Diagnosing and Treating Otitis Externa and Otitis Media in ...



Diagnosing and Treating Otitis Externa and Otitis Media in Dogs and CatsAtlantic Coast Veterinary Conference 2005Louis N. Gotthelf, DVMAnimal Hospital of Montgomery, Montgomery, AL18283129Probably one of the most common ailments of dogs seen in a veterinary practice is ear disease. From mild erythema to severe otitis media, approximately 15%-20% percent of all canine patients and approximately 6% - 7% percent of all feline patients have some kind of ear disease. In the humid climates, the incidence of otitis in dogs approaches 50%. Determining the cause of ear disease is often a difficult task.Otitis ExternaPrimary Causes of Ear DiseasePets with itchy ears may not have ear disease seen on otoscopic examination at all, but may be responding to a localized pruritus associated with an underlying pruritic disease. Since many diseases found in the ear arise as a result of an underlying skin disease, the veterinarian should also do a careful evaluation of the pet's skin to determine the underlying etiology if possible. Often, diagnosis and treatment of the underlying skin disease diminishes the severity of ear disease.Primary factors are those diseases of the skin that also have a direct effect on the skin that lines the ear canal. Diseases such as atopy, food hypersensitivity, parasites, foreign bodies, hypothyroidism and keratinizing diseases frequently result in ear disease. Predisposing Causes of Ear DiseasePredisposing factors are those things that directly change the microclimate in the ear canal. The microclimate changes include increased temperature from inflammation, increased humidity from poor ventilation and stenosis, and changes in the composition of the cerumen. Certain breeds have more cerumen glands (Cockers, Labradors, and Springers) that favor yeast growth. Humid environments and excessive moisture in the ears from swimming or bathing promote bacterial growth. Excessive trauma to the ear canal resulting from exuberant ear cleaning or trauma from instruments used in the ear canal may allow bacterial colonization. Pathological alterations to the ear canal epithelium such as fibrosis or tumors allow colonization of bacteria and yeasts along the increased surface area. These pathological changes produce fissures and deep crevices where organisms are sequestered.Perpetuating FactorsPerpetuating factors are those things that prevent normal resolution of ear disease. Bacteria, yeasts, exudates and secretions from otitis media, and contact allergies from drugs such as neomycin keep the inflammatory process going. They are not the reason for the initial onset of otitis, but until they are dealt with, the ear disease will continue. Over treatment of ear disease with ear cleaners keeps the epithelium moist and macerated. Too short a treatment duration may not rid the ear of organisms. Inappropriate antimicrobial therapy may be totally ineffective, i.e. treating an ear with yeasts by using an antibiotic.To illustrate the interaction of these factors, consider a dog with atopy that may show inflammation of the ear canal resulting in redness, swelling, heat, and pain. The atopy is the primary cause of ear disease. In fact, almost 80% of atopic dogs have otitis externa. In a cylindrical cartilage tube, such as the ear canal, inflammation decreases the lumen diameter, which tends to decrease the ventilation and drying of the ear canal. Without ventilation, the humidity level of the ear canal increases. The resulting stenosis and increased humidity are predisposing causes. Humidity is a factor favorable for bacterial growth. The bacterial otitis externa then becomes a perpetuating factor and the symptoms of ear disease will not diminish until the bacterial component is removed. However, the underlying cause of the ear disease, atopy, remains in spite of the elimination of the bacterial infection.Dermatological conditions often affect the ear canal, making it susceptible to otitis externa. Examples of primary skin diseases that may also affect the ear canal include juvenile cellulitis, autoimmune diseases such as pemphigus and systemic lupus erythematosus, keratinization disorders, and erythema multiforme (a systemic drug reaction). The ear canal is an invagination of epidermis forming a hollow skin tube in the inside of the head which ends at the eardrum. Pathological mechanisms affecting the skin of the animal have the same effect in the epithelial tube lining the ear canal. Not all cases of otitis externa are infected with bacteria or yeasts and it is a challenge for the clinician to seek out these cases and to treat them appropriately.The 4 Step Approach to Otitis Externa1. Examination of Skin and EarsIt is always important to look at the overall patient. Checking the skin for problems may alert the clinician to potential primary causes for the ear disease. Classic signs of atopy may be noted or there may be symmetrical alopecia suggesting hypothyroidism. Then the ear canal should be examined for exudates, growths, or other pathological changes. The eardrum should always be evaluated because the choice of medications and flushing agents will depend on the integrity of the eardrum. 2. Cytological Evaluation of Otic ExudateThe next step in approaching ear disease is examining a cytologic preparation of the otic exudate. Cytological examination of every infected ear should be done routinely. A sample is obtained with the use of a small tipped cotton applicator. The swab is placed through a disinfected otoscope cone placed into the vertical ear canal near the junction with the horizontal canal. The swab is extended beyond the plastic cone and pressure is applied to the ear canal epithelium as the swab is withdrawn back through the cone. In this manner, packing of wax and exudate is minimal. Every attempt is made to sample only from the horizontal canal epithelium because the vertical canal is often contaminated with a number of commensal organisms unrelated to the ear disease. The swab is then rolled onto a new, clean microscope slide by rolling the harvested material from the left ear on the left side of the slide and the swab from the right ear on the right side of the slide. The slide is labeled with the patient's name and the date of the sample. The slide is heat fixed and stained with blood stain (Diff-Quick or Wright-Giemsa). After the slide is dried, a drop of slide mounting medium (Cytoseal 60, Stephens Scientific, Riverdale, New Jersey) is applied and a coverslip placed over the material. In this manner a permanent slide is made. A drop of mineral oil can be spread on the stained slide if permanent slides are not desired. This standardized approach to making slides allows uniform identification of organisms from each ear and allows comparison of ear cytology from visit to visit.To look for ear mites under the microscope, the ear swabs are rolled in a drop of mineral oil on a microscope slide and coverslipped. Low power (40X-100X) examination reveals mites crawling across the field and/or the typical oblong dark brown Otodectes eggs may be seen.Evaluation of slides should begin with a low power (100X) overview of cell types. If there are large numbers of epithelial cells and few microorganisms, then noninfectious causes of otitis such as seborrheic diseases and hypothyroidism should be considered. Sheets of epithelial cells may indicate neoplasia as the cause of otitis externa and the presence of numerous intact non-staining epithelial cells may indicate a seborrheic condition. Inflammatory cells and acantholytic cells may indicate autoimmune disease. High power (400x) examination is needed to characterize bacteria and yeasts. Large numbers of bacteria and/or yeasts indicate secondary invaders. When neutrophils are seen in addition to bacteria or yeasts, deep infection must be considered. Ear mites are not often seen on stained ear swabs, but the eggs may be found on mineral oil preparations. When infectious organisms are seen on high power (400X) cocci are usually Staphylococci, rods are usually Pseudomonas or Proteus. Budding yeasts of Malassezia may be seen individually in the background on a roll smear, but large numbers of yeasts colonizing on exfoliated epithelial cells are indicative of secondary yeast infection. Staphylococci and Malassezia are often found together in the same ear, and there is evidence to suggest that Malassezia growth is stimulated by Staphylococci.In ear disease, many antibiotics reported as sensitive may not penetrate into the ear when administered parenterally. Topical antibiotics can achieve significantly higher concentrations in the ear canal than the MIC. The high topical antibiotic concentration may actually be effective at killing a bacteria that was reported as resistant.3. Flushing the EarsAfter the class of disease and the type of infection is determined, the next step is to sedate or anesthetize the animal so that a thorough flushing and suctioning of the ear canal can be done. It is imperative that exudates and dried medications that have accumulated in the ear canal are removed so that the canal epithelium can be evaluated. Good visualization of the ear canal after flushing helps to insure that the vertical and horizontal canals are clean and free of debris. The efficacy of otic medications is enhanced when they are applied directly onto the cleaned epithelial surface.Care must be taken in the selection of a flushing agent, since so many ear cleaners contain materials that are potentially ototoxic when the eardrum is not intact. Prior to using an ear cleaner, read the label to see if it can be used if the eardrum is damaged. Many manufacturers are now placing a warning on their labels.With so many products available to veterinarians for ear care, it is important to understand that these products often fall into one of three categories. Cerumenolytics emulsify ear wax for easy removal. Ear flushes aid in removing pus, mucus and serum from the ears. Drying agents decrease moisture in the ears and desiccate the surface keratinocytes. Moisture is a predisposing factor allowing growth of organisms in the ear canal.Until a determination of the integrity of the eardrum is made, the choice of flushing solutions should be limited to non-detergent, non-alcoholic type of flushing solutions. Physiologic saline and dilute povidone iodine are safe flushing materials to use. When used as warm solutions (98 degrees F.) these solutions act to soften wax and loosen other debris.Ear curettes are useful for scraping the ear canal to dislodge large pieces of wax and epithelial shreds. They are available in various loop sizes and angles and some have a circular cutting surface (Dermal Curettes). Curettes are also useful for