Issue: August 2006
August 01, 2006
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Acute otitis media treatment guidelines: Are prescribers using them?

Physicians should consider antibiotic susceptibility patterns concerning AOM pathogens.

Issue: August 2006
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It’s been seven years and two years since publication of two key acute otitis media treatment recommendations, the drug-resistant Streptococcus pneumoniae Therapeutic Working Group, and the American Academy of Pediatrics guideline Diagnosis and Management of Acute Otitis Media, respectively.

These guidelines offer diagnostic and treatment recommendations for antibiotic use, choice and dosing in children who have been diagnosed as having acute otitis media (AOM).

Edward A. Bell, PharmD, BCPS
Edward A. Bell

With 16 antibiotics to choose from for the treatment of AOM, these documents offer valuable information about these antibiotics and recommendations for those agents more likely to be effective in treating AOM. Have prescribing clinicians embraced these recommendations and have they altered their prescribing patterns?

In May of this year, Vernacchio and colleagues published results of a survey on physician knowledge and implementation of the AAP and American Academy of Family Physicians Guideline Diagnosis and Management of Acute Otitis Media, which was published in May 2004. Vernacchio mailed surveys from October to December 2004 to physician members of the Slone Center Office-based Research Network, a national, practice-based, pediatric research network.

Two hundred seventy-six completed surveys were returned. Of the responding physicians, 79% and 19% practiced pediatric medicine and family medicine, respectively. Ninety percent of the responders were familiar with the guideline.

Of the diagnostic modalities recommended by the guideline, pneumatic otoscopy, tympanometry, or acoustic reflectometery, 60.8%, 92.6%, and 93.4% of physicians, respectively, reported using these diagnostic modalities never or in less than 50% of patients.

Twenty-six percent of physicians reported never using pneumatic otoscopy, and 12% reported never using any of these three diagnostic methods to diagnose AOM.

Antibiotic treatment

The survey also included six clinical scenarios about antibiotic treatment choices for AOM, for which the guideline offers recommendations: AOM with no fever and mild otalgia; AOM with fever of 39.8 C and moderate otalgia; AOM in a child with non-type I hypersensitivity reaction to amoxicillin; AOM in a child with type I hypersensitivity reaction to amoxicillin; AOM failed treatment with amoxicillin 80 mg/kg to 90 mg/kg per day; and AOM failed treatment with amoxicillin-clavulanate 80 mg/kg to 90 mg/kg per day.

Physicians were asked which antibiotic they would have chosen one year prior and currently (ie, several months after publication of the guideline). For this period, agreement with guideline antibiotic recommendations increased for all of the above scenarios, with the exception of case 4, AOM in a child with type I hypersensitivity reaction to amoxicillin. Most of the surveyed physicians believed the option of observation without immediate antibiotic therapy to be reasonable, and 45% of physicians preferred using a “safety net” antibiotic prescription as a follow-up strategy for the observation option. However, physicians used observation without immediate antibiotics only in a median of 10% of diagnosed cases.

Variations in choices

Vernacchio found the most variation between the surveyed physicians’ responses and the guideline recommendations for antibiotic treatment choices.

Several points relating to physician antibiotic treatment choice compared with guideline recommendations can be made from this survey.

Surveyed physicians more frequently chose antibiotics that are not as likely to provide antibacterial activity toward the likely bacterial pathogens of AOM.

One such choice, azithromycin (Zithromax, Pfizer), was chosen more frequently than guideline recommendations in several clinical scenarios. Azithromycin was commonly chosen by physicians in case 3, child with non-type I hypersensitivity reaction to amoxicillin.

Some physicians also chose azithromycin in cases 5 and 6, where the guideline recommendations include high-dose amoxicillin-clavulanate or ceftriaxone. In cases where the causative pathogens may be more likely to include -lactamase producing bacteria, physicians not uncommonly chose antibiotics that are not as stable to -lactamase enzymes as other antibiotics (amoxicillin-clavulanate or ceftriaxone).

Although several factors can be considered when choosing an antibiotic for a specific patient, an important characteristic that may not be given enough thought, as indicated by this survey, includes antibacterial activity toward the major AOM bacterial pathogens.

Recent bacterial surveillance studies evaluating antibiotic activity toward Streptococcus pneumoniae, Haemophilus influenzae non-typeable and Moraxella catarrhalis demonstrate that antibiotics with the overall best activity toward these pathogens include amoxicillin (not -lactamase producing pathogens), amoxicillin-clavulanate, and ceftriaxone.

Amoxicillin and ceftriaxone provide excellent activity toward most S. pneumoniae isolates, and high-dose amoxicillin provides activity toward most penicillin-nonsusceptible (intermediate nonsusceptibility) S. pneumoniae and some penicillin-resistant S. pneumoniae isolates.

Activity toward S. pneumoniae by azithromycin and oral cephalosporins, recommended in the guideline, is less than amoxicillin and ceftriaxone. Amoxicillin-clavulanate and ceftriaxone provide excellent activity toward H. influenzae and M. catarrhalis, including -lactamase producing strains, although the oral cephalosporins recommended by the guideline also provide good activity toward these two pathogens. In contrast, azithromycin’s activity toward H. influenzae is poor. Some other oral cephalosporins (eg, cefprozil) identified as being used by some surveyed physicians do not provide good activity toward H. influenzae. This information may become even more applicable in recent years since approval in 2000 of the conjugated heptavalent pneumococcal vaccine (PCV7, Prevnar).

Two recently published studies evaluated the microbiology of AOM since routine administration of PCV7. Casey used tympanocentesis to assess the causative pathogens in 551 children with persistent AOM or treatment failure over three time periods: 1995-1997, 1998-2000, and 2001-2003.

