Otitis Media: A Rite of Passage

Otitis media is the most common bacterial infection among children, the second most common reason after the common cold that children go to a pediatrician,^[1] and the most frequent reason that antibiotics are prescribed children.^[1] More than 90% of children will experience at least 1 episode of otitis media by the age of 2 years, more than 75% will have acute otitis media (AOM), and more than 50% will have at least 1 episode of recurrent AOM before the age of 3 years.^[2] Management of AOM is discussed in All Otitis Is Not Created Equal: AOM vs OME in this collection. AOM, when recurrent, can significantly reduce the quality of life of patients and their parents. Recurrent AOM -- defined as 3 episodes in 6 months or 4 episodes in 1 year -- is more frequent in younger children and is a criterion for insertion of tympanostomy tubes (Figure).

Figure. Tympanostomy tubes are small devices (1-2 mm diameter) made out of silicone, polyethylene, Teflon^®, stainless steel, or titanium, that are inserted into a small incision in the tympanic membrane (tympanostomy or myringotomy) to facilitate drainage of otorrhea.

Surgical management of otitis media is indicated for treatment and management of recurrent AOM, otitis media with effusion (OME), chronic suppurative otitis media (CSOM), or AOM with complications. Complications of AOM may include spread of infection to the surrounding anatomic areas or vital structures, resulting in acute mastoiditis, facial nerve paralysis, neck abscess, meningitis, brain abscess, and hearing loss. In most of these cases, emergency surgery for drainage of the infection (pus) from the middle ear and/or the mastoid is mandated along with intravenous antibiotic therapy. The most common surgical procedure performed is placement of pressure equalizing tubes (tympanostomy tubes); the 2 most common indications are recurrent AOM and OME. OME is one of the most common causes of conductive hearing loss and associated secondary speech disorder in children. Approximately 1 million children undergo placement of tubes in the United States every year. Tympanostomy tubes allow fluid in the middle ear to drain and ventilate this space with oxygen. Tubes usually fall out of the tympanic membrane within 6-14 months.

Tympanostomy Tubes: No More Ear Infections, Right?

Conceptually, most healthcare providers think of tympanostomy tube insertion as a means of preventing the recurrence of AOM. Parents, on the other hand, have hope for an end to many sleepless nights and multiple courses of broad-spectrum antibiotics. Unfortunately for both, the grim reality is that AOM after tube insertion is common. Though once considered the exception and not the rule, recent studies report that 83% of children with tympanostomy tubes in place for 18 months will experience at least one episode of acute otitis media with tympanostomy (AOMT),^[3] and 1%-10% develop CSOM.^[4,5] For children (and their parents) afflicted with acute and/or chronic AOMT, frustration mounts; for their healthcare providers, the diagnostic and therapeutic challenges escalate.

AOMT is a bacterial infection of the middle ear space in a child who has a well-positioned and patent tympanostomy tube. The clinical presentation of AOMT is similar to that of AOM, but differences in etiology, spontaneous resolution rate, and recommended treatmentsuggest that they are not the same conditions. It is important that clinicians know the difference. The clinical presentation of AOMT is very different than AOM in children with an intact tympanic membrane. Pain and fever are absent and hearing loss is much less common. Quite often the only symptom is the sudden appearance of drainage from the external auditory canal. This drainage may be thin and milky, thick and purulent, or sticky and mucoid.

What is critical to bear in mind is that most children have one or more host factors that predispose them to recurrent and/or chronic otitis media. When the only predisposing factor is an amenable eustachian tube dysfunction (all types of eustachian tube dysfunction do not completely respond to tympanostomy tube insertion), tympanostomy tubes may prevent future episodes of otitis media altogether. Tympanostomy tubes, however, are not a "silver bullet" for all severely affected patients.

When AOMT occurs, the value of tympanostomy tubes for severely affected children should be emphasized, which highlights the need for healthcare providers to clearly understand the benefits and limitations of tympanostomy tubes. The child with recurrent AOM who is referred to an otolaryngologist for surgical consultation for evaluation for tympanostomy tube insertion has often been continuously ill and medical treatment options have been exhausted. Patients, their parents, and healthcare providers must remain balanced at this "fork in the road" and maintain reasonable expectations for outcomes.

If Tympanostomy Tubes Do Not Always Prevent Otitis Media, What Should Parents Expect?

