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THERAPEUTIC APPROACH TO OTITIS IN VETERINARY DERMATOLOGY

Anthony A. Yu DVM, MS, ACVD Guelph Veterinary Specialty Hospital

TOP 10 reasons dogs/cats visit vets VPI 2012

Top 10 Canine Claims Top 10 Feline Claims

1. Ear infections 1. Lower urinary tract diseases

2. Skin allergies 2. Stomach upsets/gastritis

3. Pyoderma (hot spots) 3. Renal failure

4. Stomach upsets 4. IBD/diarrhea

5. IBD/diarrhea 5. Skin allergies

6. Bladder diseases 6. Diabetes

7. Eye infections 7. Colitis/Constipation

8. Arthritis 8. Ear infections

9. Hypothyroidism 9. Upper respiratory virus

10. Sprains 10. Hyperthyroidism

Pseudomonas  

¨  Gram  nega-ve  rod  ¨  Saprophy-c  ¨  Ubiquitous  

¤  Stagnant  water,  taps,  drains,              ear  cleaners,  solu-ons  ¤  Individual  pipeAe  cleansers  

¨  Opportunis-c  ¤  Immunocompromised  pa-ents  ¤  Allergies  ¤  Endocrinopathies  ¤  ChemoRx    Medica-ons  

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Yu’s Goals of Treatment for Pseudomonas

¨  1) Address underlying etiologies

¨  2) Cleanse & Calm the microenvironment n Cerumenolytics; acidic component n Topical/systemic anti-inflammatory

¨  3) Address the secondary infections n Antibacterial/anti-yeast therapy

Addressing Otitis Externa

n  Perpetuating n  Bacteria n  Malassezia

n  Primary n  Foreign Body n  Ectoparasites n  Environmental n  Food Allergies n  Hypothyroidism n  Neoplasia

n  Predisposing n  Microenvironment

Neoplasia

Infection

HypoT4

Atopy

Ectoprasites

Food

Otitis Threshold

Pseudomonas  resistance  

¨  Virulence  factors:  ¤  Low  cell  wall  permeability;  B-­‐lactamases;  efflux  pumps  ¤  Plasmid,  transposon  and  bacteriophage  transfer  muta-ons  

¨  Improper  use  of  an-bio-cs  selects  for  resistance  ¤  Failure  to  reach  effec$ve  concentra$ons  at  -ssue  level  ¤  Premature  discon$nua$on  of  an-bio-cs    ¤  Lack  of  owner  compliance/adherence  is  important    

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In vitro antimicrobial activity of Pseudomonas aeruginosa isolated from dogs with otitis externa A. CORONA, A. VERCELLI and L. CORNEGLIANI Vet Derm 2012

¨  Sensitivity ¤ Piperacillin (82%), ¤ Tobramycin, gentamicin (69%, 65% respectively) ¤ Aztreonam (62%), marbofloxacin (57%)

¨  Resistance ¤ Cefalexin (97%), cefadroxil (95%), amoxicillin-clavulanate (93%) ¤  Enrofloxacin (51%)

¨  Vets should always perform C&S before starting Rx. ¨  Piperacillin should be considered as a new vet drug

Robson et al. Correlation between topical antibiotic selection, in vitro bacterial antibiotic sensitivity and clinical response in 16 cases of canine otitis externa complicated by Pseudomonas aeruginosa. Vet Derm, 2010;21;311–328.

¨  Resistance  to  many  o-c  an-bio-cs  is  rising  (Wildermuth  et  al  (2007))  n Up  to  80%  isolates  resistant  to  enrofloxacin  –  significance??    

