Pediatric Annals

Antibiotic Use for Otitis Media: Oral, Topical, or None?

Richard M Rosenfeld, MD, MPH

Abstract

Otitis media is a common hazard of early childhood that accounts for 50% of antibiotic prescribing in preschoolers.1 Every year, children in the United States experience more than 5 million episodes of acute otitis media (AOM) and 2 million episodes of otitis media with effusion (OME).2'3 Many of these episodes receive one or more courses of systemic antibiotic therapy, which adds significantly to the worldwide trend of in-creasing resistance among common respiratory tract path-ogens.4 Consequently, strategies to promote appropriate antibiotic use for otitis media are an international priority.5

1. Halasa NB, Griffin MR, Zhu Y, Edwards KM. Decreased number of antibiotic prescriptions in office-based settings from 1993 to 1999 in children less than five years of age. Pediatr Infect Dis J. 2002: 21(1 1):1023-1028.

2. American Academy of Pediatrics Subcommittee on Mangement of Acute Otitis Media. Diagnosis and management of acute otitis media. Pediatrics. 2004:1 13(5): I45I- 1465.

3. Rosenfeld RM, Culpepper L. Doyle KJ, et al. Clinical practice guideline: otitis media with effusion. Otolaryngol Head Neck Surg. 2004; 130(5 suppl):S95-S 118.

4. Jacobs MR. Worldwide trends in antimicrobial resistance among common respiratory tract pathogens in children. Pediatr Infect Dis J. 2003; 22(8 suppl):S108-S119.

5. Lieberman JM. Appropriate antibiotic use and why it is important: the challenges of bacterial resistance. Pediatr Infect Dis J. 2003; 22(12):1 143-1151.

6. Levy SB. The Antibiotic Paradox: How the Misuse of Antibiotics Destroys Their Curative Powers. 2nd ed. Cambridge, England: Perseus Publishing; 2002.

7. Ghaffar F, Muniz LS, Katz K. Effects of amoxicillin/clavulanate or azithromycin on nasopharyngeal carriage of Streptococcus pneumoniae and Haemophilus influenzae in children with acute otitis media. Clin Infect Dis.2O0O;31(4):875-880

8. Gonzales R, Malone DC, Maselli JH, Sande MA. Excessive antibiotic use for respiratory infections in the United States. Clin Infect Dis. 2001;33(6):757-762.

9. Ghaffar E Muniz LS, Katz K, et al. Effects of large dosages of amoxicillin/clavulanate or azithromycin on nasopharyngeal carriage of Streptococcus pneumoniae, Haemophilus influenzae, nonpneumococcal alpha-hemolytic streptococci, and Staphylococcus aureus in children with acute otitis media. Clin Infect Dis. 2002; 34(10):1301-1309.

10. Erickson PR, Herzberg MC. Emergence of antibiotic resistant Streptococcus sanguis in dental plaque of children after frequent antibiotic therapy. Pediatr Dent. 1999; 21(3):18l-185.

11. Shnayerson M, Plotkin MJ. The Killers Within: The Deadly Rise of Drug-Resistant Bacteria. Boston, MA: Little, Brown and Company; 2002.

12. Dagan R, Leibovitz E, Cheletz G. Leiberman A. Porat N. Antibiotic treatment in acute otitis media promotes superinfection with resistant Streptococcus pneumoniae carried before initiation of treatment. J Infect Dis. 2001; 183(6):880-886.

13. Little P, Gould C, Williamson I, et al. Reattendance and complications in randomized trials of prescribing strategies for sore throat: the medicalising effect of prescribing antibiotics. BMJ. 1997; 315(7104):350-352.

14. Rosenfeld RM, Kay DJ. Natural history of untreated otitis media. Laryngoscope. 2003; 113(10):1645-1657.

15. Rosenfeld RM. Clinical efficacy of medical therapy. In: Rosenfeld RM, Bluestone CD, eds. Evidence- Based Otitis Media. 2nd ed. Hamilton, Ontario, Canada: BC Decker; 2003:199-226.