Although a conclusion usually ends a chapter, the convention is reversed in this chapter. If one only remembers and shares this lesson with every patient and parent considering tympanostomy tube surgery, this activity will have been a success: The insertion of tympanostomy tubes decreases the frequency, severity, and duration of otitis media; nothing more and nothing less. Medicine teaches all of its disciples that there are no absolutes or guarantees. Practitioners on the front line of care for patients with otitis media can, nonetheless, make this statement to their patients and parents with reasonable confidence. Taking the statement apart for families is a very worthwhile investment of time. Simply put, explain to families that they should expect 3 things following tympanostomy tube surgery.

Impact of Tympanostomy Tubes: Frequency of Otitis Media

First, the number of ear infections should decrease. In general, nearly every study has demonstrated this outcome. It is a rare patient that continues to develop otitis media at the same or greater frequency as before tympanostomy tubes. Parents who have been traumatized by a relentless disease course with their child often react to this statement with reservation.

Impact of Tympanostomy Tubes: Severity of Otitis Media

But alas, even in children who continue to experience otitis media following tympanostomy tube insertion, the disease course is favorably modified in many ways. The fact that the severity of otitis media is mitigated resonates well with parents. In striking contrast to children without tubes, children with tubes who develop otitis media are far less symptomatic. Fever is rare and when fever occurs, it is low-grade. High fever generally signifies a concomitant infection other than otitis media, such as a severe viral respiratory tract infection, pneumonia, or influenza. Of even greater importance to parents is that otalgia is mild and may be absent altogether. In addition to middle-ear ventilation that facilitates drainage of middle-ear pus, the host inflammatory response is also down-regulated. The decrease in inflammation of the middle-ear cleft further reduces pain. Most children simply present with otorrhea in the absence of pain or fever and with signs and symptoms of a viral upper respiratory tract infection. Appetite and sleep are rarely disrupted.

Also of importance to parents, especially those of children with special needs, is that significant conductive hearing loss does not occur with AOMT. There is no known risk of speech and language delay in this setting. Finally, extremely relevant to healthcare providers and equally important to parents aware of the potential, tympanostomy tubes essentially obviate the progression of AOM to acute coalescent mastoiditis, epidural abscess, sigmoid sinus thrombosis with and without septic emboli, meningitis by direct temporal bone extension, and a host of other potentially life-threatening suppurative complications. Most parents agree that the clinical picture is far more acceptable with tubes than without tubes.

Impact of Tympanostomy Tubes: Duration of Otitis Media

The benefits do not end with decreased severity. Duration of infection, in most instances, is also decreased; a benefit that also resonates favorably with parents who have grown accustomed to protracted disease courses and the need for multiple office visits leading to several courses of oral and sometimes intramuscular broad-spectrum antibiotics -- all of this only to learn several months later that the middle-ear effusion has failed to clear. Parents become appropriately concerned that the conductive hearing loss resulting from the effusion may interfere with language development, even if all the other symptoms of the acute infection have resolved. Finally, most parents are acutely aware of the risks of exposure to systemic antibiotics. Much of the antibiotic exposure is due to the fact that a single course of antibiotics fails to cure the ear infection.

Duration of infection is reduced when a tympanostomy tube facilitates ventilation of the middle ear cleft. Importantly, resolution of infection pertains not only to the disappearance of symptoms, but also to the return of a noninflamed middle-ear cleft. The natural history of AOM in the setting of an intact tympanic membrane extends over months before the inflammatory state of the middle-ear cleft resolves. In AOMT, the duration is reduced to days-to-weeks. Not only does this reduce the morbidity of the disease, it also reduces the temptation and/or indication to use extended or multiple courses of antibiotics to achieve this return-to-normal form and function.

The Patient Has a Red Eardrum, Is It Otitis?

Parents are often unaware of the challenges associated with diagnosing AOM. Studies have demonstrated accuracy rates to be no better than a coin toss (50%) for primary care physicians.^[6] In fact, the most recently published clinical practice guideline for AOM by the joint efforts of the American Academy of Family Physicians and the American Academy of Pediatrics^[7] emphasized the reality of diagnostic uncertainty in their recommendations. This issue proved to be one of the most controversial and was met with significant resistance. There is little question that tympanostomy tubes substantially simplify the diagnosis of otitis media, hence, reducing overtreatment and undertreatment. Parents and practitioners must understand that if there is no otorrhea, there is no AOMT; just as, if there is no middle-ear effusion, there is no AOM. Often, children with infectious symptoms who have tubes are diagnosed with otitis media on the basis of a "red ear drum" in the absence of otorrhea. Sentinel to the diagnosis of AOM or AOMT is a suppurative middle-ear effusion. Adherence to this simple diagnostic principal will reduce diagnostic errors, improve utilization of antibiotics, and positively impact the impression of many parents that their child continued to develop recurrent episodes of otitis media after tympanostomy tubes were placed when, in fact, the child did not.

