THERAPY OF GRAM NEGATIVE OTITIS EXTERNA

THERAPY OF GRAM NEGATIVE OTITIS EXTERNA

Sue Paterson, M.A. Vet.M.B. D.V.D. Dip ECVD MRCVS
RCVS and European Specialist in Veterinary Dermatology
Rutland House Veterinary Hospital
St Helens, Merseyside UK

Otitis externa is defined as inflammation of the external ear canal of the dog or cat. In every case of otitis externa three different factors need to be considered these are primary, predisposing and perpetuating causes.

Primary Causes

All cases have a primary inciting factor for the inflammation which is a skin disease. Common primary causes include parasites, allergy and endocrine disease, although potentially any disease that affects the skin can affect the ear pinna and canal. In the author's clinic more than 70% of all cases of otitis externa have allergy as the underlying cause. In recurrent cases of otitis externa especially where complicated by Gram negative bacteria it is important to investigate and manage the underlying problem in addition to the infection.

Predisposing Causes

These causes increase the risk of the development of otitis externa but will not cause otitis externa in their own right. Important factors that should be considered include conformational defects, excessive moisture especially in dogs that swim, iatrogenic factors such as the use of irritant cleaners or over zealous cleaning as well as inflammatory polyps and tumours.

Perpetuating Causes

Perpetuating causes drive the disease process once it is established. Bacterial infection is a perpetuating cause. In acute cases of otitis externa the ear is usually infected with Gram positive organisms especially staphylococcus and streptococcus. However the more chronic the disease process becomes and the more topical therapy that is used the more the bacterial population will switch. Chronic cases are usually colonised by Gram-negative and anaerobic infection, especially Pseudomonas spp, coliforms, Pasteurella spp, Proteus spp. and Bacteroides spp. It is therefore important in every case of otitis externa to try and identify the primary, predisposing and perpetuating causes.

Clinical signs

Where Gram negative infection is present the ears rapidly change from being erythematous and pruritic to becoming painful often with secondary ulceration and with a profuse, malodorous discharge. In advanced cases otitis media occurs as the tympanic membrane is breached. Gram negative infection is often seen in immunosuppressed animals and in those where long-term topical steroids have been administered.

Cytology of discharge

Cytology is essential in all cases of otitis. It allows an appreciation not only of the bacteria that are present but also the presence of parasites and the nature of the inflammatory infiltrate. Cytology is a more sensitive test than culture. Cytology of the aural discharge can identify the presence of cocci or rods. Where cocci are identified they are most likely to be Staphylococcus spp. or Streptococcus spp. and therapy can be selected on an empirical basis.

Diagnostic clues from the colour and odour of the discharge may give some indication as to the type of bacteria present enabling the clinician to start the animal on drugs (table 1). However where cytology reveals rods, culture and sensitivity is obligatory and final therapeutic decisions should be based on culture and sensitivity.

THERAPY

Ear cleaning

Thorough ear cleaning is a first essential step in the therapy of any case of otitis externa. Many of the topical antibacterial agents present in proprietary ear drops are most active when the ear is clean. Some antibiotics are better in a neutral rather than acidic environment. It is best to use a limited number of ear cleaners within a practice so that you are comfortable with their mode of action and ototoxicity especially if the ear drum is ruptured. Cleaning should involve four important steps. These are first to establish the patency of the ear drum, secondly remove excessive cerumen, thirdly flush the ear and then lastly dry it.

The discharge in Gram negative infection is usually thick copious and purulent. It is common to find that the ear drum has been damaged when Gram negative infection is present. If the ear drum can not be visualised it should be assumed it is damaged. Initial flushing may thus be most safely performed using water however sterile saline and acetic acid are also generally considered to be safe. Any cleaner used should have a high degree of middle ear safety and from choice the author will avoid cleaning solution containing propylene glycol when the tympanic membrane is compromised. Flushing should involve a period of gentle institution of flush fluid followed by a period of removal. Many different ear flush systems are now available commercially. However cleaning can be achieved by gentle suction via a soft flexible tube such as a urinary catheter attached to a syringe or by absorption of fluid onto cotton wool swabs. Flush and removal cycles should be continued until no further discharge is removed on the swab or in the withdrawn fluid. Where a flush solution has antibacterial properties such as acetic acid or ethylene diamine tetra acetic acid-tris (EDTA-tris) the author will generally leave the ear canal to soak in flush solution for 10 minutes after the final flush cycle to ensure the ear canal is sterile. Acetic acid can be used at concentrations between 1.0 - 5.0% as a flush and is available as a proprietary veterinary ear wash. At a concentration of 2.5% acetic acid is effective at killing Pseudomonas spp. Acetic-acid-based products should be used with care in ulcerated ear canals. The author will generally only use these in sedated dogs where ulceration is present following up with an intravenous injection of dexamethasone to counteract any irritation caused by the soak solution. Any flush that lowers the pH of the ear should not be used directly with either fluorinated quinolones or aminoglycosides. A period of about 20 min should be left between flush and antibiotic administration. Alternatively the flush solution should be neutralised with EDTA-tris before antibiotics are applied. Chlorohexidine is recommended by some authors as a flush solution but must be used at low concentration (0.05%) to avoid ototoxicity. Although this dilution is considered to be relatively safe to the middle ear, most antimicrobial activity is lost at this level giving no significant advantage over water, which is a safer alternative. Povidone iodine is not suitable as a flushing agent. Ethylene diamine tetra acetic acid-tris (EDTA-tris) has been shown to be a useful pre-treatment flush before topical antibiotic therapy. This chemical particularly affects the cell membranes of Gram negative bacteria, rendering them more susceptible to antibiotics. This can be achieved by pre-treatment of the ear canal with 2.5 ml of EDTA-tris for 10-15 min once or twice daily for 7-10 days, prior to the application of antibiotics. This can often render bacteria thought to be resistant to particular antibiotics on in vitro tests sensitive in vivo. EDTA-tris is available in many countries as a pre-made solution or crystals. EDTA-tris also has an alkaline pH which means it can be used to neutralise acid ear cleaners that can otherwise inactivate topical antibiotic therapy (see above). EDTA-tris is water based and is thus non-irritant, in even the most sensitive ears. Prolonged use of EDTA-tris should be undertaken in combination with a drying agent to avoid recolonisation of the ears with yeast. Isopropyl alcohol is the active agent used as the base for most drying products. This is usually accompanied by weak, astringent acids such as lactic acid, malic acid, benzoic acid, salicyclic acid and boric acid, or aluminum compounds such as aluminum acetate and silicate. Although isopropyl alcohol is thought to be harmful to the middle ear if the tympanum is damaged and is probably best avoided, the ototoxicity of the other products is unknown. They do generally seem to be well tolerated in the ear although in some cases the weak acids can cause irritation.

