Bayer Dermatology Symposium - Alison L. Stone

BayerDermatology

SymposiumProceedings from the 2008 NAVC Conference

A Supplement to Compendium: Continuing Education for Veterinarians™ • Vol. 30, No. 1(A) • January 2008

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Proceedings from the 2008 NAVC Conference

A Supplement to Compendium: Continuing Education for Veterinarians™Vol. 30, No. 1(A) • January 2008

BayerDermatologySymposium

This information has not been peer reviewed and does not necessarily reflect the opinions of,nor constitute or imply endorsement or recommendation by, the Publisher or Editorial Board.

The Publisher is not responsible for any data, opinions, or statements provided herein.

Cover photo: © 2007 Alison Landis Stone

3 National Incidence of Methicillin-ResistantStaphylococcal Infections: Understanding,Treatment, and PreventionDavid Aucoin, DVM, DACVCP

8 Challenges in the Managementof PyodermaPeter J. Ihrke, VMD, DACVD

15 Diagnosis and Treatment of MangeRalf S. Mueller, DVM, PhD, DACVD, FACVSc, DECVD

22 Managing Difficult Ear InfectionsJames O. Noxon, DVM, DACVIM (Internal Medicine)

Contents

National Incidence ofMethicillin-ResistantStaphylococcal Infections:Understanding, Treatment,and PreventionDavid Aucoin, DVM, DACVCPZoasis Corporation

METHICILLIN-RESISTANTSTAPHYLOCOCCUS AUREUSMethicillin-resistant Staphylococcus aureus(MRSA) is a major nosocomial pathogen inhuman hospitals and extended-care facilitiesand of late has become a serious infectiouspathogen in the community population notexposed to these institutions. Important con-tributors to the increasing importance of thispathogen include:

• Pattern of resistance to a wide range ofantibiotics besides β-lactams (penicillinsand cephalosporins). Hospital-acquiredMRSA (HA-MRSA) had been differentiat-ed from community-acquired MRSA (CA-MRSA) by its more extensive resistance.However, lately CA-MRSA is showingmultiple resistance profiles, blurring theline between these two categories.

• Opportunistic nature of the pathogen. S.aureus is a commensal organism in people.The nasopharynx is the major source ofthe organism, although it can also be car-ried in other sites, including the intestinaltract. Studies have shown that up to 30% ofpeople have S. aureus in their nose at any

point in time. Hands are a major source oftransmission. MRSA strains are usually notconsidered more intrinsically pathogenicthan other coagulase-positive Staphylococ-cus spp; however, some strains of CA-MRSA do appear to be more infectious andreadily transmissible.

Major morbidity and mortality are asso-ciated when HA-MRSA colonizes a sus-ceptible host (e.g., hospitalized patient,immunocompromised or debilitated indi-viduals) and subsequently causes anopportunistic infection that fails torespond to conventional treatment. How-ever, CA-MRSA is now being seen in oth-erwise healthy individuals as a cause ofextensive skin infections gaining accessthrough fomites (blankets and towels) andsmall skin abrasions, leading to suppura-tive spreading lesions.

• Mechanism of resistance. There are threemechanisms of resistance in methicillin-resistant Staphylococcus organisms:—Penicillin-binding proteins (PBPs) and

the mecA gene. All penicillins andcephalosporins (β-lactams) require bind-ing to a PBP in the bacterial cell wall to

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initiate the drugs’ activity. MRSA pro-duces a defective, low-affinity PBP(PBP2a) due to the presence and activa-tion of the mecA gene. The mecA geneitself comes from a novel integrative andmobile genetic element called a staphylo-coccal chromosomal cassette (SCCmec)that is conveniently bundled withenzymes needed to excise the mecA gene

from the cassette and insert itself into thestaph’s chromosomal structure. Thismethod of resistance acquisition isunique to this mechanism, and thespread of MRSA is usually through clon-al expansion rather than the normalprocess of mutation or plasmid-mediatedtransfer. All MRSA strains can be tracedback to a single clone found in Europe inthe mid-1960s.

The binding affinity of penicillinsand cephalosporins to PBP2a is verylow, disabling the drugs’ ability to dis-rupt cell wall synthesis and renderingthe drugs ineffective. The presence ofPBP2a on a Staphylococcus organismconfers resistance to all penicillins andcephalosporins.

—Cell-wall thickening. MRSA alsopossesses a thick cell wall that makespenetration by antibiotics difficult, con-

ferring resistance to multiple antibiotics(not just β-lactams).

—Efflux pump. Acquired through othermeans than a mecA gene, these proteinsare involved in active removal of antibi-otics through a membrane-bound pump,limiting many families of antibiotics thatwork on internal cellular structures.

METHICILLIN RESISTANCE OFSTAPHYLOCOCCAL INFECTIONSIN VETERINARY MEDICINEOverviewMRSA infections have been reported in ani-mals since the mid-1990s but were considereduncommon in domestic pets and rarelycaused disease. S. aureus is not a commensalorganism of dogs or cats and is considered atransient pathogen acquired from its primaryhost, humans. Since 2002, there has been arapidly growing body of work as well as datathat show an alarming acceleration of MRSAcultures from both dogs and cats from almostall body sites routinely tested.

When present, MRSA infections that havebeen strain typed have been shown to beexactly the same organism that colonizes peo-ple and are not a new strain. Studies to dateindicate that MRSA is transmitted fromhuman to pet; because methicillin-sensitive S.aureus (MSSA) strains are not a part of thenormal colonizing flora of dogs and cats andthus only transiently colonize domestic pets, itwould be expected that horizontal transmis-sion from pet to pet or pet to human wouldnot present a major issue. However, it is notclear if these MRSA, in contrast to MSSA,remain a part of the normal commensal skinor nasal flora of pets and present a possiblereservoir for contamination.

Since 2002, there has been an

alarming acceleration of MRSA

cultures from both dogs and cats from

almost all body sites routinely tested.

Culture Incidence fromAntech DiagnosticsMRSA is most frequently cultured fromcanine wounds, abscesses, and chronic pyo-dermas. In these cultured sites, S. aureusaccounts for 3% to 5% of all bacteria cultured;this statistic has remained unchanged since2004. What has changed is the proportion ofthose S. aureus strains that are methicillinresistant. In 2005, only 19% were methicillinresistant; in 2007, the percentage had signifi-cantly increased to 42%.* This is an unusualphenomenon in veterinary medicine, whereinfectious disease experts always implicateantibiotic use in animals as contributing toincreasing antibiotic resistance in humanpathogens. In this case, S. aureus comes fromhumans, and in 2007 almost half of the S.aureus infections transmitted were methicillinresistant.* It is interesting to see that the risein antibiotic resistance in humans is nowaffecting pets.

In these same cultures, Staphylococcus inter-medius, the commensal staph of dogs and cats,is identified in 25% to 30% of all wound cul-tures. In 2004, few (<0.6%) methicillin-resis-tant S. intermedius (MRSI) organisms werecultured at Antech Diagnostics. In 2005, 3.1%of all S. intermedius strains cultured fromwounds were methicillin resistant; by 2007,the number had increased significantly to10.2% (p < 0.05).* These pathogens are nottransmitted from humans, where they playvery little if any process in infections. Theywere created most likely via horizontal trans-fer of the mecA gene from the MRSApathogens. The mechanism for this transfer isunclear; however, it has been reported that the

mecA gene is present in S. intermedius isolates,with one study demonstrating it in almost50% of isolates tested.1 The data are clear thatwhile the rate of wounds infected with Staphy-lococcus has remained the same over the past3 years, the percentage of methicillin-resistantStaphylococcus—either from humans orpets—has vastly increased.

TESTING FORMETHICILLIN RESISTANCE INSTAPHYLOCOCCAL SPECIES• Methicillin resistance can be tested using

any of the β-lactamase stable penicillindrugs (including methicillin), althoughoxacillin is most commonly used. The bor-ders of the zone of inhibition can be more

difficult to read with oxacillin due to adelayed onset of resistance observed dur-ing testing. The mecA gene is inducible, soin clinical practice a patient may appear tohave a sensitive staph when in fact theantibiotic induces its own resistance. In thelab, this means that MRSA strains appearsensitive to oxacillin at 24 hours but not at48 hours.

• The latex agglutination test for the PBP2aprotein is becoming more routine inhuman medicine as the quickest test for


In 2005, only 19% of

Staphylococcus aureus strains

were methicillin resistant; in 2007,

the percentage had significantly

increased to 42%.

*Data presented by the author at the 2008 NAVCConference.