16. Brallier JM. Medical Wit and Wisdom: from Hippocrates to Groucho Marx. Philadelphia. PA: Running Press; 1993:63-65.

17. Marcy M, Takata G, Shekelle P, et al. Management of Acute Otitis Media. Evidence Report/Technology Assessment No. 15 (Prepared by die Soutiiern California Evidencebased Practice Center under Contract No. 290-97-0001). AHRQ. Rockville, MD: Agency for Healthcare Research and Quality; May 2001. Publication No. 01-E010.

18. Rosenfeld RM. Observation option toolkit for acute otitis media. Int J Pediatr Otorhinolaryngol. 2001; 58(1): i-8.

19. Burke P, Bain J, Robinson D, Dunleavey J. Acute red ear in children: controlled trial of nonantibiotic treatment in general practice. BMJ. 1991;303(6802):558-562.

20. Damoiseaux RAMJ, van Balen FAM, Hoes AW, Verheij TJM, de Melker RA. Primary care…

Otitis media is a common hazard of early childhood that accounts for 50% of antibiotic prescribing in preschoolers.1 Every year, children in the United States experience more than 5 million episodes of acute otitis media (AOM) and 2 million episodes of otitis media with effusion (OME).2'3 Many of these episodes receive one or more courses of systemic antibiotic therapy, which adds significantly to the worldwide trend of in-creasing resistance among common respiratory tract path-ogens.4 Consequently, strategies to promote appropriate antibiotic use for otitis media are an international priority.5

Antibiotics affect society, not just the individual.6 Each course of systemic therapy creates selective pressure for resistant bacteria in the child's nasopharynx that spread readily among families, schools, and child care centers.7-10 These organisms, and those created from resistance genes on transferrable plasmids, may cause fatal infections in both healthy and immunocompromised individuals." Antibiotics not only may fail to eradicate the organisms but also can induce middle-ear effusion superinfection with resistant pneumococci from the nasopharynx.12 Additional adverse effects of antibiotic prescribing include rashes, allergic reactions, gastrointestinal upset, increased physician revisit rates, and a greater likelihood of seeking medical care for future illness.13

More than 1 00 antibiotics have been introduced during the past 60 years, increasing the annual production of broad-spectrum antibiotics from 500,000 to 50 million pounds in the US.6 Unfortunately, bacteria have a staggering evolutionary advantage over antibiotics and the humans that produce them; as the oldest known inhabitants of the planet, bacteria have been around for 3.5 of the earth's 4.5 billion year history, compared with 200,000 years for humans and 60 years for antibiotics." Moreover, bacteria are ubiquitous, saturating every square millimeter of soil and comprising 5% of our body weights (about 100 trillion bacteria per person).611 Antibiotics have stimulated unparalleled evolutionary changes in bacteria, which until recently were not evolving faster than other living beings.

Table

TABLE 1.Natural History of Otitis Media14

TABLE 1.

Natural History of Otitis Media14

Appropriate antibiotic use for otitis media begins by understanding the favorable natural history of most untreated episodes,14 the modest incremental benefit of antibiotic therapy on selected outcomes,15 and the anticipated harm-benefit ratio of therapy for a given child. Based on these considerations, current clinical practice guidelines2,3 support a more restrictive approach to antibiotic prescribing by offering the observation option to selected children with AOM and by recommending against routine therapy for OME. This article explores the evidence supporting these recommendations, plus the role of antibiotic-containing eardrops in facilitating appropriate use of systemic antibiotics in children with tympanostomy tubes.

NATURAL HISTORY OF OTITIS MEDIA

Hippocrates noted first that "Natural forces are the healers of disease," and Galen later cautioned physicians to serve as "Nature's assistant."16 Information about the natural history of untreated otitis media is plentiful but is not organized for ready access by clinicians. The best source of information regarding natural history and spontaneous resolution is systematic review of data from prospective cohort studies and untreated control groups in randomized trials.14 Only when rates of spontaneous resolution are known can the incremental benefits of therapies be judged, and prognoses formulated to guide selection of treatment alternatives.

AOM and recurrent AOM have a favorable natural history (Table 1, see page 834). Within 24 hours, 61% of placebo-treated children with AOM have symptomatic relief, increasing to 80% after 2 to 3 days. Suppurative complications are rarely observed,and are comparable whether initial antibiotics are withheld (0.12%) or provided (0.24%). 14,17 Although children with recurrent AOM enter randomized trials of antibiotic prophylaxis with a mean baseline rate of 5.5 or more annual episodes, they average only 2.8 annual episodes (0.23 per month) while on placebo between infections. Further, 41% have no additional AOM while on placebo for a median duration of 6 months, and 83% have 2 or fewer episodes.

