Chronic otitis media and cholesteatoma in adults

INTRODUCTION — Chronic otitis media (COM) is a recurrent infection of the middle ear and/or mastoid air cells in the presence of a tympanic membrane (TM) perforation. Symptoms commonly include hearing loss, aural fullness, otalgia, otorrhea, and occasionally vertigo.

Cholesteatoma is a keratinized mass of squamous epithelial cells in the middle ear or mastoid that over time can cause damage to surrounding structures in the middle ear.

The evaluation, diagnosis, and management of COM and cholesteatoma in adults are reviewed here. COM and cholesteatoma in children are reviewed elsewhere:

●(See "Chronic suppurative otitis media (CSOM): Clinical features and diagnosis".)

●(See "Chronic suppurative otitis media (CSOM): Treatment, complications, and prevention".)

●(See "Evaluation of otorrhea (ear discharge) in children", section on 'Chronic suppurative otitis media'.)

●(See "Cholesteatoma in children".)

CLASSIFICATION AND DEFINITIONS — A variety of terms are used to categorize chronic infectious or inflammatory conditions of the middle ear, according to the underlying disease process and location.

Chronic otitis media — Chronic otitis media (COM) is defined as recurrent or chronic ear infections in the setting of a tympanic membrane (TM) perforation (picture 1).

●Benign (or inactive) COM is characterized by a dry TM perforation, without active infection or otorrhea.

●Active COM is characterized by a TM perforation with otorrhea.

●Chronic suppurative otitis media (CSOM) is characterized by persistent purulent drainage through a perforated TM. The World Health Organization (WHO) defines CSOM as chronic inflammation of the middle ear (figure 1) and mastoid cavity (figure 2), which presents with recurrent ear discharge or otorrhea through a TM perforation [1]. The WHO definition requires that otorrhea be present for only two weeks, but most otolaryngologists diagnose CSOM when discharge persists despite treatment for six weeks [2] to up to three months [3].

Some otologists also classify COM based on the presence of either a chronic TM perforation ("COM mucosal disease") or cholesteatoma ("COM benign squamous disease").

Chronic otitis media with effusion (COME) is defined as an ear with an intact TM but chronic sterile effusion in the middle ear lasting at least three months [4].

Cholesteatoma — Cholesteatoma is a keratinized collection of squamous epithelial cells in the middle ear or mastoid. It may be congenital or acquired; acquired cholesteatomas may occur as a result of an intact but retracted TM (primary acquired) or as a result of TM perforation (secondary acquired) (picture 2 and picture 3 and picture 4 and picture 5). Congenital cholesteatoma is discussed in detail elsewhere. (See "Cholesteatoma in children", section on 'Congenital cholesteatomas' and 'Cholesteatoma' below.)

MICROBIOLOGY OF CHRONIC SUPPURATIVE OTITIS MEDIA — Aerobes, anaerobes, and fungi are all potential pathogens in chronic suppurative otitis media (CSOM). Although the microbiology and antibiotic susceptibility of organisms varies in CSOM, Pseudomonas aeruginosa and Staphylococcus aureus are the most commonly isolated aerobic bacteria [5-11]. The ability of these organisms to form biofilm may contribute to their frequency in CSOM [2]. The prevalence of methicillin-resistant S. aureus (MRSA) varies by region and may impact the rates of susceptibility to commonly used topical therapies (eg, fluoroquinolones) reported in the literature [8,9].

Less frequently isolated organisms include Streptococcus pneumoniae and enteric gram-negative rods such as Klebsiella, Proteus, and Escherichia coli [5-7,12]. The frequency of isolation of these organisms has been variably reported: Klebsiella (4 to 7 percent of cases), Proteus (3 to 20 percent), Escherichia coli (1 to 21 percent), Acinetobacter (1 to 3 percent), Enterobacter (0.9 to 4 percent), and S. pneumoniae (1 to 3 percent) [13]. The role of anaerobes in CSOM has been variably reported, with frequencies of anaerobic isolates ranging from 8 to 59 percent [14]. The lack of standardized technique for anaerobic sample collection and culture protocol likely accounts for this wide reported range.

Mycobacterium tuberculosis (TB) [15,16], and very rarely nontuberculous mycobacteria [17], may also cause CSOM. M. tuberculosis is particularly important to consider among patients who reside in (or who have recently resided in) TB-endemic regions. In a study from India, 5 percent of 502 patients who underwent tympanomastoidectomy were diagnosed with tuberculous otitis [18]. Pale middle-ear mucosa, pale granulations, and pale appearance of the tympanic membrane (TM) have been described as characteristic of tuberculous otitis; other features that may be variably present include multiple TM perforations, copious ear discharge, profound hearing loss, and facial paralysis [19].

Fungi, particularly Aspergillus spp and Candida spp, are rarely reported as pathogens [6,8].

Studies of CSOM differ in regard to patient age, geography, and the presence of complications such as cholesteatoma, and these differences likely impact some of the variation in reported pathogens [1,5-7]. Differences in sampling and processing techniques may also account for some of the variability observed in microbiologic diagnoses, although studies most often sample aural discharge through a sterilized otoscope [6-10]. An accurate understanding of the frequency of polymicrobial infection, particularly the extent of anaerobe involvement, is limited [10,14,20].

