ORIGINAL ARTICLES

A clinical trial of a topical preparation of miconazole, polymyxin and prednisolone in the treatment of otitis externa in dogs YP STUDDERT and KL HUGHES Department of Veterinary Science, University of Melbourne, Parkville, Victoria 3052 SUMMARY: A topical preparation containing miconazole, polymyxin and prednlsolone was shown to be more effective In the treatment of otitis externa In 167 dogs than 2 other ear preparations Containing antibiotics, an antimycotlc and a corticosteroid. With miconazole, poiymyxin and prednisolone, the recurrencerate was 26.79'0 compared with 72.6% and 54.3% when the other products were used. The mean duration of treatment required to achieve resolution of clinical signs was 9.6 days, compared with 12.2 days and 13.0 days and no cases failed to respond to treatment, compared with 17.79'0 and 14.3%. Ma/assezk canlsalone(71%) or in association with bacteria (18%) was recovered from 44 of 49 ears cultured. Aust Vet J 68: 193 -1 95

Introduction Otitis extema is a common clinical disease in dogs. Although many predisposing factors are recognised, including ear conformation, trauma, foreign bodies, and parasites (Otodectes cynotis), infection is frequently present and is the target of treatment and management strategies. A variety of topical preparations are available for treatment of otitis extema. Most contain antibioticsin combination with antiinflammatory, antiparasitic, antifungal and sometimes analgesic or anaesthetic agents. The selection of antimicrobial therapy is based on the bacterial and fungal agents most commonly recovered from affected ears, or on the results of antibiotic sensitivity tests. This report describes the effectiveness of a preparation* containing miconazole, polymyxin B and prednisolone, comparing it with other, commonly used ear preparations.

Materials and Methods Clinical Cases Naturally occurring cases of otitis extema, diagnosed from 1987 to 1989 in a breeding, boarding and training kennel of Labrador retrievers were selected for study. Most dogs were between 6 months and 2 years of age without a previous history of otitis. Diagnosis was made by otoscopic examination of the external ear canal. Inflammation, oedema, discolouration, pain, head shaking, odour and the presence of exudate or excessive wax in the canal were interpreted as signs of otitis extema. Not all f d g s were present in every case. The horizontal and vertical canals and pinna were assessed separately.

Microbiology

Ears of 49 affected dogs were cultured for bacteria and fungi. swabs were routinely inoculated on the trypticase soy agar' enriched with 7% defibriited sheep blood, MacCankey agar', Sabouraud agar' and Sabouraud agar smeared with sterile olive oil. Plates were incubated at 37°C and read at 24 h intervals for SurolanD, behringer lngelheimPly Ltd, Artarmon. New South Wales Oxoid Australia Pty Ltd, Heidelbeg West, Victoria $ Panolog@,ER Squibb and Sons Ply Ltd, Noble Park, Victoria 5 Oternam, Coopers Veterinary Products, North Ryde, New South Wales Otoderm, BeechamVeterinary Products, Clayton, victoria # Ascabiol, May & Baker Aust. Pty Ltd, Footscray, Victoria

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up to 7 d. Swabs of ear canals were also examined microscopically for the presence of mites, acarid eggs, bacteria and fungi.

Treatment Dogs with otitis extema were assigned to one of 3 groups. Group A was treated with a preparation containing 23 mg miconazole, 0.63 mg polymyxin B sulphate and 5 mg prednisolone per ml. group B with a preparationScontaining 2.5 mg neomycin sulphate, 2,500 units thiostrepton, 100,OOO units nystatin, and 1.0 mg triamcinolone acetonide per ml and group C with a preparationo containing 5 mg neomycin sulphate, 50 mg m o n o d i and 1mg betamethasone per ml. The test products were given twice daily by trained personnel. When there was a large amount of exudate occluding the canal, cleaning with an acidic propylene glycol solutiona was done before each treatment. When ear mite infestation was diagnosed, benzyl benzoate' was also given once weekly for 2 weeks. Affected ears were examined at intervals of 7 to 14duntil signs of disease had disappeared. Where there had been excessive exudate present, treatment was not continued if the only fiding was dried exudate in the absence of inflammation. Thereafter, follow up examinations were done at irregular intervals, usually not exceeding 3 mo.