¨  N=16 Pseudomonas ears ècytology and culture

¨  Empirical treatment based on cytology only (culture results withheld)

¨  15 of 16 responded to topical therapies

¨  5 of 16 “sensitive” on culture findings to treatment prescribed ¨  10 of 16 were “resistant” on culture findings to the treatment Rxd

¨  CURRENT SENSITIVITY TESTS ARE OF MINIMAL VALUE

WHEN USING TOPICAL THERAPY

Topical Otic Product Sensitivity Testing

¨  TOPS Study at OVC ¤  Testing of “resistant” Pseudomonas and MRSP otitis patients ¤ Agar dilution various antibiotic concentrations from:

n  Aminoglycosides (Gentamicin, Mometamax®; neomycin, Tresaderm®)

n  Fluoroquinolones (Marbofloxacin, Aurizon®; enrofloxacin, Baytril Otic®) n  Fusidic acid (Canaural®), polymyxins (Surolan®), Triz-EDTA®, others

¤  TOPS panels versus Kirby-Bauer/MIC to select topicals

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MIC for “resistant” cultures Pseudomonas MRSP

Biofilms

¨  EPS provides protection for bacteria

¤  Prevents dessication

¤ Enhanced cell-cell communication and alters metabolism

¤ Evasion of immune system and antimicrobials

Costerton JW. 1999.

Pseudomonas – OD and biofilm

Isolate Mean OD

Isolate Mean OD

Isolate Mean OD

Isolate Mean OD

1 0.200 13 0.572 25 0.066 37 0.542

2 0.279 14 0.522 26 0.047 38 0.137

3 0.113 15 0.453 27 0.101 39 0.303

4 0.043 16 0.455 28 0.191 40 0.05

5 0.029 17 0.065 29 0.283 41 0.159

6 0.331 18 1.395 30 1.787 42 0.334

7 0.027 19 0.008 31 0.235 43 3.543

8 0 20 0 32 0.326 44 0.222

9 0.572 21 0.057 33 1.061 45 0.081

10 0.521 22 0.047 34 0.051 46 0.254

11 0.024 23 0.319 35 0.096 47 0.022

12 0.024 24 0.153 36 1.404 48 0.076

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Pseudomonas – OD and biofilm

Isolate Mean OD Isolate Mean OD Isolate Mean OD

49 0.800 61 0.033 73 0

50 0.055 62 0.484 74 0.04

51 0.125 63 0.081 75 0

52 0 64 0.228 76 0

53 0.203 65 0.081 77 0.135

54 0.175 66 - 78 0

55 0.144 67 0.019 79 0

56 0.408 68 1.171 80 0

57 0.271 69 0 81 0.001

58 0.097 70 0.241 82 0.042

59 0.121 71 2.849 83 0.042

60 0.454 72 0.043 84 0

Results

¨  33/83 (40%) formed biofilm ¨  11/83 (13%) high biofilm producers ¨  15/83 (18%) moderate biofilm producers ¨  7/83 (8%) low biofilm producers

Results

0

20

40

60

80

100

120

140

160

180

Enro Gent Poly B Neomycin

Planktonic

Biofilm

(P < 0.0003)

Mea

n M

IC

Comparison of mean MIC of enrofloxacin, gentamicin, polymyxin B and neomycin for planktonic bacteria versus biofilm-embedded for 31 P. aeruginosa isolates

(P < 0.028)

(P < 0.049)

(P < 0.009)

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Pseudomonas and biofilm Tx

¨  Biofilm MICs were significantly lower with Triz-EDTA®

biofilm-embedded versus straight biofilm-embedded bacteria for gentamicin and neomycin ¤ Gentamicin (P < 0.04) ¤ Neomycin (P < 0.008)

¨  No significant difference ¤ Enrofloxacin (P < 0.06) ¤ Polymixin B (P < 0.52)

Treating “Resistant” Pseudomonas

¨  1) Address underlying etiology ¨  2) Clean the ear (flush w/saline +/- cleanser) ¨  3) Calm the ear canal

¤  Steroids, cyclosporine

¨  4) Tris-EDTA (T8 Solution®, Triz-EDTA®) ¤  EDTA = chelates Ca++ è porin ¤  Tris = Surfactant product è peptidoglycan ¤  Instill 15 minutes prior to medicating

¨  5) Use appropriate antimicrobial therapy Buckley  LM  et  al,  2012  TrisEDTA  +  SSD  Swinney  et  al,  2008  Triz  Plus®  (w/chx)   Ghibaudo  et  al,  2004  Triz-­‐EDTA/CHX/Enro  

Has Virbac got it right with EasOtic®?

