DIAGNOSIS AND MANAGEMENT OF OTITIS EXTERNA IN THE REAL WORLD
Paul B. Bloom, DVM, DACVD, DABVP (Canine and Feline Specialty)
Allergy, Skin and Ear Clinic for Pets, Livonia, MI. 48154
Assistant Adjunct Professor, Small Animal Medicine, Dept of Dermatology
Michigan State University, East Lansing, MI 48823
It is important to understand that ear disease is only a symptom (no more specific than
“pruritus”). As Dr Flemming Kristensen stated “A patient showing ear problems is a
dermatology case until proven otherwise”. It is appropriate therefore to approach the diagnosis
of ear disease just as you would for any other skin disease.
Obtaining a detailed history is an important first step in trying to identify the underlying
cause of the ear disease. Specific questions that should be asked include:
1.
When did the symptoms first occur? This is an important question, because
many owners will only tell you when this current episode of symptoms
occurred, not the very first time it occurred;
2.
Other than the problem the owner presents the patient for, you must ask all
owners if the dog has EVER had problems with excessive licking, scratching,
chewing, biting or rubbing. Has the dog ever had ear problems before this
episode? If so, when, with what medication and what was the response to
treatment;
3.
Where does the dog live- indoor, outdoors, both? Describe the environment,
especially the outdoor environment;
4.
Is the dog on heartworm and flea preventative? If so, what product, how often
is it administered and is it year round or seasonal?
5.
Are there any other pets in the household? If so, what kind and are they
symptomatic. If they are cats, do they go outside? ;
6.
Are any of the humans in the household showing “new” skin problems? If so,
what kind;
7.
Do they board the dog, take him to obedience school, training or to the
groomers? If so, when was the last time? ;
8.
Do they know if the parents of the dog or any siblings have ear or pruritic skin
problems? If so, what was done and what was the response? ;
9.
What does the dog eat?
10.
How do the ears seem today- is today’s presentation the best, worse or average
since the problem began?
11.
Do you notice if the symptoms were better, worse or no different or not sure
between the different seasons.
After reviewing signalment and thoroughly questioning the owner, the next step is to do a
complete physical examination – be sure to note any constitutional signs that may be present that
could explain the ear problem (eg fever associated with pemphigus, lethargy associated with
vasculitis, etc)
This is followed by a complete dermatologic examination. Because ears are really just
skin attached to the skull many diseases that affect the ears frequently will be affect the rest of
the skin and vice versa. Therefore even when a dog is presented only for otic pruritus you still
need to examine the rest of the body. And the opposite also holds true, when a dog is presented
for truncal pruritus be sure to do an otic examination. .
In order not to miss an abnormality, an otic exam should be done in a systematic manner
beginning with the pinna. You should note any alopecia, erythema, ulceration, crusting, scaling
or swelling. Then palpate the canals for pain, calcification or thickening. This is followed by an
otoscopic examination of the ear canals. Due to the curve in the external ear canal, the ear canal
must be straightened in order to see the horizontal canal and the tympanic membrane. This is
accomplished by placing the tip of the cone of the otoscope in the opening of the external ear
canal. As you advance the cone is proximally you need to pull the pinna laterally (outward). By
“stretching” the pinna laterally into a straight line horizontally the ear canal becomes straight and
allows examination of the horizontal canal and the tympanic membrane
The presence, degree and location of inflammation, ulceration & proliferative changes
should be noted (i.e. cobblestone hyperplasia). Describing the size of both the vertical and
horizontal canals along with the type, location and quantity of debris or exudate should also be
included in the medical record. Next it should be documented whether the tympanic membrane
is visualized. If it is not, then note why the membrane is not seen- is it due to swelling in the ear
canal, the presence of a ceruminolith or is there debris in the proximal horizontal canal
obstructing the view? Sometimes it is because the animal is too painful to allow deep
examination of the ear canal. If you can visualize the tympanic membrane (TM) you need
describe if it is normal in appearance or not. Changes that may be noted include discoloration or
bulging.
It is important to then evaluate for concurrent middle or inner ear disease. i,ii This is
because dogs with chronic recurrent otitis externa (OE) may have concurrent otitis media (OM).
This step may require heavy sedation or general anesthesia. Evidence of middle ear involvement
include a ruptured TM or an abnormal appearing TM (i.e. thickened, change in lucency (opaque),
bulging or discolored). Even though it has been stated that an intact TM DOESN’T rule out
otitis mediaiii that statement should be followed by "but the TM is NOT normal in appearance.
Horner’s syndrome (damage to sympathetic innervation); keratoconjunctivitis sicca
(damage to the parasympathetic component of the facial nerve) and facial nerve paralysis may be
present in cases of OM due to the close association of the respective nerves to the middle ear iv.
Deafness may also be present with OM.
