1. health and fitness
2. disease

Vet Clin Small Anim
34 (2004) 541–555
Medical therapy of otitis externa and
otitis media
Daniel O. Morris, DVM
Section of Dermatology and Allergy Department of Clinical Studies–Philadelphia,
School of Veterinary Medicine, VHUP Room 2065, 3900 Delancey Street,
University of Pennsylvania Philadelphia, PA 19104, USA
The medical approach to therapy of otitis externa and media may
currently be best described as an art rather than a science. Although the
veterinary literature evaluating diagnostic techniques for otitis has grown
considerably in the past few years, veterinary studies documenting medical
therapies (beyond ototoxicity research) are quite scarce. Review articles [1–
3] and discussions of medical approaches within the published proceedings
of continuing education meetings are not uncommon, because medical
therapy of otitis is a popular topic among veterinary practitioners.
Information based on prospective studies that adhere to the principles of
evidence-based medicine is definitely rare, however. This is not the case in
human medicine.
The potential predisposing factors and direct/indirect causes of otic
inflammation or otic immunosuppression are discussed elsewhere in this
issue. Bacterial and fungal (yeast) infections of the ear canals are thought to
be secondary problems in most cases [1]. Although veterinarians universally
agree that it is of utmost importance to resolve the primary otic disease, this
article focuses solely on medical therapy for the infectious component of
otitis externa and media.
Because dermatologists deal with otic infections on a daily basis, this
group of specialists has contributed much to the anecdotal knowledge base
on the subject. Multiple approaches are routinely discussed, which often
vary in the empiric choices of topical drugs and cleansers employed, the
frequency and technique of ear canal lavage (both in-office and as
administered by the pet owner at home), and the types and frequencies of
prophylactic therapies recommended after resolution of chronic infections.
One point of agreement (and much concern) is the growing evidence for
E-mail address: domorris@vet.upenn.edu
0195-5616/04/$ - see front matter Ó 2004 Elsevier Inc. All rights reserved.
doi:10.1016/j.cvsm.2003.10.009
542
D.O. Morris / Vet Clin Small Anim 34 (2004) 541–555
multidrug-resistant strains of Pseudomonas aeruginosa and methicillinresistant Staphylococcus spp [4–9].
Active ingredients available for otic therapy in the acute and chronic/
recurrent case of bacterial or yeast otitis are discussed here, along with the
potential topical cutaneous reactions and ototoxicities that may be
associated with them. Special considerations for treatment of attendant
otitis media/interna and resistant bacterial strains are also presented.
Topical versus systemic therapeutics: an overview
Topical therapy is key to the successful resolution of otitis externa, which
is essentially a surface infection. Unless the ear canal epithelium has been
eroded or ulcerated extensively, systemic (oral) antimicrobials are unlikely
to achieve therapeutic concentrations within the fluid and waxy exudates of
the external canals in which the infectious organisms are harbored.
Penetrating this ‘‘vat’’ of infection is best accomplished by the application
of sufficient volumes of a topical antimicrobial. The choice of active
ingredients for treatment of otitis externa is usually made empirically, based
on cytologic examination of ear canal exudates and otoscopic examination
of the inflamed canals. In contrast, the middle ear (tympanic bulla) contains
a highly vascular mucous membrane lining, which may allow for better
diffusion of drugs from the vascular compartment to the bulla space. The
choice of systemic antibiotics for treating the middle ear compartment is
preferably based on culture and susceptibility testing.
Information gleaned from culture and susceptibility testing reflects the
serum level of drug required to kill the organism in question and may not be
relevant in choosing topical antimicrobial preparations. Susceptibilities are
typically expressed as minimum inhibitory concentrations (MICs) or
reported simply as ‘‘susceptible,’’ ‘‘intermediate,’’ or ‘‘resistant’’ based on
the Kirby-Bauer disk diffusion method. For several reasons, this in vitro
information may relate poorly to the choice of topical antimicrobial. As
already mentioned, adequate levels of drug (which reach the MIC for the
organism) may not be achieved at the surface of the external ear canal
epithelium. In addition, the concentrations of specific antimicrobial
ingredients in topical preparations often greatly exceed those that could
be safely achieved in the systemic circulation. For example, an organism
that is reported to be resistant to gentamicin on a culture/susceptibility test
may not be resistant to the high concentration of gentamicin that can be
safely delivered locally within the ear canal itself. Finally, not all active
ingredients used topically are represented on standard culture/susceptibility
profiles. Therefore, veterinarians should be comfortable with basing an
empiric choice of topical antimicrobial on the cytologic identification of the
organism (or class of organism) and otoscopic evaluation of the extent of
ear canal inflammation and chronic changes. The reader is referred to the
D.O. Morris / Vet Clin Small Anim 34 (2004) 541–555
543
articles on otoscopy and cytologic/microbial evaluation of the ear canal in
this issue for a discussion of these factors.