harvesting cells for cytology when a tumor mass is anisms found as perpetuating factors of otitis externa include bacteria and yeasts. Malassezia, Staphylococci, and Pseudomonas are the most common organisms isolated from the ears of dogs. Corynebacteria, Enterococci, E.coli, Streptococci, and Proteus are also frequently isolated. Malassezia is often found in the ears of cats, but cats rarely have bacterial ear infections. Demodex mites can also be isolated from ceruminous otitis cases. The prevalence of one organism over another is determined by a variety of factors. For example, excessive cerumen production by cerumen gland hyperplasia permits Malassezia growth, while decreased immune function seen with hypothyroidism allows colonization of Staphylococci. Dogs that swim and get water in their ears are much more prone to Pseudomonas infections.4. Guidelines for Treatment of Otitis ExternaA treatment plan be formulated that is tailored specifically to the patient after the skin and ears are evaluated, the cytology is done, and the ear canal is cleansed. Corticosteroids have a definite place in the treatment of otitis externa. Systemic corticosteroids reduce the intense pruritis associated with acute otitis externa and reduce the inflammation in the epithelium of the ear canal. Systemic high doses of corticosteroids are used for several days to reduce the edema and stenosis that prevents adequate examination of the ear canal. If the ear canal is patent, then a potent topical corticosteroid such as dexamethasone, betamethasone, or fluocinolone may be used to relieve the intense pain and itching. As the otitis resolves, a less potent corticosteroid such as 1% hydrocortisone may be used in the ear to act as a preventative for inflammation in atopic dogs that may have recurrent otitis. Corticosteroids do not remove hyperplastic epithelium or glands, so if there is no response to high dose corticosteroids after 7-10 days, the stenosis is probably the result of increased tissue growth rather than inflammation.Antibiotics that kill Staphylococci, Pseudomonas and other gram negative bacteria are used in many otic preparations. Although antimicrobial therapy may temporarily relieve the symptoms of otitis externa, the symptoms may re-occur unless the underlying disease is identified and treated as well. These infectious organisms are considered to be perpetuating factors in ear disease. Topical otic formulations are made with combinations of pharmaceuticals such as antifungals, corticosteroids, insecticides, and topical anesthetics. First line antibiotics such as gentamycin, tobramycin, amikacin, neomycin, and polymyxin B are potentially ototoxic, so if there is no eardrum, these antibiotics should be avoided. In addition, neomycin has been implicated as a sensitizer in contact dermatitis in the ear. If the ear becomes worse with neomycin treatment, the antibiotic should be stopped immediately. Baytril Otic (Bayer) has recently been introduced. It is a solution that contains 0.5% enrofloxacin and 1% silver sulfadiazine. The high concentration of enrofloxacin has been demonstrated in-vitro to provide a high enough concentration to be effective against most bacteria. However, there are a number of fluoroquinolone resistant Pseudomonas bacteria being found, and so this product is not recommended for first-line use in Pseudomonas infections. It's use should be based on demonstration of susceptibility of the organism to enrofloxacin. Silver sulfadiazine may have some use against the yeasts in the ear.Systemic antibiotics may be useful in some suppurative otitis externa cases as an adjunct to ear cleansing and topical antibiotic therapy. The choice of systemic antibiotic used should be based on a culture and sensitivity showing that the bacteria is sensitive to an antibiotic that can get into the ear. Culture and sensitivity should be reserved for those otitis cases that are unresponsive to topical therapy because the sensitivity results are often misleading. If there is severe inflammation with inflammatory cells present on cytology, then using intracellular antibiotics like fluoroquinolones, azithromycin, or clindamycin may increase the success of systemic treatment.Another useful compound as an adjunct in Gram negative ear infections is tris-EDTA solution (TrizEDTA, Dermapet, Inc.). EDTA chelates metal ions, such as calcium and magnesium, which are necessary to maintain the integrity of the cell membrane. The cell membrane of these bacteria become more porous so that the antibiotic can diffuse into the bacteria and kill it. Tris buffer keeps the ear canal at pH of 8.0, which is optimum for function of the aminoglycosides and fluoroquinolones. Tris-EDTA alone has been shown in vitro to have potent bactericidal effects. Clinically, tris-EDTA is used as a pre-treatment in the external ear 5 minutes prior to the instillation of topical antibiotics. Usually treatment is done on a twice daily basis.Ear mite treatment can be done using selamectin (Revolution, Pfizer) twice a month or injectable cattle ivermectin (0.1 cc subcutaneously every 2 weeks). In young kittens otic 0.01% ivermectin (Acarexx, Blue Ridge Idexx)) or 0.1% milbemycin (Milbemite, Novartis) are safe to use. Many topicals ear mite drops containing insecticides are also available for ear mite treatment.Alterations in cerumen lipid composition caused by underlying skin diseases such as atopy or hypothyroidism may play a role in Malassezia otitis externa. Low levels of free fatty acids in surface lipids coupled with increased levels of surface triglycerides favors Malassezia infections. Diseases of the ear cause increases in the amount of sebaceous secretion and increases in the number and amount of lipid secretion from the apocrine (cerumen) glands. It has been shown that over 50% of atopic dogs have elevated Malassezia populations on their skin.To remove these lipid substrates from the ear and to treat otitis externa complicated by Malassezia, the author prefers the use of an acetic acid/boric acid solution (DermaPet Ear/Skin Cleanser, Dermapet, Inc) Acetic acid degreases the ear canal and boric acid keeps the epithelium relatively dehydrated. A topical solution of miconazole or clotrimazole may be used in the ear canal. In addition to ear cleaners , systemic oral ketoconazole or itraconazole are useful for refractory yeast otitis cases or for yeast otitis cases where there is also stenosis. These compounds may reduce the pruritis associated with the yeasts, but they have been shown not to reduce otic yeast numbers.The external canal can be cleaned by the owner at home to facilitate removal of excessive exudate accumulation associated with otitis externa/media. The ear cleaner or flush is used daily for 7-10 days by filling the ear canal to overflowing, massaging the base of the ear, and allowing the solution to remain in the ear canal for 5 minutes. The loosened debris is wiped off of the pinnal surface with a dry cotton ball. This procedure is repeated once daily. When the ear canal is clean, the cotton ball will remain fairly white when the solution is wiped away. At that time, home ear cleaning is reduced to once weekly.Otitis MediaOtitis media, an inflammatory disease in the middle ear cavity, is a common disease process that goes unrecognized in most veterinary practices. Otitis media in dogs is much more prevalent than previously thought. In dogs, secondary otitis media occurs in approximately 16% of acute otitis externa cases and as many as 50% to 80% of chronic otitis externa cases. The fact that otitis media is present in over half of canine patients with chronic otitis externa should stimulate a reformulation of the thought process when faced with these cases. Just the common history that the patient has been treated repeatedly for ear infections should alert the veterinarian to think about otitis media as a possibility. Otitis media should also be considered when presented with a patient showing any neurological disease affecting the head including vestibular disease, Horner's Syndrome, or facial nerve damage. The diagnosis of otitis media in dogs can be quite difficult to make owing to the long, bent, funnel shaped conformation of the dog's ear canal, which makes it hard to see the tympanic membrane (TM). In addition, many patients with otitis media have an intact TM giving the clinician the impression that there is nothing wrong in the middle ear. Most canine patients with otitis media also have a chronic otitis externa with pathological changes to the ear canal that cause stenosis, making visual examination of the TM impossible. It is often theorized that otitis media is an extension of otitis externa that was either not treated, improperly treated, or resistant to treatment. The end result is significant damage resulting in porosity to the eardrum over time. In cats, the diagnosis of otitis media in cats may be easier to determine with the otoscope due to their relatively short ear canals. Otitis media in cats most often results as a sequela to respiratory disease, so a history of sneezing, ocular discharge and/or nasal discharge may aid in providing a clue. Some cats with otitis media also have a visible polyp in the ear canal after the ear is cleaned of the dried exudates and mucus. Many feline otitis media cases have a dark, dried, crumbly exudate in the ear canal that mimics an ear mite infestation. Primary Otitis Media in the CatIn the cat, primary otitis media occurs as a result of infection ascending through the eustachian tube to the middle ear. An exact mechanism for the development of otitis media in the cat has not been reported, although the bacterial isolates from the bullae of cats with middle ear disease are consistent with respiratory pathogens. It has been hypothesized that chronic viral upper respiratory infection early in life may play a role in initiating otitis media in cats, since these infections and polyps occur in younger cats. However, this has not been documented with virus isolation studies. In one study, tissues from inflammatory polyps were assayed for feline calicivirus and feline herpesvirus-1 by PCR. Failure to detect either of these viruses suggests that persistence of these viruses is not associated with the development of inflammatory polyps. However, the presence of these viruses may change the ability of the auditory tube to protect the bulla from infection with other agents. In many species, including man, rats, pigs, and cattle, Mycoplasma has been reported as an inducing agent in middle ear disease. In addition to the more common Streptococci and Staphylococci isolated from clinical feline otitis media cases, organisms much more difficult to culture and identify such as Mycoplasma and Bordetella have also been