Some veterinarians will have their staff collect ear cytology samples prior to examining
the ear (as a time saver) but this makes it more difficult to evaluate the true appearance of the ear
canal. Debris may be pushed into the horizontal canal thereby limiting visualization of the
tympanic membrane due to the compacting of debris in the canal.
Now diagnostics and treatment needs to be pursued. The first step is to identify and treat
the primary (underlying) cause(s) of the ear disease. v,vi,vii,viii,ix These would include:
1. Parasitic (including Demodex, Otodectes, Sarcoptes);
2. Foreign bodies;
3. Hypersensitivities (atopy- NOTE OE may be the ONLY symptom in 3-5% of the
environmentally triggered atopic dermatitis cases and it may be UNILATERAL!!; it
may be seen in cutaneous adverse food reactions where it too may be the ONLY
symptom in up to 20% of the cases and also may be unilateral or flea allergy
dermatitis. In cases of FAD there should be involvement of the posterior 1/3 of the
body in addition to the OE;
4. Allergic or irritant contact dermatitis;
5. Endocrinopathies, keratinization or sebaceous gland disorders leading to an altered
lipid layer in the epidermis, alteration in normal keratinization or glandular function;
idiopathic seborrhea (is there such a disease?);
6. Autoimmune or immune mediated diseases (eg pemphigus complex, vasculitis- note
these diseases involve the pinna >>> canals);
7. Zinc responsive dermatosis (will involve more than the pinna);
8. Juvenile cellulitis;
9. Immunosuppressive diseases (distemper, FeLV, FIV, parvo virus);
10. Neoplasia (adenoma, adenocarcinoma) ;
11. Dermatophytosis (affects the pinna rather than the ear canal).
In addition to identifying the primary cause, secondary factors must be addressed if
possible. Secondary factors don’t cause ear disease but increases the risk of developing ear
disease and may make successful treatment more difficult. Secondary factors are: anatomical
factors (eg- long pendulous ears in the Basset Hound or stenotic ear canals in Shar Peis);
excessive moisture in ears (swimming); and iatrogenic trauma (plucking hairs from the ear
canals, cleaning ear canals with cotton tip applicators).
Lastly perpetuating factors must be identified and treated. These factors don’t initiate the
problem, but will cause the disease to continue, even with the elimination of the primary factor,
once it has been established until these factors have also been addressed. Perpetuating factors
include:
1. Bacteria (cocci most commonly Staphylococcus intermedius (acute infections), beta
hemolytic streptococci and rods most commonly E. coli, Pseudomonas spp (chronic
infections); Proteus spp, Klebsiella spp and Corynebacterium spp);
2. Fungi (Malassezia pachydermatis (which may cause a hypersensitivity reaction so
that small numbers may be significant) ;
3. Progressive pathological changes;
4. Otitis media;
5. Contact hypersensitivity/irritant;
6. Treatment errors (most commonly due to under treating the infection).
Laboratory tests are a necessary component to the proper workup of a case of canine ear
disease. CBC, serum chemistry profile, urinalysis, skin scrapings, fungal culture, endocrine
testing and skin biopsies may be necessary depending on what the differential diagnoses are for
that patient.
Cytologic examination of a roll swab sample should be performed on any exudate. The
numbers & type of bacteria, yeast and inflammatory cells should be quantitated. In cases of OE
the question of what is an abnormal number of organisms, per oil field, has not been settled.
Depending on the study, cutoff numbers, per oil immersion field, that differentiates between
normal and abnormal ears ranges from >1 Malassezia to >4 Malassezia and from >1 bacteria to
>10 bacteriax,xi It is the author’s opinion that the number of organisms present to be considered
significant is not just a “number”. The author doesn’t perform cytology on normal ears – it is
only done if the ears that are inflamed or have exudate. Therefore ANY organism seen will be
considered significant and will be treated as part of the therapy regardless of the number present.
As for follow-up cytologies, the only time cytology is performed during therapy is when the ear
is not clinically normal OR if the initial cytology had rods or WBC’s since these never should be
present in a normal ear. If there is a mixed population of organisms present at the initial
examination without rods or WBC’s and the ear is clinically normal at the recheck examination,
follow-up cytology is not performed since cocci and/or yeast may be. In a report evaluating
otitis clinical score, it was concluded that cytology was unable to differentiate between normal
and affected ears and also that cytology failed to identify clinical success in otitis treatment.xii
Bacterial culture and susceptibility (c/s) should only be rarely, if ever, performed in cases
of OE. If a c/s is performed, it should be done in conjunction with cytologyxiii. One reason that
the author doesn’t perform cultures in OE cases is that with a culture the susceptibility is based
on systemically achieved antibiotic levels (measured in microgram/ml) not topically. Since
topical medication has a 1000 fold higher concentration (milligrams/ml) the resistance reported
on the culture can’t be extrapolated to topical therapy.