It is essential in all cases of otitis externa not to reach for antibiotic therapy before adequate ear cleaning has been performed. Even when an appropriate sensitivity pattern has been identified on the basis of culture and sensitivity of the ear discharge, drugs can be ineffective due to the large amounts of material in the ear canal. Drugs such as the aminoglycosides are inactivated by pus. Gram negative infections commonly have an unpredictable sensitivity pattern and there is a temptation to reach for a potent topical therapy. However sensibly the clinician should not routinely select one of the more exotic off license drugs when a licensed veterinary ear drop is suitable. The archetypical Gram negative infection is Pseudomonas spp, however the author has encountered multiply resistant isolates of both coliforms and Proteus spp. so the same methodical approach should be employed in all cases.

Unless otitis media is present the author will generally only use topical therapy to treat otitis externa which is essentially a surface infection. Adequate volumes of medication must however be instilled into the ear canal in order to permeate the vat of purulent material it contains. This should be a minimum 0.5ml of fluid in big dogs up to 1.0ml may be necessary to reach the deeper parts of the canal.

Although culture and sensitivity can be useful when selecting medication this does only reflect the serum level of drug required to treat the organism. Levels of topical medication often greatly exceed those that can be safely achieved in the circulation. A good sensitivity to a particular antibiotic will tend to reflect a suitable topical drug for therapy. However a resistance to a particular antibiotic based on a Kirby-Bauer disk diffusion method may not reflect an in vivo resistance due to the high relative concentration of antibiotic achieved with topical drug directly into the ear.

This is the most commonly used family of topical antibiotics and includes neomycin, amikacin, gentamicin. They have good activity against Gram negative bacteria and are bactericidal working by inhibiting bacterial protein synthesis. Their antimicrobial activity is enhanced in an alkaline environment. The ear should be left for 30 - 60 minutes after an acid ear cleaner has been used to prevent inactivation of these antibiotics if used after such cleaners. These drugs are ototoxic when administered parenterally but can be used safely in otitis externa in the face of an intact tympanic membrane.

This class of antibiotics is also bactericidal working by inhibiting bacterial cell wall DNA-gyrase. Drugs in this group include enrofloxacin, ciprofloxacin, and marbofloxacin. They work in a concentration dependent manner. These drugs tend to be well tolerated and accepted as having a low ototoxicity.

This class exhibits good activity against Gram negative organisms because of their ability to penetrate the Gram negative cell membrane. Ticarcillin has been quoted most commonly for the treatment of Pseudomonas otitis externa.

Polymyxins

This group includes Polymyxin B and colistin sulphate which have good activity against Gram negative organisms. These drugs work by increasing the permeability of the bacterial cell wall leading to osmotic damage. They are reported to be ototoxic in both in vitro and in vivo.

SSD is a broad spectrum antibacterial which has excellent activity against Pseudomonas spp. It is available as a burn cream but can be mixed with sterile water to produce an emulsion which can then be instilled into the ear canal. It can be used at concentrations of 0.5- 1.0%. The ototoxicity of SSD is unknown.

Once an antibacterial agent has been selected it should be instilled into the ear canal twice daily after flushing on each occasion. Dogs should be reassessed cytologically after 2 weeks of therapy. Topical treatment should continue twice daily until there is no evidence of either an inflammatory infiltrate or bacteria. Once the ear infection has resolved some attempt should be made to manage the underlying disease process. Where an allergy has been identified then desensitization may be useful based on the results of allergy testing. The author will generally maintain animals on topical medication in the ears once or twice weekly. Where the dog will tolerate the use of an acid cleaner then this is preferable to try and prevent recolonisation of thee ear canal with bacteria. Currently she will use a cleaning solution that encompasses a combination of 1% acetic acid, 1% boric acid and 1% hydrocortisone.

Type of discharge	Possible pathogen
Dry coffee grounds	Otodectes cynotis
Moist brown exudate	Staphylococcus, Malassezia
Purulent yellow/green exudate (malodorous)	Gram-negative especially Pseudomonas spp
Ceruminous discharge (often no smell)	Allergy, endocrine, keratinisation defects, Bacteroides spp.