cultured from the middle ear of cats with otitis media. It is unclear what role these upper respiratory bacteria may play in the pathogenesis of feline otitis media. It is also unclear whether anaerobic organisms may be involved when the eardrum is intact and the auditory tube swells thus sealing these bacteria within the bulla. Often, cultures and/or cytology do not reveal an infectious organism. This raises the question of whether allergy, viruses and/or fungi have a role in feline middle ear disease. Secondary Otitis Media in CatsThe cat can have a secondary otitis media as a result of eardrum damage from ear mites or extension of a polyp through the TM. Nasopharyngeal or inflammatory polyps originate from the middle ear mucosa. A polyp is a pedunculated, protruding growth that results from chronic inflammation. Depending on their growth pattern, they can grow through the auditory tube toward the nasopharynx or they may grow through the tympanic membrane. When found in the external ear canal, the enlarging polyp mass has created a permanent opening from the external ear canal to the middle ear. Usually the presence of a polyp is associated with secondary bacterial otitis media. There is copious mucus and pus produced in these cats. When examined, the external ear canal may show liquid exudates or there may be the presence of a wax covered mass at the eardrum. Flushing the ear canal thoroughly reveals the fleshy pink to red polyp protruding into the ear canal. Secondary Otitis Media in DogsExudates and infectious organisms drain into the middle ear from the external ear canal through an eroded or ruptured eardrum and get trapped in the ventral portion of the bulla. Once the medications, chemicals in ear flushing products, and/or debris contained within the external ear canal enter the middle ear through an eroded eardrum, tissue reaction of the respiratory epithelial lining of the middle ear begins. This is called secondary otitis media. The pathogenesis of secondary otitis media in the dog is complex and often multifactorial. Due to the "L" shaped configuration of the canine external ear canal, proteolytic enzymes within exudates produced as the result of otitis externa accumulate against the thinnest portion of the eardrum. The resulting inflammation and enzymatic destruction leads to necrosis of the epithelium and supporting collagen, which results in thinning of the tympanic membrane causing it to weaken. Ulceration along the ear canal can extend to the eardrum. The ulcerated tissue leaks serum, which can cause maceration and excoriation of the epithelium. Liberation of bacterial proteases, collagenases, elastases, lysozymes from phagocytic cells, and the epidermal maceration resulting from the excessive amount of serum in the ear canal disrupt the epithelial layers of the ear canal and can lead to either erosion or rupture of the eardrum.Many cases of acute otitis media can be prevented. Special care in cleaning and attention to fluid pressure especially with the use of bulb syringes used to flush the external ear canal can prevent the high pressure from causing an iatrogenic rupture. Removal of exudates by careful flushing and suctioning of the ear canal eliminates the source of destructive enzymes acting on the eardrum. Specific therapy for infectious organisms based on cytology or culture results can shorten the course of the bacterial or fungal disease. Treatment of underlying skin disease such as atopy, food allergy, and hypothyroidism may remove or improve primary causes of otitis externa. Proper client education concerning the chronic nature of ear diseases increases owner compliance in allowing frequent rechecks to follow the progress of treatment. Recheck visits allow the veterinarian to examine the eardrum and to make changes in the treatment protocol when therapeutic response is inadequate. Whether primary or secondary, the resulting inflammation causes the lining epithelium, called the mucoperiosteum, in the bulla to change from cuboidal to pseudostratified columnar ciliated leading to an increase in the number of secretory cells and glands, further adding to the quantity of exudate. Chronic inflammation leads to mucosal ulceration and breakdown of the epithelial lining. The lamina propria thickens in response to inflammation and as vascularity increases, edema and granulation tissue form. As otitis media becomes more chronic, the lamina propria changes to dense connective tissue and bone spicules may develop within it.The cycle of inflammation, ulceration, infection, and granulation tissue formation may continue, destroying the surrounding bone. For example, septic arthritis of the ossicles may cause pain and decreased hearing owing to the fusion of these joints. The normal air conduction of sound waves is prevented and the patient may suffer decreased ability to detect high pitched sounds. With time, the ossicles are dissolved from osteomyelitis and irreversible hearing deficit occurs.Exudates and secretions formed in the bulla escape into the external ear through the ruptured eardrum and contribute to the exudate already present in the external ear canal. This large amount of liquid fills the ear canal and overflows onto the pinna when the patient shakes its head. If there is a polyp or tumor blocking the outflow of secretions and exudates from the middle ear, significant quantities of inspissated material can be present when the obstruction is removed.A fluid pressure gradient created by suppurative otitis media and increased mucus secretion prevents the eardrum from completely sealing. As the fluid pressure increases within the bulla, it is pushing against a healing eardrum with a very thin, tenuous covering. The pressure allows fluid to escape through the path of least resistance and a small hole remains in the TM. As long as there is a hole in the eardrum, this condition remains in a state of flux; i.e. fluid can enter or leave the bulla, carrying infectious materials and exudates in both directions.When the amount of middle ear secretion and exudate is decreased, when the infection is controlled by therapy, and when the fluid pressure is decreased, the eardrum can heal and otitis media is resolved. Sometimes, however, the eardrum seals but the infection is not completely resolved. If the trapped organisms lead to a return of inflammation and secretion, the eardrum can once again bulge and/or rupture. Patients with otitis media may have had a history of repeated episodes because of this alternating rupture of the TM and subsequent healing. A report by Cole, et. al. demonstrated that 70% of eardrums in documented cases of canine otitis media were intact. History and Clinical Signs of Otitis MediaIt is uncommon for a patient to present to the veterinarian with a history of acute otitis media. However, iatrogenic rupture of the eardrum during ear cleaning can lead to an inflammatory acute otitis media. A foreign body that has become lodged in the ear canal can also cause acute otitis media. For example, plant awns and foxtails often work their way through the eardrum and cause a considerable bacterial infection and inflammatory reaction in the ear canal.More commonly, a dog with otitis media will have the history of recurrent or chronic bacterial external ear infections. The mucous membrane lining the tympanic bulla reacts to foreign substances (e.g. infectious organisms, hair, cells, cerumen from the external ear canal, chemicals and pharmaceuticals used in the external canal) by producing a purulent exudate and increasing secretion of protective mucus from activated goblet cells. Dogs and cats with otitis media with an open eardrum often have a copious, malodorous liquid discharge present when the ear canal is examined with the otoscope. Additionally, it is common to see copious mucoid exudate along the floor of the horizontal canal. Although this material is usually in liquid form, the mucus and pus may be inspissated and dry. Mucus is not produced anywhere along the external ear, but it oozes from the tympanic bulla into the horizontal canal through any rent in the tympanic membrane. The presence of mucus means that there is a hole in the eardrum.Some patients will produce so much exudate that it will overflow onto the periaural region of the face or in a dog with pendulous ears, there will be dried exudate on the ear flap adjacent to the external opening of the auditory canal. Head shaking to relieve the pain and tickle associated with liquid exudate is very common in otitis media. It may be wise to check for otitis media in cases of aural hematoma. Pain on palpation of the base of the ear canal or pain on manipulation of the pinna should also alert the clinician to otitis media. Some dogs will even bite their owners while they are trying to administer medication because of the intense pain. Patients with otitis media may also be reluctant to have their mouth opened and there may be a history of reluctance to chew hard food. This is due to inflammation, swelling, and pain within the bulla, which is located adjacent to the temporomandibular joint.When otitis media affects the nerves that course around the base of the ear or through the tympanic bulla, the patient may show something as subtle as keratoconjunctivitis sicca on the ipsilateral side. This results from damage to the palpebral branch of the facial nerve. When otitis media affects the sympathetic nerves from the facial and trigeminal nerves coursing through the middle ear, the patient may show mild signs of Horner's syndrome (enophthalmos, ptosis, and miosis). Some patients may show pain, head tilt, or, with facial nerve palsy, a drooped lip, drooped ear, or loss of the ability to close the eyelid leading to exposure keratitis. Since the facial nerve courses in and around the ear canal, it is easily affected by swelling, inflammation, and trauma from the dog scratching at the base of the ear. Facial neuropathy should be suspected if there is drooping of the facial muscles and skin or drooling saliva because the lips and facial muscles cannot create an oral seal. Peripheral vestibular disease with nystagmus and circling may be evident if the infection and inflammation have affected the inner ear.An owner may present a patient for a hearing deficit. These cases should be evaluated for otitis media. Fluid in the middle ear dampens hearing. If this fluid is the result of previous flushing, it is usually absorbed within 7-10 days and the patient will regain the hearing. When the eardrum is ruptured or when the ossicles of the middle ear have sclerosed, air conduction hearing is reduced. High-pitched sound waves cannot be effectively transmitted from the ear canal to the cochlea. If a tumor or a polyp has filled the middle ear, air