Table

TABLE 2.What to Expect from Antibiotic Therapy for Otitis Media15

TABLE 2.

What to Expect from Antibiotic Therapy for Otitis Media15

The spontaneous resolution of OME also is favorable. Children with OME after an episode of untreated AOM have 59% resolution by 1 month and 74% resolution by 3 months. Children with newly diagnosed OME of unknown duration still do well, with resolution rates (B tympanogram to AJCi) increasing from 28% by 3 months to 42% by 6 months (see Table 1 footnote for definition of tympanogram types). Success rates nearly double with a criterion of tympanometric improvement (B to A/C1/C2), reaching 56% by 3 months and 72% by 6 months, but relapse is common. The poorest outcomes, however, are observed for chronic OME lasting 3 months or longer, with only 25% spontaneous resolution after 6 months and 31% by 12 months.

Spontaneous resolution of AOM most likely results from the child's immune response and clearance of secretions through a patulous Eustachian tube. Complete clearance of middleear effusion, however, often lags symptom relief because of persistent inflammation and mucosal edema. Improvement in recurrent AOM is more gradual, most likely related to immune maturation, Eustachian tube growth, and regression to a mean symptom state (eg, children enter clinical trials when symptoms are most prominent, and the next likely event, irrespective of management, is improvement to a mean level). Resolution of OME is most likely a combination of drainage and absorption, as the Eustachian tube matures and the local immune response gradually declines.

Table

TABLE 3Scope of the Observation Option for AOM

TABLE 3

Scope of the Observation Option for AOM

The favorable natural history of otitis media suggests most children will improve eventually, irrespective of management. Rather than endorse nihilism, these data suggest a careful need to balance nature's accomplishments against potential therapeutic benefits. For example, although antimicrobials have proven efficacy for AOM, initial observation of selected children also can achieve excellent outcomes (as described in the next section).2·1718 Similarly, delaying interventions for recurrent AOM by 6 months often will provide relief. OME in otherwise healthy children should be documented for at least 3 months before surgery,3 but extending this to 6 months achieves a relative increase of 30% to 50% in spontaneous resolution. This also applies to children with baseline chronic OME, but longer periods of observation are often disappointing. Any decision for prolonged observation must be balanced against the potential adverse effect of persistent OME on a child's hearing, speech, overall development, and school performance.

Table

TABLE 4.Observation option for AOM

TABLE 4.

Observation option for AOM

Several precautions deserve emphasis before generalizing natural history results. Children who receive placebo or no therapy in randomized trials are not a random subset of children at risk for AOM; they tend to be older, have less severe symptoms, and have parents who consent to withholding antibiotic therapy.19 Consequently, the rates cannot be generalized to all children age 2 or younger, particularly those with severe symptoms or high fever. None of the studies reporting outcomes at 24 hours include young children, and the only recent trial limited to this age group reported only 28% symptomatic relief with placebo at 4 to 7 days.20 The risk of suppurative complications when antibiotics are initially withheld from very young or ill children is unknown, but the only reported complication with placebo for randomized controlled trials in our analyses was in a young child.20

Results for the prognosis of recurrent AOM can be generalized to a broad range of children, because few restrictions were placed on AOM severity or child age. Unlike studies of AOM therapy, where withholding antibiotics raises ethical concerns for children who are very young or very ill, children on placebo prophylaxis still receive antibiotics for individual AOM episodes. Consequently, the spontaneous improvement noted in Table 1 has the implicit assumption that each child may still receive several discrete courses of antibiotic therapy. Many studies excluded children with baseline OME, immune deficiency, cleft palate, craniofacial anomalies, or Down syndrome. Spontaneous improvement is likely to be lower in populations with baseline OME or with underlying predisposing factors for AOM or OME.

