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Pseudomonas Otitis Treatment and Prognosis

Introduction

Pseudomonas aeruginosa is the most common organism associated with chronic otitis externa and media in the dog. Clinically the ear is often ulcerated and filled with a purulent exudate. Chronic changes include hyperplasia of the canal tissue leading to stenosis. The tympanic membrane is often ruptured. Resolution of the clinical condition is not guaranteed and requires aggressive and prolonged medical management. Identification of the underlying cause of the infection may help prevent recurrence once the current infection has been resolved; however, some chronic changes are irreversible and in themselves predispose the animal to recurrent infections.

Diagnosis

The first step to diagnosing otitis externa is cytology. Dogs with Pseudomonas otitis will have a purulent exudate with numerous rod-shaped bacteria. These may be mixed with other cocci, rods, and/or Malasezzia or be present in pure culture. If a gram stain is performed, Pseudomonas is gram negative. This is a useful test to differentiate Pseudomonas from Corynebacterium sp., the latter being much easier to treat and does not require culture and susceptibility testing. If Pseudomonas is suspected, then a sample of the exudate is obtained from the junction of the horizontal and vertical canal using a sterile mini-tip culturette and submitted for aerobic culture and susceptibility.

Otoscopic examination of the ear canal is an important part of the diagnosis to assess the health of the canal and the tympanic membrane. Since dogs with Pseudomonas otitis are usually quite painful, general anesthesia is recommended. If the canals are too stenotic, a decision may be made to delay this procedure for 2 weeks, starting topical treatment and topical or systemic steroids in the interim.

CT or radiographic examination of the bulla is recommended for all cases of chronic otitis. This is usually done at the time of the general anesthesia for otoscopy. Otoscopy and flushing are performed after the imaging procedure so as not to interfere with interpretation.

Treatment

Culture and Susceptibility

Pseudomonas aeruginosa bacteria are typically multiple-drug resistant based on culture and susceptibility. This is attributed to a combination of plasmid-mediated mutations and decreased antibiotic penetration. Various studies describe the in vitro susceptibility of P. aeruginosa. Based on these studies the most effective antibiotics include tobramycin, ticarcillin, polymyxin B, imipenem, amikacin, quinolones and ceftazidime.

While often sensitive to gentamycin in vitro, many dogs come in on a topical combination product containing gentamycin with no improvement noted. Some possible explanations for this include:

  • 1. Most aminoglycosides are inactivated by purulent material, an environment commonly found in Pseudomonas ears.
  • 2. Many of the gentamycin topical preparations are in an ointment base, which may be too viscous to penetrate through the stenotic ear canal.
  • 3. The volume used may be too small to achieve an adequate concentration in the horizontal ear canal.

Of the quinolones, most strains of Pseudomonas were susceptible to marbofloxacin with lower susceptibility to enrofloxacin. In one study it was shown that resistance to enrofloxacin developed rapidly for P. aeruginosa when exposed to enrofloxacin pressure.

So why might enrofloxacin still be effective topically? Kirby-Bauer may over-estimate Pseudomonas resistance. The quinolones (marbofloxacin and enrofloxacin) are tested for susceptibility at a concentration of 5 Φg which is determined based on oral dosing and serum concentrations. When enrofloxacin is used topically a much higher concentration is achieved which may likely override some of the resistance exhibited by the bacteria.

In addition, fluoroquinolone antibiotics target two essential bacterial enzymes, DNA gyrase and topoisomerase IV. Both low and high level resistance may occur with Pseudomonas and are mediated by point mutations of gyrA and par C genes, and a decrease in the intracellular concentration of the antibiotic because of a decrease in permeability or an increase in expression of an efflux pump. In canine Pseudomonas infections, quinolone resistant strains have been shown to exhibit both a mutation in the gyrA gene and overexpression of efflux pump(s). Use of a calcium chelating agent such as Tris EDTA may help override the resistance attributed to the efflux pump.

Need for Concurrent Steroids

Because the ear canals are often stenotic, it is essential to open the canals to allow penetration of the topical treatments. This can be accomplished through systemic and/or topical corticosteroids. Often the systemic steroids are just used initially with the idea that topical steroids will maintain the canal open.