Culture-directed therapy is much more feasible with tubes in place. Whereas an invasive procedure called tympanocentesis is needed to obtain microbiologic data in the patient with AOM, otorrhea is immediately accessible for culture in the external auditory canal of the patient with AOMT. This confers several advantages. First, it has become increasingly clear that the reservoir for otitis media is the nasopharynx and that the pathogens harbored in the nasopharynx serve as pathogens for upper respiratory "field infections." The identification of these pathogens is not only useful for targeting culture-guided therapy in a child with AOMT who fails to respond to initial empiric treatment, but is also of potential benefit in the management of other respiratory tract infections in that child in the future. On a more global scale, such culture data provides an invaluable and noninvasive means for ongoing community surveillance of antibiotic resistance patterns. Parents are reassured in cases where infections recur that a "data-driven" approach can be taken rather than the empiric algorithm that failed in the past. It is critical to understand that cultures are not obtained for selection of a topical antibiotic,as the definitions of resistance and susceptibility are based on typical tissue antibiotic levels achieved with systemic administration of antibiotics. Ototopical concentrations are, on average, 1000-fold higher. In conclusion, if parents understand before surgery that tympanostomy tubes are a means to an end, not the end itself, they will better accept "the silver lining behind the cloud" of ongoing AOMT. So, how does one approach the patient with ongoing otitis media after tympanostomy tubes surgery? Let's find out.

Young Girl With Tympanostomy Tubes

The following case provides context for the remainder of the discussion. A 5-year-old girl with a history of cleft palate presents with new-onset fever and left-side otalgia. Her medical history is notable for several surgeries to repair a cleft palate and lip. She also has a history of recurrent AOM with residual OME. She had bilateral tympanostomy tubes placed during her last surgery approximately 6 months ago. Her most recent episode of AOMT, 5 months earlier, was treated with fluoroquinolone otic solution, which provided relief. Her mother reports that since that time she has been doing well, her hearing has improved, and her speech therapist is pleased with her progress. She has not been swimming since the surgery, though she does take a bath and wash her hair daily without using ear plugs. She has not complained of an earache.

Approximately 4 days ago, she developed a cough and rhinorrhea, which were not associated with fever and have not been treated. Last night she awoke crying and complaining of left-side ear pain. Her mother treated her with an over-the-counter nonsteroidal anti-inflammatory agent and "leftover" fluoroquinolone otic solution, which provided some relief. On examination this morning, she is afebrile and cooperative, though she reports that her ear "hurts" and manipulation of her left pinna causes pain. Her external canal has a small amount of slightly foul-smelling, yellow-green fluid and only the upper half of the tympanic membrane is visible, even after gentle cleaning. The tympanic membrane appears gray without obvious erythema or injection. The tympanostomy tube is not visible due to debris. Her right ear canal is clear, the tympanostomy tube is visible, the tympanic membrane is gray, and there is no drainage. The physical examination is also notable for mild rhinorrhea and pharyngeal erythema without exudate. The remainder of the exam is unremarkable.

Treatment of AOMT: Getting Down to Basics

An intact tympanic membrane prevents penetration of topical antibiotics into the middle ear. Therefore, one of the fundamental advantages of managing AOMT is the ability to use topical antibiotics in place of systemic antibiotics. There are many benefits of topical over systemic antibiotics. First, topical medication is delivered directly to the infected target organ. By bypassing the systemic circulation, pharmacokinetic factors such as solubility, intestinal absorption, and hepatic first-pass effects do not affect ultimate tissue concentrations. Perhaps more important is that, unlike systemic antibiotics, topical antibiotics do not usually contribute to the development of community-acquired antimicrobial resistance. This latter factor has become a focus of current best practice guideline development and, somewhat surprisingly, has also become a key safetysurveillance outcome measure for regulatory agencies such as the US Food and Drug Administration (FDA) and the Centers for Disease Control and Prevention.

