Acute Otitis Media
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Acute Otitis Media. Otitis Media with Effusion. It is estimated that in the US 24,000,000 AOM episodes occur yearly 6% failures ~1,500,000 failures. AOM : Spectrum of Pathogens. S. pneumoniae25  40% H. influenzae20  35% M. catarrhalis5  20% S. pyogenes 2  5%.

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Acute Otitis Media

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Acute Otitis Media


Otitis Media with Effusion


It is estimated that in the US

24,000,000 AOM episodes

occur yearly

6% failures ~1,500,000

failures


AOM : Spectrum of Pathogens

S. pneumoniae25  40%

H. influenzae20  35%

M. catarrhalis5  20%

S. pyogenes 2  5%


Risk factors for failure regardless of antibiotic

  • Age <2 years

  • Daycare

  • Recurrent AOM

  • Recurrent antibiotics in past 3 months

  • Mixed viral and bacterial infection

  • Mixed S. pneumoniae and H. influenzae infection

Leibovitz & Dagan. Infect Med 2001; 18:212–216.


The goals ofantibacterial therapy

Maximize clinical outcome by maximizing therapeutic effect

Maximum reduction in bacterial load at site of

infection, with aim of bacterial eradication

Minimize potential for emergence and selection of resistance

Maximize cost–benefit of treatment

Reduce the number of

individuals carrying

resistant bacteria

Minimize spread

of resistance


Persistence of Pathogens in MEF Day 2-7 - Placebo

S. pneumoniae

H. influenzae

Howie & Ploussard, Clin Pediatr 1972; 11:205-14


The “Pollyanna Phenomenon”

Marchant et al, J Pediat 120:72-7, 1992

Bacteriologic efficacy

in bacterial AOM

Clinical efficacy

in clinical AOM

Clinical efficacy

in bacterial AOM

Placebo


Some drugs work better than others

in bacteriologic eradication in AOM

Eradication is associated with improved clinical outcome


b

a

c

TYMPANOCENTESIS

CULTURE

The Double-Tympanocentesis Method

TREATMENT

day 1

day 4-6

day 10-12

day 21-30


62

52

40

21

15

10

9

2/22

4/41

4/19

18/29

34/85

7/46

Pnc - S

Pnc - I, R

Hi

Placebo

Cefaclor vs. Cefuroxime-Axetil: Bacteriology and Organism-specific Bacteriological Failure

CEF - AXET

CECL

84

Pnc

Hi

% bacteriologic failures

Placebo

Dagan et al, J Infect Dis 176:1253-1259, 1997

Dagan et al AAC 44:43-50, 2000


73

50

0

0

0/9

11/15

0/28

6/12

Bacteriologic Failure Rate (day 4-5) TMP/SMX

as an Example of “All-or-Non Phenomenon”

MIC<=0.5 mcg/ml

84

MIC >0.5 mcg/ml

52

% bacteriologic failures

Pnc

Placebo Pnc

Hi

Placebo Hi

Leiberman et al, Pediatr Infect Dis, 20:260-4, 2001


Bacteriological Eradication of Baseline Pathogens at day 4 to 6 by Patient and Treatment Group

Augmentin

Azithromycin

P= 0.0001

P= 0.1

P= 0.26

P < 0.0001

% with bacteriologic success

54/65

35/71

26/30

13/33

18/20

13/19

10/15

9/19


6/6

3 days (Dagan et al AAC 44:43-50, 2000)

100

0.25

5 days (Dagan et al PIDJ 19:95-104, 2000)

0.25

5/8

11/17

23/36

11/18

5/9

65

64

63

61

56

2/25

0/12

8

0

<= 0.25

> 2.0

0.5 - 1

2.0 - 4.0

Bacteriologic Failure Rate (day 4-6)

for Azithromycin

Pnc

Hi

100

90

84

80

70

60

52

% with bacteriological failure

50

40

30

20

10

0

Placebo

Placebo

Azithromycin MIC (µg/ml)

For placebo - Howie, Clin Pediatr 11:205-14,1972


Amox/CA 45

Amox/CA 90

6.3

2

5/80

2/117

Amox/Clav Pk/Pd: Regular dose (45mg/Kg/d) vs. High Dose (90mg/Kg/d): Bacteriological Failures

Hi

23.1

P = 0.01

% Bacteriologic persistence

Pnc

6

9/39

5/80

Dagan et al. Pediatr Infect Dis J 19:95–104, 2000

Dagan et al, Pediatr Infect Dis J 20:829-37, 2001


Does all this

matter?


Clinical Success: Augmentin vs. Azithromycin

Augmentin

Azithromycin

P=0.01

P=0.023

% with clinical success

80

58

87

39

83

49

Dagan et al Pediatr Inf Dis J Feb 00


How to choose

antibiotics for AOM?


AOM

1st AOM

Recurrent or

non-responsive

AOM

(no AOM in last 3 m)

  • Amox (40 - 100)

  • A/C (40 - 90)

  • Cefurox axetil

  • Ceftriaxone (1/3 doses)

  • (if unable to take PO)

  • Amox (80 - 100)

  • A/C (90)

  • Cefurox axetil

  • Ceftriaxone (3 doses)


Hold fire !!

Easier on the

trigger

  • age >= 2 yrs

  • purulent rhinitis + SOM

  • no fever, mild symptoms

  • 1st AOM

  • age < 1 yr

  • bulging yellow (pus) ear drum

  • DCC attendee

  • recurrent/non-responsive AOM

  • high fever, toxic-appearing

  • genetic risk factors

  • anatomic risk factors


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