MRSA detection. New, quick multiplexpolymerase chain reaction (PCR) can alsobe used to identify the five main SCCmectypes and will be used at Antech Diagnos-tics in 2008 to better delineate and trackthese emerging pathogens.

• The vast majority of S. intermedius isolatesin dogs and cats do not show methicillinresistance. However, literature reports onmethicillin resistance and S. intermediusisolates from dogs and cats have given con-flicting results. In a University of Ten-nessee study with 57 S. intermediusisolates, only two were methicillin resis-tant; however, 50% of isolates had the

mecA gene detected by PCR testing, sug-gesting that the gene may not have beenexpressed.1 In a University of Illinois studywith 25 methicillin-resistant S. intermediusisolates, 23 had the mecA gene, and thenon–methicillin-resistant isolates did nothave the mecA gene.2 Further work is need-ed to determine the value of mecA genedetection on veterinary isolates.

• Coagulase-negative staphylococci (such asStaphylococcus schleiferi subsp schleiferi) iso-lates in dogs and cats appear to be morecommonly detected with methicillin resis-tance than the coagulase-positive isolates.

These are usually reported from canine pyo-dermas. S. schleiferi subsp coagulans is morecommonly identified from ear cultures.Antech Diagnostics will begin reporting thespecies and subspecies of all methicillin-resistant Staphylococcus in the first quarterof 2008 to better facilitate tracking of theincidence rate of all these organisms.

TREATMENT OPTIONS FORMETHICILLIN-RESISTANTSTAPHYLOCOCCUSLack of clinical response to any β-lactam (peni-cillins or cephalosporins), even if in vitro test-ing indicates they are sensitive, indicates thatthese antibiotics should not be used to treat amethicillin-resistant Staphylococcus infection.

Other choices include:

• Chloramphenicol. Chloramphenicol re-mains the only excellent drug of choicein methicillin-resistant staphylococcalinfections with a predictable in vitro effi-cacy greater than 95% from more than1,000 cultures of methicillin-resistantStaphylococcus.—Dosing of 33 mg/kg tid in dogs—Dosing of 50 mg/cat bid

• Potentiated sulfonamides. Better-than-average success against methicillin-resis-tant Staphylococcus at 55% sensitivity;however, clinical studies in humans areconflicting as to its use even from culturedMRSA deemed sensitive in vitro.

• Clindamycin. Although found effective inmany human CA-MRSA infections, theexperience at Antech Diagnostics hasshown this antimicrobial to be effective inless than 50% of the methicillin-resistantStaphylococcus isolates.

The vast majority of Staphylococcus

intermedius isolates in dogs and

cats do not show methicillin

resistance. However, literature

reports have given conflicting results.

• Fluoroquinolones. Enrofloxacin, mar-bofloxacin, and difloxacin all show lessthan a 50% in vitro efficacy, indicating amultiple-resistance mechanism in theMRSA and MRSI that are being cultured.

• Vancomycin. Vancomycin is a drug that issensitive to the vast majority of all methi-cillin-resistant Staphylococcus organisms;however, it has several disadvantages,including the fact that it is very nephrotox-ic in dogs needing to be administered 15mg/kg q6h IV with concomitant IV fluids.

• Linezolid. One of a new family of antibi-otics (oxazolidinones), linezolid can beadministered orally or parenterally. Evalua-

tion of pharmacokinetics in dogs indicatesthe effective dose is 20 to 30 mg/kg q12h. Ithas low toxicity but is very expensive. Thisdrug should be used only if there is no otherchoice (e.g., in multidrug-resistant Staphy-lococcus). Linezolid is also effective againsteven vancomycin-resistant enterococcus.

REFERENCES1. Kania SA, Williamson NL, Frank LA, et al.

Methicillin resistance of staphylococci iso-lated from the skin of dogs with pyoderma.Am J Vet Res 2004;65(9):1265-1268.

2. Gortel K, Campbell KL, Kakoma I, et al.Methicillin resistance among staphylococciisolated from dogs. Am J Vet Res 1999;60(12):1526-1530.


Challenges in theManagement of Pyoderma

Peter J. Ihrke, VMD, DACVDSchool of Veterinary MedicineUniversity of California, Davis

P yoderma is the second most commoncause of canine skin disease. In areas of

the world that are less ideal for flea repro-duction and infestation, pyoderma is thesingle most common canine skin disease.We can define pyoderma as a pyogenic orpus-producing bacterial infection of theskin. Dogs seem uniquely susceptible toboth single-event pyoderma and recurrentpyoderma. The reasons for this may relateto various host factors that could result inenhanced susceptibility to infection. Thesefactors could include the comparativelythin, compact stratum corneum of dogs, therelative lack of intercellular lipids in thecanine stratum corneum, the lack of a lipid-squamous epithelial plug in the entrance ofcanine hair follicles, and the relatively highpH of canine skin.

CLASSIFICATION OF PYODERMAThe diversity of canine pyoderma is enor-mous. Classification of pyoderma is most use-fully based on depth of bacterial involvementas it provides information on diagnosis, dif-ferential diagnosis, likelihood of underlyingdisease, prognosis, and likely response to ther-apy. Pyoderma may be surface, affecting thestratum corneum and outer epidermis; super-

ficial, involving only the epidermis and theepithelial appendages in the dermis; or deep-er, compromising structures in the dermis andthe deep, subjacent fatty tissue. As we gainknowledge about canine skin infections, werealize that most infections seem to be sec-ondary to either underlying disease or otherunderlying factors that somehow increase thelikelihood of infection. Few pyoderma are“primary” and do not have underlying causesor triggers. If underlying causes are not found,it is likely that recurrence will follow theseeming cure. This recurrence suggests thatthe initial infection was not primary but morelikely secondary to undiagnosed underlyingdisease or unrecognized triggering factors.Superficial pyoderma is more common thandeep pyoderma. As infection proceeds deeperinto hair follicles, follicular rupture leads to agranulomatous foreign-body tissue response.Deeper infections require a more aggressivediagnostic and therapeutic approach.

BACTERIA RESPONSIBLEFOR CANINE PYODERMAStaphylococcus intermedius is by far the mostcommon pathogen in canine pyoderma. Lesscommonly, Staphylococcus aureus and Staphy-lococcus schleiferi may cause canine skin infec-

©2007

LarsChristensen/Shutterstock.com



tion. Gram-negative organisms such as Pro-teus sp, Pseudomonas sp, and Escherichia coliare more likely to be secondary invaders indeep pyoderma. Rarely, Pseudomonas aerugi-nosa and other gram-negative organisms canbe the sole pathogen. Unusual staphylococcalinfections or gram-negative organisms aremore likely to be more resistant to variousantibiotics.

MICROBIAL RESISTANCEMicrobial resistance in staphylococci isincreasing. Methicillin resistance has greatlycomplicated the use of antibiotics in humanmedicine. It is being recognized with increas-ing frequency in veterinary medicine andwill have a substantial impact on how wemanage skin disease caused by staphylococcalspecies in the future. Methicillin resistance isreported in S. aureus (hospital- or communi-ty-acquired methicillin-resistant S. aureus[HA-MRSA or CA-MRSA, respectively]), S.intermedius (MRSI), and S. schleiferi (MRSS).

Empirical treatment of staphylococcalinfection has been the norm in veterinary der-matology. Only refractory cases have beencultured routinely. This probably has led tothe lack of identification of methicillin-resis-tant strains. We may be reaching the day whenbacterial culture and sensitivity should be rec-ommended for all pyoderma cases that havenot responded to appropriate initial empiricalantibiotic therapy.

EMERGING CONCEPTSEmerging concepts that aid in the under-standing and management of deep pyodermainclude quorum sensing, biofilms, the mutantselection window hypothesis, and the mutantprevention concentration (MPC).

