a b s t r a c t

Introduction: Malignant otitis externa (MOE) is a progressive infection of the external auditory canal (EAC). This disease is rare but has severe morbidity and mortality.

Objective: This narrative review provides an overview of malignant otitis externa for emergency clinicians. Discussion: MOE is an invasive external ear infection that spreads to the temporal bone and can further progress to affect intracranial structures. Complications of advanced MOE include cranial nerve involvement, most com- monly the facial nerve, and intracranial infections such as abscess and meningitis. The most common causative agent of MOE is Pseudomonas aeruginosa, but others include methicillin-resistant Staphylococcus aureus and fungi. Major risk factors for MOE include diabetes mellitus, immunosuppression, and advanced age. Red flags for MOE include severe otalgia (pain out of proportion to exam) or severe otorrhea, neurologic deficits (especially facial nerve involvement), previously diagnosed otitis externa not responsive to therapy, and patients with major risk factors for MOE. Examination may show purulent otorrhea or granulation tissue in the EAC, and culture of EAC drainage should be performed. Diagnosis is aided by computed tomography (CT) with intravenous contrast, which may demonstrate bony destruction of the temporal bone or skull base. When suspecting MOE, early con- sultation with an otolaryngologist is recommended and antibiotics with pseudomonal coverage are needed. Most patients with MOE will require admission to the hospital.

Conclusions: MOE is a rare, yet deadly diagnosis that must be suspected when patients with immunocompromise, diabetes, or advanced age present with severe otalgia. Rapid diagnosis and treatment may prevent complications and improve outcomes.

Introduction

Malignant otitis externa (MOE) is a severe and progressive infection of the external auditory canal (EAC) [1]. This disease is uncommon, but if missed, may lead to severe complications and even death. MOE was first described in 1959 as a case of progressive Pseudomonas osteomye- litis of the temporal bone in a patient with diabetes [2]. The term “ma- lignant otitis externa” was first used in 1968 by Chandler in a case series of patients with progressive osteomyelitis of the temporal bone [3]. MOE has also been called “necrotizing otitis externa” and “skull base osteomyelitis.” [4] “Skull base osteomyelitis” most accurately de- scribes the pathophysiology of this disease, as MOE starts as an infection of the EAC which spreads to the temporal bone and skull base [5-7]. However, MOE is a different entity from skull base osteomyelitis, as skull base osteomyelitis can be caused by disease processes other than MOE such as sinusitis or mastoiditis [6,7]. From the skull base, MOE can continue to spread to intracranial structures leading to further

* Corresponding author at: 3841 Roger Brooke Dr, Fort Sam Houston, TX 78234, United States.

E-mail address: [email protected] (D.A. Long).

complications [8]. Prior to the use of antibiotic therapy, MOE had high rates of morbidity and mortality, with rates of death reported as high as 50% [3]. Even with current diagnosis and management including an- tibiotics, this disease still carries a high morbidity and mortality, with current rates of mortality estimated as high as 15% [9]. Given this high morbidity and mortality, it is vital for the emergency physician to con- sider this diagnosis when evaluating patients with severe otalgia and otorrhea. This narrative review will provide an overview of malignant otitis externa, with a focus on the clinical features, diagnosis, and man- agement of this potentially fatal condition.

Methods

The authors searched PubMed and Google Scholar for articles using the keywords “malignant otitis externa,” “necrotizing otitis externa,” and “skull base osteomyelitis.” The search was conducted from database inception to 12 January 2020. PubMed yielded 460 articles. The first 200 articles in Google Scholar were also searched as recommended by Bramer et al. [10] Authors included case reports and series, retrospective and pro- spective studies, systematic reviews and meta-analyses, clinical guide- lines, and other narrative reviews. The literature search was restricted

https://doi.org/10.1016/j.ajem.2020.04.083 0735-6757/

to studies published in English. Emergency physicians with experience in critical appraisal of the literature reviewed all of the articles and decided which studies to include for the review by consensus, with a focus on emergency medicine-relevant articles. When available, systematic re- views and meta-analyses were preferentially selected, followed sequen- tially by randomized controlled trials, prospective studies, retrospective studies, case reports, and other narrative reviews when alternate data were not available. A total of 100 resources were selected for inclusion in this review from the initial 460 resources. Many of these resources con- cerned nuclear imaging, were case reports, or focused on otolaryngology clinics and long-term therapy. Authors of this review preferentially se- lected resources pertaining to emergency medicine evaluation and management.