Ingredients of topical antibacterials
Most commercially produced topical products contain one or more active
ingredients (antibacterial, antifungal, and anti-inflammatory) in various
combinations as well as a vehicle and various solubilizers, stabilizers, and
surfactants [10]. The formulation of the topical product with regard to the
vehicle may be as important as the active ingredient to the success of therapy.
Vehicles are chosen to maximize drug solubility, to maintain drug activity
locally for the maximum period, and to minimize systemic absorption. The
most commonly used vehicles are water (which may be buffered and pHadjusted to maximize drug activity), demulcents, and emollients [10].
Demulcents are compounds of high molecular weight capable of forming
stable emulsions or suspensions of drugs that are not water soluble. They
coat and protect underlying tissue. Polyhydroxy demulcents, which are the
most hydrophilic yet potentially irritating compounds within this class, are
also the most commonly used carriers used in otic products. They include
polyethylene glycol, propylene glycol, and glycerin [10]. The former two are
commonly implicated in contact/irritant reactions in the author’s practice.
Emollients are occlusive agents used as carriers for water-insoluble drugs
and are protective and hydrating to the stratum corneum. Examples include
vegetable oils, animal fats (eg, lanolin), and hydrocarbons (eg, petrolatum,
mineral oil, paraffin) [10]. For a more complete discussion of vehicles and
excipients than can be presented here, the reader is referred to the excellent
article on otopharmacology by Wilcke [10].
Active ingredients are generally classified as antibacterials, antifungals,
and anti-inflammatories. Each is discussed in more detail.
Antibacterials
Chloramphenicol
A ‘‘first-line’’ topical antibacterial with low potency yet broad-spectrum
activity, chloramphenicol is no longer available as a commercially produced
topical product. Chloramphenicol is considered to be a bacteristatic agent
(except at high concentrations) against susceptible bacterial strains. Known
to be associated with aplastic anemia in human beings, concern over
potential drug exposure to the pet owner limited its topical use by many
veterinarians when a topical product was available.
Fusidic acid
This is a narrow-spectrum bacteristatic antimicrobial that inhibits
bacterial protein synthesis by a unique mechanism. Its spectrum is limited
544
D.O. Morris / Vet Clin Small Anim 34 (2004) 541–555
to gram-positive cocci; gram-negative bacilli are inherently resistant because
of their impermeable cell membranes [11]. The usual clinical indication is
otitis caused by staphylococcal species. Fusidic acid preparations are
unavailable in the United States, but otic preparations are used in Europe
and Canada.
Aminoglycosides
The aminoglycoside antibiotics are the most commonly used class of
topical otic products. They act on susceptible bacteria by binding to the 30s
ribosomal subunit in the bacterial nucleus, thereby inhibiting protein
synthesis, and are considered to be bactericidal. Their antibacterial spectra
vary by individual drug potency but include some aerobic gram-positive
bacteria and many aerobic gram-negative species. They are ineffective for
anaerobes and fungi [12]. Their antimicrobial activity is enhanced in an
alkaline environment, which is germane to topical therapy of the ear canal.
If acidifying cleansers are used in conjunction with aminoglycosides, the
products should be applied at least 1 hour apart. Also of noted importance
is the ototoxic potential of aminoglycosides, especially when administered
parenterally. Auditory symptoms are more common with neomycin and
amikacin, whereas vestibular symptoms are most typical of gentamicin,
especially in the cat [12]. The ototoxic potential of this class of drugs when
topically applied may be overestimated [13].
Neomycin
Often considered to be a first-line topical antibacterial [1], neomycin has
the lowest potency of the class, showing significantly less efficacy against
several gram-negative organisms; most notably Escherichia coli and
P aeruginosa. Its activity against gram-positive cocci remains quite good.
Manufactured topical products containing neomycin are plentiful and are
recommended for acute bacterial otitis in which cocci predominate
cytologically. Neomycin is one of the most commonly implicated topical
agents for contact/irritant reactions in dogs, however (Fig. 1).
Gentamicin
Considered to be a ‘‘second-line’’ antibacterial, gentamicin has intermediate potency within the class. Its activity against gram-positive cocci
is excellent; however, resistant strains of E coli and P aeruginosa are not
uncommon. Manufactured topical products containing gentamicin are
plentiful and are recommended for chronic/recurrent otitis when clinical
evidence of neomycin-resistant rods is available. In general practice, these
products are often used as first-line antibacterials. Despite continuing
anecdotal concern over the ototoxic potential of topical gentamicin, a study
in dogs designed to simulate clinical exposure via a ruptured tympanum
failed to document any toxicity [14]. In human medicine, however, the risk
D.O. Morris / Vet Clin Small Anim 34 (2004) 541–555
545
Fig. 1. A contact/irritant reaction caused by topical neomycin administration in a dog. Note
inflammation and erythema of the concave surface of the ear pinna and entrance to the vertical
canal.
of topical gentamicin ototoxicity in clinical practice is now thought to have
been underestimated in the past [15].