Quorum sensing is a mechanism by whichbacteria produce and secrete various signalingcompounds (autoinducers) that bind to recep-tors on other bacteria and activate transcrip-tion of genes. This process is responsible forcommunal behavior among bacteria andoffers clues into the processes of symbiosis,commensalism, and pathogenicity. Unlockingthe mechanisms of quorum sensing may offernew methods of controlling infection such asdisruption of quorum-sensing pathways.Biofilms are aggregates of organisms that

form on interfaces. These aggregates are muchmore protected from the toxicity of antimicro-bials or the host immune response and hence aremuch more difficult to control. Once estab-

lished, biofilms initiate a range of surface-associ-ated and diffusible signals, which may moderatethe settling behavior of other organisms. Anexample of biofilms in deep pyoderma would bethe coating on fistulous tracts and the “drainageboard effect” ventral to tracts and ulcers.The mutant selection window hypothesis

states that a “dangerous drug concentrationzone” exists and that exposure to antimicrobialconcentrations inside this zone confers a sur-vival advantage to organisms with reduced sus-ceptibility. The lower boundary of the selectionwindow is approximately the mean inhibitoryconcentration, or MIC, and the upper bound-ary is termed the mutant prevention concen-

Methicillin resistance will have a

substantial impact on how we

manage skin disease caused by

staphylococcal species in the future.


tration, or MPC. When an antibiotic is dosed atthe top of the MIC, the first decline in organismconcentration corresponds to the MIC of thewild-type bacteria. The following plateau iscaused by the presence of resistant mutant sub-populations. The second drop in organismrecovery arises when the MIC of the least sus-ceptible mutant is reached. This later value isthe MPC. Above the MPC, an organism mustacquire two concurrent resistance mutations forgrowth to occur (which is a very rare event).Within the mutant selection window, the rangeof drug concentrations exerts selective pressureon microbial growth, and cells that harbor resis-tance genes grow preferentially. Dosing guidedby traditional pharmacodynamic standardsplaces antimicrobial concentrations within themutant selection window, thus selectivelyenriching resistant mutant subpopulations.There is much interest in human medicine ondosing at or above the MPC. Newer drugs withpharmacologic properties that allow safe dosingabove the MPC will likely become more impor-tant in the management of all infections.

COMPLICATING FACTORSBoth treatment failure and recurrence ofinfection are associated with the lack of recog-nition of factors that influence prognosis andcomplicate management of all pyoderma. Themost common complicating factors includeinappropriate initial therapy, unidentifiedcoexisting and underlying skin diseases, andexternal environmental factors such as poorowner compliance.

Inappropriate Initial TherapyInappropriate initial therapy includes errorsin antibiotic selection, antibiotic dosage, andduration of therapy. If cytology shows infec-

tion to be due to cocci and antibiotic choice isempirical, an antibiotic with a known spec-trum of activity directed against S. inter-medius must be selected. Lack of responseshould initiate culture and sensitivity. Under-dosing leads to diminished therapeutic effica-cy, and overdosing is more likely to causeadverse reactions and needlessly increasesexpense. Underdosing is common in largerdogs, and overdosing is more common insmall dogs. Systemic antibiotics should beused for a minimum of 3 weeks for superficialpyoderma and 6 weeks for deep pyoderma. Ingeneral, antibiotics should be continued for aminimum of 1 week beyond apparent clinicalcure in superficial pyoderma and 3 weeksbeyond clinical cure for deep pyoderma.

Underlying Skin DiseasesUnidentified persistent underlying skin dis-eases that may complicate the initial manage-ment of pyoderma or lead to recurrence ofinfection include nonparasitic allergic skin dis-eases (canine atopic dermatitis, food allergy),parasitic allergic skin diseases (flea allergy der-matitis, sarcoptic acariasis, cheyletiellosis,demodicosis), endocrine diseases (hypothy-roidism, hyperglucocorticoidism [primary oriatrogenic]), diseases of cornification (“prima-ry seborrhea”), genodermatoses affecting thehair follicles or adnexa (follicular dysplasia,color-dilution alopecia, sebaceous adenitis),other infectious skin diseases (Malassezia der-matitis), occult neoplasia (solar-induced squa-mous cell carcinoma), and immunodeficiency(congenital, acquired).

External FactorsExternal environmental factors that influencetherapeutic success include owner compli-


ance, loss of drug via vomition, and unexpect-ed drug inactivation. Owner compliance islargely unexplored in veterinary medicine. Inhuman medicine, it has been published thatonly 40% of prescriptions are even filled andonly 40% or less of medication received istaken appropriately! Based on studies per-formed in human medicine, it is likely thatcompliance is enhanced when drugs that needto be administered only once daily are dis-pensed. This may contribute to a perceivedenhanced efficacy in once-daily antibioticssuch as enrofloxacin, cefpodoxime, mar-bofloxacin, and ormetoprim-potentiated sul-fadimethoxine. Twice-daily products such ascephalexin, clindamycin, and lincomycin mayalso offer advantages over antibiotics requir-ing administration three times daily.

UNDERLYING SKIN DISEASESAND THE MANAGEMENT OFDEEP PYODERMAThe management of deep pyoderma offersadditional challenges. Deep follicular inflam-mation frequently leads to follicular ruptureand furunculosis. Granulomatous foreign-body response directed against free keratinfrom the root sheath and hair shaft fostersscar tissue formation and sequesteredpyogranulomas. Consequentially, the dualproblems of infection and foreign-bodygranulomas coexist. Unidentified or unsuc-cessfully managed persistent underlying skindiseases are much more likely to be presentwith deep pyoderma. Additional challengesinclude antibiotic dosage problems, theimpact of sequestered foci of infection, inac-tivation of the antibiotic by pus and inflam-matory products, and the possibility ofunidentified mixed bacterial infection with

aerobic or anaerobic organisms.Unidentified or unsuccessfully managed

persistent underlying skin diseases that mostcommonly complicate the management ofcanine deep pyoderma include demodicosis,hypothyroidism, iatrogenic hyperglucocorti-coidism (especially associated with long-termmanagement of allergic skin diseases), geno-dermatoses affecting the hair follicles or adnexasuch as color-dilution alopecia and sebaceousadenitis, occult neoplasia such as solar-induced

squamous cell carcinoma, and either congeni-tal or acquired immunodeficiency.Occult demodicosis is a commonly undi-

agnosed initiator of deep pyoderma. Unex-plained pyoderma in unusual locations suchas the head and face should cue the clinicianto look for demodicosis. The index of suspi-cion for demodicosis may be low in smalllong-haired breeds. Hair loss is not a primesign of demodicosis in breeds that have longanagen hair cycles.Hypothyroidismmay allow bacterial infec-

tion to invade deeper into the skin. Contribu-tors to immune surveillance deficits such ashypothyroidism should be investigated in anydog with unexplained deep infection or infec-tion that becomes more generalized than mostpyoderma.

Based on studies performed in

human medicine, it is likely that

compliance is enhanced when drugs

that need to be administered only

once daily are dispensed.


Iatrogenic hyperglucocorticoidism is acommon and subtle occurrence noted in thelong-term management of allergic skin dis-eases and other noncutaneous diseases. In alldogs receiving long-term oral or parenteralcorticosteroids and in small dogs (less than 8kg) receiving topical, aural, or ophthalmiccorticosteroids, iatrogenic hyperglucocorti-coidism should be suspected if pyoderma isunexplainably widespread or invades moredeeply than expected. Naturally occurringCushing’s disease can also predispose to deepas well as superficial pyoderma.Genodermatoses affecting the hair follicles

or adnexa such as color-dilution alopeciaand sebaceous adenitis are underdiagnosedinitiators of deep pyoderma. Any anatomicdefect in hair follicles predisposes dogs toboth superficial and deep folliculitis. Color-dilution alopecia is seen most commonly inblue and fawn Doberman pinschers but hasbeen reported in many other breeds. Breedpredilections for sebaceous adenitis, anotherfollicular genodermatosis, have been notedfor Akitas, Samoyeds, standard poodles, andvizslas. The disease has also been reported inother breeds.Solar-induced skin disease is underdiag-

nosed in regions of the world with intensesolar exposure. It occurs in nonpigmentedand lightly haired skin exposed repetitively toexcessive ultraviolet light. Affected dogs com-monly have a history of sunbathing. Multiplestages of premalignant change (solar kerato-sis) and malignant transformation to invasivesquamous cell carcinoma occur concurrently.American Staffordshire terriers, bull terriers,“pit bulls,” basset hounds, beagles, dalmatians,greyhounds, Italian greyhounds, and whip-pets are at increased risk.

Congenital or acquired immunodeficien-cy may initiate deep pyoderma or make curemore difficult. Acquired immunodeficiencymay be seen in conjunction with underlyingdiseases such as neoplasia (especially lym-phosarcoma) or immunosuppressive therapy.

ANTIBIOTIC DOSAGE PROBLEMSMost antibiotic dosages recommended for thetreatment of pyoderma are largely empirical.Clinicians commonly use the same dosages ofantibiotics for both superficial and deep infec-tion. This can lead to the belief in increasedresistance of S. intermedius. Flexible dosagerecommendations for different infectionsshould lead to greater awareness of underdos-ing of dogs with deep pyoderma.