conduction hearing is eliminated. Bone conduction hearing is usually still present in these patients, and the pet can only hear the lower range of tones (bone conduction hearing can be demonstrated by placing your fingers in your ears and listening to the sounds around you). If there is hearing loss detected, this is usually as a result of bilateral ear disease. Unilateral hearing loss is difficult to assess in animals.If there is pharyngeal drainage of mucus and exudates resulting from otitis media, the patient may be presented for inspiratory stridor. In these cases, a pharyngeal examination may reveal a nasopharyngeal polyp interfering with breathing or thick mucus draining from the auditory osteum in the nasopharynx covering the caudal pharynx occluding the airway. Evaluation of the PatientCareful examination of the TM in the dog or cat with otitis media requires general anesthesia. It is recommended that the patient have an endotracheal tube placed in case there is a ruptured eardrum. Manipulation or flushing can cause material to drain through the eustachian tube into the nasopharynx resulting in aspiration. If there is significant stenosis of the external ear canal, either from inflammation or from permanent pathological changes to the ear canal, the eardrum may not be adequately visualized. Patient preparation using potent topical and/or systemic corticosteroids (prednisone - 1mg/lb daily for 10-14 days then taper or dexamethasone 2mg/ml at a dose of 0.1 mg/lb IM once) may be needed to reduce otic inflammation and allow examination of the TM on a subsequent visit. If permanent changes to the ear canal prevent visual determination of the integrity of the eardrum, other techniques are used to identify disease proximal to the stenosis.Recently, with the introduction of video otoscopes, it is possible to get a very detailed, magnified examination of the ear canal and the eardrum. The video otoscope provides excellent lighting at the tip of the tapered probe by transmitting light through the probe by a fiberoptic cable attached to a high output light source. Once the veterinarian is comfortable looking at normal eardrums: the location, color, clarity and the normal tension on it, then using the TM to diagnose otitis media becomes much easier. If the eardrum remains translucent, the middle ear can be transilluminated with the bright light from the video otoscope and the contents of the middle ear can be visualized.In obvious cases of canine otitis media, there is no eardrum present. The ear canal is filled with a liquid secretion, often with flecks of material mixed with it. A mucus-filled ear canal may alert the clinician to otitis media. Most patients with chronic otitis externa that has been present for 45-60 days will have a coexisting otitis media. In otitis externa, purulent exudates and proteolytic enzymes elaborated by inflammatory cells have a caustic effect on the thin epithelium of the eardrum, causing it to become necrotic, weaken and eventually rupture. When this happens, hairs, ceruminous secretions, exudates, and infectious bacteria or yeast organisms in the external ear move into the middle ear. In these patients it is difficult to visualize any part of the eardrum since it may not be present at all. Sometimes, only a small ring of granulation tissue may be seen at the annulus fibrosus where the eardrum attaches to the ear canal. That is where the eardrum was attached. With the otoscope, an otitis media case without suppuration will look like a deep dark hole. The mucosa becomes dark as it becomes hyperemic and brownish ceruminous exudates fill the bulla. There is a condition described in dogs called a false middle ear. Obstructions along the horizontal ear canal from hypertrophic or cystic glands, neoplasia, inflammation, or ceruminous plugs increase pressure on the tympanic membrane causing it to stretch and bulge into the middle ear cavity. Coupled with poor air movement through the eustachian tube, negative pressure inside the bulla pulls the eardrum even further into the middle ear cavity. A "false middle ear" may develop as a result of the distended membrane ballooning into the bulla. Examination of this ear will also show the absence of an eardrum at the end of the horizontal canal. CT scans of these ears reveal a "finger" lesion protruding into the bulla. The invaginating eardrum may collect large amounts of debris from the external canal such as keratin, wax, and desquamated epithelial cells The invaginated eardrum forms a cavity, which needs to be flushed out thoroughly. Often misdiagnosed as an otitis media case, these patients can be retrospectively diagnosed at a 2 week recheck, when the previously unseen eardrum is back in the normal location. In some cases of otitis media, the eardrum is intact but it may look abnormal. It may change color in response to inflammation on the medial side, becoming opaque and gray in color, rather than pearly and translucent. Sometimes there is fluid behind the eardrum and examination of the intact TM may indicate that it is bulging into the external ear. Purulent material in the middle ear may be seen as yellow fluid behind the eardrum. Early polyps and tumors in the middle ear may be seen as fleshy masses through the eardrum. Therefore, the presence of an eardrum does not rule out otitis media, particularly in dogs with chronic otitis externa. These dogs may have had a ruptured eardrum that healed, trapping bacteria and yeast in the tympanic bulla. Is the Eardrum Ruptured?Several techniques have been described to determine the integrity of the TM when it cannot be visualized in an ear with a stenotic external ear canal. A small diameter 3 ? Fr. to 5 Fr. catheter can be inserted into the ear canal until it stops. It is then extended and retracted to get a feel for the rigidity of the "stop." If there is a spongy feel, the eardrum is intact. If there is a definite hard feel to the "stop," the eardrum is ruptured and the catheter is hitting the medial wall of the tympanic bulla. This technique should be practiced on cadaver specimens to acquire the sensitivity.Tympanometry or impedance audiometry utilizes a sensor that measures the compliance of the eardrum in response to sound waves. It is not practical to perform this test in the veterinary clinic, as this is still a research tool in animals.An easy, indirect method for determining the integrity of the eardrum is to infuse warmed very dilute povidone iodine solution (or dilute fluorescein solution) into the ear canal with the anesthetized dog or cat in lateral recumbency. If the orange or yellow-green flushing fluid comes out of the nose or if the patient snorts out this solution through the oropharynx when pressure is applied with the flushing fluid, the eardrum is ruptured. The fluid has flowed from the external ear canal through the ruptured eardrum, into the tympanic bulla, and through the auditory tube into the nasopharynx.Another technique is to place the patient in lateral recumbency with the suspected ruptured eardrum up, then fill the ear with warmed saline and insert the tip of the video otoscope into the ear canal. By looking through the clear fluid, if air bubbles rise from the ear canal while the animal breathes, then the eardrum is ruptured. Air from the nasopharynx rises through the auditory tube into the tympanic bulla to escape from the middle ear through a ruptured eardrum.Positive contrast canalography has been described as a method for detecting a ruptured TM in dogs with otitis media. Two to five ml of dilute iodinated contrast agent is instilled into the ear canals of these anesthetized patients while in lateral recumbency with the affected ear up. The author uses 0.3ml Hypaque 50% (Nycomed) or similar contrast agent in 2.7ml saline. In a stenotic ear canal, a 3 1/2Fr. or 5Fr. catheter is threaded into the stenosis if possible. Contrast agent is then infused beyond the stenosis. An open mouth view of the bullae is then taken using a horizontal X-ray beam. If the eardrum is intact, there will be a distinct contrast/air interface at the eardrum. If the eardrum is not intact, the contrast material will enter the bulla and there will be a continuous column of contrast extending into the bulla. In normal ears, canalography was more accurate for detecting iatrogenic TM perforation than otoscopy. (10) In clinical otitis media cases, positive contrast canalography was positive in most of the cases where the eardrum was determined to be ruptured otoscopically and was positive in other cases in which the eardrum appeared to be intact otoscopically.MyringotomyTo diagnose patients with otitis media it is sometimes necessary to perform a myringotomy to get a cytology specimen and to allow for culture and antibiotic sensitivity testing on the material trapped behind the eardrum. If there is fluid pressure pushing on the eardrum or negative pressure retracting the eardrum, perforation of the eardrum using a controlled myringotomy incision will immediately relieve the intense pain associated with these pressure changes. To perform a myringotomy, the patient is anesthetized and the external ear canal is thoroughly cleaned with a disinfectant such as dilute povidone iodine. The ear canal is then dried using suction. A sterile rigid polypropylene catheter is cut to a 60 degree angle with a surgery blade to provide a sharp point. A long spinal needle can also be used to puncture the eardrum. The tip of the cut catheter is advanced under good visualization and the pars tensa is punctured at either the 5 o'clock or 7 o'clock position in order to remain away from the germinal epithelium and blood vessels overlying the manubrium of the malleus. Alternatively, a small Buck curette (2mm) can be used to make a hole in the eardrum. This instrument makes a larger hole in the eardrum and is more difficult to accurately direct to the proper site for puncture. This technique may be used to create a large hole in the eardrum to allow middle ear exudates to drain into the horizontal canal and to prevent pressure gradients from re-occurring. Larger instruments used for myringotomy cause tearing of the eardrum and should not be used.Many veterinary practices are using CO2 lasers to make the myringotomy incision. A 0.8mm X 180 mm rigid tip or a long, flexible Teflon tip can be inserted through the working channel of the Video Vetscope and can be advanced to the eardrum. Applying a pulsed, low wattage (3-4W) laser impulse melts the eardrum. The advantage of laser myringotomy is that the tip does not have to touch the eardrum, so there is less chance of contamination of the bulla with external ear canal material. In addition, the hole made by the laser is circular and takes longer to heal, which is sometimes beneficial