Acute Otitis Media: Influence of the PCV-7 vaccine on changes in the disease and its management

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Medical Education Library

Acute Otitis Media: Influence of the PCV-7 vaccine on changes in the disease and its management

J Fam Pract. 2005 November;54(11):961-968

By

Stephen Brunton, MD

Michael E. Pichichero, MD

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References

1. Fireman B, Black SB, Shinefield HR, et al. Impact of the pneumococcal conjugate vaccine on otitis media. Pediatr Infect Dis J. 2003;22:10-16.

2. Eskola J, Kilpi T, Palmu A, et al. Efficacy of a pneumococcal conjugate vaccine against acute otitis media. N Engl J Med. 2001;344:403-409.

3. Block SL, Harrison CH, Hedrick J, et al. Restricted use of antibiotic prophylaxis for recurrent acute otitis media in the era of penicillin non-susceptible Streptococcus pneumoniae. Int J Pediatr Otorhinolaryngol. 2001;61:47-60.

4. Advisory Committee on Immunization Practices. Preventing pneumococcal disease among infants and young children: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2000;49(RR-9):1-35.

5. American Academy of Family Physicians Subcommittee on Management of Acute Otitis Media. Diagnosis and management of acute otitis media. Pediatrics. 2004;113:1451-1465.

6. Dowell SF, Butler JC, Giebink GS, et al. Acute otitis media: management and surveillance in an era of pneumococcal resistance—a report from the Drug-resistant Streptococcus pneumoniae Therapeutic Working Group. Pediatr Infect Dis J. 1999;18:1-9.

7. Block SL. Causative pathogens, antibiotic resistance and therapeutic considerations in acute otitis media. Pediatr Infect Dis J. 1997;16:449-456.

8. Bluestone CD, Stephenson JS, Martin LM. Ten-year review of otitis media pathogens. Pediatr Infect Dis J. 1992;11(suppl 8):S7-S11.

9. Block SL, Hedrick J, Harrison CJ, et al. Community-wide vaccination with the heptavalent pneumococcal conjugate significantly alters the microbiology of acute otitis media. Pediatr Infect Dis J. 2004;23:829-833.

10. Casey JR, Pichichero ME. Changes in frequency and pathogens causing acute otitis media in 1995-2003. Pediatr Infect Dis J. 2004;23:824-828.

11. Centers for Disease Control and Prevention. Updated recommendations on the use of pneumococcal conjugate vaccine: suspension of recommendation for third and fourth dose. MMWR Morb Mortal Wkly Rep. 2004;53:177-178.

12. Centers for Disease Control and Prevention. Pneumococcal conjugate vaccine shortage resolved. MMWR Morb Mortal Wkly Rep. 2004;53:851-852.

13. Prevnar® (pneumococcal 7-valent vaccine) [prescribing information]. Philadelphia, Pa: Wyeth Pharmaceuticals. Rev. 01/04.

14. Watson W. Pneumococcal conjugate vaccines. Pediatr Infect Dis J. 2000;19:331-332.

15. Giebink GS. The prevention of pneumococcal disease in children. N Engl J Med. 2001;345:1177-1183.

16. Pelton SI, Loughlin AM, Marchand CD. Seven valent pneumococcal conjugate vaccine immunization in two Boston communities: changes in serotypes and antimicrobial susceptibility among Streptococcus pneumoniae isolates. Pediatr Infect Dis J. 2003;23:1015-1022.

17. Freed GL, Davis MM, Clark SJ. Variation in public and private supply of pneumococcal conjugate vaccine during a shortage. JAMA. 2003;289:575-578.

18. Centers for Disease Control and Prevention. Decreased availability of pneumococcal conjugate vaccine. MMWR Morb Mortal Wkly Rep. 2