Amikacin
Considered by the author to be a third-line antibacterial, amikacin is
most commonly indicated for chronic/recurrent otitis caused by gentamicinresistant gram-negative bacilli (especially P aeruginosa). Amikacin is not
available as a commercially produced topical product, but the injectable
product (Amiglyde) is often diluted to a concentration of 30 to 50 mg/mL
(in sterile saline or a tromethamine–ethylenediamine-tetraacetate [TrisEDTA] product) by veterinarians for topical use.
Tobramycin
Also a third-line antibacterial, indications for use of tobramycin are
similar to those for amikacin. Although an otic topical product is not
available, ophthalmic formulations are. Dilution of injectable tobramycin
(Nebcin) with sterile saline to a concentration of 8 mg/mL has been used by
the author, but the long-term stability (>1 week) of the solution is unknown
and remains a concern.
Fluoroquinolones
This class of antibiotics acts by inhibiting bacterial DNA-gyrase, which
prevents DNA supercoiling and synthesis and is thus bactericidal.
Bactericidal activity is dependent on concentration, and bacterial resistance
is known to occur by rapid mutation, especially in the presence of
subtherapeutic concentrations [16]. Fluoroquinolones have good activity
546
D.O. Morris / Vet Clin Small Anim 34 (2004) 541–555
against a wide range of gram-negative bacilli and gram-positive cocci
(including staphylococci, although activity is variable for streptococci) [12].
Their use as second- or third-line antibiotics for chronic/recurrent bacterial
otitis, especially cases associated with P aeruginosa, has become common.
Studies comparing two human-labeled topical fluoroquinolone products
(ciprofloxacin [Cipro HC otic solution] and ofloxacin [Floxin otic solution])
with polymyxin B (Cortisporin otic) have shown the fluoroquinolones to be
safe, with less ototoxic potential [17].
Enrofloxacin
This drug has long been used for resistant Pseudomonas otitis. Although
a commercially produced veterinary-labeled topical product is now available
(Baytril otic), veterinarians have used enrofloxacin topically for many years
by diluting the injectable product for otic use. Reports of resistant strains of
P aeruginosa have become common [4,5,9,18], with up to 87.5% of strains
being nonsusceptible in vitro [5].
Ciprofloxacin
With a spectrum of activity similar to that of enrofloxacin (ciprofloxacin
is an active metabolite of enrofloxacin), there may be little indication for
choosing this drug over the former now that a veterinary-labeled topical
formulation of enrofloxacin is available. Although resistance of
P aeruginosa to ciprofloxacin has been reported to be less common than
to enrofloxacin, there are also several laboratory-dependent explanations
for the discrepancy that may prove it technical rather than clinical [19].
Regardless, a human-labeled ciprofloxacin otic product (Cipro HC) is
available and has been used successfully in dogs by many veterinary
dermatologists.
Marbofloxacin
This fluoroquinolone may exhibit a better MIC for Pseudomonas spp
than enro/cipro [18]. Although unavailable in the United States as a topical
product, it is now available in Europe in an otic formulation (Aurizon).
Because an injectable product is also unavailable in the United States,
topical use has been limited; however, its systemic (oral) use in otitis media/
interna is increasing [20,21].
Carboxypenicillins
This class includes the expanded-spectrum penicillins, which exhibit
activity against gram-negative organisms (including Pseudomonas spp)
because of their ability to penetrate the gram-negative cell membrane.
Ticarcillin is the carboxycillin for which topical use has been most
commonly reported in the treatment of canine Pseudomonas otitis [22,23].
One pair of authors recommends dilution of the 6-g bottle with 12 mL of
D.O. Morris / Vet Clin Small Anim 34 (2004) 541–555
547
sterile water and the addition of reconstituted ticarcillin, 2 mL, to 40 mL of
an acidifying ear cleanser (with the remainder frozen for future use). The
stability of this solution is unknown but may not exceed 3 days [22].
Polymyxins
Polymyxin B and colistin sulfate (polymyxin E) are polypeptide
antibiotics that exert bactericidal effect by increasing permeability of the
bacterial cell membrane via chelation of membrane phospholipid components, leading to osmotic damage. The ototoxic potential of polymyxin B
has been well described experimentally in several species of animals, both in
vivo and in vitro [17,24–27]. There is speculation that the ototoxicity of
these products could be more specifically attributable to the propylene
glycol vehicle, however [26]. One positive aspect of topical polymyxin B is its
reduction of the inflammation induced by endotoxin components of gramnegative bacterial cell walls [28]. The relevance of these findings to dogs and
cats is unknown. Currently, there is no polymyxin B product marketed
specifically for otic use. Ophthalmic products are available (Polytrim
ophthalmic solution), but the author prefers to use a more cost-effective
formulation intended for dilution and use as an irrigating solution
(Neosporin GU). This product comes in 1-mL ampules containing
200,000 U of polymyxin B sulfate and 40 mg of neomycin base, and it
may be diluted with sterile water to 10,000 U/mL for otic use. Colistin
sulfate is still available under a proprietary human label (Cortisporin-TC
otic suspension).