in providing drainage.Fluid under pressure may freely flow into the horizontal canal as the perforation begins and it should be suctioned to insure that the myringotomy incision is large enough to accommodate a 3 ? Fr. or a 5 Fr. catheter. In the case of suppurative otitis media, myringotomy serves to decrease the fluid pressure behind the eardrum. The fluid escapes into the external ear canal and may continue to drain for several days, so during therapy the ear canals need to be flushed to remove this debris. The catheter is advanced through the incised TM, directed ventrally into the bulla and gentle suction is used to retrieve any material within the bulla. If a spinal needle was used, the stylet is withdrawn prior to suctioning. If the bulla is dry, 1 or 2 cc of normal saline can be infused into the bulla and then immediately retrieved. This material is submitted for cytology, bacterial culture and antibiotic sensitivity. Imaging of the Tympanic BullaRadiographic assessment of the bullae can be very helpful in determining the extent of bony involvement and determining if there is increased tissue or fluid filling the bullae. However, the absence of radiographic changes in the bullae does not rule out otitis media, especially in the more acute cases. In a dog with minimal bony changes, the bullae will appear as normal, thin circular osseous structures medial to the mandibular rami on the rostrocaudal view. If an endotracheal tube is in place, it should be temporarily removed for this view. The cortical outline will be thin and the middle of the bullae will be radiolucent, since the bullae are filled with air. When the bulla is chronically affected, either the intraluminal or extraluminal bone will show new bone production, proliferation, or bone lysis. If lytic lesions are present, differentials include neoplasia (e.g. squamous cell carcinoma) or osteomyelitis. The cartilage of the external canal may have also calcified and may be easily seen on a radiograph. Often an entire bulla will appear radiopaque, since there can be large volumes of thick exudate or tissue growths (neoplasm, polyp, or cholesteatoma) filling the air space. One or both bullae may be affected. If unilateral disease is present, a comparison between the normal and abnormal bulla makes radiographic assessment of middle ear disease easier.If large volumes of flushing solution are infused into the ear canal of a dog with a ruptured eardrum prior to radiographic assessment, a misinterpretation of the radiograph can occur, since the bulla became filled with the flushing fluid and will appear radiopaque on the radiograph. One limitation of radiographic evaluation is that old sclerotic lesions in the bulla of aged animals cannot be differentiated from more current proliferative otitis media puted tomography (CT) of the tympanic bullae, where available, may aid in differentiating bony lesions in the bulla from soft tissue reactions. Many teaching hospitals have access to CT. In the U.S., specialty referral centers are acquiring older CT scanners from human hospitals and may be able to provide this type of radiographic examination. CT may be helpful for evaluation of the horizontal ear canal and tympanic bulla when stenosis is present.Magnetic resonance imaging (MRI) of the ear is also being done to assess the middle and inner ear. The endolymph within the cochlea and semicircular canals can provide contrast visible on MRI examinations, which may be useful for evaluating the inner ear. Extension of infection into the meninges can also be detected by MRI. Therefore, an MRI may be useful in patients with neurological signs relating to middle or inner ear disease. At the present time, this technology is available to veterinary medicine on a very limited basis.OtotoxicityWhen the eardrum is perforated or totally absent, topical medications and the chemicals used in ear cleaners can gain access to the inner ear via the round and oval windows resulting in neurological ototoxicity. In addition to topical ototoxicity, many pharmacologic agents are ototoxic when administered parenterally. Careful consideration should be given to the ingredients contained in ear flush products and topical or systemic medications prior to their use. Many manufacturers of otic products are now putting warnings on the label of these products that their use should be avoided if the eardrum is not intact. In acute otitis media, the thin, permeable membranes of the round and oval windows provide easy access into the inner ear for many compounds. Access of ototoxins to the inner ear structures may be enhanced by inflammatory damage to the round window. Enzymes contained in otic exudates can cause maceration of the epithelium covering the round window increasing its permeability. It is also possible for the round window to become hyperplastic and thickened after long standing otitis media, providing a barrier to prevent these ototoxins from reaching the inner ear. If there is thick mucus found within the bulla it may act as a barrier covering the round window, effectively shielding the toxic material from contact. Because the round and oval windows cannot be visually examined it is difficult to know if the membrane is thinned or thickened. By using non-ototoxic products, this issue becomes less important. Ototoxicity results from damage to the hair cells either in the cochlea and/or in the vestibular apparatus. This results in hearing deficits, vestibular disease or both. Overt deafness or severe clinical vestibular disease (nystagmus, head tilt, and circling) may be obvious. However, subtle changes in either hearing or balance may not be detected by the owner or the veterinarian. Many ear cleaning solutions contain a mixture of ototoxic substances that may gain access to the inner ear resulting in alterations of vestibular and cochlear function. Of these compounds, chlorhexidine is probably the most toxic, especially in cats. Severe, prolonged vestibular signs can be caused by chlorhexidine and its use in ears is strongly discouraged.The aminoglycosides, polymyxins, detergents, and most alcohols routinely used in the treatment of the external ear canal are known to be toxic to the nervous structures of the inner ear. Potentially ototoxic antimicrobial pharmaceuticals are present in most topical formulations for treatment of otitis externa. An assessment of the risks of topical use of a drug or ear flush solution that may cause ototoxicity versus the therapeutic benefit must be considered when using these formulations to treat otitis media. For example, the aminoglycoside tobramycin has shown to be an effective antibiotic for many multidrug resistant Pseudomonas organisms. Although it is an aminoglycoside with potential ototoxic side effects, it is often infused into the bulla to treat the bacterial infection because of its efficacy. Many common topical antibiotics can cause ototoxicity. Gentamicin, for example, concentrates in the hair cells of the organ of Corti in the cochlea when administered parenterally. However, it may also cause vestibular signs when administered topically in the middle ear. The cell permeability is altered so the hair cells swell and become deformed. They are rendered rigid and are unable to respond to movements of the endolymph within the semicircular canals. Ataxia, head tilt and circling can result. A similar situation occurs in the cochlea when neomycin or kanamycin concentrate there. The cochlear nerve cells are damaged and cannot respond to vibrations, leading to hearing loss. There is a very short list of products that can be infused into the tympanic bulla without the risk of ototoxicity. Prior to selecting a product to use in the bulla, a study of the ingredients contained in the preparation should be evaluated to determine the ototoxic potential. For antibiotics, the fluoroquinolones (ciprofloxacin, enrofloxacin, and ofloxacin), aqueous Penicillin G, some semi-synthetic penicillins (carbenicillin and ticarcillin), and some cephalosporins (ceftazidime and cefmenoxime) are safe to use in middle ear disease. (12) The antifungals clotrimazole, miconazole, nystatin, and tolnaftate can be safely infused. The aqueous forms of the anti-inflammatories dexamethasone and fluocinolone are safe in the middle ear. Most ceruminolytics cannot be used in the bulla. The exception is squalene (Cerumene, Evsco), which has been shown to be safe. Tris-EDTA is also a safe flushing agent.Treatment of Otitis MediaPlanning treatment of otitis media requires a stepwise protocol for maximal effect. An organized approach allows the clinician to formulate treatment or change existing treatment based on observations. The steps outlined below provide a framework for treating otitis media. 1.??Access middle ear 2.??Cytology and bacterial culture 3.??Flush bulla 4.??Infuse topical medications into the bulla5.??Reduce inflammation w/corticosteroids6.??Systemic and topical antimicrobials 7.??Recheck weekly - retreat 2-3 times8.??SurgeryAccessing the middle ear by otoscopy and myringotomy is discussed above. Sample CollectionIn order to get a culture or cytology sample from the bulla in an ear without an eardrum, a sheathed catheter is used. A sterile 3 ? Fr. polypropylene urinary catheter is threaded into a 5 Fr. polypropylene urinary catheter. With the closed irrigating ends removed, the 5 Fr. catheter is first threaded through the external ear canal until it reaches the bulla. This will act as a shroud to prevent contamination of the sample with debris from the external ear canal. It should be inserted into the bulla along the floor of the horizontal canal and directed ventrally into the bulla. After this catheter is placed, the 3? Fr. catheter is threaded into the 5 Fr. catheter and it is extended beyond the cut end. The sample is aspirated with a syringe or suction apparatus using the flanged end of the 3? Fr. catheter. If no liquid is in the bulla, 1cc of sterile saline can be infused and suctioned back. Any fluid or mucus that enters the lumen of the 3 ? Fr. catheter is submitted to the laboratory for cytology and culture and sensitivity.If a myringotomy incision was made with a sharp pointed 5 Fr. catheter, as the incision is made the catheter is extended into the bulla and the contents aspirated. The lumen contents are submitted to the laboratory. If a laser myringotomy was made, a sterile catheter is inserted through the hole and a sample is taken. Cytology and Bacterial CultureIt is important to obtain samples for both cytology and bacterial culture. Many infections are polymicrobial including mixed infections of bacteria (rods and/or cocci) and yeasts. Cytology of a middle ear specimen may reveal Malassezia yeasts, which would not be reported if only bacterial culture