Royal (Dick) School of Veterinary Studies, Easter Bush Campus, University of Edinburgh, Roslin, UK
Treatment of Acute Otitis Externa
Individual bouts of otitis externa can be managed using polyvalent topical ear products with a glucocorticoid (for mild acute inflammation), an antibiotic, and an antifungal (for Malassezia). Cleaning is necessary in cases with large amounts of debris.
Recurrent and Chronic Otitis
Nearly all ear infections involve commensal (e.g., staphylococci and Malassezia) or environmental (e.g., Pseudomonas) opportunists. The vast majority are secondary to pre-existing inflammation, foreign bodies, obstruction or other primary problems. Ongoing inflammation leads to a cycle of recurrent infection and chronic inflammation leading to progressive pathological changes and end-stage otitis. The chronic inflammation makes each bout of infection harder to treat and repeated antimicrobial use may select for resistance.
Approach to Chronic or Recurrent Otitis
1. Otodectes etc., and check the tympanic membrane (see Diagnostic Approach to Otitis).
2. Identify primary, predisposing and perpetuating cause.
3. Cytology should be performed in all cases; it can be particularly useful to identify multiple organisms in mixed overgrowths or infections.
4. Culture if necessary.
Aims of Treatment
- Identify and manage the primary cause
- Correct predisposing factors
- Remove debris and discharge
- Manage the secondary infection
- Reverse chronic pathological changes
- Maintain a heathy ear canal environment
The Impact of Biofilms
Biofilms inhibit cleaning, prevent penetration of antimicrobials and provide a protected reservoir of bacteria. Antibiotics that require bacterial division will be less effective, as biofilm-forming bacteria are usually in a quiescent state. Biofilms may also enhance the development of antimicrobial resistance - a gradual decrease in antimicrobial concentration means that some bacteria could be exposed to a mutant selection window. This will lead to treatment failure and resistance.
Bacterial Culture and Sensitivity Testing
Using Cytology to Predict Susceptibility Patterns
The likely sensitivity of Malassezia and staphylococci can be predicted using knowledge of local resistance patterns and previous treatment. Gram-negative bacteria are harder to differentiate on cytology, although Pseudomonas are most common. Their susceptibility is harder to predicate, although most first-time infections will be susceptible to aminoglycosides, polymixin B, silver sulfadiazine and fluoroquinolones. However, they readily acquire multi-drug resistance (see below).
Using Bacterial Culture and Antimicrobial Sensitivity Testing
Bacterial culture and sensitivity testing can help identify organisms that are hard to differentiate on cytology (e.g., streptococci, enterococci, E. coli, Klebsiella, Proteus and coryneforms). Knowledge of their likely sensitivity patterns can help guide treatment choices.
Understanding Breakpoints and Resistance
Antimicrobial susceptibility tests do not predict the response to topical treatment. The susceptibility and resistance breakpoints are based on tissue levels following systemic dosing. A resistant result applies to the infection; this does not necessarily mean that the bacteria are resistant to the antimicrobial, as the high levels following topical treatment frequently exceed the MIC. Antibiotic sensitivity data can be used to predict the efficacy of systemic drugs, although penetration to the ear tissues is often low and high doses are needed.
Topical and Systemic Therapy
Topical therapy is preferred wherever possible. Systemic antimicrobial therapy may be less effective in erythroceruminous otitis externa as bacteria are present only in the external ear canal and cerumen. Systemic treatment may be more useful in suppurative otitis externa and/or otitis media where there is an inflammatory discharge with concurrent tissue infection. Systemic treatment is indicated when the ear canal cannot be treated topically (e.g., stenosis, compliance problems or topical adverse reactions) and in otitis media.
Topical Antimicrobials
Polymixin B, fusidic acid, florfenicol, gentamicin, enrofloxacin and marbofloxacin are suitable for most bacterial infections. Polymixin B and miconazole have synergistic activity against Pseudomonas and other gram-negative organisms, and fusidic acid and framycetin show synergistic activity against staphylococci. Fluoroquinolones, gentamicin and polymixin B are usually effective against Pseudomonas. Fusidic acid and florfenicol are effective against MRSA and MRSP. Neomycin is less potent that other aminoglycosides, although it is usually effective against gram-positive bacteria. It is important to use an adequate volume - 1 ml is sufficient for most ears.
Topical therapy achieves high local concentrations that persist. Concentrations of gentamicin were 3–15x and concentrations of miconazole are 1.2–2x the MIC90 for canine otic isolates of staphylococci and Malassezia respectively 10 days after a five day course of Easotic®. Levels of florfenicol and terbinafine are at least 1000x MIC90 for staphylococci and Malassezia for the duration of treatment with two doses of Osurnia®.
Ear Cleaning
Removal of debris and purulent material improves the efficacy of topical antibiotics, especially aminoglycosides and polymixin B. Cleaners with chlorhexidine, acids, and/or alcohols are most effective against Malassezia and bacteria. Acidic ear cleaners may inactive aminoglycosides and fluoroquinolones) although the ear canal pH rapidly returns to normal. Ceruminolytic and ceruminosolvent cleaners should be used with dry waxy debris, surfactant based cleaners with seborrhoeic discharges, and mild aqueous cleaners with purulent material and/or a ruptured tympanic membrane. Techniques include manual cleansing, bulb syringes and ear flushing.
