Hospital Medicine

Malignant otitis externa

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I. What every physician needs to know.

Malignant otitis externa (MOE), also known as necrotizing otitis externa, is an invasive bacterial infection that involves the external auditory canal and skull base. It is a complication of external otitis externa that occurs in immunocompromised patients.Pseudomonas aeruginosa is causative in 95% of cases.P. aeruginosa is a ubiquitous gram negative rod and its recovery from the external auditory canal indicates the presence of a pathogen.

Otitis externa is typically seen in elderly diabetic patients. Diabetics have an increased pH in cerumen which facilitates growth of pseudomonas. Other causative organisms includeAspergillus, Staphylococcus aureus, Proteus mirabilis, Klebsiella oxytoca, Burkholderia cepacia, andCandida parapsilosis. Infection with these organisms most commonly occurs in immunocompromised hosts such as patients with AIDS or hematologic malignancies. Diagnosis is based on clinical, laboratory, and radiographic findings.

Antipseudomonal antimicrobials are the mainstay of therapy for malignant external otitis. Prior to the development of systemic agents, the mortality from this disease approximated 50% with frequent recurrences. The cure rate has increased to 90% with the introduction of fluroquinolones.

II. Diagnostic Confirmation: Are you sure your patient has Malignant Otitis Externa?

A. History Part I: Pattern Recognition:

Symptoms:

  • Exquisite otalgia - Pain tends to be nocturnal with radiation to the temporalmandibular joint.

  • Otorrhea - Foul smelling discharge from the external auditory meatus.

  • Hearing loss or fullness - Obliteration of the external auditory canal by edema and secretions may cause hearing loss or a sensation of fullness in the ear.

  • Difficulty with mastication.

Signs:

  • Ear pain out of proportion to exam that is exacerbated by pulling on the pinna and putting pressure over the tragus.

  • Ear canal erythema and swelling.

  • Exudative discharge from the ear.

  • Decreased conductive hearing.

  • Lymphadenopathy - Postauricular, preauricular, and lateral cervical lymph nodes.

  • Facial paralysis, cranial nerve abnormalities, vertigo, or sensorineural hearing loss.

  • Trismus may occur from extension into the temporomandibular joint and the parotid gland.

  • Fungal otitis externa may show hyphae and a grayish membrane in the canal.

B. History Part 2: Prevalence:

  • Diabetes mellitus: More than 90% of cases have glucose intolerance.

  • Immunocompromised: Acquired immunodeficiency disorder, Myleoid malignancies, Immunosuppressive medications (e.g., renal transplant), chemotherapy induced bone marrow aplasia.

  • Elderly.

  • Hot, humid climates.

  • Exposure due to pseudomonas aeruginosa in water with a high chloride, e.g., swimming pools.

  • Self-inflicted or iatrogenic trauma to the external auditory canal: Ear irrigation, use of cotton swabs in the ear.

  • Rare in children: Fewer than 20 cases in the literature; immunocompromised by malignancy or malnutrition; more likely to have concomitant bacteremia

C. History Part 3: Competing diagnoses that can mimic Malignant Otitis Externa.

Simple otitis externa:

  • Responds to topical antibiotics.

  • Does not involve the structures beyond the soft tissues of the auditory canal.

Squamous cell carcinoma of external audiory canal:

  • Also presents with otalgia and otorrhea.

  • Can be differientated from MOE only by biopsy.

Otitis media:

  • External ear and canal are clear.

Chronic suppurative otitis media:

  • No pain.

  • Chronic purulent drainage occurs from a perforated TM.

Cholesteatoma:

  • Also presents with purulent drainage but pain is usually mild when present.

Mastoditis:

  • Also presents with purulent drainage but the swelling is noted behind the ear.

D. Physical Examination Findings.

Physical examination findings:

  • Ear canal erythema with purulent discharge - Granulation tissue visible in the inferior portion of the external auditory canal at the site of Santorini’s fissure (vertical fissure in the cartilaginous canal of the external auditory meatus) is pathognomic; this finding may be absent in atypical patients (e.g., HIV infected and children).

  • Conductive hearing loss.

  • Lymphadenopathy of the postauricular, preauricular, and lateral cervical lymph nodes.

  • Cranial nerve palsies - As the infection advances, osteomyelitis of the skull and TMJ can develop resulting in CN palsies. Involvement of the stylomastoid foramen will lead to facial paralysis in 25% of patients; less frequently, involvement of the jugular foramen leads to deficits in cranial nerves IX, X, and XI; children have a higher incidence of facial palsy due to their relatively undeveloped mastoid process and more medical location of the fissure of Santorini which places the facial nerve in closer proximity to the ear canal.

  • Central nervous system complications – These are rare but are the most common cause of death in MOE: meningitis; brain abscess; dural sinus thrombophlebitis.

E. What diagnostic tests should be performed?

Presumed diagnosis is based on history, physical findings, and diagnostic imaging.