Antibiotic resistance is the single most important concern in the management of infectious disease today. In 1982, the FDA stated that it was unaware of any evidence that topical antibiotics had led to an increase in infection in the general population by resistant organisms.^[8] This tenet on resistance and topical therapy holds true for short-term use in the community as long as topical drug delivery is effective. This point was corroborated by a study done in Pittsburgh in 231 consecutive children seen at the outpatient otolaryngology clinic with draining ears, from which Pseudomonas aeruginosa was isolated.^[9] In these patients, the sensitivity to polymyxin B, one of the active ingredients in Cortisporin® (hydrocortisone, neomycin, polymyxin) otic suspension, which was commonly used in the community since the 1970s, was 99.6%. Only 1 strain of P aeruginosa was shown to be resistant to polymyxin B. The authors concluded that, despite widespread use of ototopical polymyxin B in their community for nearly 3 decades, P aeruginosa resistance, known to readily occur after exposure to systemic antibiotics, had not developed. The same has been observed for topical antibiotic dermatologic and ophthalmic preparations.

Not only is microbiologic eradication using topical ciprofloxacin/dexamethasone in children with otorrhea significantly more effective than oral amoxicillin/clavulanate (81.3% vs 59.1%), but time to cessation of otorrhea is decreased (4.0 days vs 7-9 days).^[10] Importantly, while no topical treatment failure rendered new pathogens, superinfectors (new pathogens recovered or detected during therapy) or reinfectors (new pathogen recovered at the end of therapy) were detected in nearly half of patients treated with systemic therapy. Three factors likely account for this finding. First, the concentrations of topical antibiotics so far exceed the minimal inhibitory concentrations at the site of infection that eradication is more rapid and complete, thus obviating the emergence of treatment-related resistance. Second, in general, ototopical agents are used for relatively short treatment courses. Third, these infections are, by and large, community acquired in otherwise immunocompetent hosts. It is important to note that all 5 pathogens most commonly isolated from draining ears -- P aeruginosa, Streptococcus pneumoniae, Staphylococcus aureus, nontypeable Haemophilus influenzae, and Moraxella catarrhalis -- are of major concern to the CDC because of their propensity to develop resistance. All 5 pathogens should be covered empirically in the absence of a confirmatory culture. They are commonly isolated from patients of all ages and from both acutely- and chronically-draining middle ears in the face of nonintact tympanic membranes.

Resistance and pharmacokinetics are not the only advantages of topical therapy. The side effect profile of systemic agents far exceeds that of topical agents. Such untoward effects as diarrhea, nausea, rash, vomiting, abdominal pain, and headache, among others, are nonexistent with topical therapy. Far more severe side effects such as Stevens-Johnson syndrome, aplastic anemia, seizure, and anaphylaxis are equally avoided. With topical agents, only minor local irritative and allergic effects are commonly seen. A clinical trial comparing topical ofloxacin with amoxicillin/clavulanate for efficacy and safety found the incidence of treatment-related side effects associated with the ototopical agent to be 6% compared with 31% for the systemic agent.^[11]

Are Antibiotics Enough?

The need for a corticosteroid in combination with an ototopical antibiotic has been debated in the past, but as more evidence has been published, the more convincing is the argument in favor of a positive contribution of a corticosteroid. The common underlying feature of all types of otitis media is inflammation, and corticosteroids have known potent anti-inflammatory activity. Ototopical formulations combining antibiotic with a corticosteroid have advantages, including greater relief of inflammation in a shorter period of time,^[12] faster time to cessation of otorrhea, higher overall cure rates, and improved microbiologic eradication.^[13]

A study examining the efficacy difference between an antibiotic alone (topical ofloxacin) and a topical antibiotic-corticosteroid combination (ciprofloxacin/dexamethasone) in patients with AOMT revealed a significantly shorter time to resolution of otorrhea by 2 days. This same study revealed a faster time to cessation of otorrhea when a corticosteroid-antibiotic combination was used; a greater than 20% advantage was conferred by the addition of the corticosteroid at treatment day 11. The effect remained significant at 18 days as evidenced by an increase of nearly15% in resolution of otorrhea in the topical corticosteroid-antibiotic group compared with the topical antibiotic-alone group. Overall cure rates were higher in the group that was treated with topical corticosteroid-antibiotic combination therapy.^[12]

