1

Acute Otitis Media

Dr. Ghaleb Zughayar
Consultant Pediatrician and
Neonatologist.
2
Objectives
Otitis Media
Demonstrate an understanding of
pathophysiology
List the common pathogens
Demonstrate knowledge of both the
advantages and disadvantages of antibiotic
therapy
Demonstrate application of an appropriate
treatment plan

3 Rudolph's Pediatrics - 21st ed 2002
Definition
Acute Otitis Media (AOM)
acute onset of symptoms, evidence of a
middle ear effusion, and signs or symptoms of
middle ear inflammation.
Otitis Media with effusion (OME)
Presence of MEE without signs or symptoms
of infection, previously named: secretory,
serous, or glue ear.
Definition (continuous)
4
Difficult to treat AOM (20%)

Recurrent AOM: three or more episodes in the
previous six months or four or more in the preceding
twelve months.

Treatment failure AOM: a lack of improvement in
sign and symptoms within 48-72 hours of AB
treatment .
Definition (continuous).
5
Chronic Otitis media with effusion:
OME that persists beyond three months.

CSOM: purulent otorrhea that persists
for more than six weeks despite
appropriate treatment for AOM.
6 N Engl J Med 2002 347:1169-1174
Epidemiology
31 million visits to physicians annually in
U.S.
Most common diagnosis for an AB
prescription in children.
Diagnosed > 5 million times a year.
3-5 billion $/year in U.S.
50,000 deaths / year worldwide.
7
N Eng J Med 2002 347: 169-1174;
Pediatr Infect Dis J 1996 15:281-291
Pathophysiology
Eustachian tube
obstruction
Length: shorter in children
Angle: 10
o
children vs. 45
o

adult
Decreased
immunocompetence
Follows upper
respiratory infection
(URI)
Peak incidence 2 - 4 days
8 Pediatr Infect Dis J 1999 18:1-9
Risk factors
Age <2 years
Atopy
Bottle propping
Chronic sinusitis
Ciliary dysfunction
Cleft palate and craniofacial anomalies
Child care attendance
Down syndrome and other genetic conditions
First episode of AOM when younger than 6 months
of age
Immunocompromising conditions
9
Diagnosis: Clinical Manifestations
Specific
Otalgia
Otorrhea
Dizziness
Hearing loss

Non-specific
Fever (50%)
Vomiting/diarrhea
Anorexia
Irritability
10
Diagnosis: Clinical Findings
Otoscopic findings
Bulging TM
Yellow, white, or bright red color
Opacification of eardrum
Impaired visibility of ossicular landmarks
Squamous exudate
Rudolphs Pediatrics - 21
st
ed 2002
11
Pathogens
Bacterial
Streptococcus
pneumoniae
Haemophilus
influenzae
Moraxella
catarrhalis
Viral
RSV
Influenzae A & B
Parainfluenzae 1,2,
& 3
Rhinovirus
Adenovirus
Enterovirus
Coronavirus
12
Potential Complications
Hearing loss
Acute mastoiditis

Rare:
Meningitis
Subdural/extradural abscess
13
Treatment Considerations
Allergies
AOM history
Spectrum of activity
Local resistance
pattern
Recent antibiotic
treatment

Age
Duration
Compliance
Adverse drug events
Cost

14
Treatment Considerations
Drug resistant S. pneumoniae (DRSP)
incidence increasing
Patients at high risk for DRSP
Attending day care
< 2 years old
Antibiotic therapy in preceding 3 months
15
Penicillin Resistance of S. pneumoniae
U.S. 1979-2000
0
5
10
15
20
25
30
1979 1982 1985 1988 1991 1994 1997 2000
%

N
o
n
s
u
s
c
e
p
t
i
b
l
e
Intermediate Resistance High Level Resistance
16
DRSP at Childrens Hospital Boston
0
5
10
15
20
25
30
35
1
9
9
1
1
9
9
2
1
9
9
3
1
9
9
4
1
9
9
5
1
9
9
6
1
9
9
7
1
9
9
8
1
9
9
9
2
0
0
0
2
0
0
1
Intermediate
Resistant
17 Pediatr Infect Dis J 1998 17: 1084-1089
Why Focus on Pneumococcus?
Most common initial bacterial pathogen
Most common isolate after failed therapy
Least likely bacterial pathogen to self
resolve
Most likely to cause severe otitis media
Most likely to cause suppurative
complications of otitis (mastoiditis)
18 N Engl J Med 2002 347: 1169-1174
Treatment Options
AOM spontaneously resolves 40 - 60%
Symptomatic therapy
Applied heat, analgesics, antipyretics & topical
anesthetic
Adjunctive therapy
Decongestants, antihistamines, & corticosteroids
Who to treat with antibiotics?
< 2 yo
AOM s/sx 3 days
Ill-appearing patients
Patients at an increased risk of DRSP
19
Judicious Antibiotic Use
Proper diagnosis of AOM or OME before
committing to antibiotic therapy
Diagnosis of AOM requires evidence of local
inflammation & systemic symptoms
Erythema alone is not sufficient
Thickened, bulging and opaque TM
Pain
OME does not need immediate antibiotic therapy
Commonly seen with acute URI
Little or no benefit of antibiotic therapy
Persistent effusion expected for 2-3 months following
therapy for AOM, but if persists > 3 months consider re-
treatment
20
21
22
Amoxicillin: 1
st
Line Rationale
Pathogen % Cases % Resistant
to amoxicillin
% Spontaneous
resolution
S. pneumoniae
40 50 10 - 16 20
H. influenzae
20 30 35 40 50
M. catarrhalis
10 15 95 90