was submitted to the laboratory. Additionally, cytology may not reveal bacteria because they are often protected from the cytology stains by mucus. Many cytology negative specimens have been reported as culture positive. In ear disease, laboratory assessment based on culture and sensitivity does not always correlate to clinical response (see below, systemic and topical antimicrobial therapy). In cats with otitis media and polyps, the most common bacterial organism was Staphylococcus intermedius. Other bacteria have been isolated from cat middle ears including Pseudomonas, Bordetella, Bacteroides, Fusobacterium, and Mycoplasma. Fortunately, bacterial resistance problems are not usually a feature of feline otitis media. The most common microbes recovered from chronic otitis media in the dog include Pseudomonas aeruginosa and Staphylococcus intermedius. In one study, one or the other of these two bacteria was isolated in over 70% of the cases. Other isolates include Streptococci, Proteus, Klebsiella, E.coli, and some anaerobes.When microbiological samples from the middle ear were compared to the same bacterial isolates found in the horizontal canal, the antibiotic sensitivity of organisms isolated from the horizontal ear canal were different from the antibiotic sensitivity from organisms from the middle ear. This occurred in almost 80% of these cases. Flushing and Suctioning the BullaProbably the most important technique for treating otitis media is flushing the bulla. Topical otic medications cannot penetrate through the thick exudate that fills the middle ear during otitis media, so this exudate and secretory material must be removed. Additionally, many destructive enzymes that are trapped in the mucoid secretions in the bullae remain in contact with the mucoperiosteum, which prolongs the disease. Hydrating the mucus with the water in flushing solutions makes it less dense and easier to suction. Using fluid under pressure to irrigate the bulla will loosen mucus from the tissue. This material does not stick to the mucous membrane as cerumen sticks to the epithelium in the external ear canal. The fluid the author uses for flushing the bulla is warmed, very dilute povidone iodine solution in warm tap water. If there is an identifiable bacterial infection, warmed tris-EDTA is also infused into the bulla. Acidic solutions should be avoided in the middle ear to prevent pain and irritation. Using a device that delivers the fluid under high pressure allows the mucus and pus to flush out of the bulla either into the external ear canal, where it can be suctioned out, or through the auditory tube into the throat. The MedRx Earigator (MedRx, Inc., Seminole, FL) makes flushing and suctioning the tympanic bulla a simple, efficient procedure. A 5Fr. or smaller polypropylene catheter connected to the irrigation/suction unit is placed into the 2mm working channel built into the Video Vetscope. The entire cleaning process is observed on the video monitor. The catheter is advanced along the floor of the horizontal canal and is directed ventrally into the bulla. A less rigid red rubber feeding tube can be used for flushing, but it may collapse when used for suctioning. Without this equipment, catheter placement and evaluation of the efficiency of cleaning is hard to determine, but that should not deter the attempt to flush the bulla.Bulla InfusionRemoval of the mucus and pus within the tympanic bulla during the treatment of otitis media allows topical medications to penetrate in and around the thickened, folded mucoperiosteum. The use of aqueous formulations of non-ototoxic topical antibiotics, steroids, or antifungals placed on the mucoperiosteum hastens recovery from otitis media. Topical levels of these drugs may be many times the level that can be achieved using parenteral therapy even when there is severe hyperemia of the mucoperiosteum. Antibiotic concentrations are high in inflamed tissues because the increased blood flow allows increased serum levels of antibiotic to perfuse the inflamed tissue. But even these levels may not achieve the MIC necessary to kill the bacterial target. Infusing drugs into the bulla is an effective method of providing long acting high concentration effects. The tympanic bulla in the dog and cat is a deep blind pouch. When the bulla is filled with antibiotic, the fluid cannot escape easily. Because of the small diameter of the swollen auditory tube and its location high on the medial wall of the bulla, drainage from the auditory tube is unlikely. Depending on the amount of eardrum present, fluid has to traverse a jut in the petrous temporal bone, which forms the floor of the horizontal ear canal and extends into the bulla. Fluid escape from the bulla is difficult and requires severe changes in head position to allow drainage through the eardrum. If a myringotomy incision was made, it would be difficult for fluid to escape the middle ear because of the surface tension across the incision. There may be a small movement of the infused antibiotic solution into the external ear canal, which actually may be beneficial, but the majority of the topical antibiotic solution can remain within the bulla for several days after infusion.The antibiotic, antifungal, or corticosteroid solution is infused into the bulla through a small catheter placed into the bulla until the fluid overflows into the external ear canal. During the first bulla infusion, less than 1cc of solution can be infused into the inflamed bulla. The entire procedure of flushing, suctioning, and bulla infusion should be repeated weekly during therapy. With each successive treatment, the mucoperiosteum should retract slightly, increasing the volume of fluid the bulla can accommodate. Reduce Inflammation with CorticosteroidsCorticosteroids slow the intense inflammation and exudation found in middle ear disease. As described earlier, the mucoperiosteum undergoes severe pathological changes in response to inflammation. Corticosteroids can reverse some of the extensive granulation that forms in the bulla, which enhances the ability of topically applied antibiotics to penetrate into the infected tissue. The tympanic cavity is crowded out by this hyperemia and proliferating granulation tissue, so the amount of free space within the bulla decreases. Reducing the inflammation helps this lining membrane retract back toward the bone, increasing the volume within the bulla. When the eardrum heals this space should refill with air. Corticosteroids also reduce the amount of mucus produced in the bulla and decrease the viscosity of the secretions from the inflamed mucous membrane in the bulla. Changing the character of the mucus aids in its removal. Corticosteroids may also function in reducing the swelling in the auditory tube, increasing lumen diameter, which has the beneficial effect of offering limited drainage of mucus into the nasopharynx.Aqueous topical corticosteroids such as dexamethasone sodium phosphate (4mg/ml) or a DMSO/Fluocinolone combination (Synotic, Syntex) may be infused through a catheter placed into the cleaned and dried bulla. These potent topical anti-inflammatories are not ototoxic. Other potent injectable topical corticosteroids are formulated with ototoxins such as benzyl alcohol or propylene glycol, or they are in suspension. These should not be used in the bulla. If there is bacterial or fungal disease and the space in the bulla is needed for antibiotic or antifungal topical therapy, systemic corticosteroids may be used for a few weeks during the recovery phase of otitis media. High initial doses of corticosteroid are required, which mirror those used for other diseases such as inflammatory bowel disease. Patients should be screened for diabetes, hyperadrenocorticism, demodicosis, and potential pregnancy before using the high doses of corticosteroids. Prednisone or prednisolone at 1-2mg/lb daily for 2 weeks then decreasing to ? mg/lb every other day will provide high enough levels to decrease inflammation within the bulla. Owners of these animals need to be warned that there will be side effects of prednisone at this high dose. Many owners will discontinue the medication when the side effects occur. The author prefers to use a 0.1 mg/lb intravenous dose of dexamethasone (2 mg/ml) at the time of treatment and then to repeat this injection weekly at the recheck appointment if there is significant exudate that needs to be suctioned from the bulla. This has less mineralocorticoid-related side effects and prevents the owners from having the choice to stop the medication. Because many dogs with otitis media also have concurrent otitis externa, systemic corticosteroids aid in reducing the swelling and pain from otitis externa. In addition, they reduce the signs associated with atopic disease, which is a primary cause of otitis externa in the dog.Systemic and Topical AntimicrobialsThe dilemma facing the clinician treating otitis media is that systemic drug levels may not reach sufficient MIC in the bulla and topical treatment requires frequent applications. Using maximal doses of oral antibiotics along with weekly bulla infusions of a fresh supply of antibiotic increases the therapeutic successes. Topical antibiotic treatment of otitis media has gained recent favor in veterinary medicine. The use of topicals is based on the high levels of antibiotic that can be placed into the bulla coupled with the poor drainage of the tympanic bulla. Aqueous solutions of non-ototoxic antibiotics can be placed directly onto the infected mucoperiosteum. Infused antibiotics can remain in contact with the inflamed, granulating middle ear mucosa much longer because the fluid filling the bulla cannot readily escape. When topical therapy of otitis media fails it is usually the result of inability of the antibiotic to get to the bacteria. For example, there may be sequestration of bacteria within folds or pockets of granulation tissue, unexposed to the topical antibiotic. Antibiotic sensitivity patterns are important for treating otitis media when systemic antibiotics alone are used to get levels within the bulla. Unlike topical antibiotics, which can achieve many times the blood MIC, systemic antibacterial therapy for otitis media relies on lower levels of antibiotics arriving in the middle ear hematogenously or through inflammatory cells. Due to the poor blood supply in the external ear canal and middle ear, there is limited diffusion of antibiotic from the serum into the lumen of the ear canal or tympanic bulla. RechecksWith successive recheck visits, the eardrum and the horizontal canal should be examined for fluid, mucus and pus. If there is fluid within the bulla, it should be flushed out and the bulla suctioned to prepare it for re-infusion. When the weekly