Silver sulfadiazine
Used for more than three decades in human medicine as a burn wound
protectant, silver sulfadiazine (SSD) has broad-spectrum antibacterial
activity (most notably against P aeruginosa) [29] and does not interfere with
re-epithelialization and neovascularization of wounds [30]. In fact, it may
enhance wound healing [31]. The spectrum of activity includes most
pathogens associated with otitis (including methicillin-resistant staphylococci) [32], with the exception of Malassezia pachydermatis, against which
activity is low [33]. Resistant strains of P aeruginosa have been reported
[34] but are extremely rare in the author’s practice. Silver exerts its
antibacterial effect via impairment of DNA replication and bacterial cell
wall damage, leading to osmotic changes [29]. Supplied as a 1% cream
(Silvadene) and as a micronized powder (Spectrum pharmacy products;
available at: www.spectrumRx.com), concentrations as low as 0.02% have
shown 100% efficacy against P aeruginosa and Staphylococcus spp [32].
Although the cream is not readily miscible in water, a homogeneous
emulsion can be achieved with gentle mixing. The author prefers to use the
powder as a suspension in sterile water at 0.5% to 1.0%. A proprietary
548
D.O. Morris / Vet Clin Small Anim 34 (2004) 541–555
product that combines 1% SSD with 0.5% enrofloxacin (Baytril otic) is
now available. SSD has become the favored topical therapy for
Pseudomonas otitis in the author’s group practice, especially when the
external ear canals are ulcerated. Our clinical impression is that reepithelialization is hastened.
The ototoxic potential of SSD is unknown, although the collective
experience of a large group of veterinary dermatologists suggests that it is
safe for use even in the context of a ruptured tympanum. Because it is
known that significant amounts of silver can be absorbed from burn wounds
of human beings [35] and silver has the potential to produce systemic
toxicity [36,37], caution may be warranted in veterinary patients with
extensive ulceration. Evidence implicating SSD in systemic toxicity of dogs
or cats has not been reported to the knowledge of the author, and a 1%
suspension has been used in scores of dogs and several cats for more than 3
months without incident at the University of Pennsylvania.
Tromethamine–ethylenediamine-tetraacetate
This is commonly used as either a presoak or a carrier vehicle (for
aminoglycoside antibiotics) in the treatment of gram-negative infections.
EDTA promotes increased permeability to extracellular solutes and
increased sensitization to antibiotics, whereas Tris serves as a buffer [38].
Two proprietary products are now available in the United States: TRIZEDTA and a similar chemical combination of Tris and tetrasodium edetate
(T8 solution).
Antifungals
Nystatin
A polyene antifungal, nystatin binds to sterols in the fungal cell
membrane, thereby altering permeability and mediating cell death by
osmotic destruction [12]. Nystatin is primarily used to treat infections by
Candida spp, but it also exhibits activity against M pachydermatis clinically.
Nystatin is considered a first-line anti-Malassezia drug by at least one
author [1]. In an in vitro study, neomycin exhibited only partial inhibition of
M pachydermatis growth on Sabouraud’s agar [39]. Because most
preparations containing nystatin are occlusive ointments, this author
typically avoids using them in cases of exudative or ceruminous otitis
externa.
Azole antifungals
Benzimidazoles (eg, thiabendazole), imidazoles (eg, clotrimazole, miconazole, ketoconazole), and triazoles (eg, itraconazole, fluconazole) all share
D.O. Morris / Vet Clin Small Anim 34 (2004) 541–555
549
a common mode of action against fungi: disruption of cell wall ergosterol
biosynthesis via P450 enzyme inhibition [12]. An in vitro study comparing
the efficacy of the azoles against Malassezia spp yeast indicated that
thiabendazole is the least effective, followed by clotrimazole (with efficacy
comparable to nystatin), miconazole (with 10 times the potency of nystatin),
ketoconazole, and itraconazole, respectively [40]. A more recent in vitro
study showed equal efficacy of ketoconazole, itraconazole, and terbinafine
against M pachydermatis [41], whereas a Hungarian study suggested that
ketoconazole is the most effective, followed by clotrimazole, miconazole,
and nystatin, respectively [42]. Regional variation in strain susceptibility
may therefore exist.
Veterinary topical preparations of thiabendazole, clotrimazole, and
miconazole are commonly employed for the treatment of Malassezia otitis
in dogs and cats. Ketoconazole (Nizoral) is available only under human
labels as oral tablets and a topical cream. Both may be used to formulate
1% to 2% solutions for otic treatment of veterinary patients when other
more available azoles are failing clinically. A human-labeled 1% oral
itraconazole elixir (Sporanox Oral Solution) has also been used topically by
the author. Although sticky (in a syrup base), the product has been effective.
