Otitis Externa Lort Smith Ear Disease Seminar
Transcription
Otitis Externa Lort Smith Ear Disease Seminar
Otitis Clinical Approach The otic cycle of disaster •Primary cause •Predisposing factors Altered otic environment Infection End stage ear Otitis media Loss of self cleaning Fibrosis Ceruminal gland hyperplasia Dr Robert Hilton BVSc(Hons) MACVSc (Canine Medicine) Cert.VD MRCVS www.ozskinvet.com.au 0433-853560 Primary causes and perpetuation • All cases of otitis have a primary cause. Just because the primary cause is not obvious, it does not mean there is not one. • The most common primary cause of canine otitis is allergy. Atopic dermatitis and dietary allergy may manifest as otitis externa alone • Once damaged, the ear canal is not self cleaning. Ceruminal trapping and sequential exfoliation will not occur. Causes of otitis Predisposing • Anatomic – pendulous, narrow or hairy • Humidity and moisture • Inappropriate cleaning interventions Primary • • • • • • • • Allergy Keratinization disorders Endocrinopathies Immune mediated disease Foreign bodies Ear mites/parasites Foreign bodies Tumours 1 Atopic dermatitis Pemphigus foliaceus Scaling disease as a primary cause of otitis externa What Drops to Use When INTACT TYMPANIUM • Yeast + cocci with significant canal occlusion – Mometamax – Otomax • Yeast + cocci minimal canal swelling What Drops to Use When Ruptured/suspect TYMPANIUM • TRIZ EDTA plus – 0.15% Chlorhexidine – 7.5-10mg/ml Enrofloxacin – Dermotic/Suralon • Cocci and a few yeast only. Refractory yeast – Canaural • Rods (pending culture) – Mometamax, Otomax, Topigen – Gentamycin 3mg/ml – 2% Miconazole for yeast (Compounded) – 5mg/ml Chloramphenicol for anaerobe mix 2 You CAN’T TREAT OTITIS IN UNDER 3 VISITS 1. Initial plan • • • • History and derm examination Dif-Quik 2 cytology +/- culture Clean debris Start Treatment 2. Two weekly intervals treatment until clinical and cytological cure 3. Maintenance • • Weekly cleaner until self-cleaning again (maybe never) Check @ 6-8 weeks to ensure working Choosing an ear cleaner Horses for Courses The ideal ear cleaner • Kills yeast and bacteria in the presence of organic matter • Non-irritating • Safe in middle ear • Vehicle for other drugs • Dissolves cerumen • Does not exist Ear cleaners • Solvents – Isopropanol (Alpha, Kleo) – Propylene glycol (many), glycerine, oils – Squalene (safest) • Surfactants and detergents – Paws, – 1:50 Malaseb (caution!!!! Sub-therapeutic antiseptic) • Antiseptics (many). – Triz alone supports yeast/fungal overgrowth – 2% acetic acid • pH adjustors up and down!! Malic acid vs Triz 3 Tris-EDTA • Binds Ca++ ions – Increased permeability to antibiotics – Synergystic bactericidal effect • Tris buffer -> alkaline pH. Optimizes aminoglycosides and fluoroquinolones • Low ototoxicity • Vehicle for antibiotics, silver sulfadiazine, corticosteroids(?) and 0.15% chlorhexidine • Alone only fair bactericide and supports Malassezia overgrowth Clinical Biology • Over 140 species. Most saprophytic. • Specific diseases include glanders (P. mallei) and melioidosis (P. pseudomallei). • Pseudomonas aeruginosa = opportunistic pathogen. • Growth in moist environments e.g. soil, vegetation and faeces. •Ten trials Pseudomonas •162 patients •13 different pharmacological interventions. Evidence-based veterinary dermatology: a systematic review of interventions for treatment of Pseudomonas otitis in dogs Nuttall T and Cole LK: Veterinary Dermatology 18, 69– 77, 2007 “Based on the accepted criteria for quality of evidence, there is insufficient evidence for or against recommending the use of any of these treatments. Most, if not all, of therapeutic decisions in this condition are based on inadequate published data, personal experience and anecdote, rather than on evidence-based medicine.” • Motile Gram –ve aerobic rods • Can proliferate in an anaerobic environment. • Very simple nutritional requirements. May grow in almost distilled water, soap, deisel or jet fuel ("HUM” bug) • Largest and most complex bacterial genome mapped. Permits coding for resistance and adaptation 4 Pathogenic mechanisms • Rarely infects “normal” tissue, yet there is hardly any tissue that it cannot infect if the tissue defenses are compromised. • Vast array of exotoxins including toxin A which impairs protein synthesis, causing cell death (similar to Diphtheria toxin) Otoscope disinfection X Wiping and water washing X Wiping with 70% alcohol Soaking in 2% chlorhexidine Newton HM et al: Evaluation of otoscope cone cleaning and disinfection procedures commonly used in veterinary medical practices: a pilot study. Vet Dermatol. 