Other concerns include poor reproducibility of c/s results when culturing the ear. In a
study where two samples were taken for bacterial c/s from the same location in the external ear
canal of dogs who had otitis externa, there were different bacterial isolates identified 20% of the
time and the same isolate with different susceptibility patterns another 20% of the time xiv.
Eleven percent of the P. aeruginosa isolates had different susceptibility patterns. A second study
took triplicate samples and sent the samples to 3 different laboratories xv. There were 18 samples
that had Pseudomonas spp. Identified. All three laboratories only agreed on the presence of
Pseudomonas in 15 (83.35) of the ears while 2 agreed on 2 (11.1%) of the samples and on one
occasion (5.5%) only 1 laboratory identified Pseudomonas but none of the samples had identical
patterns of antibiotic susceptibility. A 3rd study was performed in which duplicate samples were
sent to the same lab1. Seventy percent of the Pseudomonas aeruginosa had different
susceptibility profiles.
There are a few possible reasons for these discrepancies. These include:
1.
Multiple strains with different susceptibilities
2.
Single strain with heteroresistances
In both of the cases the selection of which colonies are selected to be tested for
susceptibility may vary from technician to technician. . A 3rd study was performed in which
duplicate samples were sent to the same labxvi. Seventy percent of the Pseudomonas aeruginosa
had different susceptibility profiles.
These results should give you great pause as to the reliability of cultures. The author will
only take a culture in cases of OE when there are proliferative changes present AND there are
numerous rods present on cytology AND the dog has failed to respond to empirical antimicrobial
therapy. This is a very uncommon scenario. This approach is supported by a study in which the
author evaluated if there was any correlation between topical antibiotic selection, in vitro
bacterial antibiotic sensitivity and clinical response in 16 cases of canine otitis externa
complicated by Pseudomonas aeruginosa.xvii For these cases empirically selected topical
antibiotic therapy was dispensed after collecting bacterial cultures from the affected ears. All
dogs had Pseudomonas aeruginosa isolated on culture. In 10 cases, the antibiotic selected was
deemed to be resistant based on the culture, yet 8/10 responded to the selected antibiotic. One
of the 10 resistant cases needed to have a second antibiotic selected to successfully treat the
infection. This supports the observation that there is no value to performing cultures in cases of
canine otitis externa.
The MIC (broth microdilution technique) method is the “gold standard” for culture
technique therefore if a c/s is submitted, the MIC method should be used to determine the
susceptibility of the organism(s) rather than the disc diffusion method (Kirby-Bauer). This is
because the disk-diffusion susceptibility test (DDST) is only semi quantitative. This means that
the drug concentration achieved in the agar surrounding the disc can be roughly correlated with
the concentration achieved in the patient’s serum. It will only report the organism’s
susceptibility (susceptible, intermediate or resistant) based on an approximation of the effect of
an antibiotic on bacterial growth on a solid medium. Tube dilution (MIC) is quantitative, not
only reporting SIR but also the amount of drug necessary to inhibit microbial growth. The MIC
is reported as the amount of antibiotic (in µmg/ml) necessary to inhibit 90% of the tested bacteria
(the lowest concentration in the tube that is clear). This allows a clinician to not only decide
susceptible or resistant but also the proper dosage and frequency of administration of the
antibiotic. Note that if the MIC for the bacterial isolate is reported to be susceptible, there is a
greater likelihood of successful treatment (cure) than if the isolate was classified as resistant.
Treatment failure is still possible due to other drug or patient factors such as the location of the
infection and the immunologic status of the host. If the MIC value is in the intermediate
category, therapy with this drug at the usual dose will likely be unsuccessful in establishing a
cure. However, successful therapy is possible when doses higher than the label dose is used or if
the drug is concentrated in the affected organ (eg urine) or is used topically (ear). If the MIC is
in the resistant category, treatment failure is more likely because of resistance mechanisms or
inadequate drug concentrations. Lastly not only does the MIC method indicate susceptibility,
but it also implies the relative risk of emerging resistance and thus the need for a high dose.
The other limitation to the Kirby-Bauer results in regards to Pseudomonas susceptibility
is the discrepancy between it and MIC. In two studies, Kirby-Bauer underestimated P.
aeruginosa sensitivity to enrofloxacin (when compared with MIC) xviii,xix whereas in 2 other
studies Kirby-Bauer overestimated enrofloxacin susceptibility. xx,xxi Since Pseudomonas
infections is one of the most common reasons cultures are performed in cases of otitis externa,
and enrofloxacin is a commonly used antibiotic for this infection, this inability to properly
identify susceptible vs resistance to enrofloxacin is an important limitation in using Kirby-Bauer
testing..