Discussion

Pathophysiology

Similar to otitis externa (OE), MOE begins as a soft tissue infection of the EAC [2-5]. Unlike OE, the infection in MOE spreads to involve the tem- poral bone and can spread further to the skull base and intracranial structures leading to complications including cranial nerve palsies and in- tracranial infections [8]. The infection advances from the EAC to the temporal bone and skull base through the fissures of Santorini, which are small perforations in the cartilaginous portion of the base of the EAC (Fig. 1) [5,7]. As the disease expands into the skull, the normal compact bone is replaced with granulation tissue, leading to skull base

osteomyelitis [6,7], an inflammatory destructive process of bone [11]. Pro- gressive spread to the skull base foramina can result in cranial neuropa- thies, with the facial nerve the most commonly affected nerve due to its close proximity to the EAC [3,5,12]. The nerves of the jugular foramen (Cranial nerves IX, X, and XI) and cranial nerve XII in the hypoglossal canal may also be affected [5,13]. One case series of 23 Diabetic patients with MOE found cranial nerve involvement occurred in 10 patients [13]. Of these 10 patients, 6 had facial nerve involvement, and 4 had a combi- nation of involvement of other nerves including cranial nerves VI through XII [13]. In another case series in 2010 of 26 diabetic patients with MOE, 11 patients (42%) had cranial nerve involvement, with 10 (38.4%) demon- strating facial nerve involvement [14]. In severe cases with progressive spread, MOE can involve the sigmoid sinus leading to septic thrombosis of the sigmoid sinus and internal jugular vein [4,8,15]. Intracranial spread may also result in infectious complications including intracranial ab- scesses or meningitis [4,8,15]. Other reported complications of MOE in- clude parotitis and mastoiditis [16].

Pseudomonas aeruginosa (P. aeruginosa) has long been reported as the most common causative agent of MOE. P. aeruginosa,a gram-negative ob- ligate aerobe, colonizes the EAC in the setting of a moist environment or after trauma [17]. P. aeruginosa is not a normal component of ear canal flora even in diabetic patients, and its isolation should be assumed abnor- mal and pathologic [18]. A 1988 literature review of 280 cases of MOE found that 99.2% of cases were due to P. aeruginosa infection [19]. How- ever, more recent studies suggest decreasing prevalence of P. aeruginosa as the causative agent of MOE. Chen et al. in 2010 reported a 26.9% inci- dence of Pseudomonas infection in their patient cohort of 26 diabetic

Fig. 1. External and middle ear anatomy.

From https://upload.wikimedia.org/wikipedia/commons/2/29/Gray907.png.

patients [14]. In this study, the next most common pathogen identified was Klebsiella pneumoniae (19.2%) followed by fungi (15.4%). Another case series from 2010 evaluated a cohort of 51 patients with MOE;

P. aeruginosa accounted for 34% of isolated causative pathogens [20]. In a 2014 retrospective case series of 20 patients, 9 patients (45%) had cul- tures that grew P. aeruginosa and 3 three (15%) had cultures that grew methicillin-resistant Staphylococcus aureus (MRSA) [21]. In this case se- ries, all patients with P. aeruginosa had diabetes, compared to 33% of the patients with MRSA. Finally, a 2017 retrospective analysis of 28 patients found P. aeruginosa in 13 patients (46%) and MRSA in 10 patients (36%) [22]. While P. aeruginosa is the most common cause in MOE, other micro- organisms may lead to MOE, which may lead to ineffective treatment of MOE and higher likelihood of progressive disease and complications.

Fungi are another critical cause of MOE to consider in patients with human immunodeficiency virus or patients with severe immuno- suppression, such as patients with advanced cancer or history of trans- plant [23,24]. Fungal MOE is also associated with underlying chronic sinusitis and may also occur secondary to prolonged antibiotic treat- ment for MOE [25]. Aspergillus and Candida are the most common fungal species involved in MOE [25-28]. In patients with HIV, infection with

P. aeruginosa is thought to more commonly occur with CD4 counts of b100/mm³ and Aspergillus with CD4 counts b 50/mm³ [23]. Fungi should also be considered when MOE fails to respond to standard anti- microbial therapy, defined as treatment with an otherwise appropriate agent for 6 to 8 weeks [5].

