Acute Otitis Media

1. Acute Otitis Media

2. Otitis Media with Effusion

3. It is estimated that in the US 24,000,000 AOM episodes occur yearly 6% failures ~1,500,000 failures

4. AOM : Spectrum of Pathogens S. pneumoniae 25  40% H. influenzae 20  35% M. catarrhalis 5  20% S. pyogenes 2  5%

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.

6. 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

7. Persistence of Pathogens in MEF Day 2-7 - Placebo S. pneumoniae H. influenzae Howie & Ploussard, Clin Pediatr 1972; 11:205-14

8. 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

9. Some drugs work better than others in bacteriologic eradication in AOM Eradication is associated with improved clinical outcome

10. b a c TYMPANOCENTESIS CULTURE The Double-Tympanocentesis Method TREATMENT day 1 day 4-6 day 10-12 day 21-30

11. 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

12. 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

13. 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

14. 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

15. 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

16. Does all this matter?

17. 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

18. How to choose antibiotics for AOM?

19. 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)

20. 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