In a comparison of microbiologic eradication in patients with AOMT, those treated with ciprofloxacin/dexamethasone achieved a microbiologic eradication rate of 92% compared with 81.8% in patients treated with topical ofloxacin alone. Although one may be tempted to conclude from these data that topical ciprofloxacin is a "better antibiotic" than topical ofloxacin, the same result was seen when microbiologic eradication with ciprofloxacin alone was compared with ciprofloxacin/dexamethasone in patients with AOMT. In patients with AOMT caused by gram-positive pathogens, the rate of microbiologic eradication was almost 15% higher in the antibiotic-corticosteroid combination therapy group. This difference was even more striking in patients with gram-negative infections in that eradication was achieved in 89.2% of patients treated with ciprofloxacin/dexamethasone compared with 70.2% in topical ofloxacin-treated patients.^[14]

Aggressive treatment is the best approach to prevention of chronic otorrhea. Rapid cessation of otorrhea and higher cure rates, together with improved microbiologic eradication of infection, support the use of combination ototopical therapy (antibiotic plus corticosteroid) for the treatment of AOMT. However, despite its lower efficacy, clinicians may choose ototopical monotherapy over combination therapy because it is less expensive.

Ototopical Therapy: The Burden of Drug Delivery

In order to be effective, ear drops must be able to be delivered to the site of infection. Almost all cases of ototopical therapy failure are due to inadequate drug delivery. Topical drug delivery can be improved in a number of ways. Careful aural toilet is required. The external auditory canal should be mopped dry prior to instillation of ear drops. One way to improve delivery of ear drops through a tympanostomy tube is to perform a tragal pump. One finger is used to repeatedly press just in front of the tragus, which exceeds the surface tension of the tympanostomy tube and helps milk the drops through the tube. Occasionally the ear drops cannot be effectively delivered because the drainage is so copious and rapid. In such cases, irrigation of the external auditory canal using 20-50 mL of a 50:50 solution of white vinegar and sterile water or a 50:50 solution of 3% hydrogen peroxide and sterile water with a small bulb syringe can be done to remove the drainage prior to drop placement. Fenestrated otowicks may also be used for refractory AOMT to allow drainage and ventilation of the middle ear. This will also prevent ear popping with every swallow.

Steps required for optimal drug administration technique should be reviewed with parents, emphasizing that the auricle must be retracted posteriorly and superiorly in order to straighten the external auditory canal and provide a more linear path into the middle ear. Run-off should be avoided so that the concentration of the antibiotic is maintained above the minimum inhibitory concentration. Parents should also be reminded that the child should keep the treated ear in the upright position for an average of 5-10 minutes (the longer, the better) after ear drops are instilled, especially in refractory cases. This is particularly important when dealing with highly-resistant organisms.

Swelling of the middle ear mucosa or formation of granulation tissue may prevent passage of ear drops through the tympanostomy tube to the site of the infection, resulting in ototopical treatment failure. In this situation, a trial of systemic antibiotics may be indicated, but the systemic antibiotic used should be based on culture and sensitivity reports of the drainage. When a trial of an appropriate systemic antibiotic is ineffective, the child should be referred for specialist care. Possible explanations include immune deficiency, the occult presence of cholesteatoma, or mastoiditis.

Methicillin-Resistant S aureus in AOMT: Do Not Overreact

Methicillin-resistant S aureus (MRSA) is a challenge for clinicians and must be treated thoughtfully. Due to the ability of MRSA to persist and colonize the ear long after otorrhea has resolved, the treatment goal of complete eradicationis not only unrealistic, but also dangerous.

A comprehensive discussion of bacterial interference is beyond the scope of this article, but is a concept that is critical to keep in mind when approaching a child with MRSA-related otorrhea. This is so because methicillin-sensitive S aureus (MSSA) and MRSA compete for the same ecologic niches in the body (eg, the anterior nares).^[15] Systemic strategies may, in part, fail in these patients because it is virtually impossible to treat a patient with a systemic antibiotic active against MRSA and at the same time spare its ecological competitor, MSSA. This is the justification to admonish systemic antibiotic treatment to the extent possible in these patients, unless absolutely indicated. Coticchia and colleagues^[16] identified recent oral antibiotic exposure as the primary risk factor in children for the development of MRSA otorrhea. It is illogical to employ a treatment that is responsible for the disease in the first place. This is the single most important aspect of the management that is overlooked of these patients. It is also difficult for consultants to enforce because patients often seek treatment from multiple healthcare providers.

