Diagnosis and management of otitis media (Proceedings)

Before discussing otitis media (OM) I want to review the anatomy of the middle ear. The middle ear has the tympanic membrane (TM) on the lateral side and the vestibular and cochlear windows on the medial surface. The tympanic membrane slants obliquely downward and inward so as to form an angle of about 45O with the floor of the horizontal canal. Debris and medication tends to accumulate there because of this. The TM is a semitransparent epithelial structure that is divided into 2 parts. The smaller, dorsal opaque portion that is pink, and loosely attached, and contains small blood vessels is the pars flaccida. The larger gray, semitransparent ventral portion is the pars tensa.

The middle ear (tympanic cavity- TC) is an air-filled chamber that is lined by pseudostratified ciliated columnar epithelium that contains goblet cells. The TC contains 3 parts- the dorsal (the attic or epitympanic recess) that is the smallest and contains 2 of the 3 auditory ossicles- the head of the malleus and the incus. The facial nerve canal is in this portion of the TC. The middle portion of the TC is the tympanic cavity proper and it lays adjacent to the tympanic membrane. This portion of the TC contains the stapes and part of the malleus (manubrium). The stapes is attached to the vestibular window that leads to the inner ear. The manubrium of the malleus attaches to the medial surface of the tympanic membrane and is C shaped w/the bottom of the C pointing rostrally. The outline of the manubrium of the malleus may be seen through the TM when the ear is examined. The tympanic bulla (TB) is the ventral portion of the TC and is the largest of the 3 components of the TC.

Nerves that are anatomically close to, or pass through, the TC include the cranial cervical postganglionic sympathetic nerve and the facial nerve. The facial nerve travels through the TC in an incomplete bony canal, facial canal.

Etiology/Pathophysiology

OM, like OE, is usually secondary to some other primary factor. However OM may occur as a primary disease. In cats it occurs as a result of an ascending infection through the eustachian tube as a consequence of an upper respiratory viral, Mycoplasma or Bordetella infection. Cats also may get primary OM due to nasopharyngeal polyps. These polyps originate from the middle ear mucous membrane and may either grow through the eustachian tube, resulting in respiratory signs or through the TM causing both OM, and due to the obstructive nature of the mass, OE. When present in the external ear canal you will see a red mass in the horizontal ear canal. Occasionally this mass is not appreciated until the exudate and cerumene is removed from the surface of the polyp. Secondary causes of OM in cats include chronic Otodectes infestation and rarely chronic otitis externa.

In dogs, OM is most commonly the result of the spread of microorganisms from the external ear canal associated w/chronic OE. (Note- depending on the part of the country you practice, foreign bodies (grass awns) also may be a common cause) Bacteria spread to the TC through a ruptured TM. Since OE is the underlying cause, it is essential to not only address the OM and the OE but also the underlying cause of the chronic OE. It is beyond the scope of this talk to discuss the diagnosis and management of OE

Dogs do occasionally get primary OM as seen in primary secretory otitis media of CKCS (PSOM). Normally any mucous produced by the lining of the tympanic bulla's epithelial cells drain out the eustachian tube but in PSOM it has been suggested that there is a dysfunction (functional obstruction) in the eustachian tube pathway leading to accumulation of mucous in the bulla. Clinical symptoms may include: pain in the head or neck, holding the neck in a guarded position, tilting the head, scratching at the ears (without otitis externa being present), yawning excessively, crying out in pain, ataxia, facial paralysis, some loss of hearing, seizures, and fatigue. These symptoms, in many cases, are very similar to those of syringomyelia. A MRI is required to establish a definitive diagnosis since these some of these symptoms occur w/syringomyelia. In many cases the tympanic membrane will be opaque and/or bulging when viewed w/a video-otoscope.

A study in 2003 reviewed 61 cases of PSOM in CKCS in 43 dogs. Fifty seven of the 61 dogs had bulging TMs while 4 had already ruptured TMs. Fifty one dogs were treated w/myringotomy. At the first recheck after the myringotomy all dogs were either asymptomatic or had improved. The status of the TM depended on when the first recheck occurred. If the recheck was done ≤ 7 days post op, 25% of the dogs had either one or both TM healed while if >7 days, 69% had healed TMs. In the cases that had healed TM a myringotomy had to be performed to evaluate for, and to remove, the mucous from the middle ear. All dogs at that first recheck had mucous in the middle ears. Of the 51 cases where the owner did pursue treatment, 14 required two revisits, 21 required three revisits, 10 required four revisits, two required five revisits and four required six revisits before the middle ear was found to be free of mucous. All dogs were treated w/ locally and/or systemic corticosteroids. Twelve of the dogs had one or more relapses of PSOM with clinical signs and a mucus plug in the middle ear six to 18 months after treatment that required repeat myringotomy that was curative.

The TC has the same glandular epithelium (mucous membrane), as does the upper respiratory tract. Regardless of the trigger, w/ inflammation of the TC there is hyperplasia of the glands (goblet cells) of the mucous membrane that leads to increased secretions on to the surface of the TC epithelium. Bacteria associated w/the OE travel through a hole in the TM (assuming the TM is present) from the external ear canal into the TC where it gets trapped. The bacteria trapped in the TC leads to more inflammation and mucous production. As the inflammation continues the epithelium ulcerates and eventually will develop chronic, permanent changes such as fibrosis. The proteases from the bacteria and the inflammatory cells prevent healing of the TM.

