | |
| Erythromycin/sulfisoxazole | |
| Cefaclor | |
| Loracarbef | |
| Cefixime | |
| Ceftibuten | |
| Clindamycin |
Particulars of the CDC recommendations
In choosing preferred agents, the CDC gave primary consideration to pharmacokinetic/pharmacodynamic data and to clinical efficacy trials that used tympanocentesis results (especially double tympanocentesis) as evidence of diagnosis and bacteriologic outcome. Of the 16 FDA-approved drugs for the treatment of AOM, many lacked data on efficacy against multidrugresistant S pneumoniae or β-lactamaseproducing H influenzae.