With the information gathered above, the treatment is directed toward the primary
cause(s) (eg parasiticidal treatment, food trial, intradermal testing and allergen specific
immunotherapy, etc) and perpetuating factors. Ear cleaning is performed in the clinic with a
bulb syringe or by retrograde tube flushing with a red rubber tube (under anesthesia). If on the
initial examination the ear canals are swollen and painful, ear cleaning may not be performed on
the first visit, preferring to use topical glucocorticoids (GC) and systemic GC for 10-14 days to
decrease the swelling. Once the swelling has decreased it will be much easier to examine the ear
canals and visualize the TM.
Cleaning agents contain substances that soften and emulsify wax and lipids. This initial
cleaning is necessary in order to remove debris that may interfere with the effectiveness of
topical agents and to reduce inflammatory debris (bacterial toxins). The author doesn’t usually
have the owner do cleaning after the initial exam since it seems that many owners have trouble
with just medicating the ear, let alone cleaning too. Many of the cleaners have a low pH leading
to discomfort if used in an inflamed ear. A study comparing 2 ear cleaners (original formulation
and then a new formulation) noted that in 38% of the cases with the old formulation and 37.5%
of the cases with the new formulation dogs had a moderate to marked avoidance to having the
cleaner instilledxxii. This behavior was believed to be due to either a reaction to the ear cleaner or
just overall animal irritability. Also the base in the otic ointments/suspensions (mineral oil,
liquid paraffin) acts as a ceruminolytic agent. In addition, a recent study calls into question
whether any of the ear cleaners have any ceruminolytic activityxxiii. In this study the
ceruminolytic activity of 13 ear cleansers was evaluated using a standardized synthetic cerumen
(SSC) that mimics the composition and texture of canine cerumen. Of the tested products only
Cerumene®, Epiotic® and Vet Solutions Ear Cleaner® are available in the US. The test
products were incubated with mild agitation for 20 min with 500 mg of SSC previously
compacted at the bottom of a test tube. Ceruminolytic activity was then assessed by quantifying
the SSC removed by decantation. Overall, Otoclean® (OT) was most efficacious, reaching an
activity of 86–90% followed by Netaural® (NET) with a 39%, Specicare® (SP) with a 23% and
Cerumene® (CE) with an 8% ceruminolytic activity. None of the other products displayed any
ceruminolytic activity. It was concluded that, in the experimental conditions used in this study,
only 1/13 products had significant ceruminolytic activity. Please note that the company that
manufactures OT funded this study A follow up study by Robson, et al using Australian and US
products revealed that 15/24 cleaners had <5% efficacy while only 6/24 ear cleaners had >80%
efficacy-none of which are available in the USxxiv,xxv Lastly a study was performed to test the
efficacy of the 4 ear cleanser products compared to distilled water. Only the product
manufactured by the study’s sponsor performed better than distilled water.xxvi
To the author’s knowledge there are no studies showing that ear cleaning has any impact
on the treatment or prevention of otitis externa. However there is a study that evaluated the
efficacy of a dermocorticoid administered twice weekly in the ear canal as a long term
maintenance measure to prevent recurrence of OE in dogs with atopic dermatitis. Twenty atopic
dogs with relapsing (>3 episodes/year) bilateral OE were included in the study. After successful
treatment of otitis externa with a topical antibiotic-antifungal-corticoid combination, dogs’ left
and right ears were each randomly allocated to either an ear cleansing maintenance regimen once
weekly or the same regimen followed by application of three drops of 0.0584% hydrocortisone
aceponate in the ear canal two consecutive days per week. The dogs were examined on day 30
the q 60 days. At the end of the 6 month study it was determined that the probability of
remaining free of relapse was 95% in group B (cleaner plus 2 consecutive days/week of a
dermocorticoid) compared to 50% in group A (median time to relapse: 90 days) (P < 0.01) after
6 month. The authors concluded that twice weekly hydrocortisone aceponate application in the
ear canal provides an effective maintenance regimen to control canine allergic otitis. My
comment is that cleaning was not effective when compared to cleaning PLUS the steroid. I
suspect if they only did the steroid the outcome who have been the same but this was not
evaluated in this study.
There is frequently a discussion of the ototoxicity of agents put into ears. Remember that
it is inner ear damage, specifically vestibular and/or cochlear damage that occurs with ototoxic
agents, not middle ear damage. In order for a drug to cause damage to the inner ear it must either
get to the inner ear hematogenously or by traveling thru the middle ear and entering the inner ear
thru the vestibular (oval) or cochlear (round) window(s).
In humans because ofloxacin otic solution (Floxin Otic®) is the only topical agent to be
labeled by the U.S. Food and Drug Administration (FDA) for use when the tympanic membrane
is perforated, oral antibiotics have traditionally been used in this situation. However, according
to otolaryngologists because the risk of cochlear damage with the use of other topical
medications seems quite small, perforation alone is not an indication for oral antibiotics.
