Bayer Dermatology Symposium. Proceedings from the 2008 NAVC Conference

Transcription

1 Bayer Dermatology Symposium Proceedings from the 2008 NAVC Conference A Supplement to Compendium: Continuing Education for Veterinarians Vol. 30, No. 1(A) January 2008

2 Bayer Dermatology Symposium Proceedings from the 2008 NAVC Conference A Supplement to Compendium: Continuing Education for Veterinarians Vol. 30, No. 1(A) January 2008 Sponsored by an educational grant from 2008 Bayer HealthCare LLC, Animal Health Division, Shawnee Mission, Kansas Bayer and the Bayer Cross are trademarks of Bayer All Rights Reserved Printed in USA Designed and published by Veterinary Learning Systems 780 Township Line Road, Yardley, PA This information has not been peer reviewed and does not necessarily reflect the opinions of, nor constitute or imply endorsement or recommendation by, the Publisher or Editorial Board.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 Contents 3 National Incidence of Methicillin-Resistant Staphylococcal Infections: Understanding, Treatment, and Prevention David Aucoin, DVM, DACVCP 8 Challenges in the Management of Pyoderma Peter J. Ihrke, VMD, DACVD 15 Diagnosis and Treatment of Mange Ralf S. Mueller, DVM, PhD, DACVD, FACVSc, DECVD 22 Managing Difficult Ear Infections James O. Noxon, DVM, DACVIM (Internal Medicine)

4 National Incidence of Methicillin-Resistant Staphylococcal Infections: Understanding, Treatment, and Prevention David Aucoin, DVM, DACVCP Zoasis Corporation 2007 Adrian Moisel/Shutterstock.com METHICILLIN-RESISTANT STAPHYLOCOCCUS AUREUS Methicillin-resistant Staphylococcus aureus (MRSA) is a major nosocomial pathogen in human hospitals and extended-care facilities and of late has become a serious infectious pathogen in the community population not exposed to these institutions. Important contributors to the increasing importance of this pathogen include: Pattern of resistance to a wide range of antibiotics besides β-lactams (penicillins and cephalosporins). Hospital-acquired MRSA (HA-MRSA) had been differentiated from community-acquired MRSA (CA- MRSA) by its more extensive resistance. However, lately CA-MRSA is showing multiple resistance profiles, blurring the line between these two categories. Opportunistic nature of the pathogen. S. aureus is a commensal organism in people. The nasopharynx is the major source of the organism, although it can also be carried in other sites, including the intestinal tract. Studies have shown that up to 30% of people have S. aureus in their nose at any point in time. Hands are a major source of transmission. MRSA strains are usually not considered more intrinsically pathogenic than other coagulase-positive Staphylococcus spp; however, some strains of CA- MRSA do appear to be more infectious and readily transmissible. Major morbidity and mortality are associated when HA-MRSA colonizes a susceptible host (e.g., hospitalized patient, immunocompromised or debilitated individuals) and subsequently causes an opportunistic infection that fails to respond to conventional treatment. However, CA-MRSA is now being seen in otherwise healthy individuals as a cause of extensive skin infections gaining access through fomites (blankets and towels) and small skin abrasions, leading to suppurative spreading lesions. Mechanism of resistance. There are three mechanisms of resistance in methicillinresistant Staphylococcus organisms: Penicillin-binding proteins (PBPs) and the meca gene. All penicillins and cephalosporins (β-lactams) require binding to a PBP in the bacterial cell wall to Bayer Dermatology Symposium Proceedings, 2008 NAVC 3

5 initiate the drugs activity. MRSA produces a defective, low-affinity PBP (PBP2a) due to the presence and activation of the meca gene. The meca gene itself comes from a novel integrative and mobile genetic element called a staphylococcal chromosomal cassette (SCCmec) that is conveniently bundled with enzymes needed to excise the meca gene Since 2002, there has been an alarming acceleration of MRSA cultures from both dogs and cats from almost all body sites routinely tested. from the cassette and insert itself into the staph s chromosomal structure. This method of resistance acquisition is unique to this mechanism, and the spread of MRSA is usually through clonal expansion rather than the normal process of mutation or plasmid-mediated transfer. All MRSA strains can be traced back to a single clone found in Europe in the mid-1960s. The binding affinity of penicillins and cephalosporins to PBP2a is very low, disabling the drugs ability to disrupt cell wall synthesis and rendering the drugs ineffective. The presence of PBP2a on a Staphylococcus organism confers resistance to all penicillins and cephalosporins. Cell-wall thickening. MRSA also possesses a thick cell wall that makes penetration by antibiotics difficult, conferring resistance to multiple antibiotics (not just β-lactams). Efflux pump. Acquired through other means than a meca gene, these proteins are involved in active removal of antibiotics through a membrane-bound pump, limiting many families of antibiotics that work on internal cellular structures. METHICILLIN RESISTANCE OF STAPHYLOCOCCAL INFECTIONS IN VETERINARY MEDICINE Overview MRSA infections have been reported in animals since the mid-1990s but were considered uncommon in domestic pets and rarely caused disease. S. aureus is not a commensal organism of dogs or cats and is considered a transient pathogen acquired from its primary host, humans. Since 2002, there has been a rapidly growing body of work as well as data that show an alarming acceleration of MRSA cultures from both dogs and cats from almost all body sites routinely tested. When present, MRSA infections that have been strain typed have been shown to be exactly the same organism that colonizes people and are not a new strain. Studies to date indicate that MRSA is transmitted from human to pet; because methicillin-sensitive S. aureus (MSSA) strains are not a part of the normal colonizing flora of dogs and cats and thus only transiently colonize domestic pets, it would be expected that horizontal transmission from pet to pet or pet to human would not present a major issue. However, it is not clear if these MRSA, in contrast to MSSA, remain a part of the normal commensal skin or nasal flora of pets and present a possible reservoir for contamination. 4 Suppl Compend Contin Educ Vet Vol. 30, No. 1(A), 2008