examination reveals a dry canal and little liquid within the bulla, the inflammation and infection within the bulla has subsided. At this point bulla infusion treatments can be discontinued. Subsequent 2 week recheck intervals should reveal a healing eardrum.SurgeryMedical therapy of otitis media in the author's practice is 75% successful. A small number of chronic otitis media cases with severe proliferative tissue and bone spicules require total ear canal ablation and bulla osteotomy in spite of proper medical therapy.Speaker Information(click the speaker's name to view other papers and abstracts submitted by this speaker) Louis N. Gotthelf, DVMAnimal Hospital of MontgomeryMontgomery, AL Management of Pseudomonas OtitisWorld Veterinary Congress 2008Rod A.W. Rosychuk, DVM, DACVIMCollege of Veterinary Medicine and Biomedical Sciences, Colorado State UniversityFt. Collins, CO, USA18292917General CommentsPseudomonas aeruginosa is a gram-negative "rod" shaped bacteria that is ubiquitous in the environment. It is one of the more commonly encountered secondary infections associated with canine otitis externa, especially chronic otitis. It is one of the most common organisms associated with otitis media in the dog. Although other gram-negative "rod shaped" bacteria are also associated with otitis externa and media (Proteus, E. coli, Klebsiella, Enterobacter sp), Pseudomonas is the most commonly encountered. Pseudomonas and other gram-negative "rods" are not found in the cytology of normal ears. Pseudomonas is intrinsically resistant to many antibiotics and rapidly develops multi-drug resistence1,2. Pseudomonas infections are usually secondary to a primary factor that has initiated inflammation within the ear (e.g., in the dog - atopy, food sensitivity, foreign body, primary idiopathic seborrhea, hypothyroidism, autoimmune disease such as pemphigus foliaceus etc.) Predisposing factors (increased environmental humidity, swimming, hair in ears, stenotic horizontal canals) essentially amplify the deleterious effects of these primary factors. Perpetuating factors, such as proliferative changes, debris within the ears and otitis media support the persistence of disease in the ear, even if the primary factor is no longer active. Therapy for Pseudomonas infections is very importantly not only directed at resolving the infection, but also at resolving / controlling primary and perpetuating factors involved. The control of primary and perpetuating factors is also very important in preventing recurrences of infection. Clinical SignsThe presence of a Pseudomonas infection is usually heralded by the presence of purulent exudate within the ear. Affected ears are often very inflamed, swollen and painful and may be eroded or ulcerated. Pseudomonas is also a relatively common secondary infection in chronic, proliferative cases of otitis externa. Effects on TympanumPseudomonas infections are more likely to be associated with breakdown of the tympanum and the concurrent presence of otitis media. This likely has to do with the proteases produced by this organism. Otitis media is even more common if the canals are hyperplastic and stenotic. When a Pseudomonas infection is known or suspected (based on cytology or culture) and the tympanum is not visible, consideration should be given to the use of topical antibiotics / products with less potential for ototoxicity, working on the premise that the tympanum may be perforated. The presence of a Pseudomonas infection may also provide the rational for the performance of a deep ear cleaning, early in the course of the therapy. This would allow for the removal of organisms and potentially irritating debris and would also allow for the assessment of the integrity of the tympanum. Cytologic FindingsCytologic examination will reveal "rods" and usually neutrophils on cytologic examination. Pseudomonas is often the only organism associated with the infection, but can occasionally be found with other bacteria or Malassezia. CultureAcute Pseudomonas infections that have not received significant topical antibiotic therapy in the past are often treated with antibiotics chosen empirically, based on our knowledge of efficacy. These include gentamicin, polymixin B and enrofloxacin. With the advent of concurrent TrisEDTA therapy, many Pseudomonas infections may be successfully treated, even when they show resistance to the antibiotic being used (e.g., enrofloxacin or gentamicin). Culture is indicated when there is a history of unsuccessful topical therapy using these antibiotic regimens. These are usually chronic cases. Culture and sensitivity testing data is of particular importance in choosing systemic therapy. Samples for cultures should be taken from both the canals and, if involved, the middle ear. These can be combined for purposes of culture (to lessen cost). It has been shown that the strains and sensitivity patterns of Pseudomonas organisms cultured from the horizontal canal may differ from those cultured from the middle ear1. When submitting cultures from cases with suspected Pseudomonas infections, it is important to request sensitivities for antibiotics that are known to have good efficacy for treating this organism. While several of these are usually present on routine antibiograms (e.g., gentamicin, amikacin, enrofloxacin), several are not (ticarcillin, polymixin B, ciprofloxacin, marbofloxacin). These should be requested at the time of submission. It is important to note that the susceptibility or resistance to one fluoroquinolone does not imply susceptibility or resistance to all (or any) other fluoroquinolones3. Therapy General Comments1.??The overall quality and quantity of studies reporting the efficacy of various treatments for Pseudomonas infections of the ear are low4. 2.??Many of the drugs listed below have the potential to be ototoxic if they pass through a perforated tympanum into the middle ear and subsequently into the inner ear. Although the incidence of ototoxicity is low in the dog, the author does tend to choose drugs that are considered less likely to cause ototoxicity when the tympanum is perforated or if the integrity of the tympanum is unknown and there is a high index of suspicion for perforation.3.??The author prefers to dispense most topical antibiotics in "multi-dose" vials that allow the owner to draw up the medication in a graduated syringe. This facilitates more accurate dosing. Most "Golden Retriever" sized dogs receive 0.5 ml; small dogs and cats 0.3-0.4 ml and large breed dogs such as St. Bernards--0.8 mL per treatment. If the inner aspect of the pinna is involved in the pathologic process, it is imperative that the owner be instructed to topically treat these areas.4.??Tris-EDTA has been a very beneficial addition to our armamentarium of treatments for Pseudomonas otitis. Tris-EDTA has been shown to increase the susceptibility of various bacteria (Pseudomonas aeruginosa, Staphylococcus aureus, E.coli and Proteus mirabilis ) to several antibiotics (enrofloxacin, cephaloridine, or kanamycin)5. It has also been shown that Tris-EDTA has some inherent antibacterial activity6. There are currently several Veterinary Tris-EDTA products on the market. T8 solution (DVM Pharmaceuticals) also contains benzoyl alcohol, which enhances its antibacterial effects. It contains surfactants which provide some cleansing activity. There is some question about its increased potential for ototoxicity because of these additives. T8 Keto (DVM Pharmaceuticals) has an ingredient profile as for T8 but also contains ketoconazole which provides anti-Malassezia effects. TrizEDTA (DermaPet Inc.) contains TrisEDTA , but none of the additives noted above for the T8 and T8 Keto products and for this reason, has been suggested to be safe in the middle ear (not ototoxic). TrizUltra plus ketoconazole (DermaPet) contains TrizEDTA and ketoconazole. The trisEDTA products are used to flush the ear 10 minutes prior to instilling topical antibiotics such as enrofloxacin (see below). Topical Therapies for Acute, First Time or Infrequently Recurrent Pseudomonas Infections; Tympanum Intact or Thought to be IntactTopical Antibiotic-containing ProductsThe empiric antibiotics we tend to reach for when "rods" predominate on cytologic examination are:1.??Gentamicin (i.e., Otomax or Mometamax; Schering)--gentamicin is effective against a significant number of Pseudomonas strains (50-60%1,2). It is potentially ototoxic.2.??Polymixin B--polymixin B is effective against as many as 95%-100%1,2 of the Pseudomonas organisms seen in association with otitis in the USA, where polymixin B is not used in routine ear preparations. Example: Cortisporin Otic solution, Glaxo Wellcome--polymixin B, neomycin, 1% hydrocortisone. This is a human product. Polymixin B is potentially ototoxic.3.??Baytril Otic (Bayer; 5 mg/ml enrofloxacin, 10 mg/ml sliver sulfadiazine). Silver sulfadiazine is effective against a broad spectrum of gram-positive and negative bacteria, including Pseudomonas. It is, at best, only a mildly effective therapy for Malassezia. The product appears to be well tolerated within the middle ear. It does not contain a steroid. If a steroid influence is necessary (and it often is), then a steroid drop or systemic steroid therapy would be used in addition to the Baytril Otic.4.??These products are used BID initially.5.??These antibiotics also work well against other gram-negative organisms.FlushesChoices of flushes are extensive in this scenario and include: 1.??Tris-EDTA containing product (e.g., T8 solution, DVM; T8 Keto, DVM; Triz-EDTA, DermaPet). These products are used to flush the ear twice daily (about 10 minutes prior to application of topical antibiotic-containing product).2.??Acetic acid containing products (e.g., 2% acetic acid, 2% boric acid; MalAcetic Otic, DermaPet Inc. or dilute 5% white vinegar and water--1:2). Acetic acid is noted to have unique anti-Pseudomonal effects. Used once or twice daily (author usually uses it once daily). 3.??Cleanser/dryers--EpiOtic Advanced (Virbac; contains monosaccharides reported to reduce Pseudomonas adherence to epithelial cell surfaces). EpiOtic (Virbac) alone, without monosaccharides was shown in one study to have efficacy against Pseudomonas when used as the only therapy for Pseudomonas otitis (ears flushed twice daily for two weeks) 7. The salicylic acid and lactic acid along with PCMX (parachlometaxylenol) likely contributed the anti-bacterial effect associated with this product. These cleanser/dryer flushes are most routinely used once daily. Topical Therapies to Consider with More Chronic, Persistent or Very Recurrent Infections or Based on Culture and Sensitivity Testing (Potential for Ototoxicity is Noted for Each) Flushes1.??TrisEDTA containing product (see above). There is some debate as to whether the benzoyl alcohol containing products are safe within the middle ear. For this reason, the author favors the use of TrizEDTA (DermaPet) in these scenarios. However, others have used the T8 Keto product in ears with perforations and are not aware of encountering problems. 