A sign of that OM is still present is the failure for the TM to heal, while the healing of the TM is usually a good indicator that the OM is resolving. Since TC, and not the external ear canal, produces mucous, a clue that TM has not healed (or is ruptured on the initial exam) is the presence of mucous in the area of the proximal horizontal ear canal.

Diagnosis

Like most skin diseases the diagnosis of OM is based on signalment, history, physical findings and laboratory testing. Historically most dog's w/OM have a history of chronic, unresolved OE. Pseudomonas is the most common bacteria associated w/chronic, unresolved OE. Since most cases of OM are, in my experience, associated w/a ruptured TM as a consequence of chronic Pseudomonas OE, clinical signs and findings of OE will be present. Because the sympathetic innervation to the eye, parasympathetic branch of the facial nerve (innervates the lacrimal gland) and facial nerve proper all past near or through the middle ear, any of these nerves may be affected when OM is present. Horner's syndrome (ptosis, miosis, exophthalmos and prolapsed of the nictating membrane), keratoconjunctivitis sicca and facial nerve paralysis (muscles of facial expression (inability to blink, droopy eyelid, ear and lip on the affected side, etc) would be found if those nerves were damaged respectively. Damage to the auditory ossicles may result in conductive deafness. Please note that a ruptured TM (and otitis media) may be present without any of the neurological signs being present!!

Only if OM extends to otitis interna (OI) will there be vestibular signs. Signs of OI include horizontal nystagmus, asymmetrical ataxia; and head tilt, circling, falling, or rolling toward the affected side

The most straightforward method in diagnosing OM is to verify the absence of the TM. This is best done w/video otoscopy. However a common problem is that there is too much swelling to clearly evaluate the TM. In these cases a course of oral prednisone (1/4-1/2 mg/# bid) is dispensed and the patient re-evaluate in 7-14 days.

Video-otoscopy

In addition to visualizing the TM to evaluate it's integrity and it's appearance, the video otoscope can be used to look for air bubbles escaping from the TC. This is done by placing the dog in lateral recumbency filling the canal w/saline and watching the area of the TM. If air bubbles rise from this area when the dog takes a breath, you have confirmed that the TM is ruptured.

Radiology

Radiology has high specificity but poor (25%) sensitivity in diagnosing OM.

Myringotomy

Myringotomy has been reported to be the most accurate method in establishing the diagnosis of OM. In my experience, this procedure has not been as useful in diagnosing OM as in the treatment.

Treatment

Because otitis media is usually the result of chronic otitis externa and a ruptured tympanic membrane, it is important that in addition to what we discuss here, that you diagnose and manage the OE including finding the primary cause of the OE. Regrowth of tympanic membrane is an indication that the otitis media is resolving or has resolved. In normal dogs, iatrogenically ruptured tympanic membranes regrew in 14 days. In 1 study of normal dogs, the entire tympanic membrane was removed & it completely regrew in 35 days.

Since OM is almost always associated w/secondary infections, cytologic evaluation of the exudate from the middle ear is important. I prefer to do both cytology and culture and susceptibility (c/s) (both aerobic and anaerobic since anaerobic infections may occur in up to 25% of end stage otitis media cases) of material from the middle ear since cytology may identify Malassezia and rods that fail to grow on culture.

If a bacterial culture and susceptibility is submitted, the MIC method should be used to determine the susceptibility rather than the disc diffusion method (Kirby-Bauer). MIC allows you to decide not only susceptible or resistant but also the proper dosage and frequency of administration of the antibiotic.

Just as in any walled off infection, removal of exudate from the infected site is important. W/OM this is done via myringotomy and lavage of the tympanic bulla. The goal is to remove as much of the exudate as possible. If a myringotomy for lavage is performed, a cytology and c/s should also be performed at the same time. At the end of the lavage I usually will instill 1-2 cc's one of the following depending on what was found on cytology of the middle ear exudates and which antibiotics have already been used. Please note that only enrofloxacin, aqueous gentamicin and Tris EDTA and chlorhexidine have been shown NOT to affect hearing based on BAER testing (personal communication Sue Patterson). These choices include (order of preference)

1. Gentamicin (aqueous) can also be instilled in the TC (personal communication Sue Paterson). Use aqueous injectable gentamicin made by Roche (80mg/2 ml). Mix 4 vials into a bottle of TrisEDTA (with or with out chlorhexidine) and 40 cc dexamethasone SP. Instill in the tympanic bulla. In addition, have the owner flood the ear with this mixture twice daily.

