DÄ internationalArchive13/2019Otitis Externa: Investigation and Evidence-Based Treatment

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Otitis Externa: Investigation and Evidence-Based Treatment

Dtsch Arztebl Int 2019; 116(13): 224-34; DOI: 10.3238/arztebl.2019.0224

Wiegand, S; Berner, R; Schneider, A; Lundershausen, E; Dietz, A

Background: Otitis externa has a lifetime prevalence of 10% and can arise in acute, chronic, and necrotizing forms.

Methods: This review is based on publications retrieved by a selective search of the pertinent literature.

Results: The treatment of acute otitis media consists of analgesia, cleansing of the external auditory canal, and the application of antiseptic and antimicrobial agents. Local antibiotic and corticosteroid preparations have been found useful, but there have been no large-scale randomized controlled trials of their use. Topical antimicrobial treatments lead to a higher cure rate than placebo, and corticosteroid preparations lessen swelling, erythema, and secretions. Oral antibiotics are indicated if the infection has spread beyond the ear canal or in patients with poorly controlled diabetes mellitus or immunosuppression. Chronic otitis externa is often due to an underlying skin disease. Malignant otitis externa, a destructive infection of the external auditory canal in which there is also osteomyelitis of the petrous bone, arises mainly in elderly diabetic or immunosuppressed patients and can be life-threatening.

Conclusion: With correct assessment of the different types of otitis externa, rapidly effective targeted treatment can be initiated, so that complications will be avoided and fewer cases will progress to chronic disease.

LNSLNS

Otitis externa is one of the more common diseases in otorhinolaryngological practice and is also frequently encountered in primary and pediatric care. It ranges in severity from a mild infection of the external auditory canal to life-threatening malignant otitis externa. Its correct treatment requires a good understanding of the anatomy, physiology, and microbiology of the ear canal. No German guidelines deal specifically with otitis externa; it is briefly discussed in the AWMF-S2k guidelines on ear pain of the German College of General Practitioners and Family Physicians (Deutsche Gesellschaft für Allgemeinmedizin und Familienmedizin, DEGAM) (1). Here we discuss the epidemiology, etiology, and treatment of otitis externa in the light of the current scientific evidence.

Learning objectives

Readers of this article should

  • gain an overview of the epidemiology, anatomical setting, and causes of otitis externa,
  • understand the different forms of the disease, and
  • become acquainted with their treatment.

Methods

We selectively searched the PubMed database for controlled trials, guidelines, and reviews that appeared up to 30 April 2018 with the key words “otitis externa,” “acute external otitis,” “otitis externa diffusa,” “otitis externa circumscripta,” “chronic external otitis,” “otitis externa maligna,” and “otitis externa necroticans.”

Otitis externa

Otitis externa is defined as an infection of the cutis and subcutis of the external auditory canal, possibly involving the tympanic membrane and the pinna as well. Its different forms include acute diffuse otitis externa, circumscribed otitis externa, chronic otitis externa, and malignant (i.e., necrotizing) otitis externa. Its differential diagnoses include perichondritis, erysipelas, otomycosis, herpes zoster oticus, otitis externa bullosa sive hemorrhagica, otitis media (with perforation), and eczema, cholesteatoma, or carcinoma involving the external auditory canal (2).

Anatomy and physiology

The external auditory canal (ear canal) has lateral cartilaginous and medial bony portions, with an overall length of 2–3.5 cm and a diameter of 5–9 mm (Figure 1a). The skin of the bony ear canal is firmly bound to the periosteum, while the skin of the cartilaginous ear canal lies on a layer of connective tissue and contains hair follicles, sebaceous glands, and apocrine ceruminous glands, whose exudates, combined with desquamated epithelial cells, form cerumen. The cartilaginous ear canal has a roof of connective tissue; its floor contains the connective-tissue clefts of Santorini, along which infections can spread to the parotid gland, infratemporal fossa, and skull base. The sensory innervation of the ear canal is from the auriculotemporal nerve, the auricular branch of the vagus nerve, the greater auricular nerve, and the posterior auricular nerve. The ear canal is normally colonized by bacteria, above all Staphylococcus and Corynebacterium species and streptococci (3). Its pH is normally in the range of 5–5.7; the acid environment and the hydrophobic properties of the cerumen inhibit bacterial growth (2).

a) Normal right external auditory canal, with view of the eardrum. b) Swollen introitus of the right external auditory canal in a patient with acute otitis externa. c) An external auditory canal affected by bacterial otitis externa. d) Otomycosis
a) Normal right external auditory canal, with view of the eardrum. b) Swollen introitus of the right external auditory canal in a patient with acute otitis externa. c) An external auditory canal affected by bacterial otitis externa. d) Otomycosis
Figure 1
a) Normal right external auditory canal, with view of the eardrum. b) Swollen introitus of the right external auditory canal in a patient with acute otitis externa. c) An external auditory canal affected by bacterial otitis externa. d) Otomycosis

Etiology and epidemiology

Otitis externa is common all over the world, with a higher incidence in tropical than in temperate zones because of the higher temperature and humidity. Its lifetime prevalence is estimated at 10% (4). It affects adults most commonly, and children only rarely (generally aged 7 to 12) (e1). Studies from the Netherlands and the United Kingdom have shown an annual incidence of circa 1% (5, e2). The incidence is increased fivefold in swimmers (6); thus, the condition is also called “swimmer’s ear.” The pathogenesis of otitis externa is multifactorial; a list of predisposing factors is shown in Table 1.

Predisposing factors for otitis externa (modified from Schäfer et al. [7])
Predisposing factors for otitis externa (modified from Schäfer et al. [7])
Table 1
Predisposing factors for otitis externa (modified from Schäfer et al. [7])

More than 90% of cases of otitis externa are due to bacteria (6), most commonly Pseudomonas aeruginosa (22–62%) and Staphylococcus aureus (11–34%). Polymicrobial infection is common (8, e3e5). Fungi are a rare cause of acute otitis externa (10%) (e6) and a more common cause of chronic otitis externa; typical pathogens are Aspergillus (60–90%) (9) and Candida species (10–40%) (e7). Predisposing factors for fungal otitis externa include long-term antibiotic use, immunosuppression, and diabetes mellitus.

The changes in the ear canal that are seen in otitis externa (e.g., hyperkeratosis of the epidermis, chronic granulation tissue, edema, or fibrosis of the dermis) tend to narrow the canal. Epithelial cell migration normally rids the ear canal of cerumen, cellular detritus, and microorganisms. Interference with this process by inflammation or stenosis predisposes to the development and maintenance of otitis externa.

