Dermatology

Otitis Externa Series Part 2: Topical Therapy for Otitis Externa

Otitis Externa Series Part 2: Topical Therapy for Otitis Externa
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Colleen Mendelsohn, DVM, Diplomate ACVD, & Wayne Rosenkrantz, DVM, Diplomate ACVD

In Part 1 of this series—Diagnosis of Otitis Externa—the factors and causes of this disease, diagnostic testing and imaging, and ear cleaning and flushing were discussed. Visit tvpjournal.com to read this article, which was published in the September/October 2014 issue of Today’s Veterinary Practice

Ear disease accounts for up to 15% of all canine veterinary case presentations.1,2Regardless of the primary cause of otitis externa, secondary infection treatment is usually the focus of therapy.

Otic preparations that address bacterial and/or yeast infections are usually combinations of antimicrobials and corticosteroids. The large number of commercial topical otic preparations reflects the demand for these products.

It is important to understand the underlying causes of otitis, as well as factors that contribute to the condition, in order to provide targeted therapy and effective treatment (Table 1).

Table 1. Common Factors & Causes of Otitis Externa
PREDISPOSING FACTORS
  • Abnormal external ear canal and pinna conformation, such as congenital stenosis
  • Excessive moisture within ear canal
  • Adverse effects from previous treatments, such as topical reactions
PRIMARY CAUSES
  • Atopic dermatitis
  • Food allergy
  • Epithelialization disorders, such as seborrhea
  • Metabolic disorders, such as hypothyroidism
  • Neoplasia
SECONDARY CAUSES
  • Yeast overgrowth
  • Bacterial overgrowth
PERPETUATING FACTORS
  • Ear canal/pinna fibrosis and stenosis
  • Calcification of tissues
  • Neoplasia (polyps, tumors, cysts)
  • Excessive cleaning and/or inappropriate use of cleaning products2-5

OTIC CYTOLOGY

Otic cytology is an integral part of:

  • Diagnosing otic disease
  • Determining best treatment approach and maintenance protocol
  • Assessing treatment success.

Otic cytology is inexpensive, highly informative, and easily self-taught. With practice, the practitioner can quickly become familiar with samples from inflammatory lesions, including recognition of:

  • Bacteria
  • Yeast (Figure 1)
  • Dermatophyte spores and hyphae (Figure 2)
  • Other fungal conditions, such as aspergillosis or cryptococcosis
  • Parasites (Figure 3)
  • Foreign material (Figure 4).

Cytology is an integral part of therapy and needs to be performed throughout the treatment process to monitor and adjust your treatment. Part 1 of this article series provides more in-depth discussion of otic cytology.

Figure 1

Figure 1. Yeast organisms revealed on cytology of purulent otic exudate (Diff Quik; 1000×).

Figure 2

Figure 2. Fungal hyphae revealed on cytology of purulent debris from a patient with severe unilateral otitis (Diff Quik; 1000×).

Figure 3

Figure 3. Demodex mite identified on otic cytology (Diff Quik; 100×).

Figure 4

Figure 4. Accumulation of medication crystals revealed on cytology from a patient exhibiting signs of otic irritation during treatment with otic product. Otoscopic examination revealed white exudate in ear canal; cytology indicated contact irritation from medication crystals despite resolution of infection (Diff Quik, 1000×).

OTIC FORMULATIONS

General properties of topical otic formulations include 2 important components—the vehicle and the active ingredient.

Vehicle

Otic product vehicles have different properties that determine their efficacy in practice, and their functions include (Table 2):

  • Promoting delivery of active ingredients
  • Stabilizing active ingredients
  • Determining drying or occlusive properties
  • Modifying pH
  • Adding factors, such as texture and fragrance, to enhance product pleasance.

However, product vehicles can have irritant properties, which must be taken into consideration.

Table 2. Otic Formulation Vehicles
VEHICLE INDICATIONS & CONTRAINDICATIONS
Rinse solutions
  • Can be poured into the ear canal in large amounts
  • Most appropriate for cleansing and disinfecting
Lotions
  • Soothing lotions or solutions usually do not contain alcohol
  • Cooling lotions or solutions generally contain alcohol
  • Alcohol or propylene glycol tends to be drying; drying agents are often used in maintenance protocols
  • However, alcohol can be irritating, particularly in erosive and ulcerative ears
Creams Emulsions Ointments
  • Occlusive properties prevent contact with the environment
  • Creams are least occlusive, ointments are most occlusive
  • May be contraindicated in exudative otitis cases, when increased water loss and drying are desirable3,6
Table 3. Otic Formulation Active Ingredients
Acidifying agents
Alkalinizing agents
Antibiotics
Antifungals
Anti-inflammatories
Astringents
Ceruminolytic agents
Disinfectants
Keratolytic agents
Keratoplastic agents
Parasiticides
Soothing agents

Active Ingredient

When a practitioner chooses a topical otic product, appropriate treatment for the patient’s specific condition, as well as the practitioner’s familiarity with the product, must be taken into consideration. Active ingredients of topical otic preparations are often combined to reach a desired effect (Table 3).