2.??Acetic acid containing product (see above). Dilute vinegar and water (1: 2) appears to be well tolerated in the middle ear. Topical Antibiotics1.??Enrofloxacin mixes utilizing injectable (22.7 mg/ml) enrofloxacin; these formulations should be "safe" in the middle ear; ears pre-treated with TrisEDTA. a.??1:2 enrofloxacin: dexamethasone sodium phosphate (4 mg/ml for moderate steroid effect). Used BID.b.??1 part enrofloxacin to 1 part Dexamethasone phosphate to 2 parts 1% miconazole (Conofite) (for concurrent anti-Malassezia effect). Used BID.c.??Saline and enrofloxacin 1:1 to 1:2. Used BID.d.??3-4 cc enrofloxacin to 8 cc Synotic BID (for potent steroid effect; i.e., proliferative ear disease).e.??Enrofloxacin mixed with a Tris-EDTA solution: when using these products in combination, the author tries to achieve a final concentration of 10 mg/ml of enrofloxacin (i.e., 13 mL of 100 mg/ml injectable enrofloxacin per 118 ml bottle of T8 solution). Others have claimed similar success with concentrations of 4-5 mg/ml of enrofloxacin. The combination product is used BID to initiate therapy (ear is filled with the combination and massaged in). The author has used a combination of enrofloxacin and TrizEDTA (DermaPet Inc.) in middle ears, without apparent ototoxicity. Due to the lack of an anti-fungal component to this product (TrizEDTA), a flare of Malassezia otitis may occasionally be seen during therapy. However, if the T8 Keto product is used, this should not be a problem. 2.??Ticarcillin or Ticarcillin and clavulanic acid (Timentin; GlaxoSmithKline). Ticarcillin has proven to be a very beneficial therapy for resistant Pseudomonas. The re-constituted product is suggested to have a shelf life of only 2-3 days, although there is some data to suggest that it can be as long as a month. The shelf life is definitely prolonged to one month with freezing of the re-constituted product. The author uses Timentin; 3.1 gm vial; reconstitute with 26 ml (100 mg/ml); freeze in 4 ml aliquots; thaw and use each 4 ml aliquot over 2 days; 1/2 ml in each ear BID. Others have suggested: reconstitute a 6 gram vial of ticarcillin with 12 ml of sterile water. Divide equally into 2-ml portions in syringes and freeze (will remain stable for 3 months); this is the "stock solution". To make up the ear treatment solution, thaw and mix a 2 ml aliquot of concentrate with 40 ml of normal saline. Divide this into four 10-ml aliquots and freeze. Clients should keep these frozen; one aliquot should be thawed at a time, keeping it refrigerated, and used for no longer than 1 week. Anything remaining after 1 week should be discarded and another aliquot thawed. Ticarcillin appears to be well tolerated in the middle ear. 3.??Silver sulfadiazine 1% cream--very efficacious therapy (although the author has seen resistant cases)--diluted 1:9 with water (only the Silvadene product mixes well with water; generics do not mix well) or have a solution of silver sulfadiazine powder made up (Spectrum pharmacy; ; make up 1% solution)8. Ear should be cleaned prior to application to enhance efficacy. May promote re-epithelialization in ulcerated ears. Silver sulfadiazine appears to be well tolerated within the middle ear8. 4.??Amikacin injectable (dilute 250 mg/ml to 50 mg/ml) 4-8 drops of 50 mg/ml BID or tobramycin (human ophthalmologic prep.). Both aminoglycosides are potentially ototoxic and should not be used in ears with a perforated tympanum.5.??Ceftazidime--dilute to 100mg/ml and freeze in aliquots (as for ticarcillin); treat ears BID.6.??Imipenem--dilute to 50 mg/ml; treat BID. Note: due to the value of this drug in treating very resistant bacteria, it should only be used as a true "last resort" of the medical management of Pseudomonas otitis (to prevent the development of more widespread resistance). Complications of Antibiotic TherapyWhen antibiotic or antibiotic / steroid combination products are used in the ear for treating bacterial infections, it is not uncommon to see opportunistic, secondary Malassezia infections develop. These are diagnosed based on cytology and are usually readily resolved with topical +/- systemic anti-Malassezia therapy. They may be prevented with the use of a product such as T8 Keto (DVM pharmaceuticals) or TrizUltra plus ketoconazole (DermaPet), both of which contains ketoconazole. Systemic AntibioticsThere is some evidence supporting the efficacy of systemic antibiotic therapy alone in treating bacterial otitis (improving 43% or resolving 28% of cases in one study)9. Systemic antibiotic is indicated when the canals are hyperplastic or proliferative, erosive or ulcerated and/or there is otitis media or it is difficult for the owners to topically treat the ears. However, it is important to note that the author has treated many cases of Pseudomonas otitis externa +/- media with just a topical antibiotic alone (e.g., combination of Tris-EDTA and enrofloxacin or combination of ticarcillin and acetic acid flushes). The author's antibiotics of choice are ciprofloxacin (15-20 mg/kg BID) and marbofloxacin (4-5.5 mg/kg/day). This is based on in vitro data that has shown these antibiotics to be superior to other fluoroquinolones for treating Pseudomonas. Enrofloxacin would be used at a dose of 10-20 mg/kg/day. The fluoroquinolones are concentration dependent antibiotics. On an antibiogram, if the bacteria is reported as sensitive (S), the lower dosage range is used; if intermediate (I), then the higher range is used. If the bacteria is resistant (R), then particular attention should be given to the MIC for the bacteria. If the MIC for enrofloxacin is < or = to 4, then topical therapy will likely exceed the MIC and the antibiotic should be effective. If the MIC is > 4, then the bacteria should be considered resistant to enrofloxacin and a different antibiotic should be chosen. Appropriate antibiotics for systemic use are best chosen on the basis of culture and sensitivity testing. Alternative injectable systemic antibiotic considerations for very resistant Pseudomonas would include ticarcillin or ceftazidime (ticarcillin, 60-75 mg/kg BID SubQ or ceftazidime 30-50 mg/kg BID SubQ) for 2-3 weeks. These injections can be given at home by the owner.Systemic GlucocorticoidsSystemic glucocorticoids are not contraindicated in the treatment of Pseudomonas infections. An exception may exist in the presence of an osteomyelitis of the bulla or petrous temporal bone, wherein there is the potential for extension of infection in to the calvarium. Glucocorticoids will rapidly reduce inflammation and pain and facilitate the owner's ability to topically treat the ears. In general, anti-inflammatory dosages of prednisone/prednisolone are used (starting at 0.5-1.0 mg/kg/day). With chronic, proliferative otitis, it becomes important to "open up" the canals. This allows topical antibiotic to come in contact with the lining of the length of the canals. Depending on the degree of proliferation and stenosis, more aggressive glucocorticoid dosages may be required (e.g., moderate to severe proliferative changes--starting at 1-2 mg/kg/day prednisone for the first 1-2 weeks, then gradually taper).Management of Concurrent Primary and Perpetuating FactorsAs noted previously, the successful management of Pseudomonas infections also emphasizes the need to resolve/control primary and perpetuating factors that are key to the pathogenesis of otitis. This may mean initiating a restrictive diet trial to rule out or control a food sensitivity; treating with glucocorticoids for underlying allergies; emphasizing the need to have all debris removed from the ears at some time in the management of every case of otitis; resolving proliferative changes etc. Follow-Up Patients with Pseudomonas otitis externa and/or media should be rechecked every 2-3 weeks until the organism is no longer present on cytologic examination. The finding of even rare "rods" on cytologic examination warrants continued therapy. The endpoint of therapy is ideally determined by negative culture. Treatment for at least 1-2 weeks beyond apparent resolution of infection is warranted for proliferative otitis and otitis media. The duration of topical and systemic therapy for otitis media is usually at least 4-6 weeks. References 1.??Cole LK, Kwochka KW, Kowalski JJ, Hillier A. Microbial flora and antimicrobial susceptibility patterns of isolated pathogens from the horizontal ear canal and middle ear in dogs with otitis media JAVMA 1998;212;534-538. 2.??Martin Barrasa JL, Lupiola Gomez P, Gonzallez Lama Z, Tejedor Junco MT. Antibacterial susceptibility patterns of Pseudomonas strains isolated from chronic canine otitis externa. J Vet Med B Infect Dis Vet Public Health 2000; 47;191-196.3.??Cole LK, Kwachka KW, Hillier A, et al. Ciprofloxacin as a representative of disc diffusion susceptibility of enrofloxacin for bacterial organisms from the middle ear tissue of dogs with end stage otitis externa. Vet Dermatology 2006; 17 (2); 128-133. 4.??Nuttall T, Cole Lynette C. Evidence-based veterinary dermatology: a systematic review of interventions for treatment of Pseudomonas otitis in dogs. Veterinary Dermatology 2007; 18;69-77.5.??Farca AM, Piromalli G, Maffei F, et al. Potentiating effect of EDTA-Tris on the activity of antibiotics against resistant bacteria associated with otitis, dermatitis and cystitis. J. small Anim Practice 1997; 38;243-45.6.??Cole LK, Luu DH, Rajala-Schultz PJ, et al. In vitro activity of an ear rinse containing tromethamine, EDTA and benzoyl alcohol on bacterial pathogens. Am J Vet Res 2006; 67;1040-1044.7.??Cole LK, Kwochka RW, Kowalski JJ, et al. Evaluation of an ear cleanser for the treatment of infectious otitis externa in dogs, Vet Therapy 2003; 4;12-23. 8.??Palmeiro BS, Morris DO, Wiemelt SP, et al. Evaluation of outcome of otitis media after lavage of the tympanic bulla and long-term antimicrobial drug treatment in dogs: 44 cases ( 1998-2002) JAVMA 2004;225;548-553.9.??Carlotti DN, Guaguere E, Koch HJ, et al. Marbofloxacin for the systemic treatment of Pseudomonas spp. suppurative otitis externa in the dog. In: von Tscharner C, Kwochka KW, Willemse T, eds. Advances in Veterinary Dermatology 3. Oxford: Butterworth Heinemann, 1998; 463-4. Speaker Information(click the speaker's name to view other papers and abstracts submitted by this speaker) Rod A.W. Rosychuk, DVM, DACVIMColorado State UniversityFt. Collins, Colorado, USA ................
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