Miconazole is the topical agent most commonly employed against
Malassezia otitis in the author’s group practice, whereas clinical resistance
to clotrimazole has been noted on numerous occasions. Topical azole
antifungals are said to be uniformly nontoxic to the inner ear [43]. Although
antifungal ototoxicity does not seem to be clinically problematic in dogs and
cats, contact/irritant reactions may be noted with any of the azoles. It is
difficult to exclude the role of vehicle versus the azole drug in many cases,
however. Oral ketoconazole or itraconazole may be used for canine otitis
media associated with Malassezia spp, whereas itraconazole is generally
preferred for this purpose in cats [44,45].
Allylamines
This class of antimycotic agents exerts a cell-wall effect by disruption of
ergosterol biosynthesis via inhibition of squalene epoxidase. Because the
effect does not involve P450 enzymes, this class of antifungal drugs is
generally considered to be safer for mammalian use than the azole
antifungals [46]. Terbinafine has been shown to have excellent in vitro
efficacy for many species of Malassezia, including M pachydermatis [41].
Although not marketed as a topical product under a veterinary label, a 1%
human-labeled solution (Lamisil) is available over the counter in various
preparations for the treatment of tinea. Its use for Malassezia otitis in
animals has not been reported, although the author has used it successfully
in a single canine patient. Oral use of terbinafine for feline dermatophytosis
has been reported, and adverse effects were not noted [47], suggesting its
potential utility for Malassezia otitis media in cats.
550
D.O. Morris / Vet Clin Small Anim 34 (2004) 541–555
Anti-inflammatory agents
Almost every case of otitis deserves the benefits of topical corticosteroids
because of their anti-inflammatory, antiproliferative, antipruritic, and
antiexudative (glandular secretory) effects. Systemic steroids [preferably
predniso(lo)ne or methylprednisolone orally] are also highly efficacious in
reducing acute stenosis caused by edema as well as more chronic stenosis
caused by proliferative hyperplasia and fibrosis.
Topical steroids are present in a large proportion of commercially
prepared otic products, and their potency may depend not only on the
drug’s inherent anti-inflammatory quotient but on the drug concentration
and vehicle used in the product. In general, the potency of topical steroids is
assumed to concur with their biologic activities. Relative potencies
compared with hydrocortisone are: hydrocortisone (1), prednisolone (5),
triamcinolone (5), isoflupredone (14), dexamethasone (25), betamethasone
(25), and fluocinolone (100) [10]. Some authors believe that nothing more
potent than hydrocortisone should be used in cases of ulcerative
Pseudomonas otitis [48]. The reader is referred to the excellent article by
Logas [48] for more complete information regarding the indications and
uses of topical steroids. Side effects related to topical steroids include
systemic absorption with suppression of the hypothalamic-pituitary-adrenal
axis (which likely increases with the higher potency steroids) [49] and topical
contact reactions. Although well described in human beings [50], contact
allergy to topical corticosteroids has not received attention in veterinary
medicine.
The only nonsteroidal agent available in a topical otic preparation is
dimethyl sulfoxide (DMSO). In addition to its significant anti-inflammatory activity, DMSO may reduce fibroplasia [51]. A 60% DMSO solution
with 0.01% fluocinolone (Synotic) is quite useful for severe inflammatory
and hyperplastic otitis but should be used with caution in the face of
infection.
Therapy of acute otitis externa
In general a first-line antimicrobial should be chosen based on cytologic
and otoscopic findings. Twice-daily therapy for a minimum of 7 to 14 days
depending on the degree of inflammatory changes (edema, hyperplasia, and
erosion/ulceration) combined with at-home cleansing is the author’s prescribed regimen. Of utmost importance is delivering a sufficient volume of
topical agent to the canal. For example, large-breed dogs (eg, retrievers,
shepherds) should receive a minimum of 10 to 12 drops (or 1 mL) per
application. Re-evaluation at the end of the regimen to evaluate the cytologic
and otoscopic status of the ears is recommended but not mandatory for
success in most cases.
D.O. Morris / Vet Clin Small Anim 34 (2004) 541–555
551
Therapy of chronic/recurrent otitis externa
A complete history, physical examination, and otoscopic examinations to
search for predisposing, primary, and perpetuating factors are indicated. The
status of the tympanic membranes should be confirmed. If edema or
proliferative changes preclude visualization of the entire canal to the level of
the tympanum, topical therapy should be initiated based on cytologic
findings, and the patient should be discharged on an anti-inflammatory
regimen or oral predniso(lo)ne (0.5 mg/kg every 12 hours tapered weekly to
every 24 hours and then every 48 hours) and scheduled for a follow-up visit in
2 to 4 weeks for recheck. Treatment with second-line or third-line
antimicrobials may be indicated depending on the history of prior therapies.
The client should be prepared for longer term topical therapy (at least 4
weeks in duration). In extremely chronic cases, several months of rigorous
topical therapy may be necessary to return the external canals to their normal
state. Systemic antibiotics may be indicated if there is extensive tissue
swelling (potentially indicating deeper infection), ulceration, or significant
periaural dermatitis [1]. Rechecks should be scheduled every 2 to 4 weeks for
cytologic and otoscopic examination until complete resolution is achieved.