6 Culture Incidence from Antech Diagnostics MRSA is most frequently cultured from canine wounds, abscesses, and chronic pyodermas. In these cultured sites, S. aureus accounts for 3% to 5% of all bacteria cultured; this statistic has remained unchanged since What has changed is the proportion of those S. aureus strains that are methicillin resistant. In 2005, only 19% were methicillin resistant; in 2007, the percentage had significantly increased to 42%.* This is an unusual phenomenon in veterinary medicine, where infectious disease experts always implicate antibiotic use in animals as contributing to increasing antibiotic resistance in human pathogens. In this case, S. aureus comes from humans, and in 2007 almost half of the S. aureus infections transmitted were methicillin resistant.* It is interesting to see that the rise in antibiotic resistance in humans is now affecting pets. In these same cultures, Staphylococcus intermedius, the commensal staph of dogs and cats, is identified in 25% to 30% of all wound cultures. In 2004, few (<0.6%) methicillin-resistant S. intermedius (MRSI) organisms were cultured at Antech Diagnostics. In 2005, 3.1% of all S. intermedius strains cultured from wounds were methicillin resistant; by 2007, the number had increased significantly to 10.2% (p < 0.05).* These pathogens are not transmitted from humans, where they play very little if any process in infections. They were created most likely via horizontal transfer of the meca gene from the MRSA pathogens. The mechanism for this transfer is unclear; however, it has been reported that the *Data presented by the author at the 2008 NAVC Conference. meca gene is present in S. intermedius isolates, with one study demonstrating it in almost 50% of isolates tested. 1 The data are clear that while the rate of wounds infected with Staphylococcus has remained the same over the past 3 years, the percentage of methicillin-resistant Staphylococcus either from humans or pets has vastly increased. TESTING FOR METHICILLIN RESISTANCE IN STAPHYLOCOCCAL SPECIES Methicillin resistance can be tested using any of the β-lactamase stable penicillin drugs (including methicillin), although oxacillin is most commonly used. The borders of the zone of inhibition can be more In 2005, only 19% of Staphylococcus aureus strains were methicillin resistant; in 2007, the percentage had significantly increased to 42%. difficult to read with oxacillin due to a delayed onset of resistance observed during testing. The meca gene is inducible, so in clinical practice a patient may appear to have a sensitive staph when in fact the antibiotic induces its own resistance. In the lab, this means that MRSA strains appear sensitive to oxacillin at 24 hours but not at 48 hours. The latex agglutination test for the PBP2a protein is becoming more routine in human medicine as the quickest test for Bayer Dermatology Symposium Proceedings, 2008 NAVC 5

7 MRSA detection. New, quick multiplex polymerase chain reaction (PCR) can also be used to identify the five main SCCmec types and will be used at Antech Diagnostics in 2008 to better delineate and track these emerging pathogens. The vast majority of S. intermedius isolates in dogs and cats do not show methicillin resistance. However, literature reports on methicillin resistance and S. intermedius isolates from dogs and cats have given conflicting results. In a University of Tennessee study with 57 S. intermedius isolates, only two were methicillin resistant; however, 50% of isolates had the The vast majority of Staphylococcus intermedius isolates in dogs and cats do not show methicillin resistance. However, literature reports have given conflicting results. meca gene detected by PCR testing, suggesting that the gene may not have been expressed. 1 In a University of Illinois study with 25 methicillin-resistant S. intermedius isolates, 23 had the meca gene, and the non methicillin-resistant isolates did not have the meca gene. 2 Further work is needed to determine the value of meca gene detection on veterinary isolates. Coagulase-negative staphylococci (such as Staphylococcus schleiferi subsp schleiferi) isolates in dogs and cats appear to be more commonly detected with methicillin resistance than the coagulase-positive isolates. These are usually reported from canine pyodermas. S. schleiferi subsp coagulans is more commonly identified from ear cultures. Antech Diagnostics will begin reporting the species and subspecies of all methicillinresistant Staphylococcus in the first quarter of 2008 to better facilitate tracking of the incidence rate of all these organisms. TREATMENT OPTIONS FOR METHICILLIN-RESISTANT STAPHYLOCOCCUS Lack of clinical response to any β-lactam (penicillins or cephalosporins), even if in vitro testing indicates they are sensitive, indicates that these antibiotics should not be used to treat a methicillin-resistant Staphylococcus infection. Other choices include: Chloramphenicol. Chloramphenicol remains the only excellent drug of choice in methicillin-resistant staphylococcal infections with a predictable in vitro efficacy greater than 95% from more than 1,000 cultures of methicillin-resistant Staphylococcus. Dosing of 33 mg/kg tid in dogs Dosing of 50 mg/cat bid Potentiated sulfonamides. Better-thanaverage success against methicillin-resistant Staphylococcus at 55% sensitivity; however, clinical studies in humans are conflicting as to its use even from cultured MRSA deemed sensitive in vitro. Clindamycin. Although found effective in many human CA-MRSA infections, the experience at Antech Diagnostics has shown this antimicrobial to be effective in less than 50% of the methicillin-resistant Staphylococcus isolates. 6 Suppl Compend Contin Educ Vet Vol. 30, No. 1(A), 2008

8 Fluoroquinolones. Enrofloxacin, marbofloxacin, and difloxacin all show less than a 50% in vitro efficacy, indicating a multiple-resistance mechanism in the MRSA and MRSI that are being cultured. Vancomycin. Vancomycin is a drug that is sensitive to the vast majority of all methicillin-resistant Staphylococcus organisms; however, it has several disadvantages, including the fact that it is very nephrotoxic in dogs needing to be administered 15 mg/kg q6h IV with concomitant IV fluids. Linezolid. One of a new family of antibiotics (oxazolidinones), linezolid can be administered orally or parenterally. Evaluation of pharmacokinetics in dogs indicates the effective dose is 20 to 30 mg/kg q12h. It has low toxicity but is very expensive. This drug should be used only if there is no other choice (e.g., in multidrug-resistant Staphylococcus). Linezolid is also effective against even vancomycin-resistant enterococcus. REFERENCES 1. Kania SA, Williamson NL, Frank LA, et al. Methicillin resistance of staphylococci isolated from the skin of dogs with pyoderma. Am J Vet Res 2004;65(9): Gortel K, Campbell KL, Kakoma I, et al. Methicillin resistance among staphylococci isolated from dogs. Am J Vet Res 1999; 60(12): Bayer Dermatology Symposium Proceedings, 2008 NAVC 7