Results Otitis externa was diagnosed in 167 dogs. Fidings on clinical examination included mild to severe inflammation and, in most dogs, varying amounts of red-brown to black, waxy material or a gray, semi-solid exudate. One dog had a creamy white liquid discharge from which Aspergillus niger was isolated (Table 1). Ear mites or eggs were observed on direct examination or in swabs from 4 dogs. Full results of the 49 cultures are shown in Table 1. There were 324courses of treatment for otitis externa in the 167 dogs. Twenty four courses without an adequate ( 1month) follow -up examination were excluded from the study. The results of treatment are shown in Table 2. Thefirst course of treatment was satisfactory, with no recurrence during the follow-up period in 240f 39dogs(61.5%)ingroupA,26of119(21.8%)ingroupB and 5 of 9 (55.5%) in group C.The remaining 112 dogs were treated more than once or successively with different preparations. The average time of recurrence was 3.6 mo in all treatment groups. 193

et al 1983) have also found M canis to be the most common isolate from otitis externa, often in conjunction with Staphylococcus aureus. Pseudomonas aeruginosa, Proteus sp and Escherichia coli are also frequentlyrecovered from diseased ears. They were not found in this study, presumably because few infections were chronic. While clinical otitis extema has been reproduced by instilling M canis into the auditory meatus (Gustafson 19541, its role in causing natural disease i a s been debated. M canis-isregularly Discussion isolated from normal ears, but more commonly and in higher Other than in the 4 cases with ear mites, there were no obvious numbers from diseased ears (Fraser 1961; Abou-Gabel et a1 factors contributing to the occurrenceof otitis extema in the dogs 1979; Gedek et al 1979) and has variously been regarded as observed. However, the study was confined to Labrador normal flora (Baxter 1976), an opportunisticpathogen when the retrievers, a breed predisposed to otitis externa (Grono 1980; microclimate of the ear canal is favourable (Gedek et a1 1979: August 1988). Most Labradors are attracted to water, either for August 1988) or a primary pathogen (Chengappa et a1 1983). swimmingor water-play, and excessivemoisture in the ear canals Antifungal therapy alone can lead to clinicalrecovery from otitis might be expected in many, enhanced by their pendulous ears. externa (Dufait and Diercksens 1971). Both factors are important in the aetiology of otitis externa In clinical practice, economic considerationsmake it impracti(Grono 1980). Moisture may stimulate activity of ceruminous cal to cu!ture all cases of otitis externa unless they are exceptionglands in epithelium lining the external ear canal, filling the ally severe or they fail to respond to treatment with one of the lumen and favouring microbial proliferation (August 1988). several available ear preparations. Therefore, these preparations Malassezia canis (syn Mpachydermatis, Pityrosporum canis, are usually formulated for effect against a wide spectrum of Ppachydermatis) was recovered from 90% of the 49 ears culbacteria, fungi and sometimes parasites, most likely to berespontured (Table l); in two-thirds of these it was present in pure sible and to relieve clinical signs associated with the disease. If culture. M canis is a lipophilic yeast stimulated by canine mites are seen or microbiological culture and antibiotic sencerumen (Kowalski 1988; Gaball988) and the use of a selective sitivity results become available, more specific therapy can be medium enriched with unsaturated fatty acid undoubtedly enconsidered. hanced its isolation. Others (Smith 1968; Baxter and Lawler 1972; Marshall et a1 1974; Rausch and Skinner 1978; Chengappa Most ear preparations contain antibiotics effective against gram-positive and gram-negative bacteria, especially Proreus and Pseudomonas. Some include an antimycotic drug and anTABLE 1 Results of cultures from ear canals of 49 dogs with otitis tiparasitic agent. Corticosteroids are also commonly added for externs their anti-inflammatory effect, to increase lumenal diameter, thereby facilitating delivery of other active ingredients, and for Microbial growth No. of 96 symptomatic relief of pain and pruritus, but their use can lead to Isolates adrenocortical suppression (Monello et a1 1988) and elevation of some liver enzymes (Meyer et al1990). Malassezia canis alone' 35 71 M canis + staphylococci 5 10 Cutaneous reactions caused by ear preparations have been M canis + corynebacteria 1 2 reported (Scott 1977; Macy and Seim 1985). One case was M canis + other bacteriat 3 6 observed in a dog treated with preparation C. Any one of the Aspergillus niger 1 2 ingredients might have been responsible for irritation or senNo growth and negative smear 4 8 sitisation, but neomycin sulphate is a common sensitising agent in humans and is the most commoncause of drug-inducedcontact Total fungal isolation 45 92 allergic otitis in dogs (Macy and Seim 1985). However, in 3 cases yeasts were seen in smears but not isolated neomycin is also present in preparation B, which was not ast bacteria observed in smears but not isolated sociated with a similar reaction when used in a large number of dogs in this study. Topically applied miconazole has also reporTABLE 2 tedly caused erythema and alopecia in cats (Aronson and Riviere Results of treatment of otitis externa with three different otic 1983). preparations In this trial, the effectivenessof 3 earpreparations withformulations containing antibiotics, an antimycotic and a corticosteroid Observation A' Bt C§ were compared. The preparation containing miconazole, Number of courses 101 164 35 polymyxin and prednisolone (group A) gave better results in the of treatment treatment of otitis externa than the preparations containing 12.2 Average duration of 9.6 13.0 neomycin, thiostrepton,nystatin, and triamcinolone (group B) or treatment (days) neomycin, monosulfiiam and betamethasone (group C) (Table 7.3 Average follow-up 7.7 8.2 2). A shorter course of treatment was required to achieve clinical period (months) recovery and there was a lower rate of recurrence. Response to the fmt course of treatment was significantly (p4.05)better in Results of treatment 74(73.3"/0)" 45(27.4Y0)~ 1 6(45.7°/0)c Satisfactory group A than the other groups although the numbex of dogs in Unsatisfactory 27(26.7%)" 1 19(72.6%)b 1 9(54.3%)c group C was small. Most importantly,none of the cases treated recurrences 27 89 13 in group A failed to respond to therapy, i n c l d i g 14 cases that 0 29 unresponsive 5 previously were unresponsive to the other 2 preparations. 0 cutaneous reaction 0 1 Miconazole, a synthetic imidazole derivative with pronounced a n t i g a l activity, was a principle ingredient of preparation A. Surolafi,.Boehringer lngelheim Pty Ltd, Artarmon, N SW It is used topically in the treatment of dermatophytosisin animals Panolog@, ER Squibb 8 Sons Pty Ltd, Noble Park, Victoria and humans. Miconazole is also active against gram-positive 5 o t e m a . Coopers Veterinary ~mciucts,~ o r t hRY&, NSW bacteria including S aureus (Van Cutsem andThiempont 1972). a*bsc Results with different superscripts differ significantly (~4.05) Polymyxin B sulphate, the other antimicrobial ingredient in using a two-tailed Fisher's Exact Test