Pediatric Infect Dis J 1999; 18:1-9
Pediatric Infect Dis J 1998; 17:1058-1059
23
How Effective is HD (90 mg/kg/d)
Amoxicillin* Against
Pneumococcus?
Dagan et al. Poster 107, ICAAC 2000
*Study done w/ amox/clav but clav has no activity against pneumococcus
Susceptibility Bacterial
Eradication
Sensitive (MIC 0.06) 100% (61 of 61)
Intermediate (MIC 0.1-1) 100% (21 of 21)
Resistant (MIC >2) 93.5% (29 of 31)
24 Pediatr Infect Dis J 1999 18:1-9
Treatment Failure
No improvement in ear pain, fever, or
tympanic membrane otorrhea, bulging or
redness after 3 days of antibiotic therapy
2
nd
Line Therapy
DRSP
Beta-lactamase producing H.influenza and
M. cattarhalis
25
Pediatr Infect Dis J 2003 22:10-16;
Pediatr Infect Dis J 1998 17:1084-1089
Prevention
Heptavalent pneumococcal conjugate vaccine
(n=37,868)
Reduction of otitis office visits
Reduction of antibiotic prescriptions
Influenza vaccine
Goal: decrease number of URI
Breast feeding
Prophylaxis
3 episodes in 6 months or 4 episodes in 1 yr
<6 months with >1 episode
Cause of resistance in the community
26
Dutch Guidelines for AOM
Age Management Antibiotics
< 6 mo Antibiotic prescribed
re-eval at 24 hrs
Always
6-24 mo Symptomatic care
re-eval at 24 hours
High risk, no
improvement at 24
hr, otorrhea >14
days
>24 mo Symptomatic care High risk,
earache/fever >3
days, otorrhea >14
days
27
In Summary . . .
Antibiotic resistance is here
High rates of antibiotic use in children has
contributed to resistance rates
Vast majority of antibiotic use in children is
for AOM
Minimizing unnecessary antibiotic prescribing
can slow the rate of resistance
First line treatment of AOM is amoxicillin
90 mg/kg/day divided TID !!
28
Treatment
High risk
DRSP?
(Day care, <2 yo,
antibiotics within 3
months)
1
st
Line
Therapy
Treatment Failure
(Day 3)

Yes
High dose (HD)
amoxicillin,
HD Augmentin,
or cefuroxime
axetil
HD Augmentin,
cefuroxime axetil,
ceftriaxone IM x3
days,
or clindamycin
No
HD amoxicillin
29
DRSP
Beta-lactam Activity & Levels
Dowell SF et al. Pediatr Infect Dis J 1999 Apr; 18 (4): 341
30
Amoxicillin
Class
Penicillin
Considerations
Most effective PO agent vs.
DRSP
Does NOT cover beta-
lactamase producing H.
flu or M.cat
Tastes excellent
Dosing
SD: 40 mg/kg/day TID
HD: 90 mg/kg/day
TID (max 3 g/day)
Adverse Events
Rash
Diarrhea
Nausea/vomiting
Contraindications
Hypersensitivity to
penicillins
Dosage Forms
Capsule
Chewable Tab
Tablet
Suspension
31
Augmentin
Selection after HD Amoxicillin Failure
Addition of clavulanate
No additional coverage for pneumococcus
compared to amoxicillin
Augmentin ES = 90 mg/kg/d of amoxicillin which
is equivalent, NOT superior to HD amoxicillin for
DRSP
Excellent coverage for beta lactamase
positive H. flu and M. cat
32
Amoxicillin/clavulanate
(Augmentin

; Augmentin ES

; Augmentin XR

)
Class
Penicillin
Considerations
Equal DRSP coverage to
amoxicillin
Covers beta-lactamase
producing H. flu & M.cat
Food may enhance absorption,
as well as decreases GI upset
Tastes good
Dosing
HD 80 - 90 mg/kg/day TID
(except XR)(max 3g/day amox)
Adverse Events
Nausea/vomiting
Diarrhea
Rash
Contraindications
Hypersensitivity to penicillins
Dosage forms
Suspension & chewable tablets
125/31.25/5 mL, 200/28.5/5 mL,
250/62.5/5 mL, 400/57/5 mL
Susp ES 600 mg/42.9/5 mL
Tablet 250 mg, 500 mg, 875
mg (125 mg clavulanate)
Tablet XR 1000 mg/62.5 mg
33
Oral Cephalosporins:
Selection after HD Amoxicillin Failure