In deep pyoderma, sequestered foci of infec-tion impede antibiotic penetration, and keratindebris from ruptured hair follicles encouragesgranulomatous foreign-body response. Granu-lomatous inflammation prevents antibioticaccess to sites of infection. Antibiotics thatrequire microbial replication for activity, suchas penicillins, are less likely to be effective whennecrotic tissue and obstructed drainage routescreate conditions that are no longer favorablefor bacterial multiplication. Consequently,higher antibiotic doses are warranted in themanagement of chronic deep pyoderma.

Unidentified mixed bacterial infection withanaerobic as well as aerobic organisms islargely unexplored in the study of canine pyo-derma. Recent data in human medicine sug-gest that anaerobic bacteria may play a largerrole in deep infections that respond slowly orpoorly to antibiotic therapy.

Clinicians confronted with canine deeppyoderma should always ask themselves thequestion, “Why?” If an underlying manage-


ment error or an undiagnosed underlying dis-ease is present, success in managing deep pyo-derma is low.

SUCCESSFUL MANAGEMENTOF DEEP PYODERMASuccessful management of all deep pyodermarequires systemic antibiotic therapy. Topicalantibacterial shampoo therapy is commonlyused as an adjunct in the management of deeppyoderma to speed recovery, improve patientwell-being and attitude, encourage owners,and potentially prevent recurrence. Immuno-modulatory therapy is used less frequentlyand is usually an attempt to prevent or dimin-ish the frequency of recurrent superficialinfection. Extended regimens of antibioticsare used as a last resort in the management offrustrating recurrent infection.

The basic principles of successful systemicantibiotic therapy include selection of an appro-priate antibiotic, establishment of an optimaldosage, and maintenance of that dosage forenough time to ensure cure rather than tran-sient remission. Surface lesions in deep pyoder-ma commonly heal more rapidly than deeperlesions, although sequestered foci of infectionmay not be visible. Antibiotic selection caneither be empirical or based on bacterial cultureand susceptibility testing. An antibiotic chosenempirically should have a known spectrum ofactivity directed against S. intermedius andshould not be inactivated by ß-lactamases.

Bactericidal antibiotics are recommendedfor deep pyoderma and when immunosup-pression is confirmed or suspected. Pustulesor fistulous tracts should be recultured if S.intermedius has not been isolated as the pri-mary pathogen. If multiple isolates are notsensitive to one oral antibiotic, an antibiotic

that is effective against S. intermedius shouldbe instituted because staphylococci create atissue milieu favorable to the replication ofsecondary bacterial invaders.

Antibiotics most likely to be successful inthe management of deep pyoderma includeenrofloxacin, cephalexin, cefpodoxime, clin-damycin, marbofloxacin, oxacillin, and clavu-lanate-potentiated amoxicillin. More resistantS. intermedius and gram-negative isolates areseen more commonly in referral practicesthan in general practice, and resistant bacteri-al populations are identified most frequentlyin deep pyoderma.

Chronic deep pyoderma requires antibioticpenetration because sequestered foci of infec-tion and scarring prevent antibiotic access tothe site of infection. First-generation cephalo-sporins such as cephalexin feature good tovery good penetrating ability. Cefpodoximealso offers very good penetration. Uptake ofenrofloxacin by macrophages was shown toconcentrate that antibiotic at the site of deepgranulomatous infection, thus leading topotent tissue-penetrating abilities. Similar oreven better attributes may apply to other new-generation fluoroquinolones that are on thehorizon. Fluoroquinolones also offer theadvantages of once-daily dosing, activity

Uptake of enrofloxacin by macrophages

was shown to concentrate that antibiotic

at the site of deep granulomatous

infection, thus leading to potent tissue-

penetrating abilities.


against both S. intermedius and gram-negativesecondary invaders, and diminished likeli-hood of resistance. Once-daily dosing withfluoroquinolones is strongly recommendedbecause the bactericidal effect is concentra-tion dependent rather than time dependent.

Antibacterial shampoos are used as adjunc-tive therapy in the management of deep pyoder-ma. Antibacterial shampoos aid in debridement,encourage drainage, and decrease pain. Themechanisms of action decrease surface bacterialcounts and limit bacterial recolonization, hope-fully diminishing the likelihood of recurrentinfections. Improvement in patient attitude andowner encouragement are additional benefits.Antibacterial shampoos contain benzoyl perox-ide, benzoyl peroxide and sulfur, chlorhexidine,ethyl lactate, or triclosan. Twice-weekly antibac-terial shampoos are the most common recom-mendation. More aggressive topical therapy isbeneficial for the management of deep pyoder-ma. After clipping, dogs benefit from daily anti-bacterial shampoos or twice-daily whirlpools.Chlorhexidine is added to warm water.Although labor intensive, whirlpools remain anunderemployed but highly beneficial modalityof topical therapy for deep pyoderma.

REEVALUATION OF DOGSWITH PYODERMAAll dogs with pyoderma should be reevaluat-ed within 2 to 3 weeks. If substantial improve-

ment is not noted, the clinician should consid-er factors that may have complicated manage-ment. Owner compliance with the appropriatedosage and drug loss through vomition, inac-tivation by food, or malabsorption are com-mon reasons for failure. Referral to aveterinary dermatologist should be consid-ered each time clinical failure occurs.

SELECTED REFERENCESCallow JA, Callow ME. Biofilms. Prog Mol Subcell

Biol 2006;42:141-169.DeBoer DJ. Management of chronic and recurrent

pyoderma in the dog. In: Bonagura JD, ed. Kirk’sCurrent Veterinary Therapy XII. Philadelphia:WB Saunders; 1995:611-617.

DeManuelle TC, Ihrke PJ, Brandt CM, et al. Deter-mination of skin concentrations of enrofloxacinin dogs with pyoderma. Am J Vet Res 1998;59(12):1599-1604.

Drlica K, Zhao X, Blondeau JM, Jesje C. Low corre-lation between MIC and mutant prevention con-centration. Antimicrob Agents Chemother 2006;50:403-404.

Epstein BJ, Gums JG, Drlica K. The changing faceof antibiotic prescribing: the mutant selectionwindow. Ann Pharm 2004;38:1675-1682.

Gross TL, Ihrke PJ, Walder EJ, Affolter VK: SkinDiseases of the Dog and Cat: Clinical andHistopathologic Diagnosis. Oxford, England:Blackwell Science Ltd.; 2005:420-435.

Ihrke PJ. Bacterial infections of the skin. In: GreenCE, ed. Infectious Diseases of the Dog and Cat. 3rd

ed. Philadelphia: WB Saunders Co.; 2005:807-815.

Ihrke PJ, Papich MG, DeManuelle TC. The use offluoroquinolones in veterinary dermatology. VetDermatol 1999;10:193-204.

Diagnosis andTreatment of Mange

Ralf S. Mueller, DVM, PhD, DACVD, FACVSc, DECVDFaculty of Veterinary MedicineLudwig Maximilian University Munich, Germany

T he diagnosis of skin disease is often diffi-cult due to the similarity of clinical signs

of many inflammatory dermatoses. Thus, tak-ing a thorough history is extremely importantin veterinary dermatology.1

• The first important piece of informationis the breed of the patient. Some breedsare predisposed to certain skin diseases,and it may be worthwhile to keep a list ofthese breed predispositions in close reach.Bulldogs, bull terriers, Scottish terriers,shar-peis, Weimaraners, and West High-land white terriers are some of the breedspredisposed to canine demodicosis.

• Next, the age of the patient may givesome clues. Puppies are more commonlypresented with ectoparasites such as Sar-coptes scabiei, Otodectes cynotis, andDemodex canis.

• Affected sites can also fit a pattern seenmore in some diseases than others. Table1 outlines typical affected sites of certaindiseases, providing clues to the underlyingdisease.

• How long has the disease been present,how did it progress, and is it itchy? Acuteonset of severe pruritus is more likely asso-ciated with scabies. Adverse food reaction

may also sometimes have an explosiveonset.

• Are other animals in the householdaffected? Do they show cutaneous signs? Ifother animals in the household are affect-ed, contagious diseases such as scabies aremore likely. However, other animals mayserve as a reservoir for ectoparasites with-out showing clinical signs.

• Does any person in the household haveskin disease? Two zoonoses of concern inveterinary dermatology are scabies anddermatophytosis (ringworm). However, ifowners are not affected, the diseases can’tbe ruled out. Canine scabies affectinghumans occurs as an itchy papular rash incontact areas such as arms and legs days toweeks after the pet started itching.