Epithelium of the pinnae and ear canals became severely inflamed and painful in one dog several days after the beginning of treatment with preparationc. This reaction subsided soon after treatment was changed to preparation A. The case infected with A niger was in group A. Clinical signs resolved after 7 d of treatment, and there was no recurrence during the 2-month follow up period.

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preparation A, has bactericidal aCtivity against gram-negative bacteria, and there is also a synergistic effect produced in combination with miconazole (Comelissen and van den Bossche 1983). Thus, the effectivenessof preparation A may have been due to the activity of miconazole against yeasts, although ears were not cultured after trearaent to demonstrateabsence of yeasts. Yeasts are reportedly sensitive to miconazole, ketoconazole, clotrimazole, thiabendazole, nystatin and cuprimyxin. Miconazoleis recommendedfor treatment of M canis infections, while nystatin is more effective against Candida sp, which is an infrequent isolate from ears (Nicklas and Mumme 1979; Manning 1983; Wilson 1985; McKeever and Richardson 1988; Martin 1989). Macy and Seim (1985) recommended systemic treatmentwithketoconazoleforotitisextemabecauseyeastsmay be found beneath the epithelial surface. Miconazole is also effective against aspergilli (Van Cutsem and Thienpont 1972) and the one case in our study infected with A niger responded rapidly to treatment with preparation A. Gedek et a1 (1979) found that all strains of M canis, Staphylococcus sp and Streptococcus sp, isolated from ears of dogs withotitis externa were sensitive to miconazole. There was a marked reduction in the recovery rate of bacteria and M canis and clinical improvementwas observed in 86%of cases following treatment with a preparation nearly identical to that used in group A. Using a similar formulation, Ascher et a1 (1988) reported a 100% efficacy in treatment of bacterial and fungal infections of the ear in 102dogs and 28 cats.

Acknowledgment We thank Ms S Francis for supervising treatment of affected dogs and management of case records and G Anderson for statistical analysis.

