Impact of resistant pathogens on the treatment of otitis

Ear, Nose & Throat Journal, Nov, 2007 by Harvey Coates

Antibiotic treatment of such infections as acute otitis media (AOM) and acute pharyngitis has been implicated as a major cause of the spread of bacterial resistance. (1) In many First World countries, AOM is the primary reason that children are prescribed antibiotics. Indeed, the clinical outcomes of patients with AOM have dramatically changed since the emergence of bacterial resistance to commonly used antibiotics, such as amoxicillin. The treatment of other forms of otitis--otitis externa, AOM through tympanostomy tubes (AOMT), and chronic suppurative otitis media (CSOM)--has been hindered by an increase in resistant bacteria, albeit to a lesser extent than AOM.

Penicillin-resistant pneumococci and beta-lactamase--producing strains of Haemophilus influenzae and Moraxella catarrhalis are especially important in this context. (2) According to the Centers for Disease Control and Prevention (CDC), the rate of Streptococcus pneumoniae resistance to penicillin has increased by more than 300% over the past 5 years, and the rate of resistance to cefotaxime has increased by more than 1,000%. (3) In fact, some strains of pneumococci are resistant to all oral antibiotics except vancomycin.

Despite the continuing increase in bacterial resistance, the development of new antibiotics over the past decade has been relatively slow. This article explores the impact that bacterial resistance has on the current treatment of the different forms of otitis and the strategies we can follow to reduce the spread of multidrug resistance.

Risk factors for multidrug resistance

In a report of their multivariate analysis published in 2002, Ford-Jones et al identified several risk factors that predispose patients to developing resistance to pathogens: younger age, a lesser degree of maternal education, day care attendance, no history of adenoidectomy, a history of winter infections, and amoxicillin treatment during the previous 6 months. (4) The next year, Darrow et al identified several other factors that influence the etiology, prevention, and treatment of AOM, recurrent AOM, and otitis media with effusion: the presence of bacterial biofilms, a personal history of reflux, a family history of middle ear disease, and possibly a previous pneumococcal vaccination. (5) To these risk factors, Klein added recent hospitalization and a high volume of antimicrobial use in the community. (2)

Countries that restrict antibiotic use have relatively low rates of resistant pneumococci (~5%), even those countries that have very high rates of tympanostomy tube insertion (e.g., The Netherlands). (2) Conversely, countries with liberal over-the-counter antibiotic policies (e.g., Taiwan, Korea, and Southeast Asian nations) have high resistance rates ([greater than or equal to]80%). (2)

AOM and recurrent AOM

In a 10-year epidemiologic study of 2,149 children in France that concluded in 1997, Gehanno et al reported that pathogens were isolated from 70% of patients. (6) H influenzae was found in 40% of children, S pneumoniae in 31%, and M catarrhalis in 8%. The incidence of beta-lactamase--secreting H influenzae increased from 20 to 70% over the period of the study, and the incidence of penicillin-resistant S pneumoniae increased from 7 to 70%.

The finding that H influenzae is more common than S pneumoniae in AOM has been reported in other recent studies, as well. (7,8) S pneumoniae is still believed to be the most virulent pathogen in AOM and recurrent AOM. However, recent descriptions of another possible pathogen, Alloiococcus otitidis, in significant numbers of children with AOM and otitis media with effusion in Finland, Japan, and Australia have generated debate as to the significance of this new bacterium. (9-11) If this bacterium is found to be a pathogen in otitis media, then its resistance profile to amoxicillin/clavulanate, the sulfa drugs, and erythromycin may have an impact on therapy.

Changes in antimicrobial resistance patterns have resulted in changes in the first-line management of AOM in different age groups (especially in children younger than 2 years) and in those countries where the incidence of resistant bacteria is high:

* In the United States, resistance to trimethoprim/sulfamethoxazole and macrolide antibiotics is increasing. The American Academy of Pediatrics in its 2004 guidelines noted that despite the changing prevalence of bacterial pathogens and an increase in S pneumoniae resistance, amoxicillin remains the first-line antibiotic for the treatment of an initial episode of AOM. (12)

* In 2005, Brook and Gober noted that children who experienced a recurrence of AOM following amoxicillin treatment had a higher rate of recovery of antibiotic-resistant S pneumoniae and H influenzae from the nasopharynx than did children with an initial episode of AOM. (13) Children who harbor these antibiotic-resistant bacteria easily transmit them to their family members at home and to other children at day care centers; transmission is facilitated by droplet spread (i.e., sneezing) from patients with viral upper respiratory infections. The CDC recommends three antibiotics for treatment of recurrent or persistent AOM: amoxicillin/clavulanate, cefuroxime, and ceftriaxone. (14)