Cholesteatomas are not by themselves infected but may become superinfected, and the microbiology in ears with CSOM with and without cholesteatoma is similar. A study of 150 patients with CSOM and cholesteatoma found that 59 percent had cultures with a single pathogen and 41 percent had polymicrobial flora; the most common pathogens were Pseudomonas (31 percent), S. aureus (19 percent), Proteus (8 percent), and anaerobes (18 percent) [10].

PATHOGENESIS

Chronic otitis media — In adults, chronic otitis media (COM) occurs in patients with chronic perforation of the tympanic membrane (TM). Typically, there is a history of recurrent acute otitis media (AOM) infections in childhood, with longstanding (months or years) otorrhea and hearing loss that is made worse by water exposure.

Chronic ear disease typically occurs as a result of Eustachian tube (ET) obstruction from recurrent inflammation of the oropharyngeal mucosa (eg, upper respiratory tract infections, seasonal allergic rhinitis) [21,22]. Obstructive ET dysfunction leads to chronic negative middle ear pressure exerted on the TM, the most compliant boundary of the middle ear (see "Eustachian tube dysfunction"). Negative pressure pulls the TM medially, and with prolonged pressure, retraction pockets can occur, usually within the pars flaccida [23,24]. This segment comprises the upper one-sixth of the TM and lies superior to the anterior and posterior malleolar folds of the TM (figure 3).

In AOM, a purulent effusion builds up behind the TM. If the positive pressure in the middle ear exceeds the tensile strength of the TM and obstructive ET dysfunction prevents pressure equilibration, TM rupture and purulent otorrhea may occur (see "Acute otitis media in adults", section on 'Chronic tympanic membrane perforation'). In some patients who have had multiple episodes of AOM, the TM perforation may become chronic; the outer epithelial layer of the TM grows over the edges of the perforation, covering the middle fibrous and inner mucosal layers, preventing the perforation from closing.

The annulus, the ligamentous ring surrounding the TM, serves as a protective barrier against squamous epithelial migration into the middle ear. Marginal perforations (where the perforation includes the annulus) are more frequently associated with cholesteatomas compared with central perforations where the annulus is preserved [25,26]. (See 'Cholesteatoma' below.)

Pathogens reach the middle ear either through insufflation of respiratory pathogens through the ET from the nasopharynx into the middle ear or spread from the external ear canal inward through a nonintact TM [2,5]. (See 'Microbiology of chronic suppurative otitis media' above and "Eustachian tube dysfunction", section on 'Pathophysiology of Eustachian tube dysfunction'.)

Cholesteatoma — Cholesteatoma refers to a keratinized collection of squamous epithelial cells in the middle ear or mastoid process [27]. The nomenclature of cholesteatoma is misleading, with keratoma perhaps being a more accurate term, since cholesteatomas contain no cholesterol or lipids [28]. Cholesteatomas may be congenital, may occur as primary lesions, or may occur secondary to TM perforation from infection, trauma, or surgery. Congenital cholesteatomas are reviewed elsewhere. (See "Cholesteatoma in children", section on 'Congenital cholesteatomas'.)

●Primary acquired cholesteatoma – Primary acquired cholesteatomas occur most commonly as a result of obstructive ET dysfunction (picture 6) [29-31]. Prolonged exposure to negative middle ear pressure causes the TM to retract medially. A retraction pocket may eventually become trapped behind the TM (figure 4), inducing inflammatory changes [32,33]. This epithelium-lined pocket accumulates keratinized squamous debris, which forms a cholesteatoma [27,31].

With proliferation of squamous epithelium, the cholesteatoma grows in size, often eroding the scutum (the sharp bony ridge at the edge of the tympanic ring). Further infection and inflammatory changes can lead to polyps and granulation tissue throughout the middle ear and mastoid air cell tracts.

●Secondary acquired cholesteatoma – Chronic TM perforation may lead to a secondary acquired cholesteatoma in a small percentage of cases. Squamous epithelium can migrate through the TM defect into the middle ear space, with the accumulation of squamous debris resulting in development of the cholesteatoma [27,29,33].

An iatrogenic form of secondary acquired cholesteatoma may develop if squamous epithelium is inadvertently implanted in the middle ear space during a surgical procedure such as tympanoplasty [34].

Cholesteatomas may cause erosion of the ossicles in the middle ear with consequent hearing loss. In rare cases, they can erode directly into the inner ear. Although an earlier theory attributed bony erosion to pressure necrosis from the expanding cholesteatoma itself [35], several other mechanisms are now recognized as the cause of bone destruction: enzymatic breakdown of collagen by collagenase, acid phosphatase, and acid protease produced by the cholesteatoma; osteoclastic bone resorption; and pyogenic osteitis [36]. Bacterial overgrowth in the area of the cholesteatoma further contributes to the potential for bone destruction.

CLINICAL FEATURES

Chronic otitis media — Inactive (benign) chronic otitis media (COM) is usually asymptomatic and found incidentally during an ear examination.

The most common symptom of active COM is the presence of recurrent or persistent ear drainage. COM is typically painless and patients usually do not have fever or other systemic signs of infection.

Patients typically also report hearing loss, more commonly in chronic suppurative otitis media (CSOM) compared with inactive COM; the degree of hearing loss is related to the location and size of the tympanic membrane (TM) perforation, the status of the ossicles, and the duration of the damage [37].

