A Clinical guide to pediatric infectious disease

6

Otitis Media and Sinusitis

Epidemiology and Etiology

Immaturity of the eustachian tubes, coupled with a viral upper respiratory infection, can lead to stasis, congestion, and ultimately eustachian tube obstruction. Persisting obstruction of the eustachian tube can result in bacteria being aspirated and trapped in the middle ear, producing a suppurative infection. Because of the frequency of upper respiratory infections in childhood, a child in daycare or with many siblings may experience as many as 6 to 12 episodes of otitis media a year.

Presentation

Pain is considered a common feature of otitis media, which may cause disruptions in sleeping or increased irritability. Although only 25% of children with otitis media are febrile, younger children are more likely to have fever than older children.

Diagnosis

The diagnosis of acute otitis media requires several findings to be present. The first is evidence of middle ear effusion demonstrated by pneumatic otoscopy: middle ear effusion associated with acute otitis media shows impaired or absent mobility of the tympanic membrane. The second is evidence of acute inflammation of the tympanic membranes, usually as opacified bulging of the tympanic membrane or the appearance of a distinct purulent fluid level. Serous otitis media, in which the fluid behind the tympanic membrane is clear without accompanying tympanic membrane bulging, is not considered an acute infectious process and does not require treatment.

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Management

General Difficulties in Management of Otitis Media

1. There are increasing numbers of oral antibiotics available for the treatment of otitis media, all claiming to be the “best.” It should be remembered that most clinical trials evaluating antibiotics for acute otitis media are designed to show the “equivalency” necessary for U.S. Food and Drug Administration (FDA) approval. Most clinical trials do not demonstrate superiority, and because of the relatively small sample size in most clinical studies, antibiotics with limited efficacy can actually appear to be equal to superior drugs.
2. Unlike many infectious diseases, clinical specimens are not routinely collected for culture and sensitivity. The clinician, therefore, needs to examine the tympanic membrane and make a best guess as to the bacteria responsible.
3. There is increasing resistance to Streptococcus pneumoniae, the most common pathogen of otitis media. Two mechanisms of resistance have emerged. For S. pneumoniae, the most common cause of otitis media, resistance is due to alterations in penicillin-binding proteins. Resistance to S. pneumoniaeis defined by the minimal inhibitory concentration (MIC) to penicillin and to third-generation cephalosporins. Penicillin nonsusceptibility in the pneumococcus is defined when the MIC to penicillin is greater than 0.1 µg/mL. The overall rate of penicillin nonsusceptibility for pneumococcus is at least 30%. Pneumococcus isolates considered resistant to penicillin usually have MICs greater than or equal to 2.0 µg/mL; these resistant pneumococcal strains have a high likelihood of resistance to many antibacterial agents. For nonmeningeal infections, pneumococcus nonsusceptibility to third-generation cephalosporins is defined as an MIC greater than 2.0 µg/mL.
4. The other two major pathogens of otitis media are Haemophilus influenzaeand Moraxella catarrhalis. For these organisms, resistance is due to β-lactamase formation. Forty percent of Haemophilusstrains and virtually all Moraxella strains produce β-lactamase, making them resistant to amoxicillin.

Antibiotic Therapy for Otitis Media

Although there are only three major pathogens and only two major mechanisms of resistance, there are many oral antibiotics available for treatment of acute otitis media (Table 6.1). Several generalizations can be made about the many oral antibiotics available for the treatment of acute otitis media. It is important to realize that many of the newer, more expensive second- and third-generation cephalosporins actually have reduced activity against the increasing numbers of penicillin-intermediate and penicillin-resistant S. pneumoniae.

1. The first-generation cephalosporins (Cephalexin) have little gram-negative coverage and are usually used to treat gram-positive organisms such as Streptococcus

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pyogenes and Staphylococcus aureus. Generally, first-generation cephalosporins are not used in the treatment of acute otitis media.

2. The second-generation cephalosporins have moderate activity against gram-positive infections with increasing activity against gram-negative bacteria such as M. catarrhalisand nontypeable H. influenzae. Cefaclor is the least potent of these antibiotics and, because of its association with serum sickness, is generally not used. Cefuroxime (Ceftin) is the most potent of these second-generation cephalosporins against penicillin nonsusceptible pneumococcus, although it has the disadvantage of being difficult for children to accept because of poor taste. Cefprozil (Cefzil) is intermediate in both taste and potency.
3. The third-generation cephalosporins have excellent gram-negative activity. However, activity against gram-positive organisms is variable. Cefixime (Suprax) and ceftibuten (Cedax) have reduced efficacy against penicillin nonsusceptible S. pneumoniaeand are poor choices for the treatment of acute otitis media caused by this organism. These agents have good activity against penicillin-sensitive pneumococcus as well as β-lactamase–producing H. influenzaeand M. catarrhalis.
4. The macrolide antibiotics include erythromycin, clarithromycin, and azithromycin. Although these were formerly front-line therapies for sinusitis and acute otitis media, there has been increasing resistance of pneumococcus, group A streptococci, and H. influenzaeto macrolide antibiotics. Currently, about 30% of all strains of S. pneumoniaedemonstrate in vitro resistance to macrolides. Although the exact relationship of in vitro macrolide resistance to actual clinical outcome is not always clear, many specialists believe that these drugs are poor agents for the treatment of upper respiratory infections and should be reserved for use in the management of

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lower respiratory infections in children who are likely to have atypical pathogens, such as Mycoplasma pneumoniae and Chlamydia pneumoniae.