Symptoms

The characteristic symptom of acute otitis externa is severe pain in the ear (otalgia) due to irritation of the periosteum just under the thin dermis of the bony ear canal, which has no subcutis. The pain is typically worsened by pressure on the tragus or tension on the pinna. Further symptoms are otorrhea, itch, erythema, and swelling of the ear canal, potentially leading to conductive hearing loss.

Diagnosis

Otitis externa is diagnosed from the history and physical examination, including, as a minimum, otosopic or otomicroscopic examination of the ear canal and tympanic membrane (if visible), as well as examination of the pinna, the surrounding lymph nodes, and the skin. Especially if the tympanic membrane cannot be seen, screening tests of hearing or an audiological examination should be performed to rule out inner ear involvement. When the ear canal is swollen, the tuning-fork examination and the tone threshold audiogram typically reveal conductive hearing loss. The characteristic findings in acute otitis externa are pain induced by pressure on the tragus and tension on the pinna, along with swelling of the ear canal, perhaps to the point of total obstruction; the skin of the ear canal can be either erythematous or pale because of edema (Figures 1b, c). Secretion is common and can be swabbed for culture and pathogen resistance testing. Rarely, swelling makes the pinna protrude (pseudomastoiditis). Mild fever (up to 39°C) may be present; markedly higher temperatures suggest spread of the infection beyond the ear canal.

Treatment

The treatment of uncomplicated acute otitis externa consists of cleansing the ear canal, topical antiseptic and antimicrobial treatment, and adequate analgesia. Primary oral antibiotic treatment should be given only if the infection has spread beyond the ear canal, in the setting of poorly controlled diabetes mellitus or immunosuppression, or if topical treatment is not possible (10) (Figure 2). The DEGAM, in its guideline on ear pain, accordingly recommends cleansing the ear canal and using local antibiotics and/or corticosteroids as indicated, in consideration of their availability, costs, and risks. Systemic antibiotic treatment should be considered in individual cases if there are systemic manifestations, or whenever problematic organisms are found (1).

Treatment algorithm for acute otitis externa (modified from Rosenfeld et al. [8])
Treatment algorithm for acute otitis externa (modified from Rosenfeld et al. [8])
Figure 2
Treatment algorithm for acute otitis externa (modified from Rosenfeld et al. [8])

Cleansing the ear canal

Atraumatic cleansing of the ear canal consists of the removal of cerumen and exudate; the exudate may contain toxins (e.g., Pseudomonas exotoxin A [e8]) that sustain the inflammatory process and limit or prevent the efficacy of topical drugs. Cleansing should be performed by an experienced otorhinolaryngologist under microscopic vision with suction or an aural hook; injury to the ear canal must be avoided. Once a defect of the tympanic membrane has been ruled out, the ear canal can alternatively be cautiously rinsed with distilled water or normal saline. In rural areas without otolaryngology coverage, this can also be done by a general practitioner or pediatrician. Patients should not clean their own ears with cotton swabs, because microtrauma encourages bacterial invasion.

Topical treatment

Topical treatment with antiseptic agents, antibiotics, corticosteroids, and combinations of these is recommended for the treatment of uncomplicated acute otitis externa because of its safety, efficacy compared to placebo, and excellent results in randomized trials and meta-analyses (1012, e9e11). Whichever topical agent is used, 65–90% of patients improve clinically in 7–10 days (8). In a Cochrane meta-analysis of randomized controlled trials, antiseptic agents and antibiotics yielded equally good clinical results; no difference was found between single agents and combinations of agents, with or without additional corticosteroids (10). Nonetheless, the additional administration of topical steroids can lessen erythema and secretions. A few trials have shown different results from monotherapy as opposed to combination therapy, but the heterogeneity of the substances used makes it hard to draw any general conclusions (10). In a systematic review, topical antimicrobial drugs were found to increase the clinical cure rate by 46% and the bacteriological cure rate by 61% compared to placebo (11). Ototoxic substances must be avoided if the eardrum is perforated. No randomized trials have been performed on the insertion of a drug-soaked gauze strip into the ear canal as the sole treatment, but this method does seem to improve the local efficacy of topical treatment and to lessen inflammatory edema (10). The decisive factor for optimal topical treatment is patient instruction in how to apply the eardrops. The patient should lie on his or her side with the affected ear up, apply the drops in the ear canal, and keep lying on one side for 3–5 minutes thereafter. Gently moving the ear back and forth helps convey the drops to their site of action (8). The drops should be applied two to five times daily, depending on the preparation (Table 2). Topical treatment leads to a cure of acute otitis externa in 65–90% of patients in 7–10 days, whatever agent is chosen (8). In the past, dyes such as gentian violet and acid brilliant green were commonly used for the local antiseptic and desiccating therapy of various ear diseases, but these are toxic and no longer approved for aural use.

Eardrops that are approved in Germany for the topical treatment of otitis externa
Eardrops that are approved in Germany for the topical treatment of otitis externa
Table 2
Eardrops that are approved in Germany for the topical treatment of otitis externa

Topical antiseptic agents

The treatment of acute otitis externa with various topical antiseptic agents has been described, including acetic acid, chlorhexidine, aluminum acetate, silver nitrate, N-chlorotaurine, fuchsin, and eosin (5, 13, 14, e12e14). The advantage of topical antiseptic agents is their broad-spectrum efficacy. Many preparations contain alcohol, which is an effective disinfectant and, in high concentration, removes water from tissue and thus lessens edema. pH reduction by acid preparations (e.g., 2% acetic acid) inhibits bacterial growth (3, 14), as most bacteria prefer a pH-neutral environment. Thus, otitis heals more rapidly if treated in this way rather than with placebo. Acetic acid is comparably effective to antibiotic or corticosteroid drops after 7 days of treatment, but significantly less effective if treatment is needed for 2–3 weeks (10).

Topical antibiotics

Topical antibiotics should cover the most common pathogens, i.e., Pseudomonas aeruginosa and Staphylococcus aureus, and should be tailored to the drug resistance and sensitivity patterns of the cultured pathogen, if possible. The approved types of antibiotic eardrops in Germany contain quinolones (ciprofloxacin), aminoglycosides (neomycin), or polymyxins (polymyxin B) (Table 2). Compared to placebo, these lead to more rapid symptomatic relief and cure, and to lower recurrence rates (11). Quinolones are highly effective and cause no local irritation, but prolonged exposure to them can lead to resistance against this important class of antibiotics. Neomycin is effective but ototoxic and should be given only if the eardrum is intact. It also causes contact dermatitis in 15–30% of patients (9, 1517, e15). Polymyxin monotherapy is not effective against? staphylococci and other Gram-positive microorganisms (9). A Cochrane analysis showed no difference in the clinical efficacy of quinolone versus non-quinolone preparations (10). In clinical practice, just as in clinical trials, ophthalmological antibiotic preparations are sometimes used off label to treat otitis externa; the most common active substance is ofloxacin (10, 11). Topical administration results in a high local concentration of drug without the side effects of systemic treatment. Nonetheless, for the reasons just explained, topical antibiotics such as ciprofloxacin or ofloxacin should not be given any longer than necessary. Ototoxic substances must not be used if the eardrum is perforated.