Physical examination in active COM is notable for otorrhea in the presence of a perforated TM. In CSOM, there is associated purulent otorrhea and inflamed middle ear mucosa. The otorrhea may be foul smelling.

Cholesteatoma — Presenting features of patients with cholesteatoma may vary. Some patients may be asymptomatic, while others may have some combination of hearing loss, vertigo, and/or otorrhea. (See 'Cholesteatoma' above.)

Primary acquired cholesteatoma — In primary acquired cholesteatomas (occurring in the absence of TM rupture) (picture 3 and picture 4 and picture 5), hearing loss occurs later in the course since the cholesteatoma occurs in the posterosuperior quadrant of the TM, the pars flaccida, which is the nonvibratory portion of the TM (picture 6). Late conductive hearing loss may also occur due to erosion of the ossicles, typically the distal portion of the incus.

The otoscopic examination will reveal a retracted area of the TM, usually the pars flaccida but also occasionally the pars tensa, that contains squamous debris or inflammatory tissue. On examination, the surface of the cholesteatoma is often obscured by crusting or desquamated debris on its lateral surface. Retraction of the pars flaccida leads to attic cholesteatomas (cholesteatomas at the posterosuperior border of the TM) which can be particularly difficult to visualize on routine office otoscopy.

Secondary acquired cholesteatoma — Secondary acquired cholesteatomas (associated with TM perforation) are typically detected earlier than primary acquired cholesteatomas; hearing loss occurs earlier in the course due to involvement of the pars tensa, the vibratory surface area of the TM, and the inferior portion of the TM is easier to visualize on otoscopy [38].

In secondary cholesteatoma, a pearly mass is usually evident behind the TM. These cholesteatomas may appear as skin that has replaced the mucosa of the middle ear. In some cases, the TM may be intact (if a prior perforation has healed, for example), but a white mass may be visible behind the TM.

DIAGNOSIS AND EVALUATION

Establishing the diagnosis — The diagnosis of active chronic otitis media (COM; with otorrhea) can usually be established based on clinical presentation (eg, otorrhea) and a careful ear examination (ruptured tympanic membrane [TM] and serous or purulent drainage) in a primary care office. Although cholesteatomas can be visualized on routine office otoscopy, the clinical and otoscopic findings in cholesteatoma vary depending upon the type of cholesteatoma (primary or secondary acquired), and they are better visualized with otomicroscopy or otoendoscopy. Otolaryngology referral for otoscopy is generally indicated for complete evaluation of COM as it is also often necessary to remove any obstructing wax, debris, or drainage to visualize the entire TM. If the ear can be cleaned under direct vision (via an otoscope), a primary care provider may do this. However, irrigation is not recommended without verifying that there is an intact eardrum.

Inactive COM is usually asymptomatic and diagnosed when a ruptured TM is visualized on an ear examination in the absence of any ear drainage.

ENT referral for diagnostic evaluation — Patients diagnosed with active COM or cholesteatoma, or patients in whom the diagnosis remains unclear, should be referred to otolaryngology for further evaluation. Depending on acuity and severity of symptoms, urgent referral to otolaryngology or immediate referral to an emergency department should be made when there are associated cranial neuropathies, vertigo, or signs of central nervous system involvement. CT temporal bones (non-contrast) and/or MRI of the internal auditory canals with contrast can also be considered prior to the otolaryngology referral if there are concerns for an advanced infection but symptoms indicate the process is subacute or chronic rather than acute. Diagnostic evaluation performed by otolaryngology consists of obtaining specimens for culture, imaging, a formal audiometry evaluation, and, in some instances, a biopsy.

Evaluating for infection — Chronic suppurative otitis media (CSOM) should be considered an infectious entity. A cholesteatoma may or may not be present. Cultures for definitive microbiologic diagnosis and susceptibility testing should be obtained in all patients with CSOM. Susceptibility testing is important as antibiotic-resistant organisms may be present, particularly in patients who have received prolonged treatment with antibiotic ear drops [1,39]. Specimens should be sent for Gram stain and aerobic and anaerobic cultures. In some unusual or refractory cases with clinical features suggestive of tuberculous (eg, profound hearing loss, facial paralysis, pale appearance of the TM in a patient with risk factors for tuberculosis) or fungal otitis media (eg, pain, itching), cultures for these pathogens should also be sent. Specimens should be acquired through aspiration using a sterile otomicroscope, as specimens obtained by direct ear swabs are typically contaminated with flora from the outer ear canal [1,39].

Formal audiometry evaluation — Formal audiometry evaluation should be obtained in all patients with cholesteatomas and in patients with COM who report hearing loss or who have ongoing otorrhea to establish the type and degree of hearing loss.

Imaging for all patients with cholesteatomas — For all patients with cholesteatoma, we obtain computed tomography (CT) of the temporal bone without and with intravenous contrast. These images can help to define the extent of disease, whether there is erosion, fistula formation, or intracranial or labyrinthine involvement (image 1) [21,40,41]. Patients with extensive, active disease are often systemically ill and will have localizing signs of infection.

In addition, magnetic resonance imaging (MRI) should be obtained (without and with gadolinium) when intracranial complications (eg, direct extension or meningocele or encephalocele) are suspected. MRI provides excellent soft tissue detail but lacks the bony detail needed for operative planning and thus is complementary to CT [42]. MRI is also useful for following possible disease recurrence [43].