EAR CLEANING

As described in Part 1 of this article series, ear cleaning is imperative for successful otitis therapy. In many cases, the ears should be thoroughly cleaned by the veterinarian, followed by owner administration of medications at home.

Excessive cleaning by clients can be a perpetuating factor in chronic recurrent otitis. Most cleansers should be used no more than 2 to 3 times weekly, and sometimes not at all. Frequency of cleaning is based on the amount of inflammation and degree of exudate, wax, or debris that is being produced, which depends on the primary condition and perpetuating factors.

When regular cleaning is imperative, consider the patient and type and amount of exudate. For example:

  • In cases of chronic ceruminous otitis—most commonly seen in idiopathic seborrhea in cocker spaniels—regular ear cleaning and maintenance by the client is extremely important.
  • In dogs with increased ceruminous (waxy) debris build-up, ceruminolytic action is desired (Table 4).3,6,7
  • Drying cleansers can be used to prevent infection in “allergic” ears that tend to develop infections but are not severely exudative.
Table 4. Veterinary Otic Formulations
AGENT BRAND NAME ACTIVITY & INDICATIONS
CLEANSERS & RINSES
Ceruminolytics
Phytosphingosine Douxo Micellar Solution (ceva.us)
  • Anti-inflammatory/antimicrobial properties
  • Removes cellular debris and excess sebum (wax)
  • Can be used for soothing, seborrheic conditions, and maintenance
Squalene Cerumene (vetoquinolusa.com)
KlearOtic (dechra-us.com)
  • Softens and removes exudate
  • Not generally used for maintenance because it may overly strip ears affected by chronic allergic otitis
Maintenance Products
Phytosphingosine Douxo Micellar Solution (ceva.us) See above
Spherulites (lactic acid and salicylic acid) Epi-Otic Advanced(virbacvet.com)
  • Variety of acidic solutions
  • Used for mild and chronic recurrent cases of allergic and infectious otitis
  • Maintain pH of ear canals
  • Prevent bacterial adherence and overgrowth
  • Deodorizes ears
  • Spherulites and zinc help maintain healing of ear canal
  • Disinfectant, cleansing, and drying activities promote wound healing
Zinc (boric acid) Maxi/Guard Zn4.5 Otic (addisonlabs.com)
Disinfectant
Cleansing agents
Drying agents
Clean N Dry (pinnaclifeanimalhealth.com)
Epi-Otic (virbacvet.com)
MalAcetic Otic (dechra-us.com)
OtiClens (zoetis.com)
Enzymes Zymox Otic (petkingbrands.com)
  • Maintains mild to moderate cases of recurrent infectious otitis
ANTIBACTERIAL PRODUCTS
Fluoroquinolones
Enrofloxacin Baytril Otic (bayerdvm.com)
  • Bactericidal for gram negative and gram positive bacteria
  • Some products can be irritating
Orbifloxacin Posatex (merck-animal-health-usa.com)
Aminoglycosides
Gentamicin Mometamax (merck-animal-health-usa.com)
Otomax (merck-animal-health-usa.com)
Easotic (virbacvet.com)
Generic formulas: Betagen Otic (medpharmex.com)
  • Bactericidal for gram negative bacteria
  • Bactericidal for staphylococci
  • Reported ototoxicity
Neomycin Dermalone (vedco.com)
Tresaderm (us.merial.com)
Generic formulas
Other
Polymyxin Surolan (elanco.com)
  • Contains miconazole for synergistic effect against Staphylococcus and yeast
  • Effective for gram negative rods, including Pseudomonas and Escherichia coli infections
Silver sulfadiazine Baytril Otic (bayerdvm.com)
Silvadene Cream (pfizer.com)
  • Bacterial cell disruption
  • Broad spectrum antibacterial
  • Some antiyeast activity
Tromethamine (Tris) EDTA Keto-Tris Flush (ceva.us)
Keto-Tris Flush PS (ceva.us)
Tris Flush (ceva.us)
Triz EDTA (dechra-us.com)
Triz EDTA Plus (dechra-us.com)
Triz Ultra + KETO (dechra-us.com)
T8 Keto (bayerdvm.com)
  • Alkalinizing chelating agent
  • Effective for gram negative infections
  • Can be used synergistically with antibiotics, such as an aminoglycoside or fluoroquinolone
ANTIFUNGAL PRODUCTS
Clotrimazole Otomax (merck-animal-health-usa.com)
Generic formulas
  • Moderate potency against Malassezia pachydermatis
Ketoconazole Keto-Tris Flush (ceva.us)
Keto-Tris Flush PS (ceva.us)
Triz Ultra + KETO (dechra-us.com)
T8 Keto (bayerdvm.com)
  • • High potency against M pachydermatis
Miconazole Surolan (elanco.com)
Generic formulas
  • Surolan is the only remaining veterinary labeled product (2.3% concentration)
  • Numerous generic companies make a 1% lotion
Nystatin Dermalone (vedco.com)
Generic formulas
  • Polyene antifungal
  • Relatively weak against M pachydermatis
Posaconazole Posatex (merck-animal-health-usa.com)
  • Newer generation triazole
  • Potent antifungal
Thiabendazole Tresaderm (us.merial.com)
  • Benzimidazole antifungal
ANTI-INFLAMMATORY PRODUCTS
Betamethasone Otomax (merck-animal-health-usa.com)
Generic formula: Betagen Otic (medpharmex.com)
  • Potent steroid
  • 25× more potent than hydrocortisone
  • Even short term use can result in suppression of the adrenal axis and systemic effects
Dexamethasone Tresaderm (us.merial.com)
Dimethyl sulfoxide (DMSO) Synotic (zoetis.com)
  • Nonsteroidal anti-inflammatory
  • Possible antifibrotic activity
Fluocinolone acetonide Synotic (zoetis.com)
  • Potent steroid
  • 100× more potent than hydrocortisone
Hydrocortisone Malacetic HC (dechra-us.com)
Medicated Ear Hydrogel (pinnaclifeanimalhealth.com)
Zymox Otic (petkingbrands.com)
  • Hydrocortisone based products are safest
  • Generally only effective in mild allergic otitis conditions
  • Best used as maintenance product
Hydrocortisone aceponate Easotic (virbacvet.com)
  • Potent steroid
  • Minimal systemic absorption
Mometasone Mometamax (merck-animal-health-usa.com)
Posatex (merck-animal-health-usa.com)
Triamcinolone Generic formulas
  • Moderately potent steroid
  • Capable of creating systemic effects