MANAGING OTITIS MEDIA WITHOUT ANTIBIOTICS

Clinicians should consider initial observation of otitis media when the harm-benefit ratio of antibiotic therapy offers little or no advantage beyond natural history alone. Although antibiotics increase absolute resolution rates of OME by 15% over placebo (Table 2, see page 835), the benefits are short-term and transient.15 Consequently, routine antibiotic therapy for OME is not recommended, unless there are significant associated symptoms or surgery is imminent.3 Adding an oral steroid to antibiotic therapy for OME increases short-term resolution to 25%, but the unfavorable harm-benefit ratio argues against routine therapy. Similarly, antibiotic prophylaxis should rarely be used to prevent recurrent AOM, because the risk of accelerated bacterial resistance far exceeds the small benefits (Table 2) of daily low-dose antibiotics beyond the already favorable natural history (Table 1).

Table

TABLE 5.Antimicrobials Approved* to Treat Otitis Media

TABLE 5.

Antimicrobials Approved* to Treat Otitis Media

Current controversy surrounding nonantibiotic management of otitis media has centered on the observation option for AOM, which allows selected children to fight the infection on their own for 48 to 72 hours before starting antibiotics.18 This practice is based on data from randomized trials (Tables 1 and 2) that suggest most children improve from natural history alone, with antibiotics providing only a marginal benefit. Antibiotic therapy is begun, however, if symptoms persist or worsen during this initial period of observation. The observation option for AOM is an official policy in The Netherlands (for children age 6 months and older)21 and in Sweden (for children age 2 years and older).22 It is also an unofficial policy in Denmark and Norway.23 Observation recently has been endorsed by the New York State Department of Health,24 the American Academy of Pediatrics (AAP),2 and the American Academy of Family Physicians (AAFP).2

Table

TABLE 6.Recommended Antibiotics for Children With AOM2

TABLE 6.

Recommended Antibiotics for Children With AOM2

Whereas most clinicians agree that some children with AOM are suitable for initial observation, there is considerable disagreement about exactly which children should be observed. The paradigm initially proposed in New York, and later adopted by the AAP and AAFP, helps facilitate implementation (Tables 3 and 4, see page 836). Children are unsuitable for initial observation (Table 4) if they are younger than 6 months, have had AOM treatment failures or AOM relapses (within 30 days), or have immune deficiency, craniofacial anomalies, or co-existing streptococcal pharyngitis or bacterial sinusitis.

For other children, decisions are based on child age, diagnostic certainty, and illness severity. A certain diagnosis is a clinical picture suggesting AOM with a high probability of middle-ear effusion (MEE). An uncertain diagnosis is suspected AOM with anything less than a high probability of MEE as a result of obstructing cerumen, child apprehension, or other factors that impair visibility of the tympanic membrane or adequate performance of pneumatic otoscopy.

The issue of diagnostic certainty warrants further comment. An international survey of general practitioners revealed AOM diagnostic certainty of only 58% in infants, 66% in toddlers, and 73% in older children.25 Conversely, primary care practitioners in New York expressed 90% certainty (median child age 2.4), but the true prevalence of AOM was only 70% (nearly all false-positives were related to absence of MEE).26 The relative risk of receiving an antibiotic was 1.50 times higher when clinicians expressed certainty, suggesting that 26% of prescriptions potentially were unnecessary. Interobserver reliability for otitis media also is poor, with only a slight to moderate correlation between clinical diagnostic examinations of pediatric residents, pediatric otolaryngologists, and tympanometry.27 This, in part, relates to a paucity of formalized resident education in diagnosing otitis media,28 but no degree education - or experience - can eliminate all uncertainty. Therefore, uncertainty should be part of the management paradigm.

Ideal candidates for the AOM observation option are children 2 or older with nonsevere illness or an uncertain diagnosis; children age 6 months up to 2 years may also be observed when both conditions exist (Table 4). Spontaneous resolution of nonsevere illness is high, with only a small absolute increase in clinical cures for antibiotics versus placebo (96% versus 92%). 29 Conversely, initial antibiotic therapy is recommended for all children younger than 2 with a certain diagnosis of AOM, because of a poorer natural history20,30,32 and greater absolute benefit from fullcourse antibiotics (7 to 10 days) than older children.33,37

Observing AOM differs from not treating. All children should receive adequate analgesics (acetaminophen or Ibuprofen), especially for the first 24 hours after diagnosis. Analgesics, not antibiotics, are the cornerstone of initial pain relief, because the incremental benefit of antibiotics over placebo or natural history is not apparent until day 2 or later (Table 2).