Biopsy — In patients with persistent granulation tissue, those reporting pain as one of their symptoms, and those who do not respond to medical therapy after two to four weeks of treatment, we perform a biopsy to rule out a neoplastic or granulomatous process [44].

DIFFERENTIAL DIAGNOSIS — The differential diagnosis for chronic otitis media (COM) and cholesteatoma includes external otitis, granulomatous disease (eg, granulomatosis with polyangiitis, histiocytosis X), and malignancy such as nasopharyngeal carcinoma.

Many of these conditions may present with mucopurulent otorrhea, visible inflammation or granulation tissue, and/or thickening of the ear canal skin. The presence of pain or failure to respond to medical therapy should lead to further evaluation with imaging, culture and/or biopsy to establish a definitive diagnosis. (See "External otitis: Pathogenesis, clinical features, and diagnosis" and "Granulomatosis with polyangiitis and microscopic polyangiitis: Clinical manifestations and diagnosis" and "Clinical manifestations, pathologic features, and diagnosis of Langerhans cell histiocytosis", section on 'Clinical manifestations' and "Epidemiology, etiology, and diagnosis of nasopharyngeal carcinoma" and "Eustachian tube dysfunction", section on 'Obstructive dysfunction'.)

MANAGEMENT

General measures for all patients — For all patients with a chronic perforation of the tympanic membrane (TM), management includes water precautions and, for those with otorrhea, aural toilet.

Water precautions — Entry of water into the middle ear through a disrupted TM can cause infection. We advise protecting the ears while bathing/showering (eg, placing a petroleum jelly-coated cotton ball in the ear canal, or using watertight ear plugs before bathing). We also advise not submerging the head under water while swimming or bathing.

Adjunctive aural toilet — Aural toilet may be helpful for patients with otorrhea. Aural toilet describes the process of manually cleaning the ear, either by suction clearance by an otologist or by irrigation once an intact eardrum has been verified [45]. Only a sterile nontoxic irrigation solution (eg, sterile saline) should be used, and the irrigation should be administered by an otologist. Irrigation solutions should be warmed to near body temperature to prevent vertigo; the ear can then be suctioned after fluid instillation [1]. Self-irrigation or irrigation in a primary care office is not advised given the potential for harm in the setting of TM perforation.

There are no randomized controlled trials evaluating the benefit of aural toilet, although some experts believe that aural irrigation used as a supplement to antibiotic therapy can be beneficial [1,39,46]. Some irrigation solutions may be ototoxic [1,39,47]; for example, high concentrations of iodine have been shown to be ototoxic in animal models [48].

A systematic review included two studies in children that compared daily dry mopping versus no treatment found no difference between these groups, and a third study that included adults and children demonstrated no difference for daily suctioning followed by topical antibiotics compared with single suctioning followed by daily self-administered topical antibiotics [45].

Inactive chronic otitis media — Inactive chronic otitis media (COM) does not require any specific treatment beyond general water precautions if the patient is asymptomatic.

Active COM and cholesteatoma

Goals of treatment — The treatment goals of active COM and cholesteatomas are to stop otorrhea, heal the TM, eradicate infection (if present), prevent complications, and prevent recurrence. The optimal treatment strategy involves a combination of adherence to the principles of aural hygiene, the appropriate utilization of antibiotic therapy, and, in the case of cholesteatomas, surgical intervention involving the TM.

Antimicrobial therapy for chronic suppurative otitis media — In patients with chronic suppurative otitis media (CSOM), antimicrobial therapy is indicated. For most patients, initial treatment with topical antibiotic therapy alone is warranted. Systemic antibiotics are appropriate for patients with complicated or invasive ear infections and in those who have an infection with quinolone-resistant organisms. (See 'Evaluating for infection' above.)

Topical antibiotics for most patients — For patients with infected COM (with or without cholesteatoma), we recommend ciprofloxacin-dexamethasone or ofloxacin drops twice daily for a two-week course. If the diagnosis was made in a primary care setting, these topical antibiotics can be initiated prior to consultation with an otolaryngologist. We use these topical fluoroquinolones due to their acceptable safety profile and because they are the only available ototopical antibiotic agents appropriate for use in an ear with a TM perforation [39,49-54]. In patients with more extensive infection or in those in whom there is evidence of ongoing infection on examination after two weeks, extending the duration of treatment up to four weeks may provide benefit without increasing complication rates [52,55,56]. It is especially important in patients with infections unresponsive to initial topical antibiotics to obtain cultures as described above. (See 'Evaluating for infection' above.)

In patients with fluoroquinolone-resistant pathogens or those with extensive or complicated ear infections, we prefer the use of systemic antibiotics upfront. (See 'Systemic antibiotics for select patients' below.)

We advise warming the bottle in the hands for a few minutes prior to use, as instillation of cold drops may sometimes cause dizziness. The patient should lie on their opposite side (with the affected ear facing up) during and for several minutes after instillation. Pushing on the tragus several times after instillation may help facilitate movement of the drops into the middle ear.

Although topical antibiotics remain the first-line treatment for treatment of infection in CSOM [1,39,54,57], data supporting their efficacy are scarce. For example, a 2020 Cochrane review concluded that there was only low-certainty evidence supporting the efficacy of topical antibiotics compared with no treatment [58].