2006 Apr;17(2):147-50. • Some strains produce a polysaccharide slime layer that: – Protects from host immune system – Additional barrier to antiseptics and antibiotics – Enhances adhesion to fomites/otoscopes • Multiple antibiotic resistance principally by efflux pumps • Resistance by rapid mutation • Transferred horizontally via multiresistance plasmids (conjugation) •Local proliferation •Toxin production •Adhesion •Necrosis +/- Invasion •Protection from host immune system •Antibiotic resistance Predisposing factors to Pseudomonas otitis • Selection pressure due to repeated courses of antimicrobials • Moisture, especially the use of saline as an ear cleaner • Off label weak antiseptics 5 Clinical findings Otitis Media • Often history of chronicity and of failed, repeated or multiple therapies • Pain and irritation • Malodorous purulent exudate • Ulceration and severe inflammation • Otitis media • May be present despite an apparently intact tympanic membrane • Manifest as: – “Head tilting” pain – Neurological signs • Horner’s syndrome • Facial nerve deficits • Vestibular signs (otitis interna) • “Parasympatrhetic” nose or KCS If in doubt, assume otitis media to be present, Especially if tympanic membrane appears abnormal. Caution: None of these clinical signs are SPECIFIC for Pseudomonas Diagnosis - Cytology •Neutrophils •Rods Extracellular Intracellular •Only “fair” sensitivity 1/3 organisms not seen •Good specificity High% organisms seen are grown Diagnosis - culture •Variability and inconsistency of isolation of Pseudomonas and/or sensitivity data from: –Different parts of canal –Middle ear vs ear canal •Laboratory issues – 3 laboratory study Rods are a feature of: •Pseudomonas •Other Gram –ve bacteria •Diphtheroids •Anaerobes –17% of cases 1+ failed to isolate Pseudomonas –No Pseudomonas isolate returned identical sensitivity patterns (MIC based) –Agreement 81% gentamycin, 56% enrofloxacin “Veterinarians should interpret bacterial culture and susceptibility results with multiple caveats including variability between laboratories.” Schick, Angus and Coyner , 2007 6 Cultures – surrogate disks • Ciprofloxacin or moxifloxacin commonly used surrogate disks • Multiple studies have demonstrated non-equivalence. The four pillars of treatment A sample approach Cleaning under anaesthesia Tris-EDTA Antibiotics Corticosteroids What do cultures mean with respect to topical therapy? MIC’s are expressed in µgm/ml and topical therapy is in mg/ml. Cleaning • No harsh cleaners until tympanic membrane seen to be intact • Frequency depends on period canal remains exudate free Aims •Reduction of bacterial load •Eliminating nidus and substrates for bacteria •Remove inflammatory toxins •Remove organic matter that inhibits antibiotics (polymyxin and aminoglycosides) Antibiotics - Topical •No evidence if 1x or 2x day optimal •Aminoglycosides and fluoroquinolones concentration dependent •Triz EDTA vehicle often used Criteria for choice 1. Culture: choose (S) over (R) 2. Known sensitivity patterns if (R) 3. Registered over unregistered 4. Choose safer over less safe if other criteria equal 5. Be prepared to change 7 Indicative Sensitivity% data Enrofloxacin 47 Enro/Silver SD Ciprofloxacin 77 Marbofloxacin 67 Gentamycin Amikacin Tobramycin Polymyxin-B Ticarcillin Ceftazidime Neomycin 69 52 84 73 93 85 97 92 86 63 82 (1) 75 100 100 93 43 75 92 Ototoxicity issues • Nothing other than saline is safe • Incidence of ototoxicity unknown but MUCH less than the clinical use of ototoxic agents with ruptured tympanic membranes • Effect of flush under pressure vs instillation • Ototoxic vehicles (propylene glycol) 53 (1) Unpublished Laboklin data Safer agents • • • • • • • • • TRIZ EDTA 0.15% chlorhexidine Antibiotics excluding tobramycin and ticarcillin Gentamycin (!)… Paterson 2008 Silver sulfadiazine Miconazole/clotrimazole 0.15% chlorhexidine Squalene (cerumen = 6%) PHMB Polyhexamethylene biguanide 250mcg/ml (0.02%) Antibiotics - Systemic • Lack of studies to prove or disprove value • Need to understand pharmacology and kinetics of agents General Indications • Otitis media • Refractory ulceration • Impenetrable thickening • Inability to medicate • Complementing same topical medication?? Use as per deep pyoderma – 4-12 weeks or 2-3 weeks beyond clinical cure 8 Enrofloxacin kinetics Fluoroquinolone issues Boechh A et al, 1999 • Non- equivalence • Concentration dependent rather than time dependent. Post antibiotic effect. • Optimal effects when maximum concentration (Cmax) exceeds MIC (minimum inhibitory concentration) by a significant multiple. • MPC (mutant prevention concentration) may be 10-20x the MIC and can’t be determined from MIC data • Concentrates in leucocytes and higher levels in inflamed tissue • Silver sulfadiazine – additive or synergistic effects Maintenance • Identify and treat primary cause • Weekly cleaner for life – 2% acetic/boric acid – Tris edta + 0.15% chlorhexidine – Masons Otoflush • Follow up Reasons for failure • • • • • • • • Not cleaning appropriately Not treating long enough Not resolving otitis media Proliferate and end-stage ears Poor owner compliance Inappropriate antibiotics Failure to address primary cause Failure to maintain 9 Surgical treatment Lateral ear resection • Allows access to inflammatory polyps or tumours • Almost certain continued medical management will be required • • • • • Total ear ablation with lateral bulla osteotomy Failure of appropriate medical management Intractable otitis media End stage canal changes Tumours Inability or unwillingness to medicate Thank you. Any Questions? Specific references available on request 10