Children who are initially observed should receive prompt antibiotics if symptoms worsen or fail to improve within 48 to 72 hours, which occurs in about 25% to 35% of cases.38-40 Consequently, observation is only advised when appropriate follow-up and communication can be assured. A convenient way to implement the observation option is with a "safety net" antibiotic prescription,40 given to the family at the initial encounter with instructions to wait 48 to 72 hours before obtaining the medication and to call the physician's office if the prescription is filled.

MANAGING OTITIS MEDIAWITH ORAL ANTIBIOTICS

The primary role of oral antibiotic therapy for otitis media is to reduce the risk of suppurative complications in atrisk children. Suppurative complications have an incidence of about 1 in 600 and include mastoiditis, meningitis, facial paralysis, and brain abscess. Initial therapy with oral antibiotics cannot invariably prevent complications but is advised (Table 4) for all children younger than 6 months; for children ages 6 months to 2 years with a certain AOM diagnosis or severe illness (toxic appearance, temperature of 39 degrees C, or moderate to severe otalgia); and for children 2 and older with a certain AOM diagnosis and severe illness. Conversely, the ideal child for the observation option would be 2 or older with nonsevere illness (mild otalgia and temperature below 39 degrees C orally), even if the diagnosis of AOM was certain (eg, high probability of true bacterial infection).

Antibiotics are not pain relievers or antipyretics, and the majority of symptomatic relief for AOM (especially during the first 24 hours) results from spontaneous resolution and liberal use of analgesics (Ibuprofen or acetaminophen). By 4 to 7 days (Table 2), the effect of antibiotics is significant but modest; about 1 1 children need treatment (NNT = 11) to increase by one child the number with symptomatic relief above and beyond spontaneous resolution. The effect of initial antibiotics on school or work absence also is modest. One randomized trial found no significant difference between immediate versus delayed antibiotic therapy for school absence,38 and another reported a significant decrease of about 1.5 days for children who received antibiotic versus placebo.19 In another study of children with nonsevere AOM, only 3% of parents report missed days of work when using the observation option.

When a decision is reached to treat AOM with antibiotics (as initial therapy or if the observation option fails), a drug should be used that is most likely to eradicate common pathogens.41 About 25% to 50% of AOM is caused by Streptococcus pneumoniae, 15% to 30% by nontypeable Haemophilus influenzae, and 3% to 20% by Moraxella catarrhalis, of which about 0%, 50%, and 100%, respectively, produce betalactamase.2 The prevalence of pneumococcal resistance to penicillin is about 30% (range 15% to 50%), of which 50% are highly resistant strains.2 Risk factors for developing resistance in otitis media are antibiotic use, young age, daycare attendance, and prior hospitalization.42

Although 15 systemic antimicrobials have been approved by the Food and Drug Administration (FDA) for treating otitis media (Table 5, see page 837), bactériologie efficacy for AOM varies greatly among agents.43 Current recommendations from the AAP and AAFP on drug selection for AOM are summarized in Table 6 (see page 838). High dose amoxicillin-clavulanate is the drug of choice for most children with severe illness or initial treatment failure because of high bactériologie and clinical efficacy.44 Although a single intramuscular dose of ceftriaxone has comparable efficacy to a 7- to 10-day course of oral antibiotics,36·45 its use as initial empiric therapy for uncomplicated AOM should be discouraged. Liberal use of ceftriaxone may accelerate bacterial resistance and compromise efficacy as a backup for suppurative complications (for which oral alternatives do not exist). Ceftriaxone is appropriate for severe AOM associated with penicillin allergy or clinical failure of oral antibiotics.

The optimum duration of AOM therapy is controversial. Short-course therapy (3 days of azithromycin, 5 days of other antibiotics) is an option for children 2 or older, and full-course treatment (5 days of azithromycin, 7 to 10 days of other antibiotics) is better for younger children. Kozyrskyj and colleagues36 found slightly better shortterm outcomes with full-course treatment (odds ratio 1.5), but the numbers needed to treat (1 3 to 20) indicate only a small effect. The effect is more pronounced, however, for children 2 and younger, especially when attending group day care.34"37 Better outcomes with full-course therapy also have been demonstrated for children with AOM in the preceding month.46