In addition to the history, a thorough phys-ical examination is useful. As described above,the affected body sites can give clues to theunderlying etiology. The primary lesion ofcanine demodicosis is a follicular papule orpustule (for which there are only two maindifferentials: bacterial folliculitis and der-matophytosis). Scabies typically presents withnonfollicular papules, and cheyletiellosis typi-cally presents with scaly dermatitis. Ear mites


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can often be seen with otoscopic examination;the copious coffee-ground debris is classic andcan be scooped up and evaluated in mineraloil under the microscope.

DIAGNOSTIC TESTS FORECTOPARASITES IN SMALLANIMAL PRACTICESuperficial Skin ScrapingsSuperficial skin scrapings are taken from largeareas, usually to detect Sarcoptes or Cheyletiel-la.1,2 Elbows, ear margins, and the belly arecommonly scraped for Sarcoptes mites and theback for Cheyletiella mites. Mineral oil orpyrethrin ear drops should be put on thescalpel blade and the skin to make debris stickeasier and to prevent mites from crawlingaway after being scraped off. Scrapings aredone in the direction of hair growth. Of sca-bies cases, 50% may be negative on severalscrapings.3 One mite or egg is diagnostic. It isimportant to scrape over a large area; in hairydogs, this may be easier to accomplish if the

hair is clipped away first. Should such clippingbe necessary, it is important not to remove thesurface scale or crust that may be present; Sar-coptes mites are extremely superficially locat-ed within the epidermis and may be dislodgedwith such cleansing. Scissors should be usedto remove the hair and select nonexcoriatedsites, preferably with scales and papules as thelesions. Mineral oil is then applied to theaffected skin, gently scraped off the surface,and put on a slide; a cover slip is then applied,and the sample is evaluated microscopically.

Deep Skin ScrapingsDeep skin scrapings are performed to detectDemodex mites, which live in the hair follicle(often very deep). Because they are deep, it isuseful to squeeze the skin before the scrapingin an attempt to push the mites out from thedepths of the follicles.1,2 A blade covered withmineral oil should be used in the direction ofhair growth until capillary bleeding isobserved. Feet and faces are hard to scrape.

TABLE 1. Localization of Lesions and/or Pruritus of Various Skin DiseasesLocalization of Lesions and/or Pruritus Common Underlying Diseases or ConditionsExternal ear (otitis externa) Atopy, adverse food reaction, endocrine diseases

Ear mitesSecondary infections

Pinnae Atopy, adverse food reactionScabiesVasculitis, pemphigus

Head/face DemodicosisAtopy, adverse food reactionMicrosporum gypseumInsect allergies

Paws DemodicosisAtopy, adverse food reactionMalassezia dermatitisPemphigus

Shar-peis may be negative on scrapings andmay have to be biopsied for diagnosis.Although not documented, it is thought thatthese breeds have more tortuous and deeperhair follicles. More than one mite is diagnos-tic. When evaluating Demodex scrapings, it isimportant to assess and note the site of scrap-ing and the relative numbers of adults (bothlive and dead), larvae/nymphs, and eggs perlow power field (LPF). In subsequent visits,assessment of response to therapy relies on thecomparison of such numbers; the same siteshould be scraped monthly to monitor treat-ment response.

TrichogramsPositive hair plucks may render skin scrapingsunnecessary in areas that are difficult toscrape, such as the eyelids, periocular area,muzzle, or feet.4 A forceps is used to forceful-ly pluck hairs in a partially or completelyalopecic area. The hairs are then placed on aslide and evaluated under low power. Mineraloil and a cover slip should be used to preventhair from blowing around the table ratherthan remaining under the microscope. If youfind Demodex mites hanging on the hairs, youdo not need to perform a skin scraping. Thisis particularly useful when sites close to theeyes are affected or the lesions are verypainful. However, only a positive result isdiagnostic; a negative result necessitates skinscrapings.

Tape PreparationsA direct-impression technique uses clearsticky tape to collect debris from the surface ofthe skin. The tape is pressed several timessticky side down onto the skin. Next, it ispressed (also sticky side down) onto a slide.

The tape serves as a cover slip: The sample canbe evaluated even under oil immersion (witha small droplet of oil administered directly ontop of the tape). This technique is especiallyuseful for Cheyletiella mites, short-bodiedDemodex mites, and occasionally Sarcoptesmites, as a larger surface area can be sampledvery quickly.

Remember that all microscopic evaluationsfor ectoparasites should be undertaken withthe condensor of the microscope down andthe light source dimmed. A magnification of40× or 100× is usually sufficient.

SUPERFICIAL MITESScabiesScabies is a contagious disease caused by Sar-coptes scabiei var canis in dogs and by Noto-edres cati in the cat. The mite does not survive

off the host for very long. Clinically, scabiesis characterized by tremendous pruritus.Papules, scales, and crusts develop at affectedsites, typically the elbows, hocks, face, andpinnae in the dog and the face, ears, and neckin the cat. Any pruritic dog or cat could possi-bly be infested with S. scabiei or N. cati,respectively, particularly if the pruritus was ofsudden onset or if the pinnae, ventrum, andelbows are pruritic. Negative superficial skin


When evaluating Demodex scrapings,

it is important to assess and note the

site of scraping and the relative

numbers of adults (both live and dead),

larvae/nymphs, and eggs per LPF.


scrapings do not rule out scabies; thus, trialtreatment is indicated in any patient with sus-pected scabies irrespective of negative skinscrapings. In Europe, where a highly sensitiveand specific serum test is available, trial ther-apy still holds an important place in the diag-

nosis of scabies, as the tested anti-scabiesantibodies take several weeks to reach diag-nostic concentrations.

Ear MitesThese are large, white, freely moving miteswith four pairs of legs extending beyond thebody margin (except the rudimentary fourthpair on the female). The mites feed on epider-mal debris and tissue fluid from the superfi-cial epidermis. They cause intense irritationand thick reddish-brown crusts in the ears ofdogs and cats. Mites are commonly found onother areas of the body, especially the neck,rump, and tail. The parasites are highly conta-gious. Infestations of cats vary from countryto country with values as low as 3.5% in Aus-tralia and as high as 75% in the United States.

CheyletiellosisCheyletiella (“walking dandruff ”) are largemites (385 mcm) that affect cats (Cheyletiellablakei), dogs (Cheyletiella yasguri), rabbits(Cheyletiella parasitovorax), and humans(transiently affected by C. yasguri or C.

blakei). The yellowish adult mites move rapid-ly in the stratum corneum but do not burrow.They live on tissue fluid released when theyperiodically pierce the skin. The ova aresmaller than louse nits and are attached tohairs by fine fibrillar strands (not cementedfirmly to the hairs as nits). The clinical coursein small animals is chronic and typically rela-tively mild but may be severe and generalizedin 2- to 8-week-old puppies. Older individualsmay become asymptomatic carriers. Fre-quently, scaling is the only change (due tomites and keratin scales), with mild to no pru-ritus noted. Cats may develop widespreadpapulocrustous eruptions and severe pruritusin some cases.

Treatment of Superficial Mites• Moxidectin is available as a topical formu-

lation registered for the treatment ofcanine scabies5 and ear mites6 in manycountries. I use it every 2 weeks for threetreatments.

• Selamectin is a topical agent also registeredfor the treatment of scabies and ear mitesin many countries. It has also been shownto be effective against cheyletiellosis.7 I useit every 2 weeks for three treatments.

• Topical treatments include lime sulfurdips, amitraz, ivermectin, and other anti-parasitic rinses. They are used once weeklyfor 4 weeks.

• Systemic therapy may be undertaken withivermectin or milbemycin. The routineprotocol for a dog that has never previous-ly been treated with ivermectin is a slowincrease from 50 mcg/kg on day 1 to 100mcg/kg on day 2 to 150 mcg/kg on day 3 to300 mcg/kg on day 4.8 The owners must becarefully educated about the side effects

Negative superficial skin scrapings

do not rule out scabies; thus, trial

treatment is indicated in any patient

with suspected scabies.

(ataxia, bradycardia, mydriasis, respiratoryarrest, salivation, stupor, and tremors). Ifany signs of ataxia or tremors occur,administration of the drug must be discon-tinued immediately. Once the maintenancedose is reached, I continue that dose onceweekly for 3 more weeks in suspected orproven cases with scabies, cheyletiellosis,or O. cynotis infestations. Giving milbe-mycin oxime at 2 mg/kg twice weekly for 3to 4 weeks has also proven to be a very safe,easy, and successful treatment protocol forcanine scabies.

• All animals in contact with the patientneed to be treated as well!