Risk factors

The most common reported risk factor in the literature for develop- ing MOE is diabetes mellitus , with an estimated 90-100% of pa- tients with MOE having DM [13,29-31]. DM is thought to predispose patients to MOE due to microangiopathy, impaired wound healing, and a diminished immune response [32,33]. Another major risk factor for MOE is immunosuppression, such as patients suffering from HIV, transplant patients, or patients with advanced cancer [5,7]. MOE should be suspected when patients with immunosuppression present with symptoms of otitis externa, especially if they have been previously diag- nosed with otitis externa that is not responding to typical therapy [34].

While DM and immunosuppression are the two primary risk factors for MOE, several studies have found that advanced age is another impor- tant factor in the development of MOE [35,36]. A case series from 1984 re- ported several cases of MOE in patients with no underlying immunocompromising condition, with the only major identified risk fac- tor being increased age [35]. These ages of the patients in this case series was 87, 93, and 93 years. An analysis of 8300 patients hospitalized with MOE from 2002 to 2013 found that elderly patients (N65 years of age) may have an increased risk of complications from MOE and a worse prog- nosis compared to younger patients [36]. Specifically, this study reported that patients N 65 years had more inpatient procedures, longer hospitali- zations, greater odds of complications, and higher in-hospital mortality. Complications included sialadenitis, facial nerve palsy, vagus nerve dys- function, central nervous system complications, and sepsis. Another study found that patients over the age of 70 years had a 5-year survival of 44%, while patients younger than 70 had a 5-year survival of 75% [37]. Compared to adults, MOE is even rarer in children. It has been re- ported to occur in children with diabetes [5] and other immunocompro- mised conditions, including IgG deficiency [38], IgA deficiency [39], leukemia [40], neutropenia [41], and after bone marrow transplantation [42]. Overall, children diagnosed with MOE are thought to have a better

prognosis than adults [43].

Clinical manifestations

MOE presents similarly to OE in the early stages of the disease, making the diagnosis challenging. A systematic review from 2013 found a diagnostic delay averaging 70 days between first presentation and

appropriate diagnosis and therapy [44]. MOE commonly presents with se- vere, unremitting otalgia, aural fullness, and otorrhea [5]. Multiple studies have reported otalgia to be the most common presenting symptom, with pain usually worse at night [45-47]. Evidence of MOE compared to simple OE is pain out of proportion to examination and severe, purulent otorrhea [5]. MOE should also be suspected with otalgia persisting for longer than one month [22]. As MOE leads to skull base and temporal osteomyelitis, patients may experience headache, temporomandibular joint pain or dys- function, or decreased oral intake secondary to trismus [6,7]. Patients may also experience conductive hearing loss due to bony destruction from skull base osteomyelitis [6].

Physical examination findings suggestive of MOE include purulent otorrhea with a swollen, tender EAC (Fig. 2) [5]. Granulation tissue or ex- posed bone may be present on the floor of the ear canal at the bony- cartilaginous junction [44,48]. Patients early in the disease course or pa- tients with immunosuppression may lack typical granulation tissue along the floor of the EAC [49]. If visualized, the tympanic membrane typ- ically appears normal in MOE [5]. MOE may also lead to cranial neuropa- thies, most commonly the facial nerve in the stylomastoid foramen, with involvement reported in 7-46% of cases [7,22,48]. In pediatric patients MOE is thought to involve the facial nerve more frequently, which is esti- mated to occur in up to 53% of pediatric patients [43]. Increased frequency of facial nerve involvement in children is due to closer proximity of the fa- cial nerve to the stylomastoid foramen [43]. MOE may involve the cranial nerves of the jugular foramen (CNs IX, X, and XI) and the hypoglossal nerve [13]. Later findings include signs and symptoms of intracranial in- fections such as meningitis or an intracranial abscess, which are associ- ated with poor prognosis, as these findings indicate advanced disease [5,13,22]. Table 1 provides signs and symptoms suggestive of MOE.

Fig. 2. Severe otorrhea.

From https://en.wikipedia.org/wiki/Otitis_externa#/ media/File:OSC_Microbio_21_02_folliculit_(cropped).jpg.