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Volume Important

¤  0.25cc (small) ¤  0.5cc (med) ¤  0.75cc (large) ¤  1.0cc (giant)

Antibiotic therapy Gram-positive cocci ¤ Neomycin (contact rxn) ¤ Gentamicin (ototoxic?) ¤  Enrofloxacin; Marbofloxacin ¤  Silver sulfadiazene ¤  Fusidic acid ¤ Chloramphenicol (static)

Aminoglycosides should not be used if the tympanic membrane is ruptured HOWEVER, research in 10 dogs with normal and myringotomized tympanic membranes è no negative effects on neuro, behaviour, BAER 21d post-Tx Strain GM, Merchant SR, Neer TM, Tedford BL. Ototoxicity assessment of gentamicin sufate otic preparation in dogs. JAVMA 1995; 56(4); 532-538

Gram-negative rods ¤ Amikacin (ototoxic? no pus) ¤ Gentamicin (ototoxic? no pus) ¤  Framycetin (ototoxic?) ¤  Enrofloxacin; Marbofloxacin ¤  Silver sulfadiazene ¤  Polymyxin B (no pus) ¤ Ceftazidime, ticarcillin ($$) ¤  Piperacillin, Imipinem ($$$)

Study to compare owner perception of their dog’s hearing and brainstem auditory-evoked response findings in 45 dogs C. L. BALL and S. PATERSON Vet Derm 2012

¨  0 (no, MHT 25 dB or less) ¤  13/13 = 100%

¨  I (slight, MHT 26–40 dB) ¤  0/11 unilateral; 33% bilateral

¨  II (moderate, MHT 41–60 dB) ¤  0/2 unilateral; 100% bilateral

¨  III (severe, MHT 60–80 dB) ¤  0/1 unilateral; 100% bilateral

¨  IV (profound, MHT 81 dB +). ¤  100% bilateral

¨  Dogs with mild or unilateral hearing deficits adapt well

¨  Owners frequently unaware of pets’ deficits

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Otic Antibiotic Selection

¨  Systemic Antibiotics ¤  Based on current traditional C&S testing

¤  Otitis media/interna – head tilt ¤  Owners cannot administer topical therapy

¤  Stenotic canal; aggressive pet; incompetent client ¤  Adverse reactions to topical antimicrobial agents

¨  Topical Antibiotics ¨  No such thing as first line or second line

with topicals

¨  Use what works…empirical treatment first

¨  If failure, consider TOPS testing

(Biofilm +/- planktonic)

Pseudomonas  O--s  

¨  How  important  are  steroids  to  treat  Pseudomonas  o--s  externa??  

¤ The  MOST  important  component  topically  and/or  systemically    n Reduce  pain  and  pruritus  n Decrease  hyperplasia/stenosis  n Decrease  glandular  secre-ons  n Reduce  scar  -ssue    

Anti-inflammatory Systemic: ¨  Dexamethasone – 0.05-0.1mg/kg/d ¨  Prednisolone – 1-2 mg/kg/d ¨  Cyclosporine – 5 mg/kg/d Topical: ¨  Mometasone, betamethasone ¨  Dexamethasone, prednisolone ¨  Fluocinolone Acetonide w/DMSO ¨  Potent, not absorbed systemically

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Topical steroid side effects

Medication No. of dogs

No. (%) below range

No. (%) in range

No. (%) above range

Mometamax® 9 0 (0) 9 (100) 0 (0)

Panolog® 12 2 (17) 8 (67) 2 (17)

Tresaderm® 8 4 (50) 4 (50) 0 (0)

DVMaxTM 11 1 (9) 9 (82) 1 (9)

Percentage of Dogs with Corticotropin Stimulation Testing Results below, in, and above the Normal Range* after Receiving Topical Otic Medication for 7 Days

Reeder CJ; Griffin CE; Polissar NL, et al. Comparative adrenocortical suppression in dogs with otitis externa following topical otic administration of four different glucocorticoid-containing medications. Veterinary Therapeutics, 2008; 9(2): 111-121