• Initial deterioration during the first days oftreatment may occur and may be treatedwith glucocorticoids daily for 3 to 4 days atup to 1 mg/kg body weight.

DEMODICOSISEtiology of DemodicosisD. canis is an obligate parasite of the dog, andlow numbers of mites are part of the normalcutaneous fauna. The life cycle involvesfusiform eggs hatching into six-legged larvae,molting into eight-legged nymphs, and finallymaturing into adults. In the dog, D. canis isthe most commonly recognized mite, but ashort-bodied and a long-bodied Demodexspecies have also been described. When con-sidering the pathogenesis of demodicosis indogs, it is important to distinguish betweenjuvenile-onset and adult-onset generalizeddisease. In the former, certain breeds are atincreased risk. Analysis from two kennels sug-gested an autosomal recessive mode of inher-itance.9 Other predisposing factors mentionedin the literature include short hair, poor nutri-tion, stress, estrus, endoparasites, and debili-

tating disease.9 Adult-onset demodicosis canbe triggered by drugs or diseases that havealtered the immune response; chemotherapy,glucocorticoid therapy, hypothyroidism, hyper-adrenocorticism, leishmaniasis, and neoplasiashave all been associated with adult-onsetdemodicosis in dogs. However, canine adult-onset demodicosis can also be idiopathic. Incats, demodicosis is typically caused by anunderlying systemic disease!

Clinically, canine demodicosis is character-ized initially by follicular papules. However,comedones, crusting, erythema, and pustulesmay all occur, and any dog with lesional skindisease should be scraped for demodicosis.

Lesions can occur anywhere on the body,although the face and feet are not commonlyaffected.

Treatment of DemodicosisThe treatment of generalized demodicosis isoutlined below. Lime sulfur rinses (2%) week-ly for 4 to 8 weeks are recommended for thetreatment of feline demodicosis.10

Amitraz is effective against demodicosis.10

The adverse reactions associated with amitrazadministration or application are bloat, brady-cardia, hyperglycemia, hypotension, hypother-mia, polyuria, sedation, and vomiting. Clipping


When considering the pathogenesis

of demodicosis in dogs, it is

important to distinguish between

juvenile-onset and adult-onset

generalized disease.


the entire dog is essential to allow better con-tact of amitraz with the skin. All crusts shouldbe removed (preferably by shampooing with anantibacterial follicular flushing agent such asbenzoyl peroxide). The dog has to be dry com-pletely (2 to 8 hours) before being spongedwith amitraz. The person applying the treat-ment should wear protective gloves and workin a well-ventilated area. At my clinic, ownerswith asthma are advised to find somebody elseto perform the rinses. The dog should stand ina tub in the amitraz solution to allow soaking ofthe often extensively affected feet. Amitrazcauses a transitory sedative effect for 12 to 24

hours. Concentration of the drug and frequen-cy of application influences the response rate. Iuse a concentration of 600 ppm once weekly.For pododermatitis and otitis externa, a mix-ture of 1 mL of amitraz with 30 mL of mineraloil can be used topically on a daily basis. Treat-ed dogs should not get wet or be washed andshould avoid contact with water or wet grass.

Ivermectin orally at 300 to 500 mcg/kg dailyis used in the treatment of demodicosis withgood success. It must not be used in colliesand Old English sheep dogs, as it commonlycauses adverse reactions in these breeds.These reactions include ataxia, bradycardia,mydriasis, respiratory arrest, salivation, stu-

por, and tremors. In my practice, I have alsoseen other breeds affected, showing ataxia andtremors at lower doses. Thus, the routine pro-tocol for a dog that did not receive ivermectinpreviously is a slow increase from 50 mcg/kgto 100 mcg/kg to 150 mcg/kg to 300 mcg/kgon subsequent doses every day. The ownersare advised to monitor the animal carefullyduring that time for the above-mentioned sideeffects. If any signs of ataxia or tremors occur,administration of the drug must be discontin-ued immediately. Once the maintenance doseis reached, demodectic patients receive thatdose once daily until 4 weeks after the secondconsecutive negative monthly skin scraping.

Moxidectin is another milbemycin that wasevaluated for the therapy of canine general-ized demodicosis. Three studies have evaluat-ed moxidectin at 200 to 400 mcg/kg/dayorally; two of these studies employed the ini-tial gradual dose increase advocated for iver-mectin. Reported side effects were ataxia,inappetence, lethargy, and vomition. As mox-idectin is a macrocyclic lactone and has a sim-ilar mode of action to the other drugs in thisgroup, its success rate and rare adverse effectsare not surprising. However, more studieswith longer follow-up periods are needed toidentify potential benefits and disadvantagesof this drug.

Moxidectin in conjunction with imidaclo-prid has also been used for the treatment ofdemodicosis. Studies on the efficacy of thetopical formulation are ongoing, but prelimi-nary results suggest that the success rate ishighest in dogs with less severe disease andlow mite counts. In Munich, the protocol forusing topical moxidectin/imidacloprid forcanine generalized demodicosis is weeklyadministration of the product.

As moxidectin is a macrocyclic

lactone and has a similar mode of

action to the other drugs in this

group, its success rate and rare

adverse effects are not surprising.

REFERENCES1. Mueller RS. Dermatology for the Small Animal

Practitioner. Jackson, Wyoming: Teton NewMedia; 2000.

2. Bettenay SV, Mueller RS. Skin scrapings andskin biopsies. In: Ettinger SJ, Feldman EC, eds.Textbook of Veterinary Internal Medicine.Philadelphia: WB Saunders; 2005:388-391.

3. Mueller RS, Bettenay SV, Shipstone M. Value ofthe pinnal-pedal reflex in the diagnosis ofcanine scabies. Vet Rec 2001;148:621-623.

4. Bensignor E. Comparaison de trois techniquesdiagnostiques de demodecie a Demodex canischez le chien. Prat Med Chir Anim Compag2003;38:167-171.

5. Fourie LJ, Heine J, Horak IG. The efficacy of animidacloprid/moxidectin combination against

naturally acquired Sarcoptes scabiei infestationson dogs. Aust Vet J 2006;84:17-21.

6. Fourie LJ, Kok DJ, Heine J. Evaluation of theefficacy of an imidacloprid 10%/moxidectin1% spot-on against Otodectes cynotis in cats.Parasitol Res 2003;90(suppl 3):S112-S113.

7. Mueller RS, Bettenay SV. Efficacy of selamectinin the treatment of canine cheyletiellosis. VetRec 2002;151:773.

8. Mueller RS, Bettenay SV. A proposed new ther-apeutic protocol for the treatment of caninemange with ivermectin. JAAHA 1999;35:77-80.

9. Scott DW, Miller WH, Griffin CE. Small Ani-mal Dermatology. 6th ed. Philadelphia: WBSaunders; 2001:457-476.

10. Mueller RS. Treatment protocols for demodi-cosis: an evidence-based review. Vet Dermatol2004;15:75-89.


Managing DifficultEar Infections

James O. Noxon, DVM, DACVIM (Internal Medicine)College of Veterinary MedicineIowa State University

INTRODUCTIONBacterial infections of the ear are consideredperpetuating factors.1 In other words, they aresecondary to some condition or event that ini-tiates inflammation. Bacterial ear infectionsare common problems in dogs, and thoughpresent in cats, are much less common. Thebacteria isolated most often from inflamedears of the dog are Staphylococcus intermediusand Pseudomonas aeruginosa.2,3 Other bacte-ria that may be isolated include Escherichiacoli, Proteus spp, other staphylococcal species,Klebsiella spp, Enterococcus spp, Corynebac-terium spp, streptococci, Clostridium spp, andother bacteria on occasion.

GENERAL RULES OFENGAGEMENTThe successful management of any ear diseaserequires:

• Cleaning the ear canal. At some point inthe management of otitis externa or media,the ear canal should be thoroughlycleaned. This will allow better evaluationof the extent of the problem and willremove debris (e.g., wax, hair) that caninterfere with distribution, and possiblyactivation, of medications instilled into theear. Some ear cleansers, such as those con-

taining lactic acid and salicylic acid (Epi-Otic®, Virbac Animal Health), have someantibacterial properties, which may alsohelp resolve some bacterial ear infections.4

• Clear identification of the organism(s)involved. In some cases, such as when cocciare the only organisms involved and for first-time otitis cases, cytology may be sufficientto identify the types of organisms involved.

Bacterial culture is indicated when(1) cytology reveals only rod-shapedbacteria, (2) the condition is a recur-ring infection and organisms of anytype are seen on cytology, (3) theinfection has failed to respond toappropriate medications (and ownercompliance has been good), and (4)when otitis media is present.