The opinion of this author is that the concern for ototoxicity due to topical medications is
overstated. This position is supported by a consensus panel on reviewing the use of ototopical
antibioticsxxvii. In their report they stated “There have been very few irrefutable cases of
ototoxicity reported (after proper use of a topical otic preparation). Under many circumstances, it
is difficult to separate the underlying disease process, which is also known to cause ototoxicity,
from ototopical drug use.” They go on to state “For more than 40 years, the most common
treatment has been aminoglycocide combination drops. A longstanding debate over the safety of
these drops centers on ototoxicity. Even though the theoretical risk exists, there have been few
reported cases in the literature, considering the millions of doses given”.
The author has only seen one ototoxic reaction that was suspected to be due to a topical
agent and in that case the TM was intact! Therefore, agents are chosen more for their
effectiveness than the concern about ototoxicity, especially since there are very few agents that
have been proven to be safe in cases of a ruptured TM. It is more important to get rid of the
infection than to avoid (effective) drugs because of ototoxicity concerns. Also, just because the
TM is intact doesn’t mean that the barrier function is complete, therefore, even in the presence of
an intact TM it is possible to get drugs into the middle/inner ear.
After ear cleaning topical agents are dispensed. The author prefers ointments over drops
because of the impression that ointments get the drugs to the region of the tympanic membrane
better than drops do (this may be a volume issue more than the formulation- it has been reported
that it takes 1.0 cc of medication to get down to the TM in a medium sized (40 pound) sized dog
- personal communication). The other advantage of ointments is that the base vehicle in the otic
ointments (mineral oil/liquid paraffin) acts as a ceruminolytic agent.
Most topical products contain a combination of glucocorticoids, antibacterial and
antifungal agents. Antibacterial agents used topically include:
1. Broad spectrum agents (gram positive and negative organisms) –
a. Aminoglycocides
i. Decreased effectiveness in an acidified ear
ii. Inactivated by purulent debris (so they must be put in a clean ear)
iii Examples of first line
a. Neomycin
b. Gentamicin – note injectable water based gentamicin is non
toxic even if the dog has a ruptured tympanic membrane- this has
not been studied when using commercial ear products that contain
more than just gentamicinxxviii.
b. Florfenicol is a broad-spectrum, primarily bacteriostatic
i.
Doesn’t carry the risk of inducing human aplastic anemia that is
associated with chloramphenicol
c. Silver sulfadiazine compounded to a 1% solution
i. Primarily effective against rods
ii. Inactivated by purulent debris so it must be put in a clean ear
1. Narrow spectrum agents (gram negative rods) – most are reserved for resistant
gram negative infections
a. Polymyxin B - inactivated by purulent material
b. Fluoroquinolone –- decreased effectiveness in an acidified ear
i. Never a first line choice
ii. Enrofloxacin
iii. Orbifloxacin
c. Extended-spectrum penicillins (anti- Pseudomonas penicillins)
i. Susceptible to beta lactamase
ii. Penetrate Pseudomonas cell wall better than other antibiotics
iii. Increase gram negative activity but less activity gram positive and
anaerobes compared to other penicillins
iv. Carboxypenicillin
a. Ticarcillin
v. Ureidopenicillins
a. Piperacillin
b. More effective against Pseudomonas than are the
Carboxypenicillin
d. Aminoglycocide
i. Amikacin and tobramycin
a. Gram negative bacteria (including some Pseudomonas)
have less resistance to amikacin or tobramycin then
gentamicin or neomycin
b. Decreased effectiveness in an acidified ear
c. Inactivated by purulent debris so they must be put in a
clean ear
Antifungal agents used include thiabendazole (anecdotally reported to have poor efficacy
against Malassezia- is it volume related?), nystatin, clotrimazole 1%, miconazole 1 or 2%,
posaconazole 0.1% and ketoconazole 1 or 2%
Treatment of OE should include EDTA when gram negative organisms are present in
high numbers or has been recently treated. To understand the action of ethylenediaminetetraacetic acid (EDTA) solution we need to review some microbiology. A capsule surrounds
bacteria. Under the capsule is the cell wall that contains peptidoglycans. Under the cell wall is
the cytoplasmic membrane (plasma membrane, cell membrane). The cytoplasmic membrane
surrounds the cytoplasm and nuclear body. Gram negative have 2 additional layers. The outer
most is the outer cell membrane that lies between the capsule and the cell wall. The outer cell
membrane is composed of lipopolysaccharides. The other additional layer is between the cell
wall and cytoplasmic membrane, called the periplasmic space. This space contains a variety of
enzymes and other proteins that help digest and move nutrients into the cell. Gram positives do
not have the outer cell membrane (and therefore no lipopolysaccharides) or a periplasmic space
but do have a thick layer of peptidoglycans in the cell wall (vs. gram negatives which only have
a thin layer). Note the peptidoglycans are the site of action for beta-lactam antibiotics.