9 Challenges in the Management of Pyoderma Peter J. Ihrke, VMD, DACVD School of Veterinary Medicine University of California, Davis 2007 Lars Christensen/Shutterstock.com Pyoderma is the second most common cause of canine skin disease. In areas of the world that are less ideal for flea reproduction and infestation, pyoderma is the single most common canine skin disease. We can define pyoderma as a pyogenic or pus-producing bacterial infection of the skin. Dogs seem uniquely susceptible to both single-event pyoderma and recurrent pyoderma. The reasons for this may relate to various host factors that could result in enhanced susceptibility to infection. These factors could include the comparatively thin, compact stratum corneum of dogs, the relative lack of intercellular lipids in the canine stratum corneum, the lack of a lipidsquamous epithelial plug in the entrance of canine hair follicles, and the relatively high ph of canine skin. CLASSIFICATION OF PYODERMA The diversity of canine pyoderma is enormous. Classification of pyoderma is most usefully based on depth of bacterial involvement as it provides information on diagnosis, differential diagnosis, likelihood of underlying disease, prognosis, and likely response to therapy. Pyoderma may be surface, affecting the stratum corneum and outer epidermis; superficial, involving only the epidermis and the epithelial appendages in the dermis; or deeper, compromising structures in the dermis and the deep, subjacent fatty tissue. As we gain knowledge about canine skin infections, we realize that most infections seem to be secondary to either underlying disease or other underlying factors that somehow increase the likelihood of infection. Few pyoderma are primary and do not have underlying causes or triggers. If underlying causes are not found, it is likely that recurrence will follow the seeming cure. This recurrence suggests that the initial infection was not primary but more likely secondary to undiagnosed underlying disease or unrecognized triggering factors. Superficial pyoderma is more common than deep pyoderma. As infection proceeds deeper into hair follicles, follicular rupture leads to a granulomatous foreign-body tissue response. Deeper infections require a more aggressive diagnostic and therapeutic approach. BACTERIA RESPONSIBLE FOR CANINE PYODERMA Staphylococcus intermedius is by far the most common pathogen in canine pyoderma. Less commonly, Staphylococcus aureus and Staphylococcus schleiferi may cause canine skin infec- 8 Suppl Compend Contin Educ Vet Vol. 30, No. 1(A), 2008

10 tion. Gram-negative organisms such as Proteus sp, Pseudomonas sp, and Escherichia coli are more likely to be secondary invaders in deep pyoderma. Rarely, Pseudomonas aeruginosa and other gram-negative organisms can be the sole pathogen. Unusual staphylococcal infections or gram-negative organisms are more likely to be more resistant to various antibiotics. MICROBIAL RESISTANCE Microbial resistance in staphylococci is increasing. Methicillin resistance has greatly complicated the use of antibiotics in human medicine. It is being recognized with increasing frequency in veterinary medicine and will have a substantial impact on how we manage skin disease caused by staphylococcal species in the future. Methicillin resistance is reported in S. aureus (hospital- or community-acquired methicillin-resistant S. aureus [HA-MRSA or CA-MRSA, respectively]), S. intermedius (MRSI), and S. schleiferi (MRSS). Empirical treatment of staphylococcal infection has been the norm in veterinary dermatology. Only refractory cases have been cultured routinely. This probably has led to the lack of identification of methicillin-resistant strains. We may be reaching the day when bacterial culture and sensitivity should be recommended for all pyoderma cases that have not responded to appropriate initial empirical antibiotic therapy. EMERGING CONCEPTS Emerging concepts that aid in the understanding and management of deep pyoderma include quorum sensing, biofilms, the mutant selection window hypothesis, and the mutant prevention concentration (MPC). Methicillin resistance will have a substantial impact on how we manage skin disease caused by staphylococcal species in the future. Quorum sensing is a mechanism by which bacteria produce and secrete various signaling compounds (autoinducers) that bind to receptors on other bacteria and activate transcription of genes. This process is responsible for communal behavior among bacteria and offers clues into the processes of symbiosis, commensalism, and pathogenicity. Unlocking the mechanisms of quorum sensing may offer new methods of controlling infection such as disruption of quorum-sensing pathways. Biofilms are aggregates of organisms that form on interfaces. These aggregates are much more protected from the toxicity of antimicrobials or the host immune response and hence are much more difficult to control. Once established, biofilms initiate a range of surface-associated and diffusible signals, which may moderate the settling behavior of other organisms. An example of biofilms in deep pyoderma would be the coating on fistulous tracts and the drainage board effect ventral to tracts and ulcers. The mutant selection window hypothesis states that a dangerous drug concentration zone exists and that exposure to antimicrobial concentrations inside this zone confers a survival advantage to organisms with reduced susceptibility. The lower boundary of the selection window is approximately the mean inhibitory concentration, or MIC, and the upper boundary is termed the mutant prevention concen- Bayer Dermatology Symposium Proceedings, 2008 NAVC 9

11 tration, or MPC. When an antibiotic is dosed at the top of the MIC, the first decline in organism concentration corresponds to the MIC of the wild-type bacteria. The following plateau is caused by the presence of resistant mutant subpopulations. The second drop in organism recovery arises when the MIC of the least susceptible mutant is reached. This later value is the MPC. Above the MPC, an organism must acquire two concurrent resistance mutations for growth to occur (which is a very rare event). Within the mutant selection window, the range of drug concentrations exerts selective pressure on microbial growth, and cells that harbor resistance genes grow preferentially. Dosing guided by traditional pharmacodynamic standards places antimicrobial concentrations within the mutant selection window, thus selectively enriching resistant mutant subpopulations. There is much interest in human medicine on dosing at or above the MPC. Newer drugs with pharmacologic properties that allow safe dosing above the MPC will likely become more important in the management of all infections. COMPLICATING FACTORS Both treatment failure and recurrence of infection are associated with the lack of recognition of factors that influence prognosis and complicate management of all pyoderma. The most common complicating factors include inappropriate initial therapy, unidentified coexisting and underlying skin diseases, and external environmental factors such as poor owner compliance. Inappropriate Initial Therapy Inappropriate initial therapy includes errors in antibiotic selection, antibiotic dosage, and duration of therapy. If cytology shows infection to be due to cocci and antibiotic choice is empirical, an antibiotic with a known spectrum of activity directed against S. intermedius must be selected. Lack of response should initiate culture and sensitivity. Underdosing leads to diminished therapeutic efficacy, and overdosing is more likely to cause adverse reactions and needlessly increases expense. Underdosing is common in larger dogs, and overdosing is more common in small dogs. Systemic antibiotics should be used for a minimum of 3 weeks for superficial pyoderma and 6 weeks for deep pyoderma. In general, antibiotics should be continued for a minimum of 1 week beyond apparent clinical cure in superficial pyoderma and 3 weeks beyond clinical cure for deep pyoderma. Underlying Skin Diseases Unidentified persistent underlying skin diseases that may complicate the initial management of pyoderma or lead to recurrence of infection include nonparasitic allergic skin diseases (canine atopic dermatitis, food allergy), parasitic allergic skin diseases (flea allergy dermatitis, sarcoptic acariasis, cheyletiellosis, demodicosis), endocrine diseases (hypothyroidism, hyperglucocorticoidism [primary or iatrogenic]), diseases of cornification ( primary seborrhea ), genodermatoses affecting the hair follicles or adnexa (follicular dysplasia, color-dilution alopecia, sebaceous adenitis), other infectious skin diseases (Malassezia dermatitis), occult neoplasia (solar-induced squamous cell carcinoma), and immunodeficiency (congenital, acquired). External Factors External environmental factors that influence therapeutic success include owner compli- 10 Suppl Compend Contin Educ Vet Vol. 30, No. 1(A), 2008