Topical corticosteroids

Topical corticosteroids are used mainly because they lessen edema; antibacterial and antifungal effects have also been described (3). Only individual case reports on topical corticosteroid monotherapy are available (18, 19), so the evidence for this practice is still weak (10). In a few randomized controlled trials, treatment with topical combinations of antibiotics and corticosteroids lessened swelling, erythema, and secretions more effectively than antibiotics alone. The greatest difference was seen during the first few days of treatment (20, 21). High-potency corticosteroids are probably more effective than low-potency corticosteroids against pain, inflammation, and swelling (22) (Table 2).

Antifungal treatment

In case of fungal infection (Figure 1d), strips soaked in a solution of antifungal drug (ciclopirox, nystatin, clotrimazole, or miconazole) should be laid in the ear canal. Dye solutions are no longer recommended because of their potential toxicity to the inner ear and their low efficacy (23). If the eardrum is perforated, systemic antifungal treatment should be given according to the resistance and sensitivity pattern (e.g., fluconazole or itraconazole) (23).

Analgesia

Pain relief is an essential part of the treatment of acute otitis externa. Severe ear pain arises because the highly sensitive periosteum of the bony ear canal is usually involved in the inflammatory process. Suitable analgesia should, therefore, be provided, e.g., with ibuprofen or acetaminophen. Topical local anesthetics can be used as well (Table 2), unless the eardrum is perforated or a myringostomy tube is in place. Local anesthetics, however, can also mask progressive disease; if they are used, the patient should be followed up clinically in 48 hours so that the effect of treatment can be judged (8).

Oral antibiotic treatment

Despite the well-documented safety and efficacy of topical preparations, 20–40% of patients treated for acute otitis externa receive systemic antibiotics as their primary treatment (24, 25). This should be avoided in uncomplicated acute otitis externa because of the side effects and the risk of inducing drug resistance. On the other hand, oral antibiotics are indicated to treat acute otitis externa if the patient suffers from poorly controlled diabetes mellitus or immunosuppression, or if the infection extends beyond the ear canal. Antibiotics should be given that are effective against both Pseudomonas aeruginosa and Staphylococcus aureus (e.g., quinolones). Optimally, antibiotics should be tailored to the findings of bacterial culture and sensitivity testing.

Follow-up and secondary prevention

The response to treatment should be checked in 48–72 hours. If there is no response, the correctness of the diagnosis and the adequacy of treatment should be critically reconsidered, and the causative pathogen should be identified if possible. Known risk factors should be avoided to prevent further episodes of infection. In particular, the ear canal should be kept dry and should be dried with a hair dryer if water enters it (10). If the self-cleansing mechanism of the ear canal is dysfunctional, then the ear canal should be cleansed by a physician whenever the patient intends to spend a considerable amount of time swimming (e.g., a beach holiday).

Circumscribed otitis externa

Circumscribed otitis externa is an abscess-forming infection of a hair follicle (i.e., a furuncle) in the cartilaginous part of the external auditory canal, mostly due to Staphylococcus aureus. If mild, it is treated with topical antibiotic eardrops, salves, or salve strips, along with analgesics. If more severe, it is additionally treated with oral antibiotics and lancing of the furuncle, as needed.

Chronic otitis externa

Manifestations of otitis externa lasting longer than three months, or more than four attacks of otitis externa per year, are designated as chronic otitis externa. This may result from inadequately treated acute otitis externa, although 15% of cases of acute otitis externa heal within 10 days (e16), but the cause usually lies elsewhere. Involvement of the ear canal by a skin disease such as atopic dermatitis or psoriasis is common. An alkaline pH in the ear canal due to the inflammatory process can also predispose to chronic otitis externa (e17). The chronic form of the condition affects both ears in more than half of patients (26). Its typical symptoms are itch and conductive hearing loss due to obstruction, while ear pain is rare. There are two main clinical presentations: the seborrheic form is characterized by a lack of cerumen and by dry, scaly, red, or shiny skin in the ear canal, the eczematous form by moist, erythematous skin (26). Itching can lead the patient to manipulate the ear canal, leading to excoriation and, in turn, to acute inflammation. Chronic inflammation causes progressive fibrosis of the ear canal.

Treatment

The goals of treatment are to return the skin of the ear canal to its original, normal state and to promote the production of cerumen. All potential irritants, such as shampoo or soap, should be kept away from the ear, and the ear canal should be kept dry. The treatment of underlying illnesses, such as skin diseases or autoimmune disorders, is the basis of therapy. Only a few randomized controlled trials on drug therapy for chronic otitis externa have been carried out, generally on a mixture of patients with acute or chronic otitis externa, so that no explicit recommendations can be derived for the treatment of chronic otitis externa as a distinct entity (e18e20). The goal of topical treatment is to suppress chronic inflammation. Swabbing for culture, to exclude bacterial or fungal infection as the cause, is recommended. The application of strips soaked in alcohol or corticosteroid solution can locally lessen edema. In case of an acute exacerbation, topical antibacterial or antifungal drugs may be needed. Chronic otitis externa often fails to respond to treatment administered for several weeks.

Oral corticosteroids can be effective in cases resistant to other forms of treatment (27). Local treatment with tacrolimus has been described as well (28). Surgical canaloplasty to widen the ear canal is only indicated if the canal is stenotic.

Malignant (necrotizing) otitis externa

Malignant (necrotizing) otitis externa is a destructive infection of the external auditory canal with invasive perichondritis and osteomyelitis of the lateral skull base, arising mainly in elderly men who are either diabetic or immunosuppressed (29). Its incidence is not precisely known. Rare cases have been described in severely immunocompromised children, such as children with acute leukemia or who have undergone bone marrow transplantation (e21, e22). Early diagnosis is essential; intractable otitis externa should always prompt the suspicion that the patient might actually be suffering from the malignant (necrotizing) form of the condition.