Differential diagnosis

The differential diagnosis for MOE includes multiple entities, some of which are rarely encountered by the emergency physician. Conditions that may be confused with MOE include Paget’s disease, mastoiditis, keratosis obturans, seborrheic dermatitis, carcinoma of the ear canal, cholesteatoma, suppurative labyrinthitis, Otitis media, perichondritis, and otitis externa [5,6,50,51]. Two of these conditions that may easily be confused with MOE include otitis externa (OE) and mastoiditis.

OE is an infection leading to inflammation of the EAC [52]. MOE may be clinically indistinguishable from simple OE early in the disease course. OE occurs most commonly in children [53]. Risk factors include swim- ming or other outdoor water exposure, ear trauma from excessive cleaning or scratching, and use of ear devices such as earplugs or hearing aids [52,54]. Patients with OE most commonly complain of otalgia (70%), pruritis (60%), hearing loss (32%), and ear fullness (22%) [55]. On exami- nation, the patient will commonly have tenderness with tragal pressure or manipulation [55]. On otoscopy, the ear canal may be partially or completely occluded by debris or purulent drainage, but the tympanic membrane should appear normal if visualized (as seen in MOE) [56]. Ad- ditionally, the EAC typically appears erythematous and inflamed [56]. While MOE may be difficult to distinguish from OE, if the patient is well appearing and lacks risk factors for MOE, a trial of therapy for OE, such as antimicrobial drops (ciprofloxacin/hydrocortisone or polymyxin B/ neomycin/hydrocortisone) or suspension (ofloxacin) may be conducted. If improvement is seen after 3 to 4 days of topical therapy, this is strongly suggestive of OE. However, if little or no improvement is seen after one week of topical therapy, the patient likely has a diagnosis other than un- complicated OE, raising the suspicion for MOE [34,57].

MOE may also be difficult to distinguish from mastoiditis. Mastoiditis is a suppurative infection of the mastoid air cells [58]. Similar to OE, mas- toiditis occurs most commonly in children, with the majority of cases oc- curring in patients younger than 2 years [59]. Mastoiditis most commonly presents as postauricular erythema, edema, and tenderness to palpation, particularly over the mastoid bone [51]. On examination, the affected side may display a posteriorly and downwardly displaced auricle [60]. In a systemic review of diagnostic criteria for mastoiditis in pediatric pa- tients, authors found the most common signs and symptoms included malaise or lethargy (96%); abnormal tympanic membrane (82%); postauricular erythema, tenderness, and/or protrusion of the pinna (80%); fever (76%); narrowing of the EAC (71%); ear pain (67%); and otorrhea (50%) [61]. Mastoiditis most commonly occurs as a complication of otitis media, which should be seen on otoscopy of the affected side, as opposed to a healthy-appearing tympanic membrane in MOE [62]. If un- able to differentiate mastoiditis and MOE, further investigation with com- puted tomography (CT) with intravenous contrast should be pursued [63].

Diagnosis

Laboratory evaluation has limited utility in the diagnosis of MOE. The white blood cell count may be elevated in patients with MOE, but it is usually normal [12,13,22]. Inflammatory markers, particularly erythrocyte sedimentation rate and C-reactive protein (CRP),

Table 1

Red flags for malignant otitis externa.

Severe otalgia (pain out of proportion to examination) or severe otorrhea Otalgia lasting N1 month

Signs or symptoms of TMJ involvement (pain or trismus)

Neurologic deficits (especially facial nerve palsy) associated with otalgia Previously diagnosed OE that is not responding to typical therapy

Major risk factors for MOE: elderly patient (N65 years), diabetes, immunosuppression

Abbreviations: TMJ–temporomandibular joint; OE–otitis externa; MOE–malignant otitis externa.

may be used for monitoring response to treatment [64,65]. However, there is a paucity of evidence of the sensitivity for either ESR or CRP for the initial presentation of MOE. While inflammatory markers may be helpful, negative inflammatory markers do not rule out the diagnosis. However, these laboratory tests may be useful for monitoring the course of the disease and should be obtained in the Emergency Department.

Cultures of any purulent otorrhea or tissue samples of granulation tis- sue are critical in the diagnostic evaluation of MOE. Specimens should be sent for bacterial, fungal, and mycoBacterial cultures (a rare cause of chronic OM) [66,67]. As multiple pathologic organisms including bacteria and fungi can cause MOE, culture results are vital in determining appro- priate medical therapy against the causative agent [5,9]. Yields of the cul- tures will guide medical therapy over the next several weeks to months. If an inappropriate antimicrobial is utilized for treatment, the infection will continue to spread, leading to further complications and potentially even death.