2. Synotic w/70 mg of enrofloxacin added. (or 22.7 mg enrofloxacin mixed w/1 cc dexamethasone SP)

3. Ophthalmic Tobramycin (5 cc)- add 1 ½ cc dexamethasone sodium phosphate

4. Ceftazadime (Fortaz) 50 mg/ml solution followed by synotic (personal communication Lou Gotthelf)

5. As a last resort once the hearing has been lost, you can use Polymyxin B or E.

Topical Therapy

There is always a discussion of ototoxicity-associated w/medications instilled into the middle ear (either knowingly or inadvertently when the status of the TM was unknown). In dogs and cats, the incidence of ototoxicity associated topical antibiotics appears low. It appears that ototoxicity is probably more an idiosyncratic reaction than a dose related reaction.

Since the majority of dogs w/OM have a Pseudomonas infection, topical treatment is frequently the same for OM as it is for a Pseudomonas OE. Topical therapy is an important component of the treatment for OM because of the ability to reach very high tissue concentration. Weekly flushing and instillation of antibiotics into the tympanic bulla can greatly increase the success in treating OM. Concurrent use of Tris EDTA will increase the effectiveness of aminoglycocides and fluoroquinolones. Two commercial veterinary preparations are available - T8 Solution, DVM Pharmaceuticals and TrizEDTA, DermaPet. EDTA is used primarily for treatment of otitis externa and/or otitis media caused by gram-negative organisms especially Pseudomonas.

A product made by Dermapet, Triz EDTA plus contains 0.15% chlorhexidene. There is potentially a synergy between these components.

All cases of Pseudomonas otitis media cases (and externa for that matter) will have Tris EDTA as a component of the therapy, either as a mixture w/other agents or as a pretreatment followed by antibiotics. I will use silver sulfadiazine concurrently (but not simultaneously) w/Tris EDTA. In addition to Tris EDTA (or if gram positive bacteria are also present use TrizEDTA Plus which contains 0.15% chlorhexidine) I will use w/one of the following antibiotics. These antibiotics are appropriate to consider using in the presence of a Pseudomonas OE- (remember to find the underlying cause)

1. Depending on what antibiotics have been used in the past. The Tris EDTA bottle mentioned below is 4 oz (120 cc)

a. Gentamicin (100 mg/ml of injectable gentamicin) if the TM is intact

• Remove 38 cc of the Tris EDTA and add 7.2 cc of gentamicin (makes a 0.6% solution- double the normal otic preparations) and add 40 cc dexamethasone sodium phosphate

• Flood the ear bid

b. Gentamicin- aqueous injectable gentocin made by Roche (80mg/2 m). Mix 4 vials into a bottle of TrisEDTA along w/40 cc dex SP if the TM is ruptured

c. Enrofloxacin (1200 mg of enrofloxacin (use large animal injectable Enrofloxacin – 100 mg/ml)- remove 12 cc of Tris EDTA and then add the enrofloxacin and 30 cc dexamethasone sodium phosphate (4mg/ml)- flood the ear bid

• You can mix enrofloxacin and amikacin together to get a synergistic effect

d. Amikacin injectable (usually more effective than tobramycin)-

• Remove 42 cc of Tris EDTA and add 25 cc of amikacin (250 mg/ml- final concentration 25 mg/ml) and 40 cc of dex SP

• Flood the ear bid

e. Timentin (ticarcillin disodium and clavulanate potassium) - 6% solution

f. Ophthalmic Tobramycin (5 cc)- add 1 ½ cc dexamethasone sodium phosphate 1cc bid

g. Polymyxin B or E used in conjunction but not mixed w/Tris EDTA

2. I will use silver sulfadiazine (mixed 1:1 w/water) sid but not concurrently w/EDTA because of a concern that EDTA may decrease silver sulfadiazine's effectiveness by chelating the silver.

3. If Malassezia is present concurrently

a. Use an otic product containing gentamicin, betamethasone and clotrimazole (eg Otomax or Mometamax) instead of steps 1 and 2 OR

b. Use T8+keto or TrizUltra + Keto instead of TrisEDTA alone

The number one reason that I see a resistant pseudomonas infection is the failure to insist on rechecks, failure to identify the underlying cause and the casual dispensing of gentamicin or enrofloxacin containing topical medications. It is bad medicine and bad business to dispense medications without (re) evaluation of the ear.

Systemic Antibiotics

It is important to appreciate that systemic administration of antibiotics, including the fluoroquinolones, can't exceed MIC for P. aeruginosa. If the infection fails to respond to topical therapy and flushing, the addition of systemic antibiotics MAY be useful (piperacillin - 20 mg/kg TID SC or ticarcillin 50-70 mg/kg tid SC)

Systemic Steroids and Analgesics

Prednisone at 0.25-.50 mg/# bid for 7-14 days and then reassess the ears. Using systemic analgesics is also appropriate. DON'T use NSAID in combination w/oral GC. Use acetaminophen w/codeine +/- tramadol.

Systemic Antifungal Agents

If Malassezia OM is present, and fails topical therapy, then ketaconazole- 5-10 mg/kg sid-bid given w/food to enhance absorption or itraconazole 5 mg/kg sid is added to the therapy.

Treatment/Monitoring

Treatment should be continued for a minimum of 6 weeks or until 21 days past clinical resolution of the OE and the OM. Frequent rechecks are CRITICAL in monitoring and modifying the therapy. My goal is to keep these dogs out of the hands of surgeons and to avoid them having ear ablation surgery.