All ORAL cephalosporins are LESS ACTIVE
against DRSP than amoxicillin

No benefit for DRSP after failing high dose
amoxicillin
Adds improved H. flu and M. cat coverage
Stable against beta-lactamase activity

34
Cefuroxime axetil
Class
Cephalosporin (2nd
generation)
Considerations
Decreased efficacy against
DRSP
Efficacious against beta-
lactamase producing H.flu &
M.cat
Requires food for absorption
Tastes bad
Dosing
30 mg/kg/day BID
(max 1000 mg/day)

Adverse Events
Nausea/vomiting
Diarrhea
Rash

Contraindications
Hypersensitivity to
cephalosporins

Dosage forms
Suspension
Tablets
35
Cefdinir
Class
Cephalosporin (3rd
generation)
Considerations
Decreased efficacy against
DRSP
Efficacious against beta-
lactamase producing H.flu
& M.cat
Tolerable taste-
banana/strawberry
Dosing
14 mg/kg/day QD - BID
(max 600 mg/day)
Adverse Events
Nausea/vomiting
Diarrhea
Rash

Contraindications
Hypersensitivity to
cephalosporins

Dosage forms
Suspension
Tablets
36
Ceftriaxone
3
rd
Generation Cephalosporin
Option when PO therapy fails
High middle ear fluid levels
Slightly better activity than amoxicillin
No comparison trial vs. HD amoxicillin for
DRSP therapy
Requires 3 IM doses
1 dose only has ~50% eradication of
intermediate resistant strains of pneumococcus
95% eradication of resistant strains
Little data on fully resistant DRSP (PCN MIC>2)

Lebowitz E et al Pediatr Infect Dis 1998;17:1126
37
Ceftriaxone
Class
Cephalosporin
(3rd generation)
Considerations
Good coverage
against DRSP and
beta- lactamase
producing M. cat &
H. flu
Dosing
50 mg/kg QD for 3
days IM (max 1 gram)
Adverse Events
Nausea/vomiting
Diarrhea
Rash

Contraindications
Hypersensitivity to
cephalosporins

Dosage forms
IM / IV
38
Non Beta-lactam Antibiotics
Activity Against DRSP

% Isolates Susceptible
Pen-S Pen-I Pen-R
Clindamycin 98% 90% 85%
Erythromycin 96% 80% 51%
Bactrim 94% 60% 20%
Dowell SF et al. Pediatr Infect Dis J 1999
39
Clindamycin (Cleocin)
If HD Amoxicillin Failure
Excellent pneumococcal coverage
Active against 80-85% of DRSP strains
NO H. flu or M. cat coverage at all
Requires co-therapy with agent active against H flu
(Bactrim, cefixime, etc.)
Palatability issue for suspension

40
Clindamycin: Cleocin
Class
Lincosamide
Considerations
NO coverage-H. flu or M. cat
15% cross resistance with
DRSP
Consider in combo tx for
penicillin allergic patients
Tastes awful
Dosing
10 - 30 mg/kg/day TID
(max 1800 mg/day)
Adverse Events
Nausea/vomiting
Diarrhea
Rash
Increased LFTs

Contraindications
Hypersensitivity to
clindamycin

Dosage forms
Suspension
Capsules
41
Macrolides
If HD Amoxicillin Failure
Erythromycin Azithromycin- Clarithromycin

80% of penicillin intermediate and 50% of
resistant strains remain fully susceptible to
macrolides
H. influenza coverage generally less susceptible
than with beta-lactams
All have good M. cattarhallis coverage
42
Azithromycin
Class
Macrolide
Considerations
DRSP ~ 50% cross
resistance
Decreased H. flu coverage
Tastes okay - aftertaste
Dosing
10 mg/kg x1 dose then 5
mg/kg QD for 4 days
(max 500mg/250 mg)
10 mg/kg QD for 3 days
(max 500 mg)
30 mg/kg x 1 (max 1500 mg)
Adverse Events
Nausea/vomiting
Diarrhea
Abdominal pain
Rash
Contraindications
Hypersensitivity to
macrolides
Dosage forms
Injection
Suspension
Tablet
43
Trimethoprim/Sulfamethoxazole
(Bactrim)
20% of DRSP strains remain fully
susceptible to Bactrim and significantly
lower level of activity than with
macrolides or clindamycin
H. influenza and M. cattarhallis coverage
Dosing: 6-12 mg/kg/day BID

44
Is it Rational to Treat AOM with
Antibiotics to Prevent Mastoiditis?
Dutch strategy vs. US practice (100,000
children/year):
2 additional mastoiditis cases in Netherlands
7,800 more antibiotic prescriptions in US
1,600 fewer adverse drug effects in Netherlands
# needed to treat = 3,900 to prevent 1 episode
mastoiditis
Estimated antibiotic $ to prevent 1 episode = $117,000
(assumption $30/Rx)
800 ADRs to prevent 1 episode mastoiditis
Additional cost to manage ADE?
PIDJ 2001;20:140-4