Diagnosis and manifestations

In about 90% of cases, Pseudomonas aeruginosa can be isolated from the exudate in the ear canal (6, e23). Proteases released into the surrounding tissue can cause marked tissue destruction and accompanying vasculitis (30). The infection can spread along the clefts of Santorini to the parotid gland, the periauricular soft tissue, and the temporomandibular joint. Spread of infection along the skull base can lead to inner ear damage, cranial nerve deficits, venous sinus thrombosis, meningitis, and brain abscess. Otalgia is intense, but nonspecific (frequency, 84–100% [29]); along with conductive hearing loss and fetid otorrhea (frequency, 17.6–100% [29]), granulations or polyps are typically found in the floor of the ear canal (frequency, 42.1–100% [29]), sometimes with exposed bone, particularly at the junction of the bony and cartilaginous portions of the canal, due to the underlying osteitis (8) (Figure 3). Further manifestations can arise that reflect further complications. Imaging studies typically reveal soft-tissue swelling in the external auditory canal. Petrous osteomyelitis is manifested by bony destruction, usually (80%) spreading toward the temporomandibular joint and the clivus (31). The gold standard for the diagnostic imaging of petrous osteomyelitis is a combination of static and functional imaging (where available), with fluorodeoxyglcose positron-emission tomography and magnetic resonance imaging (FDG-PET/MRI) as well as high-resolution computed tomography (CT). Functional imaging enables the detection of osteitis in an early stage before bone erosion can be seen on CT (31). The advantages and disadvantages of each imaging modality for the evaluation of petrous osteomyelitis are listed in Table 3. A biopsy should always be performed to rule out a malignant tumor or cholesteatoma of the external auditory canal. Malignant otitis media is very rare in children; when it is suspected, MRI is the imaging study of choice.

Exposed bone in the floor of the external auditory canal in a patient with malignant otitis externa
Exposed bone in the floor of the external auditory canal in a patient with malignant otitis externa
Figure 3
Exposed bone in the floor of the external auditory canal in a patient with malignant otitis externa

Treatment

High-grade evidence on the treatment of malignant otitis externa is lacking (29). Pathogen-specific parenteral or oral antibiotics, tailored to the findings of sensitivity and resistance testing, are recommended for at least 4–6 weeks (29, 32), as it takes this long for the involved bone to become revascularized (33). If the sensitivity and resistance testing is not yet definitive, empirical antibiotic treatment against Pseudomonas aeruginosa should be begun, depending on the severity of the condition. Topical treatment with antiseptic or antimicrobial strips in the ear canal can be given in addition. If the condition takes a protracted course or fails to respond to medical treatment, necrotic tissue and bone sequestra should be surgically removed, because they impair the penetration of antibiotics and the body’s own defensive substances into the involved tissue (34). Extensive resection in the region of the lateral skull base does not improve the outcome. Optimal blood sugar control is mandatory. Accompanying hyperbaric oxygen therapy may increase the cure rate, but no randomized controlled trials on this topic are available (35). Regular clinical and radiological follow-up examinations are needed to document the response to treatment and to detect any recurrence. The suggested strategies range from imaging only if new symptoms arise to intermittent imaging at 2–6 week intervals until no infectious process can be seen any longer (36). Petrous bone osteomyelitis in malignant otitis externa is associated with a mortality of 10–21% (17, 3739, e24). Mortality is elevated if two or more of the following factors are present: age >70, diabetes mellitus, facial nerve palsy, or a positive CT (bone erosion, soft-tissue swelling) (40).

Conclusions for routine clinical practice

Otitis externa is diagnosed from the history and physical examination. Uncomplicated acute otitis externa can be treated to good effect with cleansing of the ear canal, antiseptic or antibiotic eardrops with or without corticosteroids, and preventive measures. Otomycosis should be treated with antifungal agents. For patients with chronic otitis externa, irritating substances should be kept away from the ear, and potential underlying diseases should be treated. Persistent otitis externa, granulation tissue, or freely exposed bone in the external auditory canal may be a sign of malignant (necrotizing) otitis externa. Early diagnosis and the rapid initiation of a 4- to 6-week course of antibiotics help lower the morbidity and mortality of this condition.

Definition
Otitis externa is defined as an infection of the cutis and subcutis of the external auditory canal, possibly involving the tympanic membrane and the pinna as well.

Anatomy and physiology
The cartilaginous ear canal has a roof of connective tissue; its floor contains the connective-tissue clefts of Santorini, along which infections can spread to the parotid gland, infratemporal fossa, and skull base.

Etiology and epidemiology
More than 90% of cases of otitis externa are due to bacteria, most commonly Pseudomonas aeruginosa and Staphylococcus aureus. Polymicrobial infection is common. Fungi are a rare cause of acute otitis externa and a more common cause of chronic otitis externa.

Symptoms
The characteristic symptom of acute otitis externa is severe pain in the ear (otalgia) due to irritation of the periosteum just under the thin dermis of the bony ear canal, which has no subcutis.

Treatment
The treatment of uncomplicated acute otitis externa consists of cleansing the ear canal, topical antiseptic and antimicrobial treatment, and adequate analgesia.

Cleansing of the external auditory canal: rationale
Atraumatic cleansing of the ear canal consists of the removal of cerumen and exudate; the exudate may contain toxins that sustain the inflammatory process and limit or prevent the efficacy of topical drugs.

Cleansing of the external auditory canal: technique
Cleansing should be performed by an experienced otorhinolaryngologist under microscopic vision with suction or an aural hook; injury to the ear canal must be avoided.

Topical treatment
Topical treatment with antiseptic agents, antibiotics, corticosteroids, and combinations of these is recommended for the treatment of uncomplicated acute otitis externa because of its safety, efficacy compared to placebo, and excellent results in randomized trials and meta-analyses.

Gauze strips
No randomized trials have been performed on the insertion of a drug-soaked gauze strip into the ear canal as the sole treatment, but this method does seem to improve the local efficacy of topical treatment and to lessen inflammatory edema.

Acetic acid
pH reduction by acid preparations (e.g., 2% acetic acid) inhibits bacterial growth, as most bacteria prefer a pH-neutral environment. Acetic acid is comparably effective to antibiotic or corticosteroid drops after 7 days of treatment.

Topical antibiotics
Topical antibiotics should cover the most common pathogens, i.e., Pseudomonas aeruginosa and Staphylococcus aureus, and should be tailored to the drug resistance and sensitivity patterns of the cultured pathogen, if possible.

Analgesia
Pain relief is an essential part of the treatment of acute otitis externa. Severe ear pain arises because the highly sensitive periosteum of the bony ear canal is usually involved in the inflammatory process.