MANAGING OTITIS MEDIAWITH ANTIBIOTIC EARDROPS

Antibiotic-containing eardrops are an efficacious, yet underused, treatment for tympanostomy tube otorrhea (TTO). Tympanostomy tube insertion is the second most common operative procedure in childhood, exceeded in frequency only by neonatal circumcision.47 More than 500,000 children receive tubes annually in the US, comprising more than 20% of all ambulatory surgery.48 About 7% of children in the US have tubes inserted by age 3.49 These already high rates may increase further, given concerns about multidrug resistant bacteria and the appeal of tubes as a preventive strategy to limit systemic antibiotics.50

For most patients with TTO, the otorrhea is brief, painless, and nonrecurrent; only about 4% develop chronic TTO (reported range of 1% to 10%).51·52 Infants and young children with tubes inserted to control recurrent AOM are more likely than older children to experience TTO, especially during the upper respiratory infection season. Acute TTO in children 2 or younger usually is caused by the typical AOM pathogens - S. pneumoniae, M. catarrhalis, or H. influenzae.51 Conversely, Pseudomonas aeruginosa and Staphylococcus aureus are more prevalent in older children, after TTO induced by water penetration (swimming or bathing), or when ear odor is present.

The natural history of untreated acute TTO is unknown but, anecdotalIy, many episodes resolve spontaneously within several days. When children 6 or younger with acute TTO received oral placebo plus daily suctioning of the tube, about one-third resolved by day 4, but the median duration of otorrhea was 8 days.53 Because most acute TTO is painless, initial management may consist of daily cleaning of the ear canal by the parents with a cotton wick or a nasal aspirator to remove secretions. Parents should be reassured that the tube is "doing its job" to drain the infection, and that there is no danger to the child's ear or hearing, even if the discharge is bloody.

Topical antibiotic eardrops are the treatment of choice for persistent or symptomatic TTO, unless there is accompanying bacterial infection that would warrant oral antibiotics (streptococcal pharyngitis, bacterial rhinosinusitis). Although systemic antibiotic (amoxicillin-clavulanate) is more effective than placebo,54 topical drops have comparable clinical efficacy (84% versus 86%), higher pathogen eradication (96% versus 67%), and fewer adverse effects (6% versus 31%).55 Moreover, topical antibiotics achieve middle-ear drug levels that are 1,000 times higher than those attainable orally,55 which maximizes efficacy (quinolones have concentration-dependent bactericidal activity) and minimizes selective pressure for bacterial resistance.54 Topical eardrops also permit ear-specific therapy, thereby avoiding unnecessary treatment of the contralateral ear and unfavorable changes in nasopharyngeal flora from systemic antibiotics.710

Quinolone eardrops (Table 5) are the only FDA-approved products for treating AOM with a tympanostomy tube or nonintact tympanic membrane. Although commonly used for TTO, drops containing neomycin and polymyxin are not recommended because they are potentially ototoxic,556 have limited efficacy against common TTO pathogens, and are not FDA-approved for use in the middle ear. Adding dexamethasone to a quinolone drop reduces the median duration of otorrhea from 6 to 4 days, which is helpful when TTO is associated with significant otalgia or behavioral changes.57

REFERENCES

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2. American Academy of Pediatrics Subcommittee on Mangement of Acute Otitis Media. Diagnosis and management of acute otitis media. Pediatrics. 2004:1 13(5): I45I- 1465.

3. Rosenfeld RM, Culpepper L. Doyle KJ, et al. Clinical practice guideline: otitis media with effusion. Otolaryngol Head Neck Surg. 2004; 130(5 suppl):S95-S 118.

4. Jacobs MR. Worldwide trends in antimicrobial resistance among common respiratory tract pathogens in children. Pediatr Infect Dis J. 2003; 22(8 suppl):S108-S119.

5. Lieberman JM. Appropriate antibiotic use and why it is important: the challenges of bacterial resistance. Pediatr Infect Dis J. 2003; 22(12):1 143-1151.

6. Levy SB. The Antibiotic Paradox: How the Misuse of Antibiotics Destroys Their Curative Powers. 2nd ed. Cambridge, England: Perseus Publishing; 2002.