12 ance, loss of drug via vomition, and unexpected drug inactivation. Owner compliance is largely unexplored in veterinary medicine. In human medicine, it has been published that only 40% of prescriptions are even filled and only 40% or less of medication received is taken appropriately! 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. This may contribute to a perceived enhanced efficacy in once-daily antibiotics such as enrofloxacin, cefpodoxime, marbofloxacin, and ormetoprim-potentiated sulfadimethoxine. Twice-daily products such as cephalexin, clindamycin, and lincomycin may also offer advantages over antibiotics requiring administration three times daily. UNDERLYING SKIN DISEASES AND THE MANAGEMENT OF DEEP PYODERMA The management of deep pyoderma offers additional challenges. Deep follicular inflammation frequently leads to follicular rupture and furunculosis. Granulomatous foreignbody response directed against free keratin from the root sheath and hair shaft fosters scar tissue formation and sequestered pyogranulomas. Consequentially, the dual problems of infection and foreign-body granulomas coexist. Unidentified or unsuccessfully managed persistent underlying skin diseases are much more likely to be present with deep pyoderma. Additional challenges include antibiotic dosage problems, the impact of sequestered foci of infection, inactivation of the antibiotic by pus and inflammatory products, and the possibility of unidentified mixed bacterial infection with aerobic or anaerobic organisms. Unidentified or unsuccessfully managed persistent underlying skin diseases that most commonly complicate the management of canine deep pyoderma include demodicosis, hypothyroidism, iatrogenic hyperglucocorticoidism (especially associated with long-term management of allergic skin diseases), genodermatoses affecting the hair follicles or adnexa such as color-dilution alopecia and sebaceous adenitis, occult neoplasia such as solar-induced 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. squamous cell carcinoma, and either congenital or acquired immunodeficiency. Occult demodicosis is a commonly undiagnosed initiator of deep pyoderma. Unexplained pyoderma in unusual locations such as the head and face should cue the clinician to look for demodicosis. The index of suspicion for demodicosis may be low in small long-haired breeds. Hair loss is not a prime sign of demodicosis in breeds that have long anagen hair cycles. Hypothyroidism may allow bacterial infection to invade deeper into the skin. Contributors to immune surveillance deficits such as hypothyroidism should be investigated in any dog with unexplained deep infection or infection that becomes more generalized than most pyoderma. Bayer Dermatology Symposium Proceedings, 2008 NAVC 11

13 Iatrogenic hyperglucocorticoidism is a common and subtle occurrence noted in the long-term management of allergic skin diseases and other noncutaneous diseases. In all dogs receiving long-term oral or parenteral corticosteroids and in small dogs (less than 8 kg) receiving topical, aural, or ophthalmic corticosteroids, iatrogenic hyperglucocorticoidism should be suspected if pyoderma is unexplainably widespread or invades more deeply than expected. Naturally occurring Cushing s disease can also predispose to deep as well as superficial pyoderma. Genodermatoses affecting the hair follicles or adnexa such as color-dilution alopecia and sebaceous adenitis are underdiagnosed initiators of deep pyoderma. Any anatomic defect in hair follicles predisposes dogs to both superficial and deep folliculitis. Colordilution alopecia is seen most commonly in blue and fawn Doberman pinschers but has been reported in many other breeds. Breed predilections for sebaceous adenitis, another follicular genodermatosis, have been noted for Akitas, Samoyeds, standard poodles, and vizslas. The disease has also been reported in other breeds. Solar-induced skin disease is underdiagnosed in regions of the world with intense solar exposure. It occurs in nonpigmented and lightly haired skin exposed repetitively to excessive ultraviolet light. Affected dogs commonly have a history of sunbathing. Multiple stages of premalignant change (solar keratosis) and malignant transformation to invasive squamous cell carcinoma occur concurrently. American Staffordshire terriers, bull terriers, pit bulls, basset hounds, beagles, dalmatians, greyhounds, Italian greyhounds, and whippets are at increased risk. Congenital or acquired immunodeficiency may initiate deep pyoderma or make cure more difficult. Acquired immunodeficiency may be seen in conjunction with underlying diseases such as neoplasia (especially lymphosarcoma) or immunosuppressive therapy. ANTIBIOTIC DOSAGE PROBLEMS Most antibiotic dosages recommended for the treatment of pyoderma are largely empirical. Clinicians commonly use the same dosages of antibiotics for both superficial and deep infection. This can lead to the belief in increased resistance of S. intermedius. Flexible dosage recommendations for different infections should lead to greater awareness of underdosing of dogs with deep pyoderma. In deep pyoderma, sequestered foci of infection impede antibiotic penetration, and keratin debris from ruptured hair follicles encourages granulomatous foreign-body response. Granulomatous inflammation prevents antibiotic access to sites of infection. Antibiotics that require microbial replication for activity, such as penicillins, are less likely to be effective when necrotic tissue and obstructed drainage routes create conditions that are no longer favorable for bacterial multiplication. Consequently, higher antibiotic doses are warranted in the management of chronic deep pyoderma. Unidentified mixed bacterial infection with anaerobic as well as aerobic organisms is largely unexplored in the study of canine pyoderma. Recent data in human medicine suggest that anaerobic bacteria may play a larger role in deep infections that respond slowly or poorly to antibiotic therapy. Clinicians confronted with canine deep pyoderma should always ask themselves the question, Why? If an underlying manage- 12 Suppl Compend Contin Educ Vet Vol. 30, No. 1(A), 2008

14 ment error or an undiagnosed underlying disease is present, success in managing deep pyoderma is low. SUCCESSFUL MANAGEMENT OF DEEP PYODERMA Successful management of all deep pyoderma requires systemic antibiotic therapy. Topical antibacterial shampoo therapy is commonly used as an adjunct in the management of deep pyoderma to speed recovery, improve patient well-being and attitude, encourage owners, and potentially prevent recurrence. Immunomodulatory therapy is used less frequently and is usually an attempt to prevent or diminish the frequency of recurrent superficial infection. Extended regimens of antibiotics are used as a last resort in the management of frustrating recurrent infection. The basic principles of successful systemic antibiotic therapy include selection of an appropriate antibiotic, establishment of an optimal dosage, and maintenance of that dosage for enough time to ensure cure rather than transient remission. Surface lesions in deep pyoderma commonly heal more rapidly than deeper lesions, although sequestered foci of infection may not be visible. Antibiotic selection can either be empirical or based on bacterial culture and susceptibility testing. An antibiotic chosen empirically should have a known spectrum of activity directed against S. intermedius and should not be inactivated by ß-lactamases. Bactericidal antibiotics are recommended for deep pyoderma and when immunosuppression is confirmed or suspected. Pustules or fistulous tracts should be recultured if S. intermedius has not been isolated as the primary pathogen. If multiple isolates are not sensitive to one oral antibiotic, an antibiotic that is effective against S. intermedius should be instituted because staphylococci create a tissue milieu favorable to the replication of secondary bacterial invaders. Antibiotics most likely to be successful in the management of deep pyoderma include enrofloxacin, cephalexin, cefpodoxime, clindamycin, marbofloxacin, oxacillin, and clavulanate-potentiated amoxicillin. More resistant S. intermedius and gram-negative isolates are seen more commonly in referral practices than in general practice, and resistant bacterial populations are identified most frequently in deep pyoderma. Uptake of enrofloxacin by macrophages was shown to concentrate that antibiotic at the site of deep granulomatous infection, thus leading to potent tissuepenetrating abilities. Chronic deep pyoderma requires antibiotic penetration because sequestered foci of infection and scarring prevent antibiotic access to the site of infection. First-generation cephalosporins such as cephalexin feature good to very good penetrating ability. Cefpodoxime also offers very good penetration. 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. Similar or even better attributes may apply to other newgeneration fluoroquinolones that are on the horizon. Fluoroquinolones also offer the advantages of once-daily dosing, activity Bayer Dermatology Symposium Proceedings, 2008 NAVC 13