Therapy of otitis media
Because otitis media is typically the result of extension of chronic otitis
externa through a ruptured tympanic membrane, all the principles discussed
for chronic/recurrent otitis externa apply here. In addition, a thorough
lavage of the bulla to remove infective and inflammatory exudates gives
medical therapy a good head start. In the case of bulla impaction with
inflammatory exudates and debris, medical failure is virtually guaranteed
without a thorough lavage.
The choice of antimicrobial agents becomes more complicated when
otitis media is involved. This author prefers to avoid the topical use of
fluoroquinolones completely unless a systemic form of the same drug is used
concurrently because of the potential for subtherapeutic concentrations of
the topical drug to reach the middle ear via the ruptured tympanum.
Development of fluoroquinolone resistance is documented to occur in vitro
with a single exposure to the drug [16].
Many veterinary dermatologists recommend starting an oral fluoroquinolone pending culture/susceptibility results. Systemic antimicrobial therapy
based on culture/susceptibility testing of samples retrieved from the middle
ear is indicated whenever possible. In fact, it has been stated that otitis
media cannot be resolved with topical therapy alone [2]. Many chronic cases
of otitis media involve P aeruginosa, however, and an oral drug is not always
available because of broad-spectrum resistance.
Several systemic antipseudomonal drugs intended for intravenous use can
also be used subcutaneously, allowing therapy by the client at home.
552
D.O. Morris / Vet Clin Small Anim 34 (2004) 541–555
Examples include meropenem (Merrem; 8 mg/kg every 12 hours) [52],
ticarcillin (Ticar; 40–80 mg/kg every 6 hours) [53], and ceftazidime (Fortaz;
30 mg/kg every 4 hours) [54]. The downfall of these systemic injectable drugs
is their extremely high cost. In cases of Pseudomonas otitis media in which
an oral antibiotic is unavailable and the cost of subcutaneous therapy is
prohibitive to the client, the clinicians in the author’s group practice have
shown success with thorough bulla lavage followed by high-throughput
topical therapy. The later entails application of large volumes (1–2 mL) of
topical drug (most often, an SSD solution) twice daily and regular (daily or
every other day) at-home flushing of the canals using an acidifying cleanser.
It is our contention that high-volume application of low-viscosity
antimicrobial preparations and cleansers promotes a continued ‘‘flushing’’
of the bullae as long as the tympani remain open.
Methicillin-resistant Staphylococcus spp also present a dilemma in
selecting a systemic antibiotic. Methicillin resistance (indicated by resistance
to oxacillin in most susceptibility profiles) confers resistance to all b-lactam
antibiotics, and many of these strains also show broad fluoroquinolone
resistance patterns. Fortunately, most strains isolated from patients
presenting to the dermatology service at the University of Pennsylvania
have been susceptible to chloramphenicol or macrolide antibiotics
(erythromycin, azithromycin [Zithromax], and clarithromycin [Biaxin]).
Regardless, the successful therapy of bacterial or fungal otitis media relies
on an initial thorough cleansing of the bulla, aggressive targeted
antimicrobial therapy for an absolute minimum of 6 to 8 weeks, and
consistent cleansing/flushing of the external canal by the client at home.
Therapy can only be discontinued when the ear canals are negative for
microorganisms on cytologic examination, the external canals have no
residual edema, and the epithelium has normalized. In some cases, the
tympanic membrane may not regenerate, although most do. In cases in
which these criteria cannot be achieved, a prophylaxis program that
incorporates regular use of cleansers and drying agents must be instituted.
The level of commitment on the part of the client cannot be overly stressed.
In the author’s group practice, the mean time to resolution of chronic otitis
media in 44 dogs was 117 86.7 days (range: 30–360 days) [20].
References
[1] Rosychuck RAW. Management of otitis externa. Vet Clin North Am Small Anim Pract
1994;24(5):921–52.
[2] Bruyette DS, Lorenz MD. Otitis externa and otitis media: diagnostic and medical aspects.
Semin Vet Med Surg 1993;8:3–9.
[3] Foster AP, DeBoer DJ. The role of Pseudomonas in canine ear disease. Compend Small
Anim Pract 1998;20:909–19.
[4] Lloyd DH. Antibiotic resistance. The challenge in small animal dermatology. In:
Proceedings of the British Veterinary Dermatology Study Group. Birmingham, UK: Leo
Animal Health; 1998. p. 8–11.
D.O. Morris / Vet Clin Small Anim 34 (2004) 541–555
553
[5] Cole LK, Kwochka KW, Kowalski JJ, Hillier A. Microbial flora and antimicrobial
susceptibility patterns of isolated pathogens from horizontal ear canal and middle ear in
dogs with otitis media. J Am Vet Med Assoc 1998;212:534–8.
[6] Tomlin J, Pead MJ, Lloyd DH, Howell S, Hartmann F, Jackson HA, et al. Methicillinresistant Staphylococcus aureus infections in 11 dogs. Vet Rec 1999;144:60–4.
