February 01, 2013
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Antimicrobial treatment of AOM, acute bacterial sinusitis in 2013

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Two of the most common clinical conditions in early childhood that lead to the prescription of antimicrobials are acute otitis media and acute bacterial sinusitis. The two are similar regarding anatomy, physiology and pathogenesis. David Parsons, MD, noted more than 15 years ago that the middle ear is a paranasal sinus, as the Eustachian tube acts in a similar fashion to the ostia of the paranasal sinuses. In both cases, the common preceding event is a viral upper respiratory infection.

The mucosal swelling of the Eustachian tube and the sinus ostia lead to impaired drainage of secretions produced by the lining of the middle ear and the paranasal sinuses, respectively. Negative pressure develops in the middle ear and sinuses, leading to aspiration of mucus and bacteria from the nasopharynx into these cavities. Functional or mechanical obstruction of the sinus ostia and Eustachian tube fosters bacterial multiplication and the development of in situ infection.

The pathogens that cause AOM and bacterial sinusitis are well known to primary care practitioners and include Streptococcus pneumoniae, nontypeable Haemophilus influenzae and Moraxella catarrhalis. Knowledge of the bacteriology of AOM derives from studies in which tympanocentesis was performed on children with acute infection. In contrast, data on the bacteriology of acute bacterial sinusitis are sparse and date back to the mid-’80s. Discussions of the microbiology and recommendations for antibiotic management of acute bacterial sinusitis have, therefore, leaned heavily on recommendations and data developed for AOM.

Ellen R. Wald

Ellen R. Wald

Pathogens to blame

Although the specific microbiologic agents causing AOM have remained stable during the past 50 years, there have been changes both in the relative prevalence of organisms causing AOM and also in the antibiotic susceptibility patterns of the otopathogens. Historically, the relative proportion of bacterial agents in AOM was S. pneumoniae at 40%; H. influenzae at 25%; and M. catarrhalis at 12%. The original distribution of bacterial pathogens in acute bacterial sinusitis was S. pneumoniae at 30%, and H. influenzae and M. catarrhalis at 20% each. S. pyogenes was a minor cause of both entities, accounting for 2% to 4% of cases.

Initially, amoxicillin was the preferred therapy for AOM. The first challenge to the effectiveness of amoxicillin arose in the mid-’70s when beta-lactamase production among H. influenzae emerged. The second challenge was the emergence of resistant S. pneumoniae in the 1990s. The mechanism of resistance, ie, alteration of penicillin binding proteins, may be overcome largely by raising the dose of amoxicillin to increase concentrations of antibiotic in the middle ear or sinus fluid.

The first pneumococcal conjugate vaccine, PCV7 (Prevnar, Pfizer), was licensed in 2000. The main purpose of the vaccine was to prevent the common invasive diseases secondary to S. pneumoniae. Many reports have demonstrated the effectiveness of this vaccine regarding the prevention of occult pneumococcal bacteremia and pneumococcal meningitis, primarily in the age group younger than 5 years. An unexpected positive outcome associated with PCV7 was a dramatic decrease in cases of invasive pneumococcal disease, not only in the recipients of the vaccine, but also in infants aged younger than 3 months (siblings and contacts of the vaccinees) and in individuals aged older than 50 years (grandparents of the vaccinees). This outcome reflects the effectiveness of the pneumococcal vaccine in decreasing nasopharyngeal colonization with vaccine strains of S. pneumoniae. Recognizing that colonization is a necessary prelude to disease, it is easy to understand how this reduction in nasopharyngeal colonization with S. pneumoniae in recipients of vaccine led to similar alterations in their direct contacts, as horizontal transmission of colonization was prevented.

Other bacteria take over

Soon after the licensure of the PCV7, there were some changes in the relative prevalence of the microbes that cause AOM, ie, a decrease in the prevalence of S. pneumoniae (including penicillin-non-susceptible S. pneumoniae) and a relative increase in the prevalence of H. influenzae. Data from national surveillance programs reporting on the susceptibility of respiratory isolates showed a trend of increasing beta-lactamase production among H. influenzae. Likewise, studies by Casey and colleagues and Block and colleagues demonstrated an increase in the proportion of AOM due to nontypeable H. influenzae and an absolute increase in the proportion of isolates that were beta-lactamase positive. This trend was altered briefly between 2005 and 2010, with the emergence of penicillin-resistant infections caused by S. pneumoniae of serotype 19A. However, the inclusion of serotype 19A in PCV13 (Prevnar13, Pfizer), the next generation of pneumococcal vaccines that was licensed in 2010, has reversed the escalation of this serotype as a cause of both invasive and local diseases.

Where are we in 2013 regarding the relative prevalence of S. pneumoniae and H. influenzae in children with AOM and acute bacterial sinusitis? What is the prevalence of beta-lactamase producing H. influenzae and penicillin-non-susceptible S. pneumoniae among middle ear and sinus isolates? The answers to these questions are necessary to guide our selection of antimicrobial agents for the common bacterial infections of childhood. Our experience after licensure of PCV7 suggests that S. pneumoniae will continue to decline as a cause of AOM, unless there is re-emergence of a virulent non-vaccine strain of S. pneumoniae that becomes dominant. This very dynamic situation underscores the importance of the continuous availability of microbiologic data that reflects local and national trends and is a call for the CDC to support the creation of a network of pediatric centers throughout the United States to collect and test respiratory isolates obtained from nasopharyngeal samples.

References:
AAP Subcommittee on Management of Acute Otitis Media. Pediatrics. 2004;113:1451-1465.

For more information:
Ellen R. Wald, MD, is the Professor and Chair of the Department of Pediatrics at the University of Wisconsin School of Medicine and Public Health in Madison, Wis. Wald is also a member of the Infectious Diseases in Children Editorial Board.

Disclosure: Wald reports no relevant financial disclosures.