1. What laboratory studies (if any) should be ordered to help establish the diagnosis? How should the results be interpreted?

Complete blood count:

  • Leukocytosis - usually present.

ESR:

  • Sensitive but not specific.

  • Can be used to monitor disease activity and response to treatment.

Gram stain and culture of ear discharge:

  • Send for aerobic, anaerobic, and fungal culture with sensitivity.

  • Culture negative: Often occurs because patients have already taken short courses of oral antibiotics or been prescribed topical antibiotic drops.

Tissue biopsy:

  • Surgical debridement with biopsy is mandatory.

  • Send for bacterial and fungal culture along with pathologic evaluation to rule out carcinoma of the ear canal.

2. What imaging studies (if any) should be ordered to help establish the diagnosis? How should the results be interpreted?

Computed tomography (CT):

  • First line diagnostic modality.

  • Allows visualization of bone erosion involving the tympanic bone and skull base.

  • Does not distinguish MOE from malignancy.

  • Can not be used to follow response to therapy.

Magnetic resonance imaging (MRI):

  • Useful to visualize soft tissue and dural involvement but not bone involvement.

  • Lower sensitivity than CT for imaging bone erosion.

  • Not generally recommended as a first line given poor detection of bone erosion.

Technetium Tc 99m:

  • Accumulates at sites of osteoblastic activity making it highly sensitive for bony infection.

  • Nonspecific and can be positive in cases of simple otitis externa and malignancy.

  • Traditional planar imaging or single photon emission computed tomography (SPECT) can be used: SPECT provides good anatomic localization and may highlight areas of bony involvement before the CT scan shows structural changes, making it the most sensitive for detection of osteomyelitis.

  • Does not normalize with treatment so can not be used to follow disease activity with treatment.

Gallium scan - gallium (67Ga):

  • More specific than bone scanning since the radioisotope is incorporated into granulocytes and bacteria.

  • Useful to follow response to treatment since uptake values return to normal with resolution of infection.

  • Expensive and time consuming.

F. Over-utilized or “wasted” diagnostic tests associated with this diagnosis.

NA

III. Default Management.

A. Immediate management.

Immediate management:

  • Hospitalization

  • Infectious disease consultation

  • Obtain cultures before initiating antibiotics to guide antimicrobial selection

Bacterial malignant otitis externa:

  • Treat with systemic antipseudomonal antibiotics.

  • Fluoroquinolones have generally replaced combination therapy with aminoglycosides or third-generation cephalosporins:

  • Initiate ciprofloxacin 400mg IV every 8 hours. Transtition to oral 750mg po twice daily once treatment response is seen.

  • Higher doses are required due to poor vascularization of the external auditory canal.

  • There is only clinical experience with ciprofloxacin, not with other fluoroquinolones.

  • Fluoroquinolone resistance among pseudomonas strains is increasing in frequency. Use sensitivity data to guide antimicrobial therapy.

SeeTable I

Table I.

Examples of antipseudomonal antibiotics
Ciprofloxacin 400mg IV every 8 hours*can transition to 750 mg orally every 12 hours at discharge
Ticarcillin-clavulanate 3 g IV every 4 hours*usually combined with an aminoglycoside**follow bacterial sensitivities and consult infectious disease for specific recommendations
Piperacillin-tazobactam 4 to 6 g IV every 4 to 6 hours *usually combined with an aminoglycoside **follow bacterial sensitivities and consult infectious disease for specific recommendations
Ceftazidime 2 g IV every 8 hours
Cefepime 2 g IV every 12 hours
Tobramycin According to patient weight: 1 to 1.66 mg per kg IV or IM every 8 hours*Combine with an antipseudomonal pencillin**Consult Pharmacy for dosage monitoring
Gentamicin According to patient weight: 1 to 1.66 mg per kg IV or IM every 8 hours*Combine with an antipseudomonal pencillin **Consult Pharmacy for dosage monitoring

Fungal malignant otitis externa:

  • Suspect if bacterial culture is negative and patient fails to respond to appropriate antibiotics.

  • Treated with liposomal amphocterin followed by oral itraconazole for up to 12 weeks.

ENT consultation:

  • Debridement of the external auditory canal and biopsy to rule out cancer are mandatory.

  • Surgical excision of infected bone is only indicated in refractory cases that fail to resolve with appropriate antimicrobial therapy.

Experimental therapies:

  • Hyperbaric oxygen: Hyperbaric oxygen has been used on occasion with mixed results and may be considered as an adjuvant treatment for refractory cases. However, there is no clear evidence to demonstrate the efficacy of hyperbaric oxygen treatment.

B. Physical Examination Tips to Guide Management.

Examine external auditory canal and tympanic membrane and follow extent of soft tissue erythema.

Examine cranial nerves.

Examine preauricular, postauricular, and cervical lymph nodes.

Formal auditologic hearing test prior to initiation of treatment.