[7] Gortel K, Campbell KL, Kakoma I, Whittem T, Schaeffer DJ, Weisiger RM. Methicillin
resistance among staphylococci isolated from dogs. Am J Vet Res 1999;60:1526–30.
[8] Ganiere JP, Medaille C, Limet A, Ruvoen N, Andre-Fontaine G. Antimicrobial activity of
enrofloxacin against Staphylococcus intermedius strains isolated from canine pyodermas.
Vet Dermatol 2001;12:171–5.
[9] Hariharan H, McPhee L, Heaney S, Bryenton J. Antimicrobial drug susceptibility of
clinical isolates of Pseudomonas aeruginosa. Can Vet J 1995;36:166–8.
[10] Wilcke JR. Otopharmacology. Vet Clin North Am Small Anim Pract 1988;18(4):783–97.
[11] Werner AH, Russell AD. Mupirocin, fusidic acid and bacitracin: activity, action and
clinical uses of three topical antibiotics. Vet Dermatol 1999;10:225–40.
[12] Plumb DC. Drug monographs. In: Veterinary drug handbook. 4th edition. Ames, IA: Iowa
State Press; 2002.
[13] Merchant SR. Ototoxicity. Vet Clin North Am Small Anim Pract 1994;24(5):971–9.
[14] Strain GM, Merchant SR, Neer TM, Tedford BL. Ototoxicity assessment of gentamicin
sulfate otic preparation in dogs. Am J Vet Res 1995;56(4):532–8.
[15] Rutka J. Update on topical ototoxicity in chronic suppurative otitis media. Ear Nose
Throat J 2002;81(Suppl 1):18–9.
[16] Brothers AM, Gibbs PS, Wooley RE. Development of resistant bacteria isolated from dogs
with otitis externa or urinary tract infections after exposure to enrofloxacin in vitro. Vet
Ther 2002;3:493–500.
[17] Russell PT, Church CA, Jinn TH, Kim DJ, John EO, Jung TTK. Effects of common
topical otic preparations on the morphology of isolated cochlear outer hair cells. Acta
Otolaryngol 2001;121:135–9.
[18] Barrasa JLM, Gomez PL, Lama ZG, Junco MTT. Antibacterial susceptibility patterns of
Pseudomonas strains isolated from chronic canine otitis externa. J Vet Med B 2000;47:
191–6.
[19] Peterson AD, Walker RD, Bowman MM, Schott H, Rosser EJ. Frequency of isolation and
antimicrobial susceptibility patterns of Staphylococcus intermedius and Pseudomonas
aeruginosa isolates from canine skin and ear samples over a 6-year period. J Am Anim
Hosp Assoc 2002;38:407–13.
[20] Palmeiro BS, Morris DO, Wiemelt SP. Therapeutic outcomes of canine otitis media
managed by an academic referral practice: a retrospective study of 44 cases. Vet Dermatol
2003;14:213.
[21] Carlotti DN, Guaguere E, Koch HJ, Guiral V, Thomas E. Marbofloxacin for the systemic
treatment of Pseudomonas spp. suppurative otitis externa in the dog. In: Kwochka KW,
Willemse T, von Tscharner C, editors. Advances in veterinary dermatology, vol. 3. Oxford:
Butterworth-Heinemann; 1998. p. 463–4.
[22] McKeever PJ, Globus H. Canine otitis externa. In: Bonagura JD, editor. Kirk’s current
veterinary therapy XII small animal practice. Philadelphia: WB Saunders; 1995. p. 647–55.
[23] Nuttal TJ. Use of ticarcillin in the management of canine otitis externa complicated by
Pseudomonas aeruginosa. J Small Anim Pract 1998;39:165–8.
[24] Wright CG, Meyerhoff WL, Halama AR. Ototoxicity of neomycin and polymyxin B
following middle ear application in the chinchilla and baboon. Am J Otol 1987;8:495–9.
[25] Jinn TH, Kim PD, Russell PT, Church CA, John EA, Jung TTK. Determination of
ototoxicity of common otic drops using isolated cochlear outer hair cells. Laryngoscope
2001;111:2105–8.
[26] Roland PS. Characteristics of systemic and topical agents implicated in toxicity of the
middle and inner ear. Ear Nose Throat J 2003;82(Suppl 1):3–8.
554
D.O. Morris / Vet Clin Small Anim 34 (2004) 541–555
[27] Parker FL, James GW. The effect of various topical antibiotic and antibacterial
agents on the middle and inner ear of guinea pigs. J Pharm Pharmacol 1978;30:
236–9.
[28] Darrow DH, Keithley EM. Reduction of endotoxin-induced inflammation of the middle
ear by polymyxin B. Laryngoscope 1996;106:1028–33.
[29] Hoffman S. Silver sulfadiazine: an antibacterial agent for topical use in burns. Scand J Plast
Reconstr Surg 1984;18:119–26.
[30] Kjolseth D, Frank JM, Barker JH, Anderson GL, Rosenthal AI, Acland RD, et al.
Comparison of the effects of commonly used wound agents on epithelialization and
neovascularization. J Am Coll Surg 1994;179:305–12.