5. Trimethoprim-sulfamethoxazole (Bactrim) was previously a mainstay of therapy for the treatment of sinusitis and acute otitis media. There has been increased resistance of S. pneumoniaeto trimethoprim-sulfamethoxazole (more than 30%), and it is no longer recommended as front-line therapy.

Treatment Recommendations

In 1999, the Centers for Disease Control and Prevention convened a working group that published recommendations regarding the treatment of acute otitis media. Initial treatment was recommended with amoxicillin at a dose of 80 to 100 mg/kg per day. Amoxicillin given at the previous standard doses of 40 to 45 mg/kg per day was determined not to achieve middle ear fluid levels that would eradicate the increasingly prevalent penicillin nonsusceptible pneumococcal strains. The increase in dosing to 80 to 100 mg/kg per day was thought to achieve higher antibiotic levels in the middle ear and be effective against these strains. This regimen would also be efficacious against M. catarrhalis and H. influenzae strains that did not produce β-lactamase.

Treatment failures, defined as lack of clinical improvement after 3 days of therapy, would likely be secondary to resistant pneumococcus or β-lactamase–producing H. influenzae or M. catarrhalis. The panel recommended the following treatment options:

• Cefuroxime axetil (Ceftin)
• Intramuscular ceftriaxone (Rocephin)
• Amoxicillin clavulanate (Augmentin)
• Clindamycin

There was excellent logic to these recommendations. However, it should be remembered that these were guidelines developed at a certain time. The panel did state that, at the time of publication, there was not enough evidence of efficacy for certain drugs against the resistant pneumococcus that may be responsible for most treatment failures. In the subsequent years, the rates of resistance of S. pneumoniae have only increased. Additional developments regarding treatment of penicillin-nonsusceptible and penicillin-resistant S. pneumoniae also include the following:

1. There remains limited clinical experience using clindamycin, and no consensus exists on the actual number of injections of intramuscular ceftriaxone required for treatment of acute otitis media. Some investigators have found that up to three intramuscular injections are needed for resolution of acute otitis media.
2. New formulations of antibiotics have become available, including high-dose amoxicillin combined with clavulanic acid (Augmentin ES, 600 mg per 5 mL).
3. Experience has increased in the treatment of resistant S. pneumoniaewith several third-generation oral cephalosporins, such as cefdinir and cefpodoxime.

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Recommendations for treatment of otitis media have recently been revised. Amoxicillin remains the initial choice for primary therapy. Children at low risk for infection with penicillin-nonsusceptible S. pneumoniae can be treated with 40 mg/kg per day in two divided doses. Even with the S. pneumoniae classified as resistant to penicillin, it is thought that high-dose amoxicillin (80 to 90 mg/kg per day) achieves sufficiently high levels in the middle ear to achieve cure. In children with increased risk for infection with penicillin-resistant S. pneumoniae, including those younger than 2 years of age, attending daycare, or having received antibiotics within the preceding 30 days, therapy should be started using the high dose of 80 to 90 mg/kg per day in two divided doses.

For children with clinically defined treatment failure at 48 to 72 hours, several antibiotics have been recommended as second-line therapy. Treatment options include the following:

• Amoxicillin clavulanate, using the high-dose formulation of 600 mg per 5 mL, given as 90 mg/kg per day of the amoxicillin component in two divided doses
• Oral therapy with cefdinir, cefuroxime axetil, or cefpodoxime
• Intramuscular ceftriaxone, 50 mg/kg for one to three doses

As resistance patterns change, recommendations will need to be updated.

Treatment Delay

As antibiotic resistance becomes more prevalent, there is continued discussion about treatment delay in otitis media. It has been determined that a significant percentage of acute otitis media resolves in 2 to 7 days without antibiotic therapy. An increasing strategy, particularly in foreign countries, is to withhold treatment in a patient with early otitis media. Children are then rechecked in 48 to 72 hours to determine whether infection has resolved. Delaying treatment does not substantially increase the risk for complications, including the rate of severe mastoiditis.

Surgical Management of Otitis Media

The role of surgical intervention in patients with otitis media, particularly recurrent otitis media, is often debated. There is concern about the effect of recurrent otitis media and persistent middle ear effusions in young children at the age of language development. Various studies have addressed the issue of developmental outcomes in children with persistent otitis media and effusions. Although a variety of conclusions have been drawn, a recent study reported no improvement in the developmental outcomes at 3 years in children who had prompt insertion of tympanostomy tubes by 9 months of life. Tympanostomy tube insertion in children is often still considered if there is chronic effusion lasting 3 months or longer, documented hearing loss, or recurrent otitis media, defined as three or more episodes during the previous 6 months or four or more episodes during the past year.