The efficacy data on the superiority of topical fluoroquinolones compared with other topical antibiotics are also scarce. In a randomized trial of 155 adults with CSOM treated with 10 days of topical ciprofloxacin (0.2 percent) compared with 138 patients treated with 10 days of topical polymyxin B, neomycin, and hydrocortisone therapy (PNH), 91 percent of the ciprofloxacin group and 87 percent of the PNH group were considered cured (absence of otorrhea or only culture-negative drainage) when examined two to seven days after completing therapy [55]. At one month, of the 83 percent of patients that attended a follow-up visit, 5 percent had relapse of otorrhea (4 percent of the ciprofloxacin group and 6 percent of the PNH group). Although several studies suggest that fluoroquinolone drops may be superior to topical aminoglycoside agents, data were limited by small sample sizes [5,52,54,59,60]. However, it should be emphasized that only fluoroquinolone drops are approved for use in ears with TM perforation as other agents (including topical aminoglycoside agents) may be ototoxic and should be avoided [49,50]. (See "External otitis: Treatment", section on 'Non-intact (perforated) tympanic membrane'.)

Topical antibiotics are still preferred as initial management of CSOM compared with systemic antibiotics despite poor-quality data. A systematic review of nine randomized trials (833 participants) concluded that although the trials were generally of poor methodologic quality and had short follow-up, topical fluroquinolones were better than systemic antibiotics at clearing discharge at two weeks, both for systemic non-fluoroquinolone and fluoroquinolone agents (relative risk [RR] 3.21, 95% CI 1.88-5.49; and RR 3.18, 95% CI 1.87-5.43, respectively) [54]. Theoretically, topical therapy may be more effective than systemic antibiotics due to the difficulty of systemic drug penetration through the devascularized mucosa of the middle ear and mastoid. Additionally, initial use of topical therapy may be preferable to systemic antibiotics because the increased local concentration of topical agents may decrease the development of antibiotic resistance as well as limit systemic absorption [1,39,61,62]. There are reports of increasing quinolone resistance in COM with the use of topical therapy [11], so use of systemic antibiotics may play an increasing role in patients with CSOM because only topical ciprofloxacin and ofloxacin are safe to use in ears with TM perforation [49,50] (See "External otitis: Treatment", section on 'Non-intact (perforated) tympanic membrane'.)

Use of topical corticosteroids is generally not recommended. Although the 2004 American Academy of Otolaryngology-Head and Neck Surgery (AAO-HNS) consensus panel supported its consideration if granulation tissue is present, there is a lack of evidence to evaluate the benefit of the addition of a topical corticosteroid to topical antibiotic therapy [39].

Systemic antibiotics for select patients — Systemic antimicrobials are appropriate for patients with persistent infection despite appropriate topical therapy, those with invasive ear infections that demonstrate systemic symptoms/signs of infection (eg, fever, leukocytosis) and/or extension of infection beyond the middle ear, and those who have CSOM with quinolone-resistant organisms. Selection of antimicrobial agents should be guided by microbiologic diagnosis and susceptibility data [1,9,11,39,54]. (See 'Evaluating for infection' above.)

Empiric treatment while waiting for culture data should be based upon the individual's previous cultures (if available), prior antibiotic exposure history, and local antibiotic resistance profiles. Empiric antimicrobial therapy should be active against S. aureus (including methicillin-resistant S. aureus [MRSA]) and P. aeruginosa. However, it is important to consider that previous antibiotic exposure may induce bacterial resistance and potential failure of topical therapy with quinolones. In one study including 231 outpatients with CSOM, 88 had otorrhea that failed to resolve after two to three weeks of ciprofloxacin drops. In all 88 patients, ciprofloxacin-resistant P. aeruginosa was isolated [11].

Examples of empiric, antibiotic combinations that will provide broad-spectrum coverage, including against MRSA anaerobes and fluoroquinolone-resistant P. aeruginosa, include vancomycin plus metronidazole plus either cefepime or ceftazidime. Although vancomycin plus piperacillin-tazobactam will provide similar coverage, this combination has been associated with renal toxicity so is generally avoided. Once cultures have returned, the antibiotics can be tailored to those results, including a change to oral antibiotics if this is indicated by clinical diagnosis and response to therapy. The duration of antibiotic therapy depends on the clinical diagnosis of a particular case. For example, patients with uncomplicated COM due to resistant organisms may require only a short course (eg, 7 to 14 days) of culture-directed therapy, while patients with infection that has extended beyond the middle ear (eg, causing septic sigmoid vein thrombophlebitis) may require many weeks of therapy. Consultation with an infectious disease physician should be considered in such cases.

High-quality data supporting the efficacy of systemic antibiotics versus topical fluoroquinolones are lacking. Trials have either not included culture-directed therapy (ie, no initial ear cultures were obtained) or have not provided long-term follow-up [63], so it is difficult to draw any conclusions. The value of combination therapy versus topical alone also has not been well studied. A trial in Pakistan randomized 100 patients with CSOM to received either topical ciprofloxacin or topical plus oral ciprofloxacin and found high rates of success in resolution of ear drainage at one week in both groups (96 versus 98 percent) [64]. However, no cultures were obtained initially, and no information about long-term follow-up was provided.