References Abou-Gabel M, Chastain CB and Hogle RM (1979) Mykosen 22192 Aronson AL and Riviere JE (1983) In Current Veterinary Therapy Vlll, edited by Kirk RW, Saunden. Philadelphia, p 123 Ascher F,Maynard L, Hewe D. Allaire-R,Simon J and Boujalliat JC (1988) Pratique Medicale & Chirurgicale de I'Animol de Compgnie 23273. Abstract 1733, Small Animal Abstracts 1988,14188 August JR (1988) Vet Clin North Am 1873 1 Baxter M (1976)J Small Anim Pract 1723 1 Baxter M and Lawler DC (1 972)NZ Vet J 20:29 Chengappa MM, Maddux RL and Greer SC (1983) Vet Med Sm Anim Clin 78343 Comelissen F and Van den Bossche H (1983) Chemotherapy29419 Dufait R and Diercksens Y (1971) VlaamsDierg Tidy 40147 Fraser G (1961)5CompPathol71:1 Gabal MA (1988) Mycopathologia 10493 Gedek B, Brutzel K, Gerlach R, Netzer F. Rocken H et a1 (1979) Vet Rec 104 138 Grono JX (1980) In Current Veterinary Therapy VII, edited by Kirk RW. Saunders, Philadelphia, p 461 Gustafson BA (1954)Nord Vet Med 6434 Kowalski JJ (1988) Vet Clin North Am 18743 McKeever PJ and Richardson HW (1988) Comp Anim Pract 2:24 MacyDandSeimHB(1985)Proc53rdAnnMeetAmAnimH~pAssoc. p 1u) Manning TO (1983)InCurrentVeterinaryTherapyVIlI,edited by KirkRW, Saunders, Philadelphia, p 466 Marshall MJ. Hams AM and Home JE (1974)J Small Anim Pracf 15401 Martin W (1989) Small Animal Therapeutics,Wright, London, p 35 Meyer DJ, Moriello KA, Feder BM, Fehrer-Sawyer SL and Maxwell AK (1990)JAm Vet Med Assoc 196743 Monello KA, FehrerSawyer SL, Meyer DJ and Feder B (1988) J Am Vet Med Assoc 193329 Nicklas VW and Mumme J (1979) Tierarztl Umchau 34606 Rausch FD and Skinner GW (1978) Mod Vet Prac 73:914 Scott DW (1977)Feline Pract 7:47 Smith JMB (1968) Awl Vet J 44:413 Van Cutsem JM and Thienpont D (1972) Chemotherapy 17392 Wilson JF (1985)DermatolReports 4:7

Australian VeteriMryJournat, '40168, No 6, June 1991

BOOK REVIEWS Coiour Atlas for the Diagnosis of Bacteria/ Pathogens in Animals, (Farbatlas zur Diagnose bakterieller lnfectionserregerder Tiere), WolfgangBisping and Gunter Amtsberg, Paul Parey Scientific Publishers, Berlin, 1988, pp 339, US$230. This atlas contains 220 illustrations (180 in colour) and 96 tables. The text is presented in 2 columns on each page with the originalGerman in one column and the English translation in the other. The legends to all colour illustrations are also in both languages. The exception to this format are the tables and flow charts, which are of full page width and presented in English, which was a plus for a monolingual English speaker, such as this reviewer. The translation has been well done with the text free flowing and easy to follow. There is a sprinkling of e m , but those noted were more likely to have been in the original than in the translation. For example, in the section on staphylococcus, reference is made to DNAasecontainingrather than DNA-containing media. The book progresses through the various bacteria of veterinary importance in a conventional systematic way, commencing with the gram-positive cocci. For each species there is a section on occurrence and veterinary signifkance, morphology(in infected tissue smears), culture (media and cultural conditions), biochemical properties (used in identification), and other criteria of diagnostic significance to relevant bacteria. Useful flow charts summarise procedures for isolating and identifying species within genera. The colour plates demonstrate the microscopic and colonial morphology of the most important species and are adequate to good, rather than excellent in quality. The book provides a very well thought out illustratedoverview of veterinary diagnostic bacteriology. Veterinary bacteriologists and students of veterinary bacteriology should f i d it a useful reference. It would be worth considering by practitioners who like to dabble in bacteriology. As a bonus you can also brush up on your German as you learn to recognise bacteria!

Kevin Whithear ELISA Technology In Diagnosis and Research, edited by GW Burgess, Graduate School of Tropical Veterinary Science, James Cook University of North Queensland, Townsville,Queensland, 1988,pp 34 1. This book was prepared as a basis for a 2-week course held at the James CookUniversity. The aim of the course was to deliver practical information on the present state of development of immunoassay technology. It has 10 chapters and 39 sections prepared by 27 contributors. The introduction looks at important aspects of immunology and reviews basic and advanced principles of developing enzymelinkedimmunosorbentassays (ELISA). Major topics are: preparation and use of antigens, coating the solid-phase matrix,blockers, diluents, enzyme conjugates and substrates; production of monoclonal antibodies and their application in ELIS A; epidemiological evaluation and considerations of immunological tests; sensitivity and specifcity; automation of immunoassays including quality control aspectsand antigen detection using ELISA. The second part deals mainly with specific applications of the ELISA in the diagnosis of viral, bacterial and parasiticinfections, and the detection of hormones, toxins, antibioticsand pesticides. The major topics include: antigenic structureof viruses, bacteria and parasites; immune responses to these; strategies for the development of ELISA; antibody, antigen and hapten detection; problems associated withELISA; criteria for selecting a test; and future prospects for immunoassays. This useful publicationprovides comprehensiveinformationon the applications of ELISA technology, refers to some of its limitations and is a good source of reference.

RB Gasser 195

A clinical trial of a topical preparation of miconazole, polymyxin and prednisolone in the treatment of otitis externa in dogs.

A topical preparation containing miconazole, polymyxin and prednisolone was shown to be more effective in the treatment of otitis externa in 167 dogs ...
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