Imaging

Nuclear scanning was previously considered the imaging modality of choice for diagnosis of MOE [68,69]. However, this is not available in the ED and is best for monitoring Disease progression rather than making the Initial diagnosis [68]. With its rapid availability and diagnostic accu- racy, computed tomography (CT) of the head with intravenous contrast is the first line imaging modality for diagnosis of MOE in the ED (Fig. 3). In a 2007 study, CT scanning was found to be very sensitive in diagnosing MOE, with all 22 patients having CT findings indicative of MOE [13]. CT has provided poorer diagnostic yield in other studies, with sensitivity re- ported as low as 48% in a case series of 25 patients [12]. High-resolution CT can evaluate for soft tissue and bony abnormalities associated with MOE and may delineate the extent of bony erosion and skull deminerali- zation [68]. However, early in the disease course, CT scan will likely be nonspecific and may only show soft tissue swelling around the EAC [68,70]. These soft tissue changes may be visualized on CT as obliteration of normal fat planes [68]. Soft tissue and fat plane changes may be en- hanced with the use of intravenous contrast, which may also aid in diag- nosing Intracranial complications, such as septic thrombosis or intracranial abscesses [68]. The most frequent route of spread of MOE (ap- proximately 80%) is through the temporal bone with invasion of the tem- poromandibular joint and erosion of the clivus [71-73]. Osseous changes may be visualized along this anatomic path as the infection spreads, al- though this may be a later finding in the disease course [70]. Additionally, the jugular foramen, stylomastoid foramen, and lacerum foramen may be involved with MOE, which are likely to result in cranial neuropathies [68]. MRI is better than CT for detecting soft tissue changes, especially in- volvement of the medullary bone spaces [70]. Involvement of the retrocondylar fat pad and parapharyngeal spaces on MRI may be an early diagnostic finding [74]. MRI is also more sensitive at detecting complications of MOE such as thrombosis and intracranial infection [68]. However, MRI is less sensitive for bony erosion and furthermore may not be available in the ED and is more likely to be ordered as an in-

patient test [5,68].

If there is concern for Cerebral venous thrombosis or septic thrombosis as a complication of MOE, further imaging including CT ve- nography or magnetic resonance venography is recommended for diag- nosis if initial CT does not diagnose CVT [75-78]. Concomitant CVT or septic thrombosis affects management, as CVT requires anticoagulation or thrombolytic therapy and septic thrombosis additionally requires broad spectrum antibiotics [79-82]. Local thrombolytic therapy or open thrombectomy is reserved for patients for CVT with severe neuro- logic deterioration [83-85].

Diagnostic criteria

Cohen and Friedman in 1987 examined diagnostic criteria of MOE, dividing factors into major criteria and minor criteria [86]. According

Fig. 3. CT of the head and neck demonstrating necrotizing otitis externa. Image A with white arrow demonstrating swelling of the left external auditory meatus, pinna, and periauricular soft tissue. Image B with white arrows demonstrating spreading infection to the parotid and masticator space. Dr. Charlie Chia-Tsong Hsu, Radiopaedia.org, rID: 19938.

to this strategy, patients must have all major criteria for the diagnosis of MOE. While these criteria may be used by the otolaryngology (ENT) sur- geon, several of the major criteria are not applicable to the emergency physician upon patient presentation in the ED. However, these criteria are helpful for an emergency physician, as presence of these factors should increase suspicion for MOE (Table 2).

Prognosis

Several factors are associated with poor outcome in patients with MOE. Thakar et al. in 1996 proposed a staging system for MOE, with each progressive stage associated with an increased risk for complica- tions and death (Table 3) [87]. In a retrospective review from 2004 to 2014, Stevens et al. identified factors associated with poor outcomes, in- cluding facial nerve palsy, fungal etiology of MOE, relapse of MOE, need for surgery, and major radiographic findings [88]. In this study, radio- graphic criteria included findings of bone erosion, intracranial involve- ment, or nasopharyngeal involvement on either CT or MRI. These findings suggest the infection has broken its anatomic boundaries and spread to adjacent tissue compartments. In this study, there was a 42% mortality in the patients in the severe cohort (defined as two or more of the above risk factors), compared to a 0% mortality in the patients in the non-severe cohort (none of the above risk factors) [88]. The over- all disease mortality was 17.8% in this study, further emphasizing the high potential lethality from MOE and need for early identification and treatment [88].