Systemic Antimicrobials (See Notes on Responsible Antimicrobial Use in Treating Pyoderma)
Penetration of antibiotics with a low volume of distribution into ear tissues is limited. Fluoroquinolones have a high volume of distribution and penetrate well. However, these should be used at high dose in end-stage otitis externa and media (e.g., 10–20 mg/kg for enrofloxacin).
Pseudomonas Otitis
Pseudomonas are inherently resistant to many antibiotics and readily develop further resistance if treatment is ineffective. Other anti-Pseudomonas antibiotics are often expensive, not licensed for animals and have to been given parenterally if used systemically.
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Antibiotics useful in resistant Pseudomonas otitis
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Ciprofloxacin·
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0.2% sol. 0.15–0.3 ml/ear q 24 h
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Enrofloxacin
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15–20 mg/kg PO q 24 h; 2.5% injectable sol. diluted 1:4 with saline or Epiotic® topically q 24 h; 22.7 mg/ml sol. 0.15–0.3 ml/ear q 24 h
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Marbofloxacin
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5–10/kg PO q 24 h; 1% injectable sol. diluted 1:4 with saline topically q 24 h; 20 mg/ml sol. 0.15–0.3 ml/ear q 24 h
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Ofloxacin
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0.3% 0.15–0.3 m/ear q 24 h
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Carbenicillin*
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10–20 mg/kg IV q 8 h
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Clavulanate-ticarcillin*#
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15–40 mg/kg IV q 8 h; reconstituted injectable sol. 0.15–0.3 m/ear q 12 h; 160 mg/ml sol. 0.15–0.3 ml/ear q 12 h
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Ceftazidime·#
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25–50 mg/kg IV q 8 h; 100 mg/ml 0.15–0.3 ml/ear q 12 h
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Silver sulfadiazine q
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Dilute 0.1–0.5% in saline
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Amikacin*
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10–15 mg/kg SC q 24 h; 50 mg/ml 0.15–0.3 ml/ear q 24 h
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Gentamicin
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5–10 mg/kg SC q 24 h
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Tobramycin’
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Use eye drops or 8 mg/ml injectable sol. 0.15–0.3 ml/ear q 24 h
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* - not licensed for animals; # - reconstituted sol. stable for up to 7 days at 4°C or 1 month frozen; q - silver sulfadiazine shows additive activity with gentamicin and fluoroquinolones.
Potential Toxicity
Ticarcillin, polymyxin B, neomycin, tobramycin and amikacin are potentially ototoxic. Neomycin can cause contact reactions. Enrofloxacin, marbofloxacin, ceftazidime, silver sulfadiazine and soluble gentamicin appear to be safe in the middle ear.
Treatment of Biofilms and Mucus
Biofilms can be physically broken up and removed by thorough flushing and aspiration. TrizEDTA and 2% n-acetylcysteine can disrupt biofilms. Systemic n-acetylcysteine (NAC; 600 mg q 12 h) can help dissolve biofilms in the middle ear and other mucous surfaces. NAC and bromhexine can help drainage of mucus in PSOM and feline inflammatory otitis media.
TrizEDTA
TrizEDTA damages bacterial cell walls and increases antibiotic efficacy. It is best given 20–30 minutes before the antibiotic but can be co-administered. It is well tolerated and non-ototoxic. It shows additive activity with chlorhexidine, gentamicin and fluoroquinoles. Solutions of 0.6% enrofloxacin, 0.2% marbofloxacin, 0.3% gentamicin, 0.1% amikacin, 2.8% ticarcillin and 1.7% ceftazidime in TrizEDTA are effective against many multidrug resistant bacteria including Pseudomonas.
Anti-Inflammatory Treatment
Reducing pruritus, swelling, exudation and tissue proliferation is a key goal, and maintenance treatment is necessary in ongoing conditions (e.g., atopic dermatitis). Dexamethasone helps reverse the ototoxic effect of Pseudomonas. Systemic treatment is necessary in cases with severe ear canal stenosis, and/or generalized inflammatory skin disease.
Ear Wicks
Polyvinyl acetate ear wicks can be cut to size and inserted into the ear canal under anaesthesia, soaked with an antibiotic, TrizEDTA and/or steroid solution and left for 3–10 days, applying the ear solution once daily. The wicks absorb discharge and draw the antibiotic solution into the ear canals. Steroid soaked wicks can prevent stenosis following laser surgery to remove polyps etc. They may prevent drainage from the middle ear in discharging otitis media though.
Treating Otitis Media
Debris must be flushed out under general anaesthesia by passing a catheter into the middle ear. Otitis media may need 3–4 weeks (and possibly longer) systemic treatment, which is a problem if parenteral drugs are used. Pseudomonas infections, however, usually clear quickly once effective cleansing, antimicrobial treatment and control of the primary cause are established. Other options include instilling antimicrobials into the middle ear every 3–10 days (e.g., enrofloxacin, marbofloxacin or gentamicin), using large volumes of topical therapy, or combining systemic and topical therapy.
Compliance and Adherence
Poor compliance or adherence will compromise efficacy and encourage resistance. This can be improved by:
- Using medication that the owner is able and wants to administer
- Giving written instructions
- Showing how to administer topical therapy and clean the ears
- Using precise terminology - e.g., ‘every 12 hours’ instead of ‘twice daily’
- Follow up and communication
- Analgesia to facilitate cleaning and medication