Circumscribed otitis externa
Circumscribed otitis externa is an abscess-forming infection of a hair follicle (i.e., a furuncle) in the cartilaginous part of the external auditory canal, mostly due to Staphylococcus aureus.

Chronic otitis externa
The typical symptom is itch. There are two main clinical presentations: the seborrheic form is characterized by a lack of cerumen and by dry, scaly, red, or shiny skin in the ear canal, the eczematous form by moist, erythematous skin.

Malignant (necrotizing) otitis externa
Malignant (necrotizing) otitis externa is a destructive infection of the external auditory canal with invasive perichondritis and osteomyelitis of the lateral skull base, arising mainly in elderly men who are either diabetic or immunosuppressed.

Petrous osteomyelitis
The gold standard for the diagnostic imaging of petrous osteomyelitis is a combination of static and functional imaging (where available), with FDG-PET/MRI as well as high-resolution CT.

Resistance to treatment
If the condition takes a protracted course or fails to respond to medical treatment, necrotic tissue and bone sequestra should be surgically removed, because they impair the penetration of antibiotics and the body’s own defensive substances into the involved tissue.

Conflict of interest statement
The authors state that they have no conflict of interest.

Manuscript submitted on 1 June 2018, revised version accepted on 21 January 2019.

Translated from the original German by Ethan Taub, M.D.

Corresponding author
Prof. Dr. med. Susanne Wiegand
HNO-Universitätsklinik Leipzig
Liebigstr. 10–14
D-04103 Leipzig, Germany
susanne.wiegand@medizin.uni-leipzig.de

Supplementary material
For eReferences please refer to:
www.aerzteblatt-international.de/ref1319