Multiple studies have evaluated utilizing facial nerve palsy as a prog- nostic indicator. Facial nerve involvement has been suggested as a poor

prognostic indicator of MOE, indicating advanced disease [71]. How- ever, Mani et al. and Soudry et al. compared patients with MOE with and without facial nerve involvement and found no difference in sur- vival between groups [13,89]. While the prognostic capability of facial nerve involvement in patients with MOE is controversial, signs of intra- cranial infection associated with MOE, such as meningitis, abscess for- mation, or septic venous thrombosis, are commonly fatal and represent late stage MOE [48].

Management

If the clinician suspects MOE based on history and examination or imaging reveals a definitive diagnosis, ENT consultation is recom- mended. If consultation with an ENT specialist is not available, empiric antimicrobial therapy in addition to initial diagnostic modalities should be initiated, and the patient should be transferred to a center with an ENT service.

When MOE is suspected, discussion with an Infectious Disease spe- cialist is recommended to assist with determining the appropriate ther- apy. Appropriate antimicrobial therapy can prevent bony destruction and further spread of MOE to intracranial structures [3-5]. Cultures of EAC drainage should be obtained prior to antimicrobial therapy, as cul- ture results will guide the course of treatment. Fluoroquinolones cover

P. aeruginosa and additionally have excellent bone penetration, making them the usual first line therapy [5,9]. Ciprofloxacin is the most com- monly used fluoroquinolone, and long-term monotherapy for 6-8 weeks with oral ciprofloxacin (750 mg by mouth twice per day) has been proposed as the initial antibiotic regimen [30]. However,

Table 2

Diagnostic criteria of MOE.

Adapted from Cohen D, Friedman P [86].

Major criteria Minor criteria

Table 3

Staging of malignant otitis externa. Adapted from Thakar et al. [87]

Pain Pseudomonas in culture

Exudate Diabetes mellitus

Edema Advanced age (N65)

Granulations Cranial nerve involvement

Microabscesses (observed during surgery) Positive radiograph^a Positive Technetium-99 bone scan Debilitating conditions

^a Bony erosion or skull demineralization of the temporal bone on computed tomogra-

Stage 1

Stage 2

Stage 3

Necrotizing external otitis (otalgia, granulation tissue of EAC); no cranial nerve involvement

Limited skull base osteomyelitis (lateral to jugular foramen); may have facial nerve involvement

Extensive skull base osteomyelitis (jugular foramen and further Intracranial extension); may have CN IX, X, XI, XII involvement or intracranial infection

phy or magnetic resonance imaging. Abbreviations: EAC–external ear canal; CN–cranial nerve.

ciprofloxacin has poor Gram-positive bacteria coverage and additionally does not cover MRSA.

Fluoroquinolone-resistant P. aeruginosa varies greatly across differ- ent clinical settings, with resistance rates as high as 30-33% in some set- tings [29,72]. Multidrug-resistant (MDR) or extensively drug resistant (XDR) pathogens have provided challenges in treatment of infections. MDR and XDR P. aeruginosa was evaluated in a 2018 meta-analysis that included 54 articles [91]. This meta-analysis defined MDR as resis- tance to at least one antibiotic in three or more classes of antibiotics, and XDR was defined as non-susceptibility to at least one agent in all but two or fewer antimicrobial categories. This meta-analysis found that prior use of fluoroquinolones (odds ratio 2.2) and prior ICU stay (odds ratio 3.59) were significant risk factors for acquisition of MDR

P. aeruginosa. Specifically, prior use of fluoroquinolones, presence of an

indwelling airway, co-existing diabetes mellitus, and nosocomial resi- dence were risk factors for quinolone-resistant P. aeruginosa. If concern for quinolone-resistant P. aeruginosa is present, other agents that have anti-Pseudomonal activity include piperacillin-tazobactam, ceftazidime, cefepime, and meropenem [90-92]. Increasing prevalence of MDR or- ganisms makes gathering EAC cultures and tissue specimens essential, as specimen results can assist in determining appropriate antimicrobial therapy. If available, previous culture results should be reviewed prior to administering antibiotics.