15 against both S. intermedius and gram-negative secondary invaders, and diminished likelihood of resistance. Once-daily dosing with fluoroquinolones is strongly recommended because the bactericidal effect is concentration dependent rather than time dependent. Antibacterial shampoos are used as adjunctive therapy in the management of deep pyoderma. Antibacterial shampoos aid in debridement, encourage drainage, and decrease pain. The mechanisms of action decrease surface bacterial counts and limit bacterial recolonization, hopefully diminishing the likelihood of recurrent infections. Improvement in patient attitude and owner encouragement are additional benefits. Antibacterial shampoos contain benzoyl peroxide, benzoyl peroxide and sulfur, chlorhexidine, ethyl lactate, or triclosan. Twice-weekly antibacterial shampoos are the most common recommendation. More aggressive topical therapy is beneficial for the management of deep pyoderma. After clipping, dogs benefit from daily antibacterial shampoos or twice-daily whirlpools. Chlorhexidine is added to warm water. Although labor intensive, whirlpools remain an underemployed but highly beneficial modality of topical therapy for deep pyoderma. REEVALUATION OF DOGS WITH PYODERMA All dogs with pyoderma should be reevaluated within 2 to 3 weeks. If substantial improvement is not noted, the clinician should consider factors that may have complicated management. Owner compliance with the appropriate dosage and drug loss through vomition, inactivation by food, or malabsorption are common reasons for failure. Referral to a veterinary dermatologist should be considered each time clinical failure occurs. SELECTED REFERENCES Callow JA, Callow ME. Biofilms. Prog Mol Subcell Biol 2006;42: DeBoer DJ. Management of chronic and recurrent pyoderma in the dog. In: Bonagura JD, ed. Kirk s Current Veterinary Therapy XII. Philadelphia: WB Saunders; 1995: DeManuelle TC, Ihrke PJ, Brandt CM, et al. Determination of skin concentrations of enrofloxacin in dogs with pyoderma. Am J Vet Res 1998; 59(12): Drlica K, Zhao X, Blondeau JM, Jesje C. Low correlation between MIC and mutant prevention concentration. Antimicrob Agents Chemother 2006; 50: Epstein BJ, Gums JG, Drlica K. The changing face of antibiotic prescribing: the mutant selection window. Ann Pharm 2004;38: Gross TL, Ihrke PJ, Walder EJ, Affolter VK: Skin Diseases of the Dog and Cat: Clinical and Histopathologic Diagnosis. Oxford, England: Blackwell Science Ltd.; 2005: Ihrke PJ. Bacterial infections of the skin. In: Green CE, ed. Infectious Diseases of the Dog and Cat. 3 rd ed. Philadelphia: WB Saunders Co.; 2005: Ihrke PJ, Papich MG, DeManuelle TC. The use of fluoroquinolones in veterinary dermatology. Vet Dermatol 1999;10: Suppl Compend Contin Educ Vet Vol. 30, No. 1(A), 2008

16 Diagnosis and Treatment of Mange Ralf S. Mueller, DVM, PhD, DACVD, FACVSc, DECVD Faculty of Veterinary Medicine Ludwig Maximilian University Munich, Germany 2007 Steve Ellis/Shutterstock.com The diagnosis of skin disease is often difficult due to the similarity of clinical signs of many inflammatory dermatoses. Thus, taking a thorough history is extremely important in veterinary dermatology. 1 The first important piece of information is the breed of the patient. Some breeds are predisposed to certain skin diseases, and it may be worthwhile to keep a list of these breed predispositions in close reach. Bulldogs, bull terriers, Scottish terriers, shar-peis, Weimaraners, and West Highland white terriers are some of the breeds predisposed to canine demodicosis. Next, the age of the patient may give some clues. Puppies are more commonly presented with ectoparasites such as Sarcoptes scabiei, Otodectes cynotis, and Demodex canis. Affected sites can also fit a pattern seen more in some diseases than others. Table 1 outlines typical affected sites of certain diseases, providing clues to the underlying disease. How long has the disease been present, how did it progress, and is it itchy? Acute onset of severe pruritus is more likely associated with scabies. Adverse food reaction may also sometimes have an explosive onset. Are other animals in the household affected? Do they show cutaneous signs? If other animals in the household are affected, contagious diseases such as scabies are more likely. However, other animals may serve as a reservoir for ectoparasites without showing clinical signs. Does any person in the household have skin disease? Two zoonoses of concern in veterinary dermatology are scabies and dermatophytosis (ringworm). However, if owners are not affected, the diseases can t be ruled out. Canine scabies affecting humans occurs as an itchy papular rash in contact areas such as arms and legs days to weeks after the pet started itching. In addition to the history, a thorough physical examination is useful. As described above, the affected body sites can give clues to the underlying etiology. The primary lesion of canine demodicosis is a follicular papule or pustule (for which there are only two main differentials: bacterial folliculitis and dermatophytosis). Scabies typically presents with nonfollicular papules, and cheyletiellosis typically presents with scaly dermatitis. Ear mites Bayer Dermatology Symposium Proceedings, 2008 NAVC 15