Surgical treatment

General principles — Surgical treatment is indicated for all patients with cholesteatomas and those who develop complications of COM. The goal is to remove infected tissue in the middle ear or mastoid and to repair ear damage that results in hearing loss. Surgical therapy is guided by the following principles:

●Eradication of irreversible disease – Abnormal squamous epithelium (cholesteatoma), polypoid disease, and infected bone must be removed in order to create a dry, safe ear that is free of infection [27].

●Preservation of anatomic contour – It is important to preserve the acoustic characteristics of the ear, when possible, though some patients with intractable disease will require a more aggressive approach that may impact conductive hearing. (See 'Mastoidectomy' below.)

●Reconstruction of the sound transformer mechanism – Ossicular prostheses are available for reconstruction. The presence of healthy, nondiseased mucosa is critically important to achieve success [27,65]. (See 'Ossicular chain reconstruction' below.)

●Restoration of tympanic and mastoid aeration – Aeration is required for both maintenance of a disease-free state and for maximal auditory function [66,67].

Long-term monitoring (physical examination, imaging, and audiometry) is essential to rule out recurrent disease in the middle ear or mastoid and to maximize cavity hygiene [68].

Cholesteatoma removal — Cholesteatoma removal is typically performed in conjunction with tympanoplasty and, if the lesion extends superiorly or posteriorly, mastoidectomy [69]. While concurrent treatment of allergic disease, chronic sinusitis, and adenotonsillar hypertrophy is helpful in managing any underlying causes, none of these measures will prevent the need for eventual surgical excision.

Surgical approaches to cholesteatoma are determined by three principal considerations:

●The extent of the disease

●The size and pattern of mastoid pneumatization

●Eustachian tube (ET) dysfunction

The surgical techniques that are employed for cholesteatoma are classified as tympanoplasty with or without mastoidectomy and with or without ossicular reconstruction.

Tympanoplasty — In common practice, tympanoplasty refers to reconstructive surgery of the TM and ossicular chain. More formally, tympanoplasty is a procedure to eradicate disease in the middle ear and reconstruct the ossicular chain, which may or may not involve TM grafting or mastoid surgery (see 'Mastoidectomy' below). The decision of whether to proceed with tympanoplasty rests upon a number of principles, including the desire to improve hearing and/or the need to close off the middle ear to avoid infection when water enters the canal.

Tympanoplasty is generally performed a minimum of three months after infection has been eradicated.

Tympanoplasty is typically carried out through either an endaural (within the ear) incision for smaller cholesteatomas or a postauricular incision for larger ones [70].

The two main types of tympanoplasty are medial graft and lateral graft tympanoplasty. The medial graft technique is useful for most central perforations. Although a more surgically demanding procedure, the lateral graft technique affords better visualization of the anterior TM and is useful for difficult marginal or large perforations.

Mastoidectomy — Mastoidectomy is a crucial component of surgical treatment when cholesteatoma extends beyond the middle ear space, when mastoid cells become chronically infected with buildup of granulation tissue that prevents proper aeration of the mastoid, or when there is a subperiosteal abscess over the surface of the mastoid cortex (figure 5).

Mastoidectomy involves opening the mastoid air cells (figure 2) with preservation of the tegmen tympani, sigmoid sinus, facial nerve, vestibular labyrinth, and ossicles (figure 1). The goal of surgery is eradication of disease and improved aeration of the mastoid-middle ear system.

Intact canal wall versus canal wall down surgical approaches differ in their exposure, technical difficulty, prospects for postoperative hearing, and postoperative care.

In intact canal wall mastoidectomy, the air cells of the mastoid are removed while the posterior bony external auditory canal wall is kept intact. This provides greater postoperative care convenience and often promotes better conductive hearing. Maintaining the bony canal obviates the need for water precautions and typically provides a better fit for a hearing aid if one is needed. However, intact canal wall mastoidectomy procedures can be technically more challenging and have a higher rate of recurrent cholesteatoma than canal wall down procedures [71].

Recurrent cholesteatomas are more common in intact canal wall procedures due to the formation of retraction pockets in the grafted TM into the middle ear, epitympanum, or facial recess [68,71]. An intact canal wall procedure for cholesteatoma usually requires surgical reexploration within one year to rule out residual or recurrent disease; residual or recurrent cholesteatoma is found in reexploration of canal wall intact procedures in approximately one-third of cases [68,71]. Reexploration enables the detection of lesions that are typically less than 5 mm in greatest diameter and enables complete removal with minimal dissection. Multiple recurrences of cholesteatomas are not uncommon. In some cases, a very active recurrent cholesteatoma found during the second-stage procedure may warrant a more radical procedure in which the canal wall is removed.

In many cases, the extent of disease or the need for greater exposure in cholesteatoma removal mandates a canal wall down mastoidectomy, with removal of the posterior bony external auditory canal. This exteriorizes the entire mastoid cavity, promoting maximal mastoid aeration and allowing long-term monitoring for recurrence of cholesteatoma. Open-cavity techniques typically lead to a decrease in hearing [72], and there is a risk of recurrent discharge from bacterial or fungal overgrowth on retained debris within the open cavity. This underscores the need for postoperative vigilance over years and maintenance of a clean, safe cavity with regular cleaning by an otolaryngologist (picture 7). It is crucial that a wide meatoplasty be performed to enable inspection of the complete extent of the mastoid cavity.

