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.
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Acute Otitis media_2007.ppt
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
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
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
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)
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
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?