17 TABLE 1. Localization of Lesions and/or Pruritus of Various Skin Diseases Localization of Lesions and/or Pruritus External ear (otitis externa) Pinnae Head/face Paws Common Underlying Diseases or Conditions Atopy, adverse food reaction, endocrine diseases Ear mites Secondary infections Atopy, adverse food reaction Scabies Vasculitis, pemphigus Demodicosis Atopy, adverse food reaction Microsporum gypseum Insect allergies Demodicosis Atopy, adverse food reaction Malassezia dermatitis Pemphigus can often be seen with otoscopic examination; the copious coffee-ground debris is classic and can be scooped up and evaluated in mineral oil under the microscope. DIAGNOSTIC TESTS FOR ECTOPARASITES IN SMALL ANIMAL PRACTICE Superficial Skin Scrapings Superficial skin scrapings are taken from large areas, usually to detect Sarcoptes or Cheyletiella. 1,2 Elbows, ear margins, and the belly are commonly scraped for Sarcoptes mites and the back for Cheyletiella mites. Mineral oil or pyrethrin ear drops should be put on the scalpel blade and the skin to make debris stick easier and to prevent mites from crawling away after being scraped off. Scrapings are done in the direction of hair growth. Of scabies cases, 50% may be negative on several scrapings. 3 One mite or egg is diagnostic. It is important to scrape over a large area; in hairy dogs, this may be easier to accomplish if the hair is clipped away first. Should such clipping be necessary, it is important not to remove the surface scale or crust that may be present; Sarcoptes mites are extremely superficially located within the epidermis and may be dislodged with such cleansing. Scissors should be used to remove the hair and select nonexcoriated sites, preferably with scales and papules as the lesions. Mineral oil is then applied to the affected 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 Scrapings Deep skin scrapings are performed to detect Demodex mites, which live in the hair follicle (often very deep). Because they are deep, it is useful to squeeze the skin before the scraping in an attempt to push the mites out from the depths of the follicles. 1,2 A blade covered with mineral oil should be used in the direction of hair growth until capillary bleeding is observed. Feet and faces are hard to scrape. 16 Suppl Compend Contin Educ Vet Vol. 30, No. 1(A), 2008

18 Shar-peis may be negative on scrapings and may have to be biopsied for diagnosis. Although not documented, it is thought that these breeds have more tortuous and deeper hair follicles. More than one mite is diagnostic. 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 low power field (LPF). In subsequent visits, assessment of response to therapy relies on the comparison of such numbers; the same site should be scraped monthly to monitor treatment response. Trichograms Positive hair plucks may render skin scrapings unnecessary in areas that are difficult to scrape, such as the eyelids, periocular area, muzzle, or feet. 4 A forceps is used to forcefully pluck hairs in a partially or completely alopecic area. The hairs are then placed on a slide and evaluated under low power. Mineral oil and a cover slip should be used to prevent hair from blowing around the table rather than remaining under the microscope. If you find Demodex mites hanging on the hairs, you do not need to perform a skin scraping. This is particularly useful when sites close to the eyes are affected or the lesions are very painful. However, only a positive result is diagnostic; a negative result necessitates skin scrapings. Tape Preparations A direct-impression technique uses clear sticky tape to collect debris from the surface of the skin. The tape is pressed several times sticky side down onto the skin. Next, it is pressed (also sticky side down) onto a slide. The tape serves as a cover slip: The sample can be evaluated even under oil immersion (with a small droplet of oil administered directly on top of the tape). This technique is especially useful for Cheyletiella mites, short-bodied Demodex mites, and occasionally Sarcoptes mites, as a larger surface area can be sampled very quickly. Remember that all microscopic evaluations for ectoparasites should be undertaken with the condensor of the microscope down and the light source dimmed. A magnification of 40 or 100 is usually sufficient. SUPERFICIAL MITES Scabies Scabies is a contagious disease caused by Sarcoptes scabiei var canis in dogs and by Notoedres cati in the cat. The mite does not survive 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. off the host for very long. Clinically, scabies is characterized by tremendous pruritus. Papules, scales, and crusts develop at affected sites, typically the elbows, hocks, face, and pinnae in the dog and the face, ears, and neck in the cat. Any pruritic dog or cat could possibly be infested with S. scabiei or N. cati, respectively, particularly if the pruritus was of sudden onset or if the pinnae, ventrum, and elbows are pruritic. Negative superficial skin Bayer Dermatology Symposium Proceedings, 2008 NAVC 17

19 Negative superficial skin scrapings do not rule out scabies; thus, trial treatment is indicated in any patient with suspected scabies. scrapings do not rule out scabies; thus, trial treatment is indicated in any patient with suspected scabies irrespective of negative skin scrapings. In Europe, where a highly sensitive and specific serum test is available, trial therapy still holds an important place in the diagnosis of scabies, as the tested anti-scabies antibodies take several weeks to reach diagnostic concentrations. Ear Mites These are large, white, freely moving mites with four pairs of legs extending beyond the body margin (except the rudimentary fourth pair on the female). The mites feed on epidermal debris and tissue fluid from the superficial epidermis. They cause intense irritation and thick reddish-brown crusts in the ears of dogs and cats. Mites are commonly found on other areas of the body, especially the neck, rump, and tail. The parasites are highly contagious. Infestations of cats vary from country to country with values as low as 3.5% in Australia and as high as 75% in the United States. Cheyletiellosis Cheyletiella ( walking dandruff ) are large mites (385 mcm) that affect cats (Cheyletiella blakei), dogs (Cheyletiella yasguri), rabbits (Cheyletiella parasitovorax), and humans (transiently affected by C. yasguri or C. blakei). The yellowish adult mites move rapidly in the stratum corneum but do not burrow. They live on tissue fluid released when they periodically pierce the skin. The ova are smaller than louse nits and are attached to hairs by fine fibrillar strands (not cemented firmly to the hairs as nits). The clinical course in small animals is chronic and typically relatively mild but may be severe and generalized in 2- to 8-week-old puppies. Older individuals may become asymptomatic carriers. Frequently, scaling is the only change (due to mites and keratin scales), with mild to no pruritus noted. Cats may develop widespread papulocrustous eruptions and severe pruritus in some cases. Treatment of Superficial Mites Moxidectin is available as a topical formulation registered for the treatment of canine scabies 5 and ear mites 6 in many countries. I use it every 2 weeks for three treatments. Selamectin is a topical agent also registered for the treatment of scabies and ear mites in many countries. It has also been shown to be effective against cheyletiellosis. 7 I use it every 2 weeks for three treatments. Topical treatments include lime sulfur dips, amitraz, ivermectin, and other antiparasitic rinses. They are used once weekly for 4 weeks. Systemic therapy may be undertaken with ivermectin or milbemycin. The routine protocol for a dog that has never previously been treated with ivermectin is a slow increase from 50 mcg/kg on day 1 to 100 mcg/kg on day 2 to 150 mcg/kg on day 3 to 300 mcg/kg on day 4. 8 The owners must be carefully educated about the side effects 18 Suppl Compend Contin Educ Vet Vol. 30, No. 1(A), 2008