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Mösges R, Domröse CM, Löffler J: Topical treatment of acute otitis externa: clinical comparison of an antibiotics ointment alone or in combination with hydrocortisone acetate. Eur Arch Otorhinolaryngol 2007; 264: 1087–94 CrossRef MEDLINE
21.
Mösges R, Schröder T, Baues CM, Sahin K: Dexamethasone phosphate in antibiotic ear drops for the treatment of acute bacterial otitis externa. Curr Med Res Opin 2008; 24: 2339–47 CrossRef MEDLINE
22.
Roland PS, Younis R, Wall GM: A comparison of ciprofloxacin/
dexamethasone with neomycin/polymyxin/hydrocortisone for otitis externa pain. Adv Ther 2007; 24: 671–5 CrossRef MEDLINE
23.
Tietz HJ: Pilzbedingte Otitis externa. Wie werden Gehörgangsmykosen lege artis behandelt? HNO-Nachrichten 2014; 44: 42 CrossRef
24.
McCormick AW, Whitney CG, Farley MM, et al.: Geographic diversity and temporal trends of antimicrobial resistance in streptococcus pneumoniae in the United States. Nat Med 2003; 9: 424–30 CrossRef MEDLINE
25.
Bhattacharyya N, Kepnes L: Initial impact of the acute otitis externa clinical practice guideline on clinical care. Otolaryngol Head Neck Surg 2011; 145: 414–7 CrossRef MEDLINE
26.
Kesser BW: Assessment and management of chronic otitis externa. Curr Opin Otolaryngol Head Neck Surg 2011; 19: 341–7 CrossRef MEDLINE
27.
Golder J: Oral steroids in the treatment of otitis externa. Aust Fam Physician 1999; 28: 775 MEDLINE
28.
Caffier PP, Harth W, Mayelzadeh B, Haupt H, Scherer H, Sedlmaier B: Topische Immunmodulation. Ein Meilenstein in der Behandlung der therapieresistenten nichtinfektiösen chronischen Otitis externa? HNO 2008; 56: 530–7 CrossRef MEDLINE
29.
Mahdyoun P, Pulcini C, Gahide I, et al.: Necrotizing otitis externa: a systematic review. Otol Neurotol 2013; 34: 620–9 CrossRef MEDLINE
30.
Tisch M, Maier H: Otitis externa necroticans. Laryngorhinootol 2006; 85: 763–9 CrossRef MEDLINE
31.
van Kroonenburgh AMJL, van der Meer WL, Bothof RJP, van Tilburg M, van Tongeren J, Postma AA: Advanced imaging techniques in skull base osteomyelitis due to malignant otitis externa. Curr Radiol Rep 2018; 6: 3 CrossRef MEDLINE PubMed Central
32.
Conterno LO, da Silva Filho CR: Antibiotics for treating chronic osteomyelitis in adults. Cochrane Database Syst Rev 2009; (3): CD004439 CrossRef
33.
Courson AM, Vikram HR, Barrs DM: What are the criteria for terminating treatment for necrotizing (malignant) otitis externa? Laryngoscope 2014; 124: 361–2 CrossRef MEDLINE
34.
Tisch M, Lorenz KJ, Harm M, Lampl L, Maier H: Otitis externa necroticans. Kombinierter Einsatz von chirurgischer Therapie, Antibiose, spezifischen Immunglobulinen und hyperbarer Sauerstofftherapie – Ergebnisse des Ulmer Therapiekonzepts. HNO 2003; 51: 315–20 CrossRef MEDLINE
35.
Phillips JS, Jones SE: Hyperbaric oxygen as an adjuvant treatment for malignant otitis externa. Cochrane Database Syst Rev 2013; (5): CD004617 CrossRef
36.
Le Clerc N, Verillaud B, Duet M, Guichard JP, Herman P, Kania R: Skull base osteomyelitis: incidence of resistance, morbidity, and treatment strategy. Laryngoscope 2014; 124: 2013–6 CrossRef MEDLINE
37.
Stevens SM, Lambert PR, Baker AB, Meyer TA: Malignant otitis externa: a novel stratification protocol for predicting treatment outcomes. Otol Neurotol 2015; 36: 1492–8 CrossRef MEDLINE
38.
Chen CN, Chen YS, Yeh TH, Hsu CJ, Tseng FY: Outcomes of malignant external otitis: survival vs mortality. Acta Otolaryngol 2010; 130: 89–94 CrossRef MEDLINE
39.
Glikson E, Sagiv D, Wolf M, Shapira Y: Necrotizing otitis externa: diagnosis, treatment, and outcome in a case series. Diagn Microbiol Infect Dis 2017; 87: 74–8 CrossRef MEDLINE
40.
Stern Shavit S, Soudry E, Hamzany Y, Nageris B: Malignant external otitis: factors predicting patient outcomes. Am J Otolaryngol 2016; 37: 425–30 CrossRef MEDLINE
e1.
Hajioff D, MacKeith S: Otitis externa. BMJ Clin Evid 2015; 06: 510.
e2.
Mustafa M, Patawari P, Sien MM, Muniandy RK, Zinatara P: Acute otitis externa: pathophysiology, clinical presentation, and treatment. IOSR 2015; 14:73–8.
e3.
Ong YK, Chee G: Infections of the external ear. Ann Acad Med Singapore 2005; 34: 330–4.
e4.
Musso MF, Crews JD: Infections of the external ear. Inf Dis Ped Otolaryngol 2016: 15–28.
e5.
Ijaz T, Anjum AA, Aslam S, Raja SA, Khawaja AR, Ljaz S: Microbial profiling and risk factors assessment for otitis media and otitis externa. Advancements in Life Sciences 2014: 191–6.
e6.
Boustred N: Practical guide to otitis externa. Aust Fam Physician 1999; 28: 217–21 MEDLINE
e7.
Kaur RK, Mittal N, Kakkar M, Aggarwal AK, Mathur MD: Otomycosis: a clinico mycologic study. Ear Nose Throat J 2000; 79: 606–9 MEDLINE
e8.
Al-zubaidy BJ, Abdulrahman TR, Ahmed WA: Detection of exo a gene in Pseudomonas aeruginosa from human and dogs using polymerase chain reaction. IOSR 2014; 9: 38–41 CrossRef
e9.
Connon SJ, Grunwaldt E: Treatment of otitis externa with a tropical steroid-antibiotic combination. Eye Ear Nose Throat Mon 1967; 46: 1296–1302 MEDLINE
e10.
Cannon S: External otitis: controlled therapeutic trial. Eye Ear Nose Throat Mon 1970; 49: 186–9 MEDLINE
e11.
Freedman R: Versus placebo in treatment of acute otitis externa. Ear Nose Throat J 1978; 57: 198–204 MEDLINE
e12.
Kime CE, Ordonez GE, Updegraff WR, Glassman JM, Soyka JP: Effective treatment of acute diffuse otitis externa: II. A controlled comparison of hydrocortisone-acetic acid, nonaqueous and hydrocortisone-neomycin-colistin otic solutions. Curr Ther Res Clin Exp 1978; 23 (Suppl 5): 3–14.
e13.
Clayton MI, Osborne JE, Rutherford D, Rivron RP: A double-blind, randomized, prospective trial of a topical antiseptic versus a topical antibiotic in the treatment of otorrhoea. Clin Otolaryngol Allied Sci 1990; 15: 7–10 CrossRef
e14.
Lambert IJ: A comparison of the treatment of otitis externa with Otosporin and aluminium acetate: a report from a services practice in Cyprus. J Royal Col Gen Pract 1981; 31: 291–4 MEDLINE PubMed Central
e15.
Devos SA, Mulder JJ, van der Valk PG: The relevance of positive patch test reactions in chronic otitis externa. Contact Dermatitis 2000; 42: 354–5.
e16.
Mösges R, Domröse C: Otitis externa — Ihr Leitfaden zur Therapie. MMW 2008; 150: 41–3.
e17.
Martinez Devesa P, Willis CM, Capper JW: External auditory canal pH in chronic otitis externa. Clin Otolaryngol Allied Sci 2003; 28: 320–4 CrossRef
e18.
Cannon SJ, Grunwaldt E: Treatment of otitis externa with a tropical steroid–antibiotic combination. Eye Ear Nose Throat Mon 1967; 46: 1296–302 MEDLINE
e19.
Worgan D: Treatment of otitis externa. Report of a clinical trial. Practitioner 1969; 202: 817–20 MEDLINE
e20.