In patients who appear ill with signs of sepsis, Systemic Infection, or intracranial spread, broad-spectrum antimicrobial coverage is war- ranted. Antimicrobial coverage for concern for sepsis from an intracra- nial source or abscess includes vancomycin (20 mg/kg IV) and one of the following: cefepime (2 g IV), ceftazidime (2 g IV), or meropenem (2 g IV) [93,94]. If a patient has a severe penicillin allergy, meropenem (2 g IV) can be substituted for cefepime. If concern for an intracranial ab- scess is present, metronidazole (500 mg IV) should be added to the pre- viously mentioned regimen [93,94].

In patients with HIV, severe immunosuppression, or MOE that has failed antibiotic therapy, fungal etiologies of MOE should be suspected [15,95-97]. If the emergency physician is concerned for a fungal etiology of MOE, antifungal therapy should be discussed with Infectious Disease and ENT specialists. Amphotericin B is the most commonly used anti- fungal in the treatment of fungal MOE [26,27,95-98]. Given the poten- tial for significant toxicity, liposomal amphotericin B is utilized when available [26,27,95,96]. Other agents that have been utilized for fungal MOE are itraconazole, voriconazole, and caspofungin [99].

Topical agents, while the treatment of choice of OE, are not recom- mended for treatment of MOE [5,31,72]. Topical agents may decrease the likelihood of obtaining an accurate culture and lead to the potential for increased Antimicrobial resistance [5].

A potential adjunctive therapy for MOE is Hyperbaric oxygen (HBO). HBO is thought to increase the partial pressure of oxygen and may lead to increased oxidative killing of bacterial pathogens [5]. Case reports suggest improved outcomes with the use of HBO in MOE [100,101]. One report described a patient with MOE and facial nerve palsy that im- proved after use of HBO [100], and another described a patient with MOE and Optic neuritis that was refractory to Standard therapy and only improved after the use of HBO [101]. However, a Cochrane review in 2013 found no randomized controlled trials comparing HBO to stan- dard treatment with antibiotics and/or surgery and concluded that there was no evidence for the efficacy of HBO in the management of MOE [102].

Disposition

Patients who are well-appearing with adequate pain control, normal oral intake, no immunocompromise, no cranial nerve involvement, and ENT follow up may be appropriate for discharge with oral antibiotics. However, most patients will require admission, especially those with severe pain, stage 2 or 3 MOE, clinical suspicion of fungal etiology,

immunocompromise, cranial nerve involvement, or for those with diffi- culty obtaining follow up.

Conclusions

MOE is an invasive infection of the external auditory canal that may spread to the temporal bone and skull base. Clinicians should consider this diagnosis in patients presenting with severe otalgia or otorrhea, es- pecially if they have pain out of proportion to exam, temporomandibu- lar joint involvement, or any neurologic deficits. Important risk factors for MOE include diabetes, advanced age, and immunocompromised sta- tus. Delayed diagnosis is associated with higher likelihood for intracra- nial complications and death. The initial imaging modality for diagnosis is CT scan of the head with IV contrast, which may show bony erosion. Treatment is aimed at Pseudomonas aeruginosa, as this is the most common etiology. The most commonly used antibiotic for MOE is ciprofloxacin, but clinicians should consider risk factors for fluoroquinolone-resistant Pseudomonas. Prior to antimicrobial therapy, cultures of any drainage and tissue specimens of granulation tissue should be obtained. Most patients require admission, but a select pa- tient population may be appropriate for discharge if follow up is ensured.

Declaration of competing interest

None.

Acknowledgements

DL, AK, and BL conceived the idea for this manuscript and contrib- uted substantially to the writing and editing of the review. We would like to thank Dr. David Talan for his contributions and for reviewing this manuscript prior to submission. This manuscript did not utilize any grants or funding, and it has not been presented in abstract form. Ap- proval to submit this review to American Journal of Emergency Medicine was granted by Dr. J Douglas White. This clinical review has not been published, it is not under consideration for publication elsewhere, its publication is approved by all authors and tacitly or explicitly by the re- sponsible authorities where the work was carried out, and that, if ac- cepted, it will not be published elsewhere in the same form, in English or in any other language, including electronically without the written consent of the copyright-holder. This review does not reflect the views or opinions of the U.S. government, Department of Defense, U.S. Army,

U.S. Air Force, or SAUSHEC EM Residency Program.

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