No controlled prospective studies are available that compare intact canal versus canal wall down procedures. Outcomes reported from case series comparing the two techniques likely involve selection bias, as intact canal wall mastoidectomies tend to be reserved for more limited disease while more extensive cholesteatomas will often be treated with canal wall down mastoidectomies. A 2014 systematic review of studies of cholesteatoma treated with mastoidectomy was unable to come to conclusions about best practices; individual studies reported different outcome measures and could not be compared [73].

Mastoid cavities are occasionally obliterated using homograft or allograft materials. Advantages of obliteration include less cold sensitivity, improved hearing, and decreased drainage [74]. However, such reconstructions may be susceptible to recurrent infection either due to primary infection of the graft material or blockage of adjacent air cell tracts and susceptible to recurrent disease if the primary cholesteatoma matrix was not completely eradicated [75].

Ossicular chain reconstruction — Cholesteatoma and COM have the propensity to erode bone. In many cases, the small ossicular chain bones (malleus, incus, and stapes) are either partially or totally destroyed secondary to cholesteatoma and chronic infection. The long process of the incus, due to its relatively scant vascular supply, appears especially vulnerable to bony destruction (picture 8) [76].

When chronic ear disease results in significant hearing loss due to ossicular involvement, an important component of surgical therapy is hearing rehabilitation surgery with reconstruction of the ossicular chain. Ossicular chain reconstruction employs a partial or total prosthesis to provide a medium for sound conduction where ossicular discontinuity is present.

Hearing rehabilitation surgery is frequently performed as part of a second-stage procedure after tympanomastoidectomy [76,77]. With improvements in prosthesis material selection and design, combined with a better understanding of indications for ossicular reconstruction, hearing rehabilitation is often successfully achieved in the treatment of chronic ear disorders. Closure of the air-bone gap to within 20 dB has been reported in 80 percent of patients [78].

COMPLICATIONS — A number of complications may result from chronic otitis media (COM) and cholesteatoma.

Mastoiditis — Mastoiditis is an infection of the mastoid bone in the skull, most often arising as a complication from COM or a cholesteatomas.

●Epidemiology – Acute mastoiditis occurs more commonly in children than adults, although its incidence has declined dramatically with the routine use of antibiotics for the treatment of acute otitis media. It is a rare occurrence in adults but can complicate chronic suppurative otitis media (CSOM) with or without cholesteatoma. One study that reviewed almost 3000 cases of CSOM over a nine-year period in Turkey reported 25 cases of mastoid abscess [79].

●Clinical features – A spectrum of disease is associated with mastoiditis. Mastoid effusion is often seen on computed tomography (CT) scan in patients with both acute otitis media (AOM) and CSOM but is not usually clinically significant. Symptomatic coalescent mastoiditis is a rare complication of both AOM and CSOM but can be serious due to proximity of the mastoid to the posterior cranial fossa, lateral sinuses, facial nerve canal, semicircular canals, and the petrous tip of the temporal bone (image 2 and image 3 and image 4).

Clinical mastoiditis may present with fever, posterior ear pain and/or local erythema over the mastoid bone, edema of the pinna, or a posteriorly and downward displaced auricle (picture 9). In coalescent mastoiditis, CT demonstrates characteristic loss of the trabecular bone (image 2) [80].

Mastoiditis complicating CSOM can result in bony erosion and temporal lobe abscess or can cause septic thrombosis of the lateral sinus (figure 5).

●Diagnosis CT without and with contrast should always be obtained when mastoiditis is suspected. If there is a concern for an intracranial process (ie, sigmoid sinus thrombosis, intracranial abscess), then a magnetic resonance imaging (MRI) should also be obtained. Patients with acute mastoiditis should be admitted to the hospital, and intravenous (IV) antibiotics should be started. Blood cultures and cultures of ear drainage (obtained via otomicroscopy) should ideally be obtained prior to initiation of antibiotics.

●Antimicrobial therapy – Empiric antibiotics for the treatment of acute mastoiditis presenting as a complication of COM and cholesteatoma should include coverage for S. aureus (including methicillin-resistant S. aureus [MRSA]), Pseudomonas, enteric gram-negative rods, and anaerobes, as well as common organisms of AOM such as S. pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis. Antibiotic therapy should then be adjusted based upon culture results if necessary. Possible empiric antibiotic regimens include vancomycin plus metronidazole plus either cefepime or ceftazidime; vancomycin plus piperacillin-tazobactam is avoided due to concern for renal toxicity with this combination. If there is no or inadequate response to IV antibiotic therapy after two to three weeks of therapy, then surgical intervention is warranted.

●Surgical intervention – Surgical intervention is warranted in patients with mastoiditis who do not respond to IV antimicrobial therapy alone. This typically involves mastoidectomy for debridement of necrotic bone with adjunctive myringotomy (see 'Mastoidectomy' above). When cholesteatoma is present, a tympanomastoidectomy is performed to remove both the necrotic bone in the mastoid and the cholesteatoma. (See 'Surgical treatment' above.)

Facial nerve palsy — CSOM with or without cholesteatoma can be complicated by facial nerve palsy. This can occur through involvement of the dehiscent facial nerve canal or through direct bony erosion [80,81]. The onset of unilateral facial paralysis is usually gradual. In one case series of 70 patients with complicated CSOM, 14 percent of the patients had accompanying facial palsy [82]. Management of facial paralysis in the setting of CSOM, with or without cholesteatoma, requires surgical intervention [80]. (See 'Surgical treatment' above.)