20 (ataxia, bradycardia, mydriasis, respiratory arrest, salivation, stupor, and tremors). If any signs of ataxia or tremors occur, administration of the drug must be discontinued immediately. Once the maintenance dose is reached, I continue that dose once weekly for 3 more weeks in suspected or proven cases with scabies, cheyletiellosis, or O. cynotis infestations. Giving milbemycin oxime at 2 mg/kg twice weekly for 3 to 4 weeks has also proven to be a very safe, easy, and successful treatment protocol for canine scabies. All animals in contact with the patient need to be treated as well! Initial deterioration during the first days of treatment may occur and may be treated with glucocorticoids daily for 3 to 4 days at up to 1 mg/kg body weight. DEMODICOSIS Etiology of Demodicosis D. canis is an obligate parasite of the dog, and low numbers of mites are part of the normal cutaneous fauna. The life cycle involves fusiform eggs hatching into six-legged larvae, molting into eight-legged nymphs, and finally maturing into adults. In the dog, D. canis is the most commonly recognized mite, but a short-bodied and a long-bodied Demodex species have also been described. When considering the pathogenesis of demodicosis in dogs, it is important to distinguish between juvenile-onset and adult-onset generalized disease. In the former, certain breeds are at increased risk. Analysis from two kennels suggested an autosomal recessive mode of inheritance. 9 Other predisposing factors mentioned in the literature include short hair, poor nutrition, stress, estrus, endoparasites, and debilitating disease. 9 Adult-onset demodicosis can be triggered by drugs or diseases that have altered the immune response; chemotherapy, glucocorticoid therapy, hypothyroidism, hyperadrenocorticism, leishmaniasis, and neoplasias have all been associated with adult-onset demodicosis in dogs. However, canine adultonset demodicosis can also be idiopathic. In cats, demodicosis is typically caused by an underlying systemic disease! Clinically, canine demodicosis is characterized initially by follicular papules. However, comedones, crusting, erythema, and pustules may all occur, and any dog with lesional skin disease should be scraped for demodicosis. When considering the pathogenesis of demodicosis in dogs, it is important to distinguish between juvenile-onset and adult-onset generalized disease. Lesions can occur anywhere on the body, although the face and feet are not commonly affected. Treatment of Demodicosis The treatment of generalized demodicosis is outlined below. Lime sulfur rinses (2%) weekly for 4 to 8 weeks are recommended for the treatment of feline demodicosis. 10 Amitraz is effective against demodicosis. 10 The adverse reactions associated with amitraz administration or application are bloat, bradycardia, hyperglycemia, hypotension, hypothermia, polyuria, sedation, and vomiting. Clipping Bayer Dermatology Symposium Proceedings, 2008 NAVC 19

21 the entire dog is essential to allow better contact of amitraz with the skin. All crusts should be removed (preferably by shampooing with an antibacterial follicular flushing agent such as benzoyl peroxide). The dog has to be dry completely (2 to 8 hours) before being sponged with amitraz. The person applying the treatment should wear protective gloves and work in a well-ventilated area. At my clinic, owners with asthma are advised to find somebody else to perform the rinses. The dog should stand in a tub in the amitraz solution to allow soaking of the often extensively affected feet. Amitraz causes a transitory sedative effect for 12 to 24 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. hours. Concentration of the drug and frequency of application influences the response rate. I use a concentration of 600 ppm once weekly. For pododermatitis and otitis externa, a mixture of 1 ml of amitraz with 30 ml of mineral oil can be used topically on a daily basis. Treated dogs should not get wet or be washed and should avoid contact with water or wet grass. Ivermectin orally at 300 to 500 mcg/kg daily is used in the treatment of demodicosis with good success. It must not be used in collies and Old English sheep dogs, as it commonly causes adverse reactions in these breeds. These reactions include ataxia, bradycardia, mydriasis, respiratory arrest, salivation, stupor, and tremors. In my practice, I have also seen other breeds affected, showing ataxia and tremors at lower doses. Thus, the routine protocol for a dog that did not receive ivermectin previously is a slow increase from 50 mcg/kg to 100 mcg/kg to 150 mcg/kg to 300 mcg/kg on subsequent doses every day. The owners are advised to monitor the animal carefully during that time for the above-mentioned side effects. If any signs of ataxia or tremors occur, administration of the drug must be discontinued immediately. Once the maintenance dose is reached, demodectic patients receive that dose once daily until 4 weeks after the second consecutive negative monthly skin scraping. Moxidectin is another milbemycin that was evaluated for the therapy of canine generalized demodicosis. Three studies have evaluated moxidectin at 200 to 400 mcg/kg/day orally; two of these studies employed the initial gradual dose increase advocated for ivermectin. Reported side effects were ataxia, inappetence, lethargy, and vomition. 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. However, more studies with longer follow-up periods are needed to identify potential benefits and disadvantages of this drug. Moxidectin in conjunction with imidacloprid has also been used for the treatment of demodicosis. Studies on the efficacy of the topical formulation are ongoing, but preliminary results suggest that the success rate is highest in dogs with less severe disease and low mite counts. In Munich, the protocol for using topical moxidectin/imidacloprid for canine generalized demodicosis is weekly administration of the product. 20 Suppl Compend Contin Educ Vet Vol. 30, No. 1(A), 2008

22 REFERENCES 1. Mueller RS. Dermatology for the Small Animal Practitioner. Jackson, Wyoming: Teton New Media; Bettenay SV, Mueller RS. Skin scrapings and skin biopsies. In: Ettinger SJ, Feldman EC, eds. Textbook of Veterinary Internal Medicine. Philadelphia: WB Saunders; 2005: Mueller RS, Bettenay SV, Shipstone M. Value of the pinnal-pedal reflex in the diagnosis of canine scabies. Vet Rec 2001;148: Bensignor E. Comparaison de trois techniques diagnostiques de demodecie a Demodex canis chez le chien. Prat Med Chir Anim Compag 2003;38: Fourie LJ, Heine J, Horak IG. The efficacy of an imidacloprid/moxidectin combination against naturally acquired Sarcoptes scabiei infestations on dogs. Aust Vet J 2006;84: Fourie LJ, Kok DJ, Heine J. Evaluation of the efficacy of an imidacloprid 10%/moxidectin 1% spot-on against Otodectes cynotis in cats. Parasitol Res 2003;90(suppl 3):S112-S Mueller RS, Bettenay SV. Efficacy of selamectin in the treatment of canine cheyletiellosis. Vet Rec 2002;151: Mueller RS, Bettenay SV. A proposed new therapeutic protocol for the treatment of canine mange with ivermectin. JAAHA 1999;35: Scott DW, Miller WH, Griffin CE. Small Animal Dermatology. 6 th ed. Philadelphia: WB Saunders; 2001: Mueller RS. Treatment protocols for demodicosis: an evidence-based review. Vet Dermatol 2004;15: Bayer Dermatology Symposium Proceedings, 2008 NAVC 21