C. Laboratory Tests to Monitor Response To, and Adjustments in, Management.

Weekly ESR to assess response to treatment.

Weekly CBC, C7, LFTS while receiving intravenous antibiotics to identify potential side effects.

D. Long-term management.

Formal auditological hearing test after completion of treatment.

Prolonged treatment of 6-8 weeks is usually required depending on clinical symptoms (night pain), physical findings.

E. Common Pitfalls and Side-Effects of Management.

Common pitfalls:

  • Always obtain cultures of ear discharge prior to initiation of antibiotics.

  • Consider fungal infection if bacterial cultures are negative or if infection is not responsive to traditional antibiotics.

IV. Management with Co-Morbidities.

A. Renal Insufficiency.

Adjust doses of antimicrobials.

Monitor creatinine clearance, especially with use of aminoglycosides.

B. Liver Insufficiency.

No change in standard management.

C. Systolic and Diastolic Heart Failure.

No change in standard management.

D. Coronary Artery Disease or Peripheral Vascular Disease.

No change in standard management.

E. Diabetes or other Endocrine issues.

Strict blood glucose control in previously diagnosed diabetics.

Screen for diabetes mellitus in all patients.

F. Malignancy.

Discontinue chemotherapy until infection resolved.

G. Immunosuppression (HIV, chronic steroids, etc).

Discontinue immunosuppressive medications if possible.

Screen for HIV in all non-diabetic patients.

H. Primary Lung Disease (COPD, Asthma, ILD).

No change in standard management.

I. Gastrointestinal or Nutrition Issues.

Ensure adequate nutritional status.

J. Hematologic or Coagulation Issues.

Evaluate for neutropenia, if present perform a diagnostic work up. Reverse causative etiology if possible.

K. Dementia or Psychiatric Illness/Treatment.

No change in standard management.

V. Transitions of Care.

A. Sign-out considerations While Hospitalized.

  • Check ESR prior to discharge

  • Follow up on bacterial and fungal culture and sensitivies

  • Follow up on pathology report from biopsy

  • Consult ENT if development or worsening of cranial nerve palsies

  • Consult Neurology if development or worsening of cranial nerve palsies or if concerned for meningitis, dural sinus thrombophlebitism, or brain abscess

  • Check MRI if concerned for cranial nerve palsies, or CNS complications

B. Anticipated Length of Stay.

5-7 days.

C. When is the Patient Ready for Discharge.

  • Afebrile x 24 hours

  • Improvement in leukocytosis if present

  • Decline in ESR

  • Establishment if long term venous catheter if discharged on IV antibiotics

  • Absence of cranial nerve palsies

  • No evidence of meningitis, brain abscess, or dural thrombophlebitis

D. Arranging for Clinic Follow-up.

1. When should clinic follow up be arranged and with whom.

  • Infectious disease - 1 week

  • ENT - 2 weeks

  • General medicine with diabetes education and review of blood sugar log - 2 weeks

2. What tests should be conducted prior to discharge to enable best clinic first visit.

  • Gallium bone scan - baseline

  • ESR prior to ID appointment in 1 week

3. What tests should be ordered as an outpatient prior to, or on the day of, the clinic visit.

  • Gallium bone scan - At 6 weeks

  • ESR - Weekly

E. Placement Considerations.

NA

F. Prognosis and Patient Counseling.

  • Importance of follow up with infectious disease and ENT specialist

  • Importance of taking full course of prescribed antibiotics - 90% are cured with appropriate treatment

  • Importance of strict blood glucose control

  • Keep ears dry

  • Do not put anything in ear canal, e.g., cotton swabs

  • Use ear protection with showering or swimming

  • Avoid irritants to the ear canal, e.g., hairsprays, hair dyes

  • Lower cranial nerve palsies generally resolve but patients may have incomplete recovery of facial nerve function

VI. Patient Safety and Quality Measures.

A. Core Indicator Standards and Documentation.

No joint commission core measures.

B. Appropriate Prophylaxis and Other Measures to Prevent Readmission.

DVT prophylaxis with heparin 5,000 units subcutaneously three times per day.

VII. What's the evidence?

Grandis, JR, Branstetter, BF, YuVL. "The changing face of malignant (necrotising) external otitis: clinical, radiological, and anatomic correlations". Lancet Infect Dis. vol. 4. 2004. pp. 34-39.

Carfrae, M, Kesser, B. "Malignant Otitis Externa". Otolaryngol Clin N Am. vol. 41. 2008. pp. 537-549.

Handzel, O, Halperin, D. " Necrotizing (Malignant) External Otitis.". Am Fam Physician 2003. vol. 68. 2003. pp. 309-312.

Guss, J, Ruckenstein, M, Flint, P. " Infections of the External Ear Malignant Otitis Externa.". Cummings Otolaryngology: Head & Neck Surgery,. 2010. pp. 1944-1949.

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