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Chronic Suppurative Otitis Media

Epidemiology and Etiology

The most common cause of chronic ear drainage in pediatrics is chronic suppurative otitis media (CSOM). CSOM is defined as a chronic infection of the middle ear and mastoid associated with a nonintact tympanic membrane or a tympanostomy tube. CSOM may develop following an episode of acute otitis media with perforation and subsequent development of chronic drainage. CSOM may also be caused by a chronic perforation of the tympanic membrane in which the middle ear becomes infected by environmental organisms. The bacteria causing CSOM often differ from those of acute otitis media; the most common organisms involved include Pseudomonas aeruginosa and S. aureus. Rarely, this condition can be caused by Candida species or anaerobic bacteria.

Presentation

Affected children present with a history of ear drainage for many weeks. Typically, these children have had numerous courses of oral antibiotics.

Diagnosis

Diagnosis is usually suggested by the history. Culture of the ear drainage that yields the typical bacteria in the correct clinical context also suggest the diagnosis.

Management

Management of the chronic draining ear can begin on an outpatient basis. Culture of ear drainage can be obtained to document the typical pathogens of CSOM. In the past, a variety of ototopical agents were used. These medications were often ophthalmologic drops, which lacked efficacy against the typical CSOM pathogens and were potentially ototoxic. Ofloxacin is a topical fluoroquinolone that has been approved for use in children with tympanostomy tubes. This is now often considered a front-line ototopical agent when CSOM is diagnosed. In addition to antimicrobial therapy, good aural toilet is necessary. Children may need daily visits to the otolaryngologist for suctioning and installation of appropriate topical agents in the middle ear.

If a patient fails to respond to ototopical therapy, consideration of parental antibiotics may be needed. Because there is no approved oral antimicrobial for treatment of

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Pseudomonas species infection in children, hospitalization may be needed for administration of an appropriate intravenous drug such as ceftazidime. Computed tomography may be necessary at this time to document chronic osteomyelitis or a mass lesion.

Sinusitis

Etiology

Like otitis media, bacterial sinusitis is believed to be the result of a preceding viral upper respiratory infection that predisposes to a secondary bacterial infection.

Presentation

The diagnosis of bacterial sinusitis is based on the history of upper respiratory infection. Children with high fever and purulent nasal discharge for 3 to 4 days should have the diagnosis considered. Children with persistent symptoms that last longer than 10 to 14 days are considered to have a high probability of a bacterial infection.

Diagnosis

The gold standard of the diagnosis of sinusitis is the recovery of more than 10⁴ colony forming units/mL from a sinus aspirate, although this procedure will not be routinely employed in the pediatric office. Thus, the diagnosis of bacterial sinusitis is based on clinical criteria. As mentioned earlier, the basis for the clinical diagnosis of sinusitis is the presence of persistent symptoms. An upper respiratory infection that has lasted longer than 10 to 14 days is the best feature distinguishing sinusitis from a routine viral infection. Severe symptoms, defined as a temperature of at least 38.8°C (102°F) with purulent nasal discharge for at least 3 consecutive days, are also acceptable clinical criteria.

The physical examination is not particularly helpful in distinguishing between viral upper respiratory infection and sinusitis. Transillumination of the sinuses has been proposed, although reviews have suggested that this is difficult to perform correctly and is not reliable in young children. Imaging studies are not necessary to establish a diagnosis of sinusitis in children younger than 6 years of age. Plain films and computed tomography of the paranasal studies show mucosal thickening in both viral and bacterial upper respiratory disease. For the general practitioner, the history and duration of symptoms are the basis for an accurate diagnosis of bacterial sinusitis.

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Management

The microbiology of acute sinusitis is similar to that of acute otitis media. The principal bacterial pathogens include S. pneumoniae, nontypeable H. influenzae, and M. catarrhalis. The increasing resistance of S. pneumoniae to penicillin and the large percentage of Moraxellaand Haemophilus strains that produce β-lactamase also affect the treatment of sinusitis in children. Because organisms and resistance profile are similar, current recommendations for the treatment of otitis media can generally be applied to sinusitis.

Selected Readings

American Academy of Pediatrics. Subcommittee on Management of Sinusitis and Committee on Quality Improvement. Clinical practice guideline: management of sinusitis. Pediatrics 2001;108(3)798–808.

Bluestone CD, Klein JO. Chronic suppurative otitis media. Pediatr Rev 1999;20(8):277–279.

Bluestone CD. Role of surgery for otitis media in the era of resistant bacteria. Pediatr Infect Dis J 1998;17(11):1090–1098.

Faden H, Duffy L, Boeve M. Otitis media: back to basics. Pediatr Infect Dis J 1998;17:1105–1112.

Paradise JL, Dollaghan CA, Campbell TF, et al. Otitis media and tympanostomy tube insertion during the first three years of life: developmental outcomes at the age of four years. Pediatrics 2003;112(2):265–277.

Rosenfeld RM, Vertrees JE, Carr J, et al. Clinical efficacy of antimicrobial drugs for acute otitis media: meta-analysis of 5,400 children from thirty-three randomized trials. J Pediatr 1994;124(3):355–367.