Acute otitis media: Making sense of recent guidelines on antimicrobial treatment

Implementing guideline recommendations in clinical practice

Amoxicillin usually first choice. Of the available oral agents, amoxicillin has the greatest in vitro activity against pneumococci.^2,20 In addition to an excellent pharmacokinetic profile, amoxicillin has a long history of safety and clinical efficacy when used to treat AOM. Because resistant S pneumoniae are highly prevalent in the US, a higher dose of amoxicillin (80–90 mg/kg/d in divided doses) has become the first-line therapy.^2-4

Covering for β-lactamase-producing pathogens. However, increasing the amoxicillin dose does not cover the patient at risk for infection with β-lactamase-producing pathogens. In this case, add the β-lactamase inhibitor, clavulanate, to amoxicillin (Augmentin ES), or choose a cephalosporin with good activity against S pneumoniae and good β-lactamase stability.

What to do when initial treatment fails. Treatment failure can occur for a variety of reasons besides poor drug efficacy: incorrect diagnosis, poor compliance, inadequate drug dose or frequency, atypical pharmacokinetics or pharmacodynamics, concurrent viral infection, or highly resistant bacteria.¹² In most cases in which amoxicillin therapy fails, there is no single perfect alternative. That is why several antimicrobials are recommended as second-line agents by the various guidelines. Without firm identification of a causative agent by tympanocentesis, select an agent effective against β-lactamaseproducing pathogens and multi-drug-resistant S pneumoniae.^2,2,12

Abandoned treatments. Trimethoprim/sulfamethoxazole and erythromycinsulfisoxazole are no longer recommended as first- or second-line treatments for AOM, except as alternatives for patients with severe penicillin-allergy. Recent studies have shown substantial pneumococcal resistance to these agents.^2,10,21

Azithromycin widely used but not recommended. Azithromycin is commonly used for AOM in children, largely because of its compliance-enhancing feature as a once-per-day treatment given for 1, 3, or 5 days. However, no guideline endorses azithromycin for AOM unless the patient is allergic to penicillin. The reason no expert group recommends azithromycin is a consequence of pivotal double tympanocentesis studies conducted by Dagan et al²² and Hoberman et al.²³ In the work by Dagan, eradication of S pneumoniae by azithromycin was slower than with amoxicillin/clavulanate,²² and slower eradication impacts clinical outcomes.²⁴ But more important, Dagan et al showed that azithromycin was no more effective than placebo in eradicating H influenzae.²²

Consider compliance-enhancing factors. Key factors are taste of suspension, dosing frequency, and duration of therapy. A drawback with several of the antibiotics recommended by guidelines is their taste (TABLE 5). Intramuscular ceftriaxone is an alternative for resistant bacterial strains and for those patients who experience nausea or simply refuse oral medications. However, in cases of resistant S pneumoniae, ceftriaxone typically must be administered in 3 separate injections, which is not only unappealing for young children, but difficult for parents to comply with because of additional office visits and costs.^3,12

The factor most likely to enhance compliance is a shorter course of therapy. Evidence is strong and growing stronger that a 5-day course of therapy is as effective as a 10-day course. In a 1997 review of the data²⁶ and a meta-analysis,²⁷ it was suggested that data were sufficient to recommend a 5-day antibiotic course for AOM in children unless the child was less than 2 years of age or otitisprone. Subsequently, conflicting data have been published (TABLE 6, available online at www.jfponline.com).

Guidelines vary in their endorsement of 5-day vs 10-day or variable regimens for treatment of AOM; most favor the 10-day course for younger children (defined as <2 years old to <6 years old), pending further studies. Nevertheless, shorter courses of therapy are preferable whenever possible because the evidence suggests shorter courses improve compliance, decrease the selection of resistant pathogens, and preclude surreptitious use of leftover antibiotics retained from longer courses.²⁸

TABLE 5
Comparative taste ratings for antibiotic suspensions

What’s on the horizon

Research continues on the effect of the heptavalent pneumococcal conjugate vaccine (PCV7) on reducing the prevalence of AOM. In the first studies, the vaccine’s efficacy in preventing otitis media of any origin was 6% to 7%.^29,30 However, the PCV7 may be more beneficial for children with AOM than initially calculated; among those 24 to 59 months of age who have a history of recurrent AOM, the vaccine’s effect is greater.⁸ Other pneumococcal conjugate vaccines containing more serotypes are being developed and tested. Their impact on AOM remains to be determined.