 

ANTIMICROBIAL THERAPY

Topical antimicrobial therapy for active infections is imperative to success. The antimicrobial agent best utilized is initially often chosen empirically based on:

  • Cytologic examination of ear canal exudate
  • Otoscopic evaluation of the ear canal.

Antibacterial Therapy

Several veterinary topical otic formulations contain antibacterial agents (Table 4).

The use of bacterial culture and sensitivity (C/S) of otic exudate to determine antibiotic selection is controversial.

The concentration of antibiotics in topical otic preparations is much higher than those tested at the laboratory to determine the minimum inhibitory concentration (MIC) of any bacteria. Thus, some bacteria with a low MIC (that would usually be considered resistant) may actually prove to be sensitive to topical otic preparations. However, when the MIC is 0, complete bacterial resistance is likely, and use of an antimicrobial at any concentration against the resistant organism will not be helpful.

In general, C/S tends to be more useful when there is:

  • Persistence of bacteria despite antibiotic therapy
  • Middle ear involvement.2,3

When treating with antimicrobials:

  • Use fluoroquinolones with caution against Staphylococcus species; reports demonstrate an increased likelihood of oxacillin-resistant bacteria development.8
  • Consider pretreating the ear canal with a product containing tromethamine ethylenediaminetetraacetate (Tris EDTA) prior to administration of a topical antibiotic when addressing resistant bacterial infections, especially gram negative infections, such as Pseudomonas aeruginosa.
  • Tris EDTA has both antibacterial properties and synergistic bactericidal activity with aminoglycosides and fluoroquinolones.

Silver sulfadiazine may be used instead of other antibiotics for treatment of some bacterial infections, although accumulation of medication debris in the ear canal may limit its long-term use. Newer generation colloidal silver-based products are now becoming available.

Antifungal Therapy

Malassezia pachydermatis is the most common isolate from diseased ears.2,4 Numerous products are available to address yeast otitis (Table 4). In many cases of mild allergic yeast otitis, decreasing otic inflammation with a topical glucocorticoid alone can resolve the infection.

  • Thiabendazole, clotrimazole, and miconazole are used alone or, more commonly, in combination with a corticosteroid and antibiotic.
  • Ketoconazole is available in combination with Tris EDTA.2,3,9

In chronic recurrent yeast otitis, the use of products that contain boric or acetic acid can be effective in preventing recurrence of infection.9

  • Boric acid solutions are:
  • Generally effective at managing chronic recurrent yeast otitis
  • Effective in treating mild to moderate acute yeast otitis9
  • Not apparently effective against bacterial organisms.
  • Acetic acid solutions may markedly irritate the ear canal, especially at concentrations of 2% or higher.

ANTI-INFLAMMATORY THERAPY

The majority of antimicrobial topical formulations contain anti-inflammatory agents (Table 4), which aid in decreasing inflammation of the ear canal associated with:

  • Primary ear disease
  • Secondary infections.

