Download 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