This document provides an overview of acute otitis media including pathophysiology, common pathogens, risk factors, diagnosis, treatment considerations and options. It discusses the increasing prevalence of antibiotic resistant Streptococcus pneumoniae and recommends high dose amoxicillin as first line treatment. It outlines second line options including augmentin, oral cephalosporins, ceftriaxone, clindamycin or macrolides if amoxicillin fails or for patients at high risk of resistant S. pneumoniae. The document emphasizes judicious antibiotic use guided by diagnosis and local resistance patterns.

1. 1
Acute Otitis Media
Sarah Jones, PharmD
Infectious Disease Clinical Pharmacist
Children's Hospital Boston

2. 2
Objectives
 Demonstrate an understanding of
pathophysiology
 List the common pathogens in acute otitis media
 Demonstrate knowledge of both the advantages
and disadvantages of antibiotic therapy
 Demonstrate application of concepts in
development of an appropriate treatment plan

3. 3
Rudolph's Pediatrics - 21st ed 2002
Definition
 Acute Otitis Media (AOM)
 “Inflammation of middle ear resulting in an effusion
and associated with systemic signs of illness”
 Otitis Media with effusion (OME)
 “Effusion of the middle ear without evidence of an
acute or systemic infection”

4. 4
N Engl J Med 2002 347:1169-1174
Prevalence
 31 million visits to physicians annually in U.S.
 Most common diagnosis for an antibiotic
prescription in children
 Diagnosed > 5 million times a year

5. 5
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: 10o
children vs. 45o
adult
 Decreased
immunocompetence
 Follows upper
respiratory infection
(URI)
 Peak incidence 2 - 4 days

6. 6
Pediatr Infect Dis J 1999 18:1-9
Risk factors
 Upper respiratory infection
 < 6 yo
 Day care
 Non-breast fed infants
 Passive smoking
 Immunocompromised
 Eustachian tube dysfunction

7. 7
Diagnosis: Clinical Manifestations
 Specific
 Otalgia
 Otorrhea
 Dizziness
 Hearing loss
 Non-specific
 Fever (50%)
 Vomiting/diarrhea
 Anorexia
 Irritability

8. 8
Diagnosis: Clinical Findings
 Otoscopic findings
 Bulging TM
 Yellow, white, or bright red color
 Opacification of eardrum
 Impaired visibility of ossicular landmarks
 Squamous exudate
Rudolph’s Pediatrics - 21st ed 2002

9. 9
Pathogens
Bacterial
 Streptococcus
pneumoniae
 Haemophilus influenzae
 Moraxella catarrhalis
Viral
 RSV
 Influenzae A & B
 Parainfluenzae 1,2, & 3
 Rhinovirus
 Adenovirus
 Enterovirus
 Coronavirus

10. 10
Potential Complications
 Hearing loss
 Acute mastoiditis
Rare:
 Meningitis
 Subdural/extradural abscess

11. 11
Treatment Considerations
 Allergies
 AOM history
 Spectrum of activity
 Local resistance pattern
 Recent antibiotic
treatment
 Age
 Duration
 Compliance
 Adverse drug events
 Cost

12. 12
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

13. 13
Penicillin Resistance of S. pneumoniae,
U.S. 1979-2000
0
5
10
15
20
25
30
1979 1982 1985 1988 1991 1994 1997 2000
%
Nonsusceptible
Intermediate Resistance High Level Resistance

14. 14
DRSP at Children’s 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

15. 15
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)

16. 16
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

17. 17
Principles of 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 for diagnosis
 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

18. 18
Treatment
High risk
DRSP?
(Day care, <2 yo,
antibiotics within
3 months)
1st 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 Usual or HD
amoxicillin

19. 19
Amoxicillin: 1st 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

20. 20
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)

21. 21
DRSP: Beta-lactam Activity & Levels
Dowell SF et al. Pediatr Infect Dis J 1999 plus cefdinir

22. 22
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

23. 23
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
 2nd Line Therapy
 DRSP
 Beta-lactamase producing H.influenza and
M. cattarhalis

24. 24
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

25. 25
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

26. 26
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

27. 27
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

28. 28
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

29. 29
Ceftriaxone:
3rd 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

30. 30
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

31. 31
Activity of Non Beta-lactam
Antibiotics Against DRSP
% Isolates Susceptible
Pen-S Pen-I Pen-R
Clindamycin 98% 90% 85%
Erythromycin 96% 80% 51%
TMP/SMX 94% 60% 20%
Dowell SF et al. Pediatr Infect Dis J 1999

32. 32
Clindamycin (Cleocin®)
Selection after 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
(TMP/SMX, cefixime, etc.)
 Palatability issue for suspension

33. 33
Clindamycin: Cleocin®
 Class
 Lincosamide
 Considerations
 NO coverage for 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 LFT’s
 Contraindications
 Hypersensitivity to clindamycin
 Dosage forms
 Suspensio
 Capsules

34. 34
Macrolides:
Selection after 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

35. 35
Azithromycin
 Class
 Macrolide
 Considerations
 DRSP ~ 50% cross resistance
 Decreased H. flu coverage
 Tastes bad - lasting 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

36. 36
Trimethoprim/Sulfamethoxazole
(Bactrim®)
 20% of DRSP strains remain fully susceptible
to TMP/SMX but significantly lower level of
activity than with macrolides or clindamycin
 H. influenza and M. cattarhallis coverage
 Dosing: 6-12 mg/kg/day BID

37. 37
Pediatr Infect Dis J 2002 21:599-604
Future Options
 Fluoroquinolones
 Good activity against S. pneumoniae
 Avoid use in children because lack of FDA indication
 Gatifloxacin - being studied in pediatric AOM
 10 mg/kg/dose IV or PO Q24 hours
 Ketolides
 Advanced generation macrolide
 Activity against resistant S. pneumoniae increased
 Telithromycin (Ketek®
) recently approved

38. 38
Pediatr Infect Dis J 2003 22:10-16; Curr
Opin Infect Dis 2000 13:165-170;
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 within 6 months or 4 episodes within 1 year
 <6 months with >1 episode
 Cause of resistance in the community

39. 39
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

40. 40
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
 No. needed to treat is 3,900 to prevent 1 episode
mastoiditis
 Estimated antibiotic cost to prevent 1 episode = $117,000
(assumption $30/Rx)
 800 adverse drug reactions to prevent 1 episode mastoiditis
 Additional cost to manage ADE?
PIDJ 2001;20:140-4

41. 41
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 rise of resistance incidence
 First line treatment of AOM is amoxicillin
90 mg/kg/day divided TID !!

42. 42
Case
3 yo with moderate to severe otalgia, bulging TM, treated with
amoxicillin 45 mg/kg/day divided TID
Returns at 3 days with complaint of continual otalgia, low-grade
fever, and unchanged exam
What are the 2nd line options in the current era of
antimicrobial resistance?
What would the best alternative to amoxicillin be
for this patient if penicillin allergic?