Topical EDTA solution has a direct bactericidal action against bacteria by chelating metal
ions important for the integrity of the bacterial cell wall. EDTA also stimulates the release of
outer cell membrane lipopolysaccharides (LPS), proteins, and other cell contents. The end result
of these actions is the leakage of cell solutes leading to cell death and better drug penetration and
antimicrobial activity. Note - since EDTA stimulates the release of LPS from the outer
membrane it is less effective at inhibiting gram-positive than gram-negative bacteria because
gram-positive bacteria lack an outer membrane.
Pseudomonas bacteria have an efflux pump that is mediated by the MEX gene. This
protein pumps the drugs out the bacteria, rendering the antibiotic ineffective. EDTA blocks this
pump thereby allowing the antibiotic to accumulate in the bacteria. xxix
To maximize its bactericidal activity it is essential for EDTA to be in an environment
with an alkaline pH. Appropriate pH (8.0) is maintained by combining it with buffers such as
tromethamine (TRIS) hydrochloride. This alkaline pH also decreases the bacterial MIC for an
aminoglycocide or a fluoroquinolone. It is therefore useful to use TrisEDTA prior to instilling
either of these antibiotics. The ear canal should be filled with the solution prior to instilling the
topical antibiotic (15-30 minutes before is ideal). This is done q 12 hrs. EDTA is used primarily
for treatment of otitis externa and/or media caused by gram-negative organisms especially
Pseudomonas.
There is a product that contains 0.15% chlorhexidene in addition to the trisEDTA. The
combination of these 2 ingredients is beneficial due to the synergistic effect between EDTA and
chlorhexidenexxx. The addition of the chlorhexidene extends the antimicrobial spectrum to
include cocci in addition to the rods. There are 2 studies that support the effectiveness of this
combination.xxxi,xxxii. The limitations of these studies are they in vitro studies and they used a 30
minute contact time. Whether these results can be repeated in vivo has not been studied. Since
the author uses this product in combination with other topical agents, it is impossible to draw an
accurate conclusion.
In regards to safety of the chlorhexidene in otic products, a study reported the effects of
instilling 0.2% chlorhexidene into the ear canals of dogs with experimentally ruptured tympanic
membranesxxxiii. In this study, 0.2% chlorhexidene was instilled in greyhound’s ear canals bid
for 21 days. At the end of the study there were neither clinical vestibular signs nor BAER
changes noted. THIS DOESN’T APPLY TO CATS!!!. A study instilling 0.05% chlorhexidene
once every other day for 3 treatments into the middle ear of cats concluded that even this
concentration of chlorhexidene may cause hearing loss in a cat xxxiv. The authors did a
subsequent studyxxxv in which they evaluated vestibular effects of infusing chlorhexidene into the
middle ear of cats. That study concluded that exposure of the middle ear to even dilute
concentrations of chlorhexidene (0.05%) were likely to cause vestibular disturbances.
GC's are an essential component of topical treatment. Successful treatment of OE
frequently requires topical GC and in fact the author has seen cases resolve where the only
change in therapy was the addition of topical GC. GC are antipruritic, anti-inflammatory,
decreases glandular secretions (cerumen), decreases pain and swelling and decreases
hyperplasia- all properties that can help restore the normal barrier function to the epithelium of
the ear canal. When using topical GC it is best to begin with the most potent form and if GC are
needed long term go to less potent (and less side effects) forms (in decreasing potencymometasone>betamethasone= hydrocortisone aceponate > fluocinolone>
triamcinolone>dexamethasone> prednisolone> hydrocortisone). Note- even though
hydrocortisone aceponate is classified as an intermediate potent glucocorticoid, equal to that of
betamethasone 17-valerate, it has an improved benefit/risk ratio due to its decrease incidence of
skin atrophyxxxvi. REMEMBER topical steroids are systemically absorbed and can lower thyroid
hormone concentrations; elevate liver enzymes, suppress the hypothalamus- pituitary-adrenal
axis and even cause pu/pd.xxxvii
The author has rarely used systemic antibiotics when treating OE. This approach is
supported by the previously mentioned consensus panelxxvii who stated “In most cases of
uncomplicated AOE, topical antibiotics are the first-line treatment choice. There is no evidence
that systemic antibiotics alone or combined with topical preparations improve treatment outcome
compared with topical antibiotics alone”. In addition it has been shown that in humans that
administering oral antibiotics in cases of OE will1. Increase the risks of adverse effects
2. Enhance the environment for the production of resistant organisms
3. Increase the time to clinical cure
The only time that they use oral antibiotics in humans that have OE is if
1. The infection has spread beyond the ear canal or
2. Uncontrolled diabetes or
3. Immunocompromise or
4. Hx of local radiotherapy or
5. Inability to deliver topical antibiotics
In addition systemic antibiotics increase the risks of adverse effects and enhancing the
environment for the production of resistant organisms. In humans it has been reported to
increase the time to clinical cure and do not improve outcomes compared with a topical agent
alone in uncomplicated otitis externa xxxviii,xxxix In humans systemic antibiotics are recommended
to be used only when the infection has spread beyond the ear canal, or when there is uncontrolled
diabetes, immunocompromise, a history of local radiotherapy, or an inability to deliver topical
antibiotics.