Smith RB, Moodie J: A general practice study to compare the efficacy and toler- ability of a spray (“Otomize”) versus a standard drop formulation (“Sofradex”) in the treatment of patients with otitis externa. Curr Med Res Opin 1990; 12: 12–8 CrossRef MEDLINE
e21.
Sobie S, Brodsky L, Stanievich JF: Necrotizing external otitis in children: report of two cases and review of the literature. Laryngoscope 1987; 97: 598–601 MEDLINE
e22.
Tezcan I, Tuncer AM, Yenicesu I, et al.: Necrotizing otitis externa, otitis media, peripheral facial paralysis, and brain abscess in a thalassemic child after allogeneic BMT. Pediatr Hematol Oncol 1998; 15: 459–62 CrossRef MEDLINE
e23.
Bovo R, Benatti A, Ciorba A, Libanore M, Borrelli M, Martini A: Pseudomonas and aspergillus interaction in malignant external otitis: risk of treatment failure. Acta Otorhinolaryngol Ital 2012; 32: 416–9 MEDLINE PubMed Central
e24.
Loh S, Loh WS: Malignant otitis externa: an Asian perspective on treatment outcomes and prognostic factors. Otolaryngol Head Neck Surg 2013; 148: 991–6 CrossRef MEDLINE
Department of Otorhinolaryngology, Head and Neck Surgery, University Hospital Leipzig: Prof. Dr. med. Susanne Wiegand, Prof. Dr. med. Andreas Dietz
Department of Pediatrics, University Hospital Carl Gustav Carus Dresden, TU Dresden: Prof. Dr. med. Reinhard Berner
Institute of General Practice, Technical University of Munich:
Prof. Dr. med. Antonius Schneider
HNO-Praxis Lundershausen, Erfurt: Dr. med. Ellen Lundershausen
a) Normal right external auditory canal, with view of the eardrum. b) Swollen introitus of the right external auditory canal in a patient with acute otitis externa. c) An external auditory canal affected by bacterial otitis externa. d) Otomycosis
a) Normal right external auditory canal, with view of the eardrum. b) Swollen introitus of the right external auditory canal in a patient with acute otitis externa. c) An external auditory canal affected by bacterial otitis externa. d) Otomycosis
Figure 1
a) Normal right external auditory canal, with view of the eardrum. b) Swollen introitus of the right external auditory canal in a patient with acute otitis externa. c) An external auditory canal affected by bacterial otitis externa. d) Otomycosis
Treatment algorithm for acute otitis externa (modified from Rosenfeld et al. [8])
Treatment algorithm for acute otitis externa (modified from Rosenfeld et al. [8])
Figure 2
Treatment algorithm for acute otitis externa (modified from Rosenfeld et al. [8])
Exposed bone in the floor of the external auditory canal in a patient with malignant otitis externa
Exposed bone in the floor of the external auditory canal in a patient with malignant otitis externa
Figure 3
Exposed bone in the floor of the external auditory canal in a patient with malignant otitis externa
Predisposing factors for otitis externa (modified from Schäfer et al. [7])
Predisposing factors for otitis externa (modified from Schäfer et al. [7])
Table 1
Predisposing factors for otitis externa (modified from Schäfer et al. [7])
Eardrops that are approved in Germany for the topical treatment of otitis externa
Eardrops that are approved in Germany for the topical treatment of otitis externa
Table 2
Eardrops that are approved in Germany for the topical treatment of otitis externa
1.Leitlinie der Deutschen Gesellschaft für Allgemeinmedizin und Familienmedizin (DEGAM): Ohrenschmerzen. www.awmf.org/uploads/tx_szleitlinien/053–009l_S2k_Ohrenschmerzen_2014–12-verlaengert.pdf (last accessed on 25 January 2019).
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4. Raza SA, Denholm SW, Wong JC: An audit of the management of otitis externa in an ENT casualty clinic. J Laryngol Otol 1995; 109: 130–3 CrossRef MEDLINE
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8. Rosenfeld RM, Schwartz SR, Cannon CR, et al.: Clinical practice guideline: acute otitis externa. Otolaryngol Head Neck Surg 2014; 150(1 Suppl): S1-S24 CrossRef CrossRef CrossRef CrossRef CrossRef CrossRef CrossRef CrossRef CrossRef CrossRef CrossRef CrossRef
9. Sander R: Otitis externa: A practical guide to treatment and prevention. Am Fam Physician 2001; 63: 927–37 MEDLINE
10. Kaushik V, Malik T, Saeed SR: Interventions for acute otitis externa. Cochrane Database Syst Rev 2010; (1): CD004740 CrossRef
11. Rosenfeld RM, Singer M, Wasserman JM, Stinnett SS: Systematic review of topical antimicrobial therapy for acute otitis externa. Otolaryngol Head Neck Surg 2006; 134 (4 Suppl): 24–48 CrossRef MEDLINE
12. Mösges R, Nematian-Samani M, Hellmich M, Shah-Hosseini K: A meta-analysis of the efficacy of quinolone containing otics in comparison to antibiotic-steroid combination drugs in the local treatment of otitis externa. Curr Med Res Opin 2011; 27: 2053–60 CrossRef MEDLINE
13. van Hasselt P, Gudde H: Randomized controlled trial on the treatment of otitis externa with one per cent silver nitrate gel. J Laryngol Otol 2004; 118: 93–6 CrossRef MEDLINE
14. Neher A, Nagl M, Appenroth E, et al.: Acute otitis externa: efficacy and tolerability of N-chlorotaurine, a novel endogenous antiseptic agent. Laryngoscope 2004; 114: 850–4 CrossRef MEDLINE
15. Sood S, Strachan DR, Tsikoudas A, Stables GI: Allergic otitis externa. Clin Otolaryngol Allied Sci 2002; 27: 233–6 CrossRef
16. Rutka J: Acute otitis externa: treatment perspectives. Ear Nose Throat J 2004; 83 (9 Suppl 4): 20–1 MEDLINE
17. Fischer M, Dietz A: Die akute Otitis externa und ihre Differentialdiagnosen. Laryngorhinootol 2015; 94: 113–25 CrossRef MEDLINE
18. Emgard P, Hellstrom S: A group III steroid solution without antibiotic components: an effective cure for external otitis. J Laryngol Otol 2005; 119: 342–7 CrossRef MEDLINE
19. Emgard P, Hellstrom S, Holm S: External otitis caused by infection with pseudomonas aeruginosa or candida albicans cured by use of a topical group III steroid, without any antibiotics. Acta Otolaryngol 2005; 125: 346–52 CrossRef MEDLINE
20. Mösges R, Domröse CM, Löffler J: Topical treatment of acute otitis externa: clinical comparison of an antibiotics ointment alone or in combination with hydrocortisone acetate. Eur Arch Otorhinolaryngol 2007; 264: 1087–94 CrossRef MEDLINE
21. Mösges R, Schröder T, Baues CM, Sahin K: Dexamethasone phosphate in antibiotic ear drops for the treatment of acute bacterial otitis externa. Curr Med Res Opin 2008; 24: 2339–47 CrossRef MEDLINE
22. Roland PS, Younis R, Wall GM: A comparison of ciprofloxacin/
dexamethasone with neomycin/polymyxin/hydrocortisone for otitis externa pain. Adv Ther 2007; 24: 671–5 CrossRef MEDLINE
23. Tietz HJ: Pilzbedingte Otitis externa. Wie werden Gehörgangsmykosen lege artis behandelt? HNO-Nachrichten 2014; 44: 42 CrossRef
24. McCormick AW, Whitney CG, Farley MM, et al.: Geographic diversity and temporal trends of antimicrobial resistance in streptococcus pneumoniae in the United States. Nat Med 2003; 9: 424–30 CrossRef MEDLINE