23 Managing Difficult Ear Infections James O. Noxon, DVM, DACVIM (Internal Medicine) College of Veterinary Medicine Iowa State University 2007 Chin Kit Sen/Shutterstock.com INTRODUCTION Bacterial infections of the ear are considered perpetuating factors. 1 In other words, they are secondary to some condition or event that initiates inflammation. Bacterial ear infections are common problems in dogs, and though present in cats, are much less common. The bacteria isolated most often from inflamed ears of the dog are Staphylococcus intermedius and Pseudomonas aeruginosa. 2,3 Other bacteria that may be isolated include Escherichia coli, Proteus spp, other staphylococcal species, Klebsiella spp, Enterococcus spp, Corynebacterium spp, streptococci, Clostridium spp, and other bacteria on occasion. GENERAL RULES OF ENGAGEMENT The successful management of any ear disease requires: Cleaning the ear canal. At some point in the management of otitis externa or media, the ear canal should be thoroughly cleaned. This will allow better evaluation of the extent of the problem and will remove debris (e.g., wax, hair) that can interfere with distribution, and possibly activation, of medications instilled into the ear. Some ear cleansers, such as those containing lactic acid and salicylic acid (Epi- Otic, Virbac Animal Health), have some antibacterial properties, which may also help resolve some bacterial ear infections. 4 Clear identification of the organism(s) involved. In some cases, such as when cocci are the only organisms involved and for firsttime otitis cases, cytology may be sufficient to identify the types of organisms involved. Bacterial culture is indicated when (1) cytology reveals only rod-shaped bacteria, (2) the condition is a recurring infection and organisms of any type are seen on cytology, (3) the infection has failed to respond to appropriate medications (and owner compliance has been good), and (4) when otitis media is present. Administration of glucocorticoids, which are almost always helpful. Glucocorticoids have anti-inflammatory effects and therefore reduce inflammation, reduce edema and swelling to allow topical medications better access in the canal, and reduce pain and pruritus associated with inflammation (allowing better patient compliance with application of medications). Glucocorticoids can be applied topically and/or systemically, depending on the severity of the 22 Suppl Compend Contin Educ Vet Vol. 30, No. 1(A), 2008

24 hyperplastic changes, pain, and the owner s ability to apply medications. Addressing hyperplastic changes immediately. Severe hyperplastic changes interfere with application of topical medications and trap exudate and debris in the ear canal. Patients with hyperplastic changes are treated with oral prednisone (at 1 to 2 mg/kg PO once daily for 7 to 10 days, then every other day for five to seven doses), topical glucocorticoids (e.g., fluocinolone plus dimethyl sulfoxide [DMSO]), and/or intralesional glucocorticoids (e.g., triamcinolone) if the changes result in complete closure of the ear canal. PHARMACOLOGIC CONSIDERATIONS Antimicrobial therapy may be delivered systemically or topically. The advantage clinicians have in the management of ear infections is the option to deliver the medication by the topical route. This allows us to deliver the medication directly to the area affected and deliver the antimicrobial agent in concentrations that greatly exceed concentrations that can be achieved by systemic routes. This option is especially of interest when considering the use of concentration-dependent antibiotics, such as fluoroquinolones or aminoglycosides. Because of the topical option available to manage otitis externa and media, bacterial culture and susceptibility data often misrepresent the effectiveness of an antimicrobial agent for ear infections. Minimum inhibitory concentrations (MICs) are of the greatest value because they may indicate that an antibiotic cannot achieve inhibitory concentrations, even at the highest concentrations reached by instilling concentrated antibiotics directly into the ear. In contrast, Kirby- Bauer results will provide information on the resistance or susceptibility of an organism based on known or extrapolated breakpoint concentrations, which may be greatly exceeded by the direct instillation of a drug into the ear. Important Concept: An antibiotic may still be effective in treating a bacterial skin infection, even though a culture and susceptibility test (using Kirby-Bauer methods) indicates that the organism is resistant to that drug. In addition, the location of the infection within the ear plays an important role in management of the infection. Middle ear infections (i.e., otitis media) generally require thorough cleaning of that ear cavity to facilitate treatment. Certainly, infections within the middle ear are more difficult to reach with topical medications, although that also depends on the integrity of the tympanic membrane. Topical medications may reach the middle ear if the eardrum is ruptured; however, in those cases it is appropriate to employ systemic therapy, as well as any topical treatment that might be indicated. VETERINARY FORMULATIONS There are a limited number of veterinary otic products for use in dogs and cats (Table 1). The antibacterial agents found in products available in the United States include antibiotics (enrofloxacin, gentamicin, neomycin, thiostrepton) and antiseptics (acetic acid, aluminum acetate). Antimicrobials found in commercial otic preparations Bayer Dermatology Symposium Proceedings, 2008 NAVC 23

25 TABLE 1. Veterinary Products Used to Treat Otitis Externa in Dogs and Cats Name Antibacterial Agent(s) Other Ingredients Drops/mL Recommended Dosing Maximum Duration Animax (Pharmaderm Neomycin Nystatin drops Variable Animal Health) Thiostrepton Triamcinolone Variable frequency Baytril Otic (Bayer) Enrofloxacin 30 <35 lb: 5 10 drops bid 14 days Silver sulfadiazine >35 lb: drops bid Bur-Otic HC Aluminum acetate Hydrocortisone drops daily 5 days (Virbac Animal Health) Propylene glycol Conofite (Schering- Miconazole 44 Light covering NG Plough Animal Health)* MalAcetic HC Acetic acid Hydrocortisone 41 Apply liberally NG (DermaPet) Boric acid Mometamax (Schering- Gentamicin Clotrimazole 40 <30 lb: 4 drops daily 7 days Plough Animal Health) Mometasone >30 lb: 8 drops daily Otomax (Schering- Gentamicin Clotrimazole 37 <30 lb: 4 drops daily 7 days Plough Animal Health)** Betamethasone >30 lb: 8 drops daily Synotic (Fort Dodge Flucinolone drops bid 14 days Animal Health) Dimethyl sulfoxide Propylene glycol T8 Keto (DVM Tris-EDTA Pharmaceuticals)* Ketoconazole 24 Flush liberally NG Tresaderm (Merial) Neomycin Thiabendazole drops bid 7 days Dexamethasone Propylene glycol TrizULTRA+KETO Tris-EDTA (DermaPet)* Ketoconazole 23 Apply liberally NG *Not labeled for use in ears but often recommended for use in otitis. **Similar products are available from various companies but were not evaluated. NG = not given. 24 Suppl Compend Contin Educ Vet Vol. 30, No. 1(A), 2008