What about Burow’s HC solution

¨  Burow’s Solution, Compounded ¤ 1% HC + Burow’s solution (aluminum acetate) + PG

¨  BurOtic HC®, Virbac ¤ 1% HC+ Burow’s solution (aluminum acetate)+ Acetic acid

¨  Good for maintenance ¨  Anti-inflammatory ¨  Antimicrobial

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Pseudomonas  treatment  end  point  

¨  Clinical  picture  misleading  

¨  Cytologically  nega-ve  

¨  Consider  culture  ¤ Chronic  recurrent  cases    ¤  If  using  systemic  an-bio-cs  

¤ When  cytologically  nega-ve  ¤ Con-nue  treatment  un-l  results  return  

2012 National Pentathlon Ashtyn – Gold Youth D; Alyssa – Silver Youth B

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Malassezia Otitis

¨  Secondary problem ¤ Allergies ¤ Ceruminous otitis ¤ Pinna often involved

¨  Cytology ¤ culture not necessary UNLESS ULCER - Candida

Malassezia Otitis Externa

¨  Address underlying etiology

¨  Calm the microenvironment ¤ Topicals +/- Systemic (Atopica®, steroids)

¨  Address the yeast ¤ Cerumenolytics/Astringents

n Otoclean®, EpiOtic®, Vet Solutions® Ear Cleanser, Douxo® Micellar Solution, Malacetic Ear/Skin Cleanser®

¤ Topical +/- systemic anti-yeast

Antifungal products

¨  MALASSEZIA spp. ¤ Clotrimazole (Mometamax®, Aurizon®) ¤ Enilconazole (Imaverol®) ¤ Miconazole (Surolan®) ¤ Silver Sulfadiazene (Baytril Otic®) ¤ Posaconazole (Posatex®) ¤ Systemic: ketoconazole, itraconazole, fluconazole, terbinafine

¨  CANDIDA spp ¤ Nystatin (Panalog®, Canaural®)

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Malassezia  treatment  end  point  

¨  Clinical  picture  more  consistent  

¨  Cytology  =  WNL  ¨  AND  clinical  symptoms  normalize  

¨  Op-mal  -me  for  recheck  ¤ Depends  on  pa-ent  response  ¤ Depends  on  product  ¤ Depends  on  residual  effects  

è Mometamax q24h 7d??

¨  October 2010 ¤ Myah Gonzalez – G. Ret. – Malassezia ¤ Pugsley Wong - Pug – mixed infection ¤ Pretty Kitty Dell – DMH – Malassezia

¨  7 days Mometamax® then stopped ¤ D7 cytology – CS improved

- organisms still present

¨  D10 cytology – all ear WNL ¨  Residual effect of Mometamax®

¤ Recheck in 10 days, not 7 days

Prince Phillip Games 2012 National Champs

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Bruet V et al. Aural hemtoma in dogs: evaluation of a simplified medical treatment using in situ methylprednisolone acetate Vet Derm 2012;23 Suppl:34

¨  N=19 dogs (Golden, Lab, Frenchie), Oniris, France ¨  Unilateral (17/19); right ear (14/17) ¨  Procedure:

¤  ID underlying etiology or associated issues ¤ D0 = sedate, drain, flush, inject 2mg/kg MPA ¤ D7=+/- repeat ¤ D15=+/- surgery

¨  N=18 cases resolved (D0(11), D7(7)) ¨  Recurrence = 6/18 (15d(1), 1mo(3), 2mo(1), 3mo(1)) ¨  68% success (12/19)

Intralesional Triamcinolone a salvage technique prior to TECA-BO

n  Corticosteroid with antifibroblastic activity

n  Main goal: n  Decrease inflammation n  Dissolve calcification n  Avoid TECA and bulla osteotomy

n  Dose: n  Clean ear thoroughly under sedation +/- GA n  6-10 mg per ear in ring block formation n  1 injection every 2 weeks for 3 treatments n  Use Luer-Lock or swedged-on needle n  Address secondary infections topically n  Address underlying etiology

2006 (August) Craig Griffin Clinical Techniques in Small Animal Practice

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Response after 2 injections 2 weeks apart @ 4 week recheck

è