Systemic antibiotics or antifungal agents are used occasionally if otitis media (OM) with
bacteria, other than Pseudomonas (see below about Pseudomonas), or Malassezia are present on
cytology. Instead the author will sedate the dog and q 2-3 days take a red rubber tube and infuse
the tympanic cavity (see below). If the OM infection is due to Pseudomonas it is unlikely that
systemic antibiotics will be useful anyways. This is because systemic administration of
antibiotics, including the fluoroquinolones, can’t exceed the MIC for P. aeruginosa in the ear
canal. Since P. aeruginosa is the most common pathogen associated with OM in dogs, systemic
administration of antibiotics will only select for more resistant organisms. Since it has been
documented in humans that high drug concentration may be achieved in the middle ear when
topical antibiotics are used, in cases of OM, topical treatment is the author’s mainstay therapy.
This is achieved by instilling a mixture of EDTA (4 ml), dexamethasone SP (30 cc) and an
antibiotic (enrofloxacin, gentocin or amikacin) q 2-3 days until the tympanic membrane is
healed. This is performed by using a 8 french red rubber tube, cutting off the tip, and after heavy
sedation, blindly feeding the tube as proximally into the ear canal as possible (only place you can
be is in the tympanic cavity unless the TM has regrown) and instilling 4-5 cc of the mixture. The
different combinations I use in the middle ear are
1. Use injectable gentocin and add 360 mg to a 4 oz bottle of TrisEDTA and 120
mg dexamethasone SP. Instill in the tympanic bulla. In addition, have the owner
flood the ear with this mixture twice daily. OR
2. Enrofloxacin (1200 mg of enrofloxacin (use large animal injectable Enrofloxacin
– 100 mg/ml) and 120 mg dexamethasone sodium phosphate (4mg/ml) mix with 4
oz of TrisEDTA- flood the ear bid OR
3. Amikacin injectable- 4 oz of Tris EDTA and add 10 cc of amikacin (250 mg/mlfinal concentration 20 mg/ml- the same as the fortified ophthalmic product) and
120 mg dexamethasone sodium phosphate. Flood the ear bid
a. You can mix enrofloxacin and amikacin together to get a synergistic effect
Note that the owners still need to treat the OE at home with topical medications.
Systemic glucocorticoids are used if the ear canals are edematous, ulcerated and/or
stenotic. Even proliferative changes may decrease with steroid administration since secondary
edema may be present. Prednisone at 0.25-.50 mg/# bid for 7-14 days is dispensed and a
reassessment is made in 7-14 days. At that time if the canals are completely open and the ulcers
are healed, the prednisone can be discontinued. If the ears are better but not normal then make a
clinical decision is made whether to maintain or decrease the dose for another 7-14 days. Again
reassessment should be done in 7-14 days. If the ear canals are not opened by this second
recheck, a total ear canal ablation with a bullae osteotomy would most likely need to be
performed.
There are a variety of “long lasting” ear products that are instilled into ears q 7-14 days
(or for 1 product only 1 treatment is needed). At this time there are only 2 FDA approved
products. They are relatively new so the author has only treated a few cases with them.
Treatment is very easy but there has been a mixed response to therapy. The jury is still out as to
where these products will fit into our armentarium for the treatment of otitis externa. I would
encourage you to only use FDA approved products- there has been deafness associated with
some of the lanolin based products.
Specific scenarios- note for any of the treatments the key to success is filling the ear
canal with whichever product you choose to use. The recommended low volume (5-8
drops) of the otic product is a frequent cause for failure to respond to treatment.
1. Acute otitis (and/or infrequent) externa treatment overview. It is important to
differentiate whether this is a first time occurrence, a recurrence or an unresolved
infection. The only way to know this is to do follow-up examinations on ALL
cases of OE. Remember that the absence of symptoms is not synonymous with
resolution of the disease. This means that owners are unable to determine
whether the infection is resolved and the dog must be rechecked. If this is the
first episode, discuss the possible predisposing, primary and perpetuating causes
and foreshadow that additional testing may be necessary in the future. In this
situation, begin with eliminating easily diagnosed primary causes (foreign bodies,
parasites, masses, etc). During the examination be sure to evaluate the status of
the tympanic membrane. Perform cytology to identify secondary infections
and/or inflammatory cells. Treatment should be directed toward both the
infectious component and the inflammatory component. Treatment should be for
7-14 days. At the end of the treatment, while still on therapy, a recheck
examination should be performed!! If the ear appears normal clinically continue
the treatment for another 7-10 days. If the ear is not clinically normal OR there
were rods OR WBC on the initial cytology, a repeat cytology should be
performed. Treat accordingly. The author prefers ointments over drops when
treating otitis externa. Since all the otic ointments contain steroids and an
antimicrobial agent, the author uses a combination product.