• Administration of glucocorticoids, whichare almost always helpful.Glucocorticoidshave anti-inflammatory effects and there-fore reduce inflammation, reduce edemaand swelling to allow topical medicationsbetter access in the canal, and reduce painand pruritus associated with inflammation(allowing better patient compliance withapplication of medications). Glucocorti-coids can be applied topically and/or sys-temically, depending on the severity of the

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07ChinKitSen/Shutterstock.com



hyperplastic changes, pain, and the owner’sability to apply medications.

• Addressing hyperplastic changes imme-diately. Severe hyperplastic changes inter-fere with application of topical medicationsand trap exudate and debris in the earcanal. Patients with hyperplastic changesare treated with oral prednisone (at 1 to 2mg/kg PO once daily for 7 to 10 days, thenevery other day for five to seven doses),topical glucocorticoids (e.g., fluocinoloneplus dimethyl sulfoxide [DMSO]), and/orintralesional glucocorticoids (e.g., triamci-nolone) if the changes result in completeclosure of the ear canal.

PHARMACOLOGICCONSIDERATIONSAntimicrobial therapy may be delivered sys-temically or topically. The advantage clini-cians have in the management of earinfections is the option to deliver the medica-tion by the topical route. This allows us to

• deliver the medication directly to the areaaffected and

• deliver the antimicrobial agent in concen-trations that greatly exceed concentrationsthat can be achieved by systemic routes.

This option is especially of interest when con-sidering the use of concentration-dependentantibiotics, such as fluoroquinolones oraminoglycosides.Because of the topical option available to

manage otitis externa and media, bacterialculture and susceptibility data often misrep-resent the effectiveness of an antimicrobialagent for ear infections. Minimum inhibito-ry concentrations (MICs) are of the greatestvalue because they may indicate that an

antibiotic cannot achieve inhibitory concen-trations, even at the highest concentrationsreached by instilling concentrated antibi-otics directly into the ear. In contrast, Kirby-Bauer results will provide information onthe resistance or susceptibility of an organ-ism based on known or extrapolated break-point concentrations, which may be greatlyexceeded by the direct instillation of a druginto the ear.

Important Concept: An antibioticmay still be effective in treating a bac-terial skin infection, even though aculture and susceptibility test (usingKirby-Bauer methods) indicates thatthe organism is resistant to that drug.

In addition, the location of the infectionwithin the ear plays an important role in man-agement of the infection. Middle ear infec-tions (i.e., otitis media) generally requirethorough cleaning of that ear cavity to facili-tate treatment. Certainly, infections within themiddle ear are more difficult to reach withtopical medications, although that alsodepends on the integrity of the tympanicmembrane. Topical medications may reachthe middle ear if the eardrum is ruptured;however, in those cases it is appropriate toemploy systemic therapy, as well as any topicaltreatment that might be indicated.

VETERINARY FORMULATIONSThere are a limited number of veterinary oticproducts for use in dogs and cats (Table 1). Theantibacterial agents found in products available intheUnitedStates include antibiotics (enrofloxacin,gentamicin, neomycin, thiostrepton) and antisep-tics (acetic acid, aluminum acetate). Antimicro-bials found in commercial otic preparations


TABLE1.

VeterinaryProductsUsedtoTreatO

titisExternainDogsandCats

Nam

eAntibacteria

lAgent(s)

Other

Ingredients

Drops/m

LRecommendedDosing

Maximum

Duration

Animax®(Pharmaderm

Neomycin

Nystatin

493–5drops

Variable

AnimalHealth)

Thiostrepton

Triamcinolone

Variablefrequency

Baytril®Otic

(Bayer)

Enrofloxacin

__30

<35lb:5–10dropsbid

14days

Silversulfadiazine

>35lb:10–15

dropsbid

Bur-Otic®H

CAluminum

acetate

Hydrocortisone

385–10

dropsd

aily

5days

(VirbacAnimalHealth)

Propyleneglycol

Conofite®(Schering-

Miconazole

__44

“Lightcovering”

NG

Plough

AnimalHealth)*

MalAcetic®H

CAcetic

acid

Hydrocortisone

41“Applyliberally”

NG

(DermaPet)

Boricacid

Mom

etam

ax®(Schering-

Gentamicin

Clotrimazole

40<30lb:4

dropsd

aily

7days

Plough

AnimalHealth)

Mom

etasone

>30lb:8

dropsd

aily

Otomax®(Schering-

Gentamicin

Clotrimazole

37<30lb:4

dropsd

aily

7days

Plough

AnimalHealth)**

Betamethasone

>30lb:8

dropsd

aily

Synotic®(FortDodge

__Flucinolone

394–6dropsbid

14days

AnimalHealth)

Dimethylsulfoxide

Propyleneglycol

T8Keto™

(DVM

__Tris-ED

TAPharmaceuticals)*

Ketoconazole

24“Flush

liberally”

NG

Tresaderm®(Merial)

Neomycin

Thiabendazole

405–15

dropsbid

7days

Dexam

ethasone

Propyleneglycol

TrizULTRA

+KET

O™

__Tris-ED

TA(DermaPet)*

Ketoconazole

23“Applyliberally”

NG

*Notlabeledforu

seinearsbutoftenrecommendedforu

seinotitis.

**Similarproductsareavailablefrom

variouscom

paniesbutw

erenotevaluated.

NG=notgiven.


outside the United States include polymyxin Bsulfates, norfloxacin, marbofloxacin, and fusidicacid. In addition, there are several veterinaryproducts that are used in the ear canal eventhough they are not labeled for use in the ear.These products have not undergone the require-ments for labeling and are generally labeled as“lotions” or “flushes.” Because so few commer-cial otic products are available for veterinariansto use in bacterial ear infections, a large numberof “homemade” formulations have been pro-moted at continuing education seminars and arespread by word of mouth throughout the veteri-nary community. Certainly, many of these workvery well; however, the majority have not beentested for safety or to ensure that the activeingredients have remained active when mixedwith other products.

TOPICAL THERAPYOverall success of antibacterial therapydepends on:

• Efficacy of the active ingredients

• Route of administration of antibacterialmedications

• Removal of obstructions (e.g., wax, hair)from the ear canal

• Technique that is used to instill topicalmedications

• Formulation of the medication

• Volume of medication instilled

• Integrity of the tympanic membrane

• Treatment duration

In all cases in which topical therapy is used,the owners must be educated about the appli-cation of the medication. Training shouldinclude having the owner instill medication inthe presence of the veterinarian or technician.

Owners should be taught to massage ears for15 to 30 seconds after instilling medicationsand use proper amounts of medications.Ear medications most often come in the

form of an ointment (emulsions of lipid inwater) or a solution (aqueous or other carri-ers). Emulsions containing lipids will enhancepenetration of the active ingredient into theskin of the ear; however, most of these oint-ment formulations are so viscous that they failto penetrate deep into the ear canal. They areespecially ineffective in the presence of a heavygrowth of hair in the canal. Less viscous med-ications are more likely to allow medication todistribute deeper into the canal, especiallywhen there is a significant amount of hair inthe ear canal or the canal is hyperplastic.Once-daily treatment is generally sufficient

for most cases of otitis, although severe infec-tions may benefit from twice-daily treatment.Treatment should be continued until there isno clinical or cytologic evidence of active dis-ease. The minimum recommended treatmenttime (with topical therapy) is 30 days.

Volume of Medication: The volumeofmedication applied into the ear dur-ing treatment appears to be critical.Enoughmedication should be appliedto ensure delivery to the deepest partof the ear canal (by the tympanum).Failure to apply sufficient quantities topenetrate to these areas seems to be amajor cause of treatment failure.

Recommended Volumes byWeight of Animal

<10 kg 0.4–0.5 mL10–20 kg 0.5–0.7 mL>20 kg 0.7–1.0 mL

The integrity of the tympanic membrane iscritical in determining the best treatment. To


the author’s knowledge, no commercial earmedications have been evaluated for thepotential to cause ototoxicosis if the medica-tion is instilled into the middle ear. The bestpractice is to avoid topical therapy if the tym-panic membrane is torn or absent. However,there are some clinical indications, basedentirely on anecdotal evidence, that vinegar:water (1:2), dilute ticarcillin (3%) in saline,dilute enrofloxacin, and enrofloxacin (par-enteral formulation) are anecdotally consid-ered safe in dogs.