7. Ghaffar F, Muniz LS, Katz K. Effects of amoxicillin/clavulanate or azithromycin on nasopharyngeal carriage of Streptococcus pneumoniae and Haemophilus influenzae in children with acute otitis media. Clin Infect Dis.2O0O;31(4):875-880

8. Gonzales R, Malone DC, Maselli JH, Sande MA. Excessive antibiotic use for respiratory infections in the United States. Clin Infect Dis. 2001;33(6):757-762.

9. Ghaffar E Muniz LS, Katz K, et al. Effects of large dosages of amoxicillin/clavulanate or azithromycin on nasopharyngeal carriage of Streptococcus pneumoniae, Haemophilus influenzae, nonpneumococcal alpha-hemolytic streptococci, and Staphylococcus aureus in children with acute otitis media. Clin Infect Dis. 2002; 34(10):1301-1309.

10. Erickson PR, Herzberg MC. Emergence of antibiotic resistant Streptococcus sanguis in dental plaque of children after frequent antibiotic therapy. Pediatr Dent. 1999; 21(3):18l-185.

11. Shnayerson M, Plotkin MJ. The Killers Within: The Deadly Rise of Drug-Resistant Bacteria. Boston, MA: Little, Brown and Company; 2002.

12. Dagan R, Leibovitz E, Cheletz G. Leiberman A. Porat N. Antibiotic treatment in acute otitis media promotes superinfection with resistant Streptococcus pneumoniae carried before initiation of treatment. J Infect Dis. 2001; 183(6):880-886.

13. Little P, Gould C, Williamson I, et al. Reattendance and complications in randomized trials of prescribing strategies for sore throat: the medicalising effect of prescribing antibiotics. BMJ. 1997; 315(7104):350-352.

14. Rosenfeld RM, Kay DJ. Natural history of untreated otitis media. Laryngoscope. 2003; 113(10):1645-1657.

15. Rosenfeld RM. Clinical efficacy of medical therapy. In: Rosenfeld RM, Bluestone CD, eds. Evidence- Based Otitis Media. 2nd ed. Hamilton, Ontario, Canada: BC Decker; 2003:199-226.

16. Brallier JM. Medical Wit and Wisdom: from Hippocrates to Groucho Marx. Philadelphia. PA: Running Press; 1993:63-65.

17. Marcy M, Takata G, Shekelle P, et al. Management of Acute Otitis Media. Evidence Report/Technology Assessment No. 15 (Prepared by die Soutiiern California Evidencebased Practice Center under Contract No. 290-97-0001). AHRQ. Rockville, MD: Agency for Healthcare Research and Quality; May 2001. Publication No. 01-E010.

18. Rosenfeld RM. Observation option toolkit for acute otitis media. Int J Pediatr Otorhinolaryngol. 2001; 58(1): i-8.

19. Burke P, Bain J, Robinson D, Dunleavey J. Acute red ear in children: controlled trial of nonantibiotic treatment in general practice. BMJ. 1991;303(6802):558-562.

20. Damoiseaux RAMJ, van Balen FAM, Hoes AW, Verheij TJM, de Melker RA. Primary care based randomised double blind trial of amoxicillin versus placebo for acute otitis media in children aged under 2 years. BMJ. 2000:320(723 1):350-354.

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38. Little P, Gould C, Williamson I, et al. Pragmatic randomised controlled trial of two prescribing strategies of childhood acute otitis media. BMJ. 2001; 322(7282):336-342.

39. Pshetisky Y, Naimer S, Shvartzman P. Acute otitis media: a brief explanation to parents and antibiotic use. Fam Pract. 2003; 20(4):417-419.

40. Siegel RM, Kiely M, Bien JP, et al. Treatment of otitis media with a safety-net antibiotic prescription. Pediatrics. 2003; 112(3 pt 1):527-531.

41. McCracken GH Jr. Prescribing antimicrobial agents for treatment of acute otitis media. Pediatr infect Dis J. 1999; 18(12):1141-1146.

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TABLE 1.

Natural History of Otitis Media14

TABLE 2.

What to Expect from Antibiotic Therapy for Otitis Media15

TABLE 3

Scope of the Observation Option for AOM

TABLE 4.

Observation option for AOM

TABLE 5.

Antimicrobials Approved* to Treat Otitis Media

TABLE 6.

Recommended Antibiotics for Children With AOM2

10.3928/0090-4481-20041201-09

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