Intracranial complications — Intracranial complications of CSOM are potentially life-threatening and require immediate intervention. They include suppurative thrombophlebitis of the lateral and/or cavernous sinuses, meningitis, and intracranial abscesses (figure 5). These complications are rare in the era of effective antibiotics, with one large review estimating an overall rate of 0.1 to 2.0 percent [79]. In a retrospective chart review involving 33 patients over a 15-year period in Brazil, meningitis and intracranial abscess were the most common serious problems [83].

Signs and symptoms of intracranial involvement include severe earache, seizures, fever, constant and persistent headache, nausea and vomiting, or focal neurologic symptoms. Patients who present with these findings should be evaluated and treated promptly, with consultations from otolaryngology, neurology, and infectious disease. Broad-spectrum empiric IV therapy with activity against MRSA and Pseudomonas, as well as pathogens of meningitis, should be initiated as soon as possible. (See 'Systemic antibiotics for select patients' above and "Initial therapy and prognosis of community-acquired bacterial meningitis in adults", section on 'Antibiotic regimen'.)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Acute otitis media, otitis media with effusion, and external otitis".)

SUMMARY AND RECOMMENDATIONS

●Definitions – Chronic otitis media (COM) is a recurrent infection of the middle ear and/or mastoid air cell tract in the presence of a tympanic membrane (TM) perforation.

•Inactive COM is a TM perforation without otorrhea while active COM is characterized by the presence of otorrhea.

•Chronic suppurative otitis media (CSOM) is diagnosed when there is persistent purulent drainage through a perforated TM.

•Cholesteatoma refers to a keratinized, desquamated epithelial collection in the middle ear or mastoid and may occur secondary to TM perforation but also may occur as a primary lesion.

●Microbiology of CSOM – Aerobes, anaerobes, and fungi are all potential pathogens in CSOM, although Pseudomonas aeruginosa and Staphylococcus aureus are the most commonly isolated aerobic bacteria. Less frequently, Enterobacterales, anaerobes, or fungi are isolated. (See 'Microbiology of chronic suppurative otitis media' above.)

●Pathogenesis – Chronic ear disease occurs as a result of Eustachian tube (ET) dysfunction with negative middle ear pressure causing rupture of the TM. Cholesteatomas may occur as primary lesions or may be secondary to TM perforation or surgery. Cholesteatomas may result in erosion of the ossicles in the middle ear and consequent conductive hearing loss and rarely cause a sensorineural hearing loss due to erosion into the labyrinth. (See 'Pathogenesis' above.)

●Clinical features

•Inactive (benign) COM is usually asymptomatic while the most common symptom of active COM is the presence of recurrent or persistent ear drainage. COM is typically painless and patients usually do not have fever or other systemic signs of infection. (See 'Clinical features' above.)

•Cholesteatomas are often asymptomatic or may be associated with hearing loss, dizziness, and/or otorrhea. The presence of cholesteatoma should always be investigated in patients with CSOM and usually requires otomicroscopy. (See 'Clinical features' above.)

●Diagnosis – The diagnosis of active COM (COM with otorrhea) can usually be established based on clinical presentation (eg, otorrhea) and a careful ear examination (ruptured TM and serous or purulent drainage) in a primary care office. Cholesteatomas can be visualized on routine office otoscopy but are better visualized with otomicroscopy or otoendoscopy. (See 'Establishing the diagnosis' above.)

●Evaluation – Otolaryngology referral for otoscopy is generally indicated for complete evaluation of COM. The referral serves to collect cultures and susceptibility testing in cases of CSOM, perform audiometry, evaluate imaging findings, and determine the need for and/or perform a biopsy. (See 'ENT referral for diagnostic evaluation' above.)

●Management

•General measures – General measures include water precautions for all patients with a perforated TM and aural toilet for patients with active COM. (See 'General measures for all patients' above.)

•Inactive COM – Inactive COM does not require any specific treatment beyond general water precautions if the patient is asymptomatic. (See 'Inactive chronic otitis media' above.)

•Active COM and cholesteatoma – The treatment goals of active COM and cholesteatomas are to stop otorrhea, heal the TM, eradicate infection (if present), prevent complications, and prevent recurrence. The optimal treatment strategy involves a combination of adherence to the principles of aural hygiene, the appropriate utilization of antibiotic therapy, and, in the case of cholesteatomas, surgical intervention involving the TM. For initial treatment of CSOM in most patients, we recommend a topical quinolone antibiotic rather than a systemic antibiotic (Grade 1B). An exception to this is if patient is known to have a causative fluoroquinolone-resistant pathogen; in these cases, non-fluoroquinolone systemic antibiotics should be initiated instead. (See 'Active COM and cholesteatoma' above.)

●Complications – Complications of CSOM include mastoiditis, facial nerve palsy, suppurative thrombophlebitis of the lateral or cavernous sinuses, meningitis, and intracranial abscesses. (See 'Complications' above.)

ACKNOWLEDGMENT — The editorial staff at UpToDate acknowledge Rachel Baden, MD, and Mary LaSalvia, MD, who contributed to an earlier version of this topic review.