Microbiology of AOM

Results of this study indicated a significant decrease in S. pneumoniae and a significant increase in H. influenzae as causative pathogens. Also identified was a significant increase in the proportion of H. influenzae producing -lactamase enzymes.

In the 2001-2003 period, H. influenzae was the predominant pathogen (57%) compared with S. pneumoniae (31%).

Block found similar results in a study of children with severe or refractory AOM, comparing the periods 1992-1998 and 2000-2003 - before and after use of PCV7.

In this study, the proportion of S. pneumoniae decreased from 48% to 31% and H. influenzae increased from 41% to 56%.

In the double-tap study of high-dose amoxicillin in children with AOM by Piglansky, the predominant pathogens isolated from children failing high-dose amoxicillin were -lactamase producing organisms. In Dagan’s double-tap study of high-dose amoxicillin-clavulanate, pathogens were eradicated from 96% of evaluable children. These studies indicate that the use of antibiotics with good activity toward -lactamase producing pathogens may be increasingly relevant.

Data from the studies described above suggest that physicians should consider greater use of amoxicillin-clavulanate and ceftriaxone, as these antibiotics provide excellent activity toward the major otic pathogens, including -lactamase producing strains.

Additionally, increased AOM cure rates are likely to be obtained with less use of azithromycin, as this antibiotic, although perhaps convenient, does not provide as good antibacterial activity toward S. pneumoniae as amoxicillin. Its activity toward -lactamase producing strains of H. influenzae and M. catarrhalis is low.

In his excellent review of using cephalosporins in penicillin- or amoxicillin-allergic children (Type I reaction), Pichichero states that cefdinir, cefuroxime and cefpodoxime can be safely prescribed, as these antibiotics possess differing chemical side chains than penicillin or amoxicillin.

The AAP and the American Academy of Family Physicians both recommended if patients are allergic to amoxicillin, cefdinir, cefpodoxime, or cefuroxime can be used.

The risk of a serious allergic reaction occurring in such children is no greater than innonallergic children.

Although the survey discussed above represents only a fraction of practicing physicians prescribing antibiotics for children with AOM, and thus may not be applicable to other prescribers, it does offer potential useful insight into some physicians’ treatment strategies.

Conclusion

Perhaps the most important implication is diagnosis of AOM.

Many published AOM trials and meta-analyses have been criticized for poor methodology of diagnostic criteria of AOM for study patient inclusion, saying they fall short.

The AAP guideline Diagnosis and Management of Acute Otitis Media recommends pneumatic otoscopy, tympanometry or acoustic reflectometry to aid in the diagnosis of AOM (vs. visualization alone), while still allowing for some uncertainty in providing an accurate diagnosis.

It is unfortunate that over 60% of surveyed physicians used pneumatic otoscopy either never or in fewer than 50% of children, or that 12% reported never using any of these diagnostic measures in the survey described above.

The diagnosis of AOM in a child who likely has otitis media with effusion contributes to the unnecessary use of antibiotics.

Antibiotic choice differed among these surveyed physicians and antibiotics recommended by the AAP guideline. Reasoning behind surveyed physicians’ antibiotic choices was not given in this study, although caregiver pressure for antibiotic preference may have been a factor.

Although antibiotic administration issues are important (eg, easy dosing regimens), it is vitally important for physicians to consider current antibiotic susceptibility patterns toward AOM pathogens, especially in light of changing microbiologic patterns of AOM.

A recent extensive review (Pichichero) of the use of penicillin or amoxicillin and cephalosporin antibiotics in children with a history of antibiotic allergy is helpful to clarify when cephalosporins can be used in such children.

Labeling a child as “penicillin-allergic” or “amoxicillin-allergic” significantly limits antibiotic choice for AOM, relegating the use of less effective agents, when it is likely that certain cephalosporins or even amoxicillin can continue to be safely used.

With the AAP guideline now in print for more than two years, additional surveys examining physicians’ prescribing habits, including reasoning for antibiotic choice, would be welcomed.

For more information:
  • Vernacchio L. Knowledge and practices relating to the 2004 acute otitis media clinical practice guideline: A survey of practicing physicians. Pediatr Infect Dis J. 2006;25:385-389.
  • American Academy of Pediatrics. Diagnosis and management of acute otitis media. Pediatrics. 2004;113:1451-1465.
  • Jacobs MR. The Alexander Project 1998-2000: Susceptibility of pathogens isolated from community-acquired respiratory tract infection to commonly used antimicrobial agents. J Antimocrob Chemother. 2003;52:229-246.
  • Casey JR. Changes in frequency and pathogens causing acute otitis media in 1995-2003. Pediatr Infect Dis J. 2004;23:824-828.
  • Block SL. Community-wide vaccination with the heptavalent pneumococcal conjugate significantly alters the microbiology of acute otitis media. Pediatr Infect Dis J. 2004;23:829-833.
  • Piglansky L. Bacteriologic and clinical efficacy of high dose amoxicillin for therapy of acute otitis media in children. Pediatr Infect Dis J. 2003;22:405-412.
  • Dagan R. Bacteriologic and clinical efficacy of high dose amoxicillin/clavulanate in children with acute otitis media. Pediatr Infect Dis J. 2001;20:829-837.
  • Wald ER. Acute otitis media: more trouble with the evidence. Pediatr Infect Dis J. 2003;22:103-104.
  • Pichichero ME. A review of evidence supporting the American Academy of Pediatrics recommendation for prescribing cephalosporin antibiotics for penicillin-allergic patients. Pediatrics. 2005;115:1048-1057.