a. In cases of an acute infection there are a variety of products that are
effective and would be appropriate to dispense (note most products will
contain a combination of 3 of these drugs- antifungal, antibiotic and
steroid). First line antibiotics include neomycin, gentocin, miconazole
(Malassezia and Staphylococcus), polymyxin (gram negative), florfenicol
(Malassezia and Staphylococcus)
b. The only time this is altered is if there are heavy rods or just rods present,
which is very rare in this scenario. In that case the author would use
TrisEDTA, silver sulfadiazine and either gentamicin or polymyxin B (see
below – Pseudomonas)
c. If the dog is painful, systemic GC and analgesics (tramadol, gabapentin
and/or Tylenol with codeine) are added to the treatment.
2. If initially TM the is not visible due to swelling of the ear canals oral prednisone
½-1mg/#/day for 10-14 days will be added to the topical treatment. Because of
the potency of fluocinolone or mometasone a product that is a mixture of
fluocinolone with DMSO) and/or an otic that contains mometasone will be
included in the therapy. Many times an analgesic is added as previously
described (NO NSAID!).
a. A recheck examination will be performed in 10-14 days. If the TM is
visible and the swelling resolved, then only the prednisone can be stopped.
All the other treatment should be continued.
b. If the TM is not visible but the swelling has resolved, then an ear lavage
via FOEVO under general anesthesia should be performed.
c. If at the 10-14 day recheck the TM is not visible and the swelling has
NOT resolved, continue the prednisone for another 10-14 days and then
recheck.
i. If the ear canals are still narrowed at the next recheck, perform (or
refer) a total ear ablation with a bullae osteotomy.
3. In cases of chronic (recurrent and/or unresolved) otitis externa, it is essential to
determine if it is recurrent or unresolved. If it is unresolved is it because of owner
compliance? If it is poor compliance then this problem must be resolved! If it is
recurrent (or unresolved with good owner compliance) in addition to the above, a
very aggressive search is performed to identify and treat the primary, perpetuating
and secondary factors. Treatment should be for a minimum of 30 days. As
above, GC will be an important component of therapy.
a. Choose an antibiotic from the first line tier that hasn’t been used recently.
If all have been used then go to the second tier amikacin, fluoroquinolones. If there is concurrent yeast then change to any of the other
antifungal products reserving the posaconazole product for second tier
since it is mixed with a fluoroquinolone.
b. If rods are present then use-Triz-Edta and silver sulfadiazine as part of the
multimodal treatment
c. Because of the association of the use of fluoroquinolones (FQ) and the
development of MRSA, and the use of FQ and the development of
extended spectrum beta- lactamase (ESBL) producing E.coli, the author
rarely uses fluoroquinolones for the treatment of otitis externa. This
concern is supported by many different sources. In the BSAVA “Guide to
the Use of Veterinary Medicines” xl it discusses the prudent use of
antimicrobial agents. In regards to all fluoroquinolones (FQ) it states “that
in all species fluoroquinolones and third- and fourth-generation
cephalosporins should be used judiciously and never considered as firstchoice options”. The concern with using FQ is that, according to
information from the CDC website, “a major limitation of
fluoroquinolones is that resistant mutants can be selected with relative
ease, leading to relapse and treatment failure”. In addition it has been
observed that there is a significant association between total
fluoroquinolone use within human hospitals and percentage of S. aureus
isolates that were MRSA.xli Association between fluoroquinolone
exposure and the induction of mecA-positive S. aureus (MRSA) and the
increase in the resistance index for methicillin resistance has been noted. xlii
Lastly it has been widely reported that there is an association between FQ
use and clinically significant MRSAxliii,xliv xlv
i. The only time the author will use enrofloxacin or orbifloxacin is
when the infection has failed to respond to the author’s aggressive
therapy. The author prefers the later product due to the inclusion of
steroids in the lotion. If using the former, dexamethasone should be
added to achieve a final concentration if 0.1% dexamethasone.
Pseudomonas infections are especially challenging because of Pseudomonas’ intrinsic
multidrug resistance (MDR)xlvi. Many of the clinically relevant resistance mechanisms in
Pseudomonas aeruginosa are attributed to synergy between its outer membrane that has a
very low permeability to drugs and the presence of an active drug efflux pump (MEX).
Because of the intrinsic MDR, Pseudomonas infections successful treatment must be
aggressive before other resistance develops.
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