[31] Lansdown ABG, Sampson B, Laupattarakasem P, Vuttivirojana A. Silver aids healing in
the sterile skin wound: experimental studies in the laboratory rat. Br J Dermatol 1997;137:
728–35.
[32] Marone P, Monzillo V, Perversi L, Carretto E. Comparative in vitro activity of silver
sulfadiazine, alone or in combination with cerium nitrate, against staphylococci and gramnegative bacteria. J Chemother 1998;10:17–21.
[33] Schmidt A. In vitro activity of climbazole, clotrimazole, and silver sulphadiazine against
isolates of Malassezia pachydermatis. Zentralblatt Fuer Veterinaermedzin Reihe B 1997;44:
193–7.
[34] Modak SM, Fox CL. Sulfadiazine silver-resistant Pseudomonas in burns. New topical
agents. Arch Surg 1981;116:854–7.
[35] Tsipouras N, Rix CJ, Brady PH. Solubility of silver sulfadiazine in physiological media and
relevance to treatment of thermal burns with silver sulfadiazine cream. Clin Chem 1995;41:
87–91.
[36] Gamelli RL, Paxton TP, O’Reilly M. Bone marrow toxicity by silver sulfadiazine. Surg
Gynecol Obstet 1993;177:115–20.
[37] Kulick MI, Wong R, Okarma TB, Falces E, Berkowitz RL. Prospective study of side effects
associated with the use of silver sulfadiazine in severely burned patients. Ann Plast Surg
1985;14:407–9.
[38] Blue JL, Wooley RE, Eagon RG. Treatment of experimentally induced Pseudomonas
aeruginosa otitis externa in the dog by lavage with EDTA-tromethamine-lysozyme. Am J
Vet Res 1974;35:1221–3.
[39] Maestrone G, Thompson E, Yeisley H, Mitrovic M. In vitro activity of antimicrobial agents
against Pityrosporum canis. Vet Med Small Anim Clin 1976;71:1681–3.
[40] Lorenzini R, Mercantini R, De Bernardis F. In vitro sensitivity of Malassezia spp. to
various antimycotics. Drugs Exp Clin Res 1985;11(6):393–5.
[41] Gupta AK, Kohli Y, Li A, Faergemann J, Summerbell RC. In vitro susceptibility of the
seven Malassezia species to ketoconazole, voriconazole, itraconazole and terbinafine. Br J
Dermatol 2000;142:758–65.
[42] Kiss G, Radvanyi SZ, Szigeti G. New combination for the therapy of canine otitis externa.
I: microbiology of otitis externa. J Small Anim Pract 1997;38:51–6.
[43] Tom LW. Ototoxicity of common topical antimycotic preparations. Laryngoscope 2000;
110:509–16.
[44] Morris DO. Malassezia dermatitis and otitis. Vet Clin North Am Small Anim Pract 1999;
29:1303–10.
[45] Pinchbeck LR, Hillier A, Kowalski JJ, Kwochka KW. Comparison of pulse
administration versus once daily administration of itraconazole for the treatment of
Malassezia pachydermatis dermatitis and otitis in dogs. J Am Vet Med Assoc 2002;220:
1807–12.
[46] Gupta AK, Sauder DN, Shear NH. Antifungal agents: an overview. Part II. J Am Acad
Dermatol 1994;30:911–34.
[47] Kotnik T. Drug efficacy of terbinafine hydrochloride (Lamisil) during oral treatment of
cats, experimentally infected with Microsporum canis. J Vet Med B 2002;49:120–2.
D.O. Morris / Vet Clin Small Anim 34 (2004) 541–555
555
[48] Logas D. Appropriate use of glucocorticoids in otitis externa. In: Bonagura JD, editor.
Kirk’s current veterinary therapy XIII small animal practice. Philadelphia: WB Saunders;
2000. p. 585–6.
[49] Walsh P, Aeling JL, Huff L, Weston WL. Hypothalamus-pituitary-adrenal axis
suppression by superpotent topical steroids. J Am Acad Dermatol 1993;29:501–3.
[50] Lauerma AI, Reitamo S. Contact allergy to corticosteroids. J Am Acad Dermatol 1993;28:
618–22.
[51] Alsup EM, DeBowes RM. Dimethyl sulfoxide. J Am Vet Med Assoc 1984;185:1011–4.
[52] Bidgood T, Papich MG. Plasma pharmacokinetics and tissue fluid concentrations of
meropenem after intravenous and subcutaneous administration in dogs. Am J Vet Res
2002;63:1622–8.
[53] Papich MG. Antibacterial drug therapy. Clin Pharmacol Ther 1998;28:215–31.
[54] Moore KW, Trepanier LA, Lautzenhiser SJ, Fialkowski JP, Rosin E. Pharmaco-kinetics of
ceftazidime in dogs following subcutaneous administration and continuous infusion and
the association with in vitro susceptibility of Pseudomonas aeruginosa. Am J Vet Res 2000;
61:1204–8.