Topical use of corticosteroids as anti-inflammatory agents is necessary to decrease inflammation and pain in the ear canal when treating otitis. Topical use is less likely to result in adverse clinical signs compared with systemic use; however, many commonly used corticosteroids, such as betamethasone and dexamethasone, have shown systemic absorption to some extent.10

Mometasone is a potent glucocorticoid that has minimal systemic absorption, making it potentially less of a concern for adrenal axis suppression; it also has longer residual effects, allowing for once daily therapy.

Hydrocortisone aceponate is converted to HC17 propionate, a highly active anti-inflammatory with potency equivalent to that of dexamethasone. Further, absorption through the skin and ear causes the drug to become deactivated, allowing it to be excreted without causing systemic effects.1

Hydrocortisone can potentially be used for chronic recurrent allergic otitis, but is not usually beneficial in acute, exudative, or proliferative otitis.2,3 Maintenance products containing hydrocortisone need to be selected on a case-by-case basis, depending on their efficacy in controlling inflammation.

MAINTENANCE THERAPY

Cases of chronic recurrent otitis are usually secondary to an inadequately controlled primary condition, which can result in damage to the ear canal lining and the normal physiologic mechanism for ear cleaning, further complicating the chronicity. Also, undiagnosed and/or uncontrolled otitis media can cause chronic otitis externa.

Preparations designed for long-term control are combinations of:

  • Mild cleansers
  • Drying agents or disinfectants
  • Sometimes antimicrobial agents.

See Goals of Maintenance Therapy for further information.

C/S = culture and sensitivity; MIC = minimum inhibitory concentration; Tris EDTA = tromethamine ethylenediaminetetraacetate

References

  1. Wohlrab J, Beck GM, Neubert RH, et al. Hydrocortisone aceponate activity and benefit/risk ratio in relation to reference topical glucocorticoids. Skin Pharmacol Physiol 2010; 23(4):177-182.
  2. Mendelsohn CM. Topical antimicrobial for otitis. In Bonagura JD, Twedt DC (eds): Kirk’s Current Veterinary Dermatology XV. St. Louis: Elsevier, 2012, pp 462-465.
  3. Rosenkrantz WS, Mendelsohn CL. Dermatologic therapy. In Miller W, Griffin CE, Campbell K (eds): Muller and Kirk’s Small Animal Dermatology, 7th ed. St. Louis: Elsevier, 2013, pp 109-183.
  4. Morris DO. Medical therapy of otitis externa and otitis media. Vet Clin North Am Small Anim Pract2004; 34(2):541-555.
  5. Saridomichelakis MN, Farmaki R, Leontides LS, Koutinas AF. Aetiology of canine otitis externa: A retrospective study of 100 cases. Vet Dermatol 2007; 18(5):341-347.
  6. Cole LK, Luu DH, Rajala-Schultz PJ, et al. In vitro activity of an ear rinse containing tromethamine, EDTA, benzyl alcohol and 0.1% ketoconazole on Malassezia organisms from dogs with otitis externa. Vet Dermatol 2007; 18(2):115-119.
  7. Gortel, K. Otic flushing. Vet Clin North Am Small Anim Pract 2004; 34(2):557-565.
  8. Morris DO, Rook KA, Shofer FS, Rankin SC. Screening of Staphylococcus aureus, Staphylococcus intermedius, and Staphylococcus schleiferi isolates obtained from small companion animals for antimicrobial resistance: A retrospective review of 749 isolates (2003-04). Vet Dermatol 2006; 17(5):332-337.
  9. Mendelsohn CL, Griffin CE, Rosenkrantz WS, et al. Efficacy of boric-complexed zinc and acetic-complexed zinc otic preparations for canine yeast otitis externa. JAAHA 2005; 41(1):12-21.
  10. Reeder CJ, Griffin CE, Polissar NL, et al. Comparative adrenocortical suppression in dogs with otitis externa following topical otic administration of four different glucocorticoid-containing medications. Vet Ther 2008; 9(2):111-121.

F02_BColleen Mendelsohn, DVM, Diplomate ACVD, is a veterinarian at the Animal Dermatology Clinic in Tustin, California, where she completed her residency. She received her DVM from University of California—Davis, completed an internship at the Animal Emergency Clinic and Animal Specialty Group in San Diego, and practiced general medicine prior to joining ADC.

F01_cWayne Rosenkrantz, DVM, Diplomate ACVD, is cofounder of Animal Dermatology Clinics, with locations in California, Indiana, Kentucky, Georgia, and Perth, Australia. He is a clinical instructor for Western University College of Veterinary Medicine and serves as an instructor for the European School of Advanced Veterinary Studies. He is a past president of the ACVD executive board and currently a board member of the World Association for Veterinary Dermatology.

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