SYSTEMIC THERAPYIn GeneralTopical therapy is considered sufficient tomanage most bacterial infections of the exter-nal ear canal, if the above recommendations(listed in the Topical Therapy section) are fol-lowed. Systemic therapy is indicated when:

• The infections are recurring and severe

• There are concurrent infections elsewhere,such as on the skin, that are caused by thesame organism

• Owners are incapable of instilling topicalmedications (e.g., elderly owners, ownerswith arthritis)

• The patient is uncooperative due to pain ortemperament

• There are severe hyperplastic changes inthe ear canal that preclude the ability oftopical medications to distribute deep intothe canal

• Inflammatory cells are abundant on cytology

• Otitis media is present

In general, the choice of antimicrobial forsystemic therapy may be based on historicalevidence of efficacy for staphylococci, although

these organisms can develop resistance to thecommonly used antibiotics. Culture and sensi-tivity data should be used to help select the bestantimicrobial for systemic therapy againstPseudomonas bacteria.

Pseudomonas OtitisPseudomonas ear infections are often consid-ered the most difficult of ear infections toclear. Unfortunately, there are very few studiesof topical and/or systemic therapies that pro-vide sufficient evidence of the efficacy of themany options for treatment of Pseudomonasear infections that are discussed in the litera-ture.5 However, several therapeutic options areconsidered clinically effective for these infec-tions, despite the lack of good studies to sup-port those clinical impressions.6–10 Sometreatment options include:

• Topicals containing polymyxin B sulfatesare available as various ophthalmologicpreparations for use in humans (neomycin,polymyxin B sulfates, and 0.1% dexametha-sone ophthalmic solution) and as variousotic preparations for humans (neomycin,polymyxin B sulfates, and 1% hydrocorti-sone). It may be useful to pretreat with Tris-EDTA. Most Pseudomonas isolates are verysensitive to this antibiotic; however, poly-myxin is not active in suppurative environ-ments, so it is important to clean the earthoroughly before using this antibiotic.

• Topical tobramycin (available as generic oph-thalmic drops). Other aminoglycosides,including gentamicin and amikacin, areoften effective for Pseudomonas infections.Ototoxicity is a potential problem withaminoglycosides. These agents should not beused if the tympanic membrane is ruptured.


• Topical fluoroquinolone antibiotics, suchas Baytril® Otic (Bayer), which containsenrofloxacin and silver sulfadiazine (SSD).Enrofloxacin is a very effective antibioticfor the treatment of Pseudomonas infections.(Susceptibility data may be misleadingbecause the concentrations of enrofloxacinachieved in the ear can greatly exceed theserum concentrations.)

• Silver sulfadiazine has been demonstratedin vitro to be highly effective against resis-tant strains of Pseudomonas. SSD is com-mercially available as a 1% cream, whichcan be diluted 1:9 in water, and as a 1% solu-tion in Baytril.7

• Topical ticarcillin–clavulanic acid (Timen-tin®, GlaxoSmithKline).8 This antibioticretains activity for 24 to 36 hours at roomtemperature or when refrigerated.

At Iowa State University, we diluteone 3.1 g vial of Timentin with 100mL sterile saline; 1.0 mL aliquots ofthe 3% suspension are drawn intoindividual syringes (with about 0.5mL air), and the syringes are frozen.The content of one syringe isinstilled into each infected ear twicedaily (thus, four syringes daily forbilateral disease). Each vial ofTimentin will make enough medica-tion to treat a dog with bilateral dis-ease for 25 days. Frozen ticarcillinwill remain active for approximately30 days.

• Tris-EDTA solution. Two commercialproducts (TrizEDTA™, DermaPet; T8Solution®, DVM Pharmaceuticals) con-tain this solution. (Both products are alsoavailable containing ketoconazole to pro-

vide anti-yeast activity when indicated.)There is good evidence that T8 Solution ismore appropriate for staphylococcalinfections, while both T8 Solution andTrizEDTA are highly effective forPseudomonas infections. These productsare usually administered into the infectedear 15 to 30 minutes before an antibiotic isadministered. They are well documentedto enhance the activity of some antibi-otics, especially aminoglycosides and flu-oroquinolones.9

Systemic antibiotic therapy (e.g., enro-floxacin or other fluoroquinolones based onculture and sensitivity results) is indicated forotitis media when the tympanic membrane isintact. Systemic medications are generally nothighly effective if used without concurrenttopical antimicrobial therapy.10 If the tympanicmembrane is completely absent, thoroughmiddle ear flushing is recommended. Antibi-otics, such as enrofloxacin and ticarcillin, maybe infused directly into the middle ear. (Nostudies have been conducted to confirm theirsafety when used in this manner, but abundantanecdotal evidence suggests these drugs aresafe when infused directly into the middle ear.)One very important key to successful treat-

ment of Pseudomonas otitis is the concurrentuse of glucocorticoids, preferably systemically.Glucocorticoids reduce the pain that is associ-ated with this condition—and thus will makeapplication of topical medications easier andmore effective. In addition, glucocorticoidsreduce the inflammation, which also reducesthe discomfort and swelling that accompaniesthis condition. Naturally, any allergy testingshould be done before initiation of glucocorti-coid therapy.


Key Point: Glucocorticoid therapyis an important and necessary com-ponent of the treatment of Pseudo-monas infections of the external earcanal!

Of course, proper cleaning of the ear, systemictherapy with an appropriate antimicrobialagent, and management of the primary factorare also part of managing Pseudomonas infec-tions of the ear!

Key Point: Patients with Pseudo-monas infections tend to get othersecondary infections, most oftenyeast infections, immediately afterthe Pseudomonas is cleared. Thislikely occurs because application oftopical medications to clear the bac-terial infection tends to leave theinflamed ear moist and thus moresusceptible to yeast infections.Therefore, we recommend prophy-lactic anti-yeast therapy be initiatedas soon as the bacterial componentof the otitis is controlled.

SUMMARYBacterial infections of the ear may be success-fully managed if the above principles are fol-lowed. The keys to successful managementinclude thorough cleaning of the ear canal andmiddle ear (if necessary), identification of thecausative organism through cytology and/orculture, selection of an appropriate antimicro-bial agent and delivery system, proper applica-tion of medicine into the ear, identificationand control of the primary and other perpetu-ating factors, and good follow-up otic care.

REFERENCES1. Morris DO. Medical therapy of otitis externa

and otitis media. Vet Clin N Am 2004;34:541-555.

2. Hariharan H, Coles M, Poole D, et al. Updateon antimicrobial susceptibilities of bacterialisolates from canine and feline otitis externa.Can Vet J 2006;47:253-255.

3. Cole LK, Kwochka KW, Kowalski JJ, et al.Microbial flora and antimicrobial susceptibili-ty patterns of isolated pathogens from the hor-izontal ear canal and middle ear in dogs withotitis media. JAVMA 1998;212:534-538.

4. Cole LK, Kwochka KW, Kowalski JJ, et al.Evaluation of an ear cleaner for the treatmentof infectious otitis externa in dogs. Vet Ther2003;4:12-23.

5. Nuttall T, Cole LK. Evidence-based veterinarydermatology: a systematic review of interven-tions for treatment of Pseudomonas otitis indogs. Vet Dermatol 2007;18:69-142.

6. Barrasa JLM, Gómez PL, Lama PG, et al. Anti-bacterial susceptibility patterns of Pseudo-monas strains isolated from chronic canineotitis externa. J Vet Med 2000;17:191-196.

7. Noxon JO, Kinyon JM, Murphy DP. Minimalinhibitory concentrations of silver sulfadi-azine on Pseudomonas aeruginosa and Staphy-lococcus intermedius isolates from the ears ofdogs with otitis externa. 13th Proc AnnuMem-bers Meet ACVD/AAVD 1997:72-73.

8. Nuttell TJ. Use of ticarcillin in the manage-ment of canine otitis externa complicated byPseudomonas aeruginosa. J Small Anim Pract1998;39:165-168.

9. Farca AM, Piromalli G, Maffei F, et al. Poten-tiating effect of EDTA-Tris on the activity ofantibiotics against resistant bacteria associatedwith otitis, dermatitis, and cystitis. J SmallAnim Pract 1997;38:243-245.

10. Carlotti DN, Guaguère E, Koch HJ, et al. Mar-bofloxacin for the systemic treatment ofPseudomonas spp. suppurative otitis externain the dog. In: von Tscharner C, Kwochka KW,Wilemse T, eds. Advances in Veterinary Der-matology 3. Oxford: Butterworth Heinemann;1998:463-464.

Copyright © 2007. James O. Noxon. Printed with permission.

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