For reasons mentioned throughout this article, topical strategies are preferable to systemic strategies for the treatment of MRSA otorrhea and should be considered first-line therapy when possible. Initial treatment with ototopical ofloxacin or ciprofloxacin/dexamethasone is reasonable. Most often however, these preparations have already been empirically prescribed and have failed.

Eradication of MRSA from the ears of 16 patients presenting with MRSA otorrhea and treated with mupirocin ointment vs ofloxacin drops was examined in a randomized, controlled study.^[17] Mupirocin ointment at a dose of 0.6 mg was administered locally to the tympanic membrane and to the promontory around and through the perforation with its adjacent external ear canal 1 to 4 times for 2 or 3 weeks at the clinic. The control group consisted of 10 patients with MRSA otorrhea who were treated with "ofloxacin drops administered daily by the patients at home for 2 or 3 weeks." Only 40% of topical ofloxacin-treated patients were successfully treated vs 100% of the mupirocin-treated patients (P <.001). Despite such efficacy, mupirocin resistance has been reported and, although unlikely, one may see treatment failures in MRSA otorrhea patients due to resistance.^[18] Most cases of mupirocin-resistant MRSA strains have been recovered from patients with distinct clinical and epidemiologic characteristics that rarely apply to children with community-acquired otorrhea. There are no reported series of children with MRSA otorrhea and significant high-level mupirocin resistance. The absence of such case reports notwithstanding, it is possible that such a case of high-level mupirocin-resistant MRSA otorrhea could present and that an alternative topical medication might be needed.

Retapamulin ointment (1%) is now commercially available and represents the first of a new class of topical antibiotics, the pleuromutilins. It has a unique mechanism of action that interferes with multiple aspects of protein synthesis. Early data suggests that retapamulin may be as much as 32 times more potent against S aureus in vitrothan mupirocin, and that retapamulin has a lower minimal inhibitory concentration than mupirocin against drug-resistant S aureus.^[19] It remains to be seen whether or not such impressive in vitro data will pass the test of time as this drug becomes more widely used. It is also important to note that no clinical superiority has been demonstrated in human trials and it must always be remembered that in vitro results do not necessarily correlate with clinical efficacy. At this time, however, it is a reasonable topical alternative in cases where other topical therapies have failed due to resistance.

A final simple, accessible, and cost-effective strategy for the treatment of these patients as well as for the prevention of contagion, is bathing in bleach (1 tsp per gallon of water or ¼ cup to a bathtub for at least 15 minutes) 3 times per week for 30 days. An alternative is to swim in a chlorinated pool at the same frequency for the same duration of time. Alternative antiseptics include 2% chlorhexidine-impregnated wash clothes, hexachlorophene detergent cleanser (pHisoHex®), and chlorhexidine topical (Hibiclens®).

Summary

In summary, the DOs and DON'Ts of effective management of MRSA-related AOMT are:

• DO identify the reservoir of colonization and consider barriers to isolate the source (most often the skin on the external auditory canal) of MRSA from the middle ear (ie, reconstruct and close perforations of the tympanic membrane).
• DO restore physiologic homeostasis of the external auditory canal.
• DO respect the "tincture of time" as colonization and bacterial replacement is often delayed.
• DO rely on topical antibiotics as the mainstays of treatment.
• DON'T chase MRSA with systemic antibiotics labeled "susceptible" in vitro, such as trimethoprim/sulfamethoxazole, linezolid, or vancomycin
• DON'T overoperate (ie, mastoidectomy)

And finally, remember that all that drains is not infectious AOMT. In refractory cases, rare diagnoses and additional comorbidities must be sought. Unusual pathogens, such as mycobacterium, may be very difficult to isolate in culture and may require tissue biopsy, skin testing, special stains, or sophisticated identification techniques to diagnose. Undiagnosed illnesses such as diabetes and immunodeficiency syndromes may be present. A variety of IgE-mediated conditions may also exist. Skull base osteomyelitis may represent a significant extension of the infection, requiring protracted systemic antibiotic therapy. Benign (ie, histiocytosis X) and malignant (squamous cell or adenocarcinoma, rhabdomyosarcoma) tumors may present as refractory otorrhea, especially when the ear drainage is unilateral or bloody.

Supported by an independent educational grant from Alcon.