25. Bhattacharyya N, Kepnes L: Initial impact of the acute otitis externa clinical practice guideline on clinical care. Otolaryngol Head Neck Surg 2011; 145: 414–7 CrossRef MEDLINE
26. Kesser BW: Assessment and management of chronic otitis externa. Curr Opin Otolaryngol Head Neck Surg 2011; 19: 341–7 CrossRef MEDLINE
27. Golder J: Oral steroids in the treatment of otitis externa. Aust Fam Physician 1999; 28: 775 MEDLINE
28. Caffier PP, Harth W, Mayelzadeh B, Haupt H, Scherer H, Sedlmaier B: Topische Immunmodulation. Ein Meilenstein in der Behandlung der therapieresistenten nichtinfektiösen chronischen Otitis externa? HNO 2008; 56: 530–7 CrossRef MEDLINE
29. Mahdyoun P, Pulcini C, Gahide I, et al.: Necrotizing otitis externa: a systematic review. Otol Neurotol 2013; 34: 620–9 CrossRef MEDLINE
30. Tisch M, Maier H: Otitis externa necroticans. Laryngorhinootol 2006; 85: 763–9 CrossRef MEDLINE
31. van Kroonenburgh AMJL, van der Meer WL, Bothof RJP, van Tilburg M, van Tongeren J, Postma AA: Advanced imaging techniques in skull base osteomyelitis due to malignant otitis externa. Curr Radiol Rep 2018; 6: 3 CrossRef MEDLINE PubMed Central
32. Conterno LO, da Silva Filho CR: Antibiotics for treating chronic osteomyelitis in adults. Cochrane Database Syst Rev 2009; (3): CD004439 CrossRef
33. Courson AM, Vikram HR, Barrs DM: What are the criteria for terminating treatment for necrotizing (malignant) otitis externa? Laryngoscope 2014; 124: 361–2 CrossRef MEDLINE
34. Tisch M, Lorenz KJ, Harm M, Lampl L, Maier H: Otitis externa necroticans. Kombinierter Einsatz von chirurgischer Therapie, Antibiose, spezifischen Immunglobulinen und hyperbarer Sauerstofftherapie – Ergebnisse des Ulmer Therapiekonzepts. HNO 2003; 51: 315–20 CrossRef MEDLINE
35. Phillips JS, Jones SE: Hyperbaric oxygen as an adjuvant treatment for malignant otitis externa. Cochrane Database Syst Rev 2013; (5): CD004617 CrossRef
36. Le Clerc N, Verillaud B, Duet M, Guichard JP, Herman P, Kania R: Skull base osteomyelitis: incidence of resistance, morbidity, and treatment strategy. Laryngoscope 2014; 124: 2013–6 CrossRef MEDLINE
37. Stevens SM, Lambert PR, Baker AB, Meyer TA: Malignant otitis externa: a novel stratification protocol for predicting treatment outcomes. Otol Neurotol 2015; 36: 1492–8 CrossRef MEDLINE
38. Chen CN, Chen YS, Yeh TH, Hsu CJ, Tseng FY: Outcomes of malignant external otitis: survival vs mortality. Acta Otolaryngol 2010; 130: 89–94 CrossRef MEDLINE
39. Glikson E, Sagiv D, Wolf M, Shapira Y: Necrotizing otitis externa: diagnosis, treatment, and outcome in a case series. Diagn Microbiol Infect Dis 2017; 87: 74–8 CrossRef MEDLINE
40. Stern Shavit S, Soudry E, Hamzany Y, Nageris B: Malignant external otitis: factors predicting patient outcomes. Am J Otolaryngol 2016; 37: 425–30 CrossRef MEDLINE
e1.Hajioff D, MacKeith S: Otitis externa. BMJ Clin Evid 2015; 06: 510.
e2.Mustafa M, Patawari P, Sien MM, Muniandy RK, Zinatara P: Acute otitis externa: pathophysiology, clinical presentation, and treatment. IOSR 2015; 14:73–8.
e3. Ong YK, Chee G: Infections of the external ear. Ann Acad Med Singapore 2005; 34: 330–4.
e4. Musso MF, Crews JD: Infections of the external ear. Inf Dis Ped Otolaryngol 2016: 15–28.
e5. Ijaz T, Anjum AA, Aslam S, Raja SA, Khawaja AR, Ljaz S: Microbial profiling and risk factors assessment for otitis media and otitis externa. Advancements in Life Sciences 2014: 191–6.
e6.Boustred N: Practical guide to otitis externa. Aust Fam Physician 1999; 28: 217–21 MEDLINE
e7.Kaur RK, Mittal N, Kakkar M, Aggarwal AK, Mathur MD: Otomycosis: a clinico mycologic study. Ear Nose Throat J 2000; 79: 606–9 MEDLINE
e8.Al-zubaidy BJ, Abdulrahman TR, Ahmed WA: Detection of exo a gene in Pseudomonas aeruginosa from human and dogs using polymerase chain reaction. IOSR 2014; 9: 38–41 CrossRef
e9.Connon SJ, Grunwaldt E: Treatment of otitis externa with a tropical steroid-antibiotic combination. Eye Ear Nose Throat Mon 1967; 46: 1296–1302 MEDLINE
e10.Cannon S: External otitis: controlled therapeutic trial. Eye Ear Nose Throat Mon 1970; 49: 186–9 MEDLINE
e11.Freedman R: Versus placebo in treatment of acute otitis externa. Ear Nose Throat J 1978; 57: 198–204 MEDLINE
e12.Kime CE, Ordonez GE, Updegraff WR, Glassman JM, Soyka JP: Effective treatment of acute diffuse otitis externa: II. A controlled comparison of hydrocortisone-acetic acid, nonaqueous and hydrocortisone-neomycin-colistin otic solutions. Curr Ther Res Clin Exp 1978; 23 (Suppl 5): 3–14.
e13.Clayton MI, Osborne JE, Rutherford D, Rivron RP: A double-blind, randomized, prospective trial of a topical antiseptic versus a topical antibiotic in the treatment of otorrhoea. Clin Otolaryngol Allied Sci 1990; 15: 7–10 CrossRef
e14.Lambert IJ: A comparison of the treatment of otitis externa with Otosporin and aluminium acetate: a report from a services practice in Cyprus. J Royal Col Gen Pract 1981; 31: 291–4 MEDLINE PubMed Central
e15.Devos SA, Mulder JJ, van der Valk PG: The relevance of positive patch test reactions in chronic otitis externa. Contact Dermatitis 2000; 42: 354–5.
e16.Mösges R, Domröse C: Otitis externa — Ihr Leitfaden zur Therapie. MMW 2008; 150: 41–3.
e17.Martinez Devesa P, Willis CM, Capper JW: External auditory canal pH in chronic otitis externa. Clin Otolaryngol Allied Sci 2003; 28: 320–4 CrossRef
e18.Cannon SJ, Grunwaldt E: Treatment of otitis externa with a tropical steroid–antibiotic combination. Eye Ear Nose Throat Mon 1967; 46: 1296–302 MEDLINE
e19. Worgan D: Treatment of otitis externa. Report of a clinical trial. Practitioner 1969; 202: 817–20 MEDLINE
e20.Smith RB, Moodie J: A general practice study to compare the efficacy and toler- ability of a spray (“Otomize”) versus a standard drop formulation (“Sofradex”) in the treatment of patients with otitis externa. Curr Med Res Opin 1990; 12: 12–8 CrossRef MEDLINE
e21.Sobie S, Brodsky L, Stanievich JF: Necrotizing external otitis in children: report of two cases and review of the literature. Laryngoscope 1987; 97: 598–601 MEDLINE
e22. Tezcan I, Tuncer AM, Yenicesu I, et al.: Necrotizing otitis externa, otitis media, peripheral facial paralysis, and brain abscess in a thalassemic child after allogeneic BMT. Pediatr Hematol Oncol 1998; 15: 459–62 CrossRef MEDLINE
e23.Bovo R, Benatti A, Ciorba A, Libanore M, Borrelli M, Martini A: Pseudomonas and aspergillus interaction in malignant external otitis: risk of treatment failure. Acta Otorhinolaryngol Ital 2012; 32: 416–9 MEDLINE PubMed Central
e24.Loh S, Loh WS: Malignant otitis externa: an Asian perspective on treatment outcomes and prognostic factors. Otolaryngol Head Neck Surg 2013; 148: 991–6 CrossRef MEDLINE