Specific Treatment Recommendations

Under general anesthesia, the ear canal is flushed out using saline. There is seldom a lot of waxy exudate in the canal with Pseudomonas otitis. If the tympanic membrane is ruptured, the bulla is also flushed using a tomcat catheter. If the tympanic membrane is intact, I do not necessarily perform a myringotomy at this time. Use of a video otoscope has greatly improved our ability to effectively flush the ear canal and visualize the region of the tympanic membrane.

Initially, I treat Pseudomonas otitis empirically with a combination of Tris EDTA and enrofloxacin at a final concentration of 20 mg/ml. This is achieved by the addition of 20 ml of enrofloxacin (100mg/ml) to 80 ml Tris EDTA I have the owners instill large volumes into the affected canal(s) twice daily, massage the base of the ear and try to prevent the dog from shaking his head for at least 5 minutes. The excess is not wiped from the canal. If there is no improvement in 2 weeks, then other topical antimicrobials are tried.

Oral prednisone is often prescribed at a dose of 1 mg/kg orally daily for 5-7 days, then every other day for an additional week. In addition, a topical corticosteroid is often used. I either use topical fluocinolone/DMSO or topical dexamethasone.

Other Treatment Options

Enrofloxacin can be used topically 10-20 minutes following application of Tris EDTA. The injectable preparation (22.7 mg/ml) can be instilled directly into the ear canal. This would be used instead of mixing enrofloxacin into the Tris EDTA, not if the combination product failed. A commercial product available in the US contains a lower concentration of enrofloxacin (5 mg/ml) with silver sulfadiazine in a viscous base. A commercial suspension available in Europe contains marbofloxacin (3 mg/ml), clotrimazole (10 mg/ml), and dexamethasone (0.9 mg/ml).

Tobramycin Ophthalmic solution - this product can be used with a dropper bottle. ml should be instilled into each affected ear twice daily.

Polymyxin B - Polymyxin B is administered 10-20 minutes following Tris EDTA application. One-half ml is instilled into each affected ear twice daily. The polymyxin is prepared by mixing 50 ml saline into a vial containing 500,000 U polymyxin B. This gives a final concentration of 10,000 U/ml and is stable for 60 days when refrigerated. This product is potentially ototoxic.

Ticarcillin - Ticarcillin is a carboxycillin that has shown efficacy against Pseudomonas. The only formulation available to us is ticarcillin-clavulanic acid. Reconstitute the 3 gm vial with 6 ml saline and freeze in 2 ml aliquots. These are stable for 3 months. Thaw one 2 ml aliquot and dilute with 40 ml saline (25 mg/ml), divide into 10 ml- aliquots and freeze. Remove one 10 ml aliquot at a time and apply ml twice daily into affected ear, following application of Tris EDTA.

Amikacin - Make a 50mg/ml otic preparation by mixing 3 ml amikacin (250 mg/ml) with 12 ml glycerine. Apply ml twice daily into affected ear, following application of Tris EDTA. This product is potentially ototoxic.

Silver sulfadiazine - This product is supplied as a 1% cream or a micronized powder. This can be mixed as a suspension in sterile water at 0.5% to 1.0%.

Use of Systemic Antibiotics

We do not use systemic antibiotics for otitis externa or media. The only class of oral antibiotics that may be efficacious for Pseudomonas otitis are fluoroquinolones. It is difficult to achieve adequate concentrations in the ear tissue and middle ear with these antibiotics, even if maximum doses are administered. Most other anti-pseudomonas antibiotics are given parenterally. Our success rate has not diminished since managing otitis in this manner.

Prognosis

Pseudomonas otitis can be very frustrating to manage; however, the prognosis depends more on the degree of secondary changes than the presence of the organism itself. If the canal cannot be opened up to allow medication to penetrate, then the prognosis for medical cure is guarded.

Keys to successful management of Pseudomonas otitis include opening the ear canal, cleaning the canal and middle ear when indicated, using large volumes of topical medication, using solutions rather than ointments for optimal penetration into the canal, and frequent follow-up examinations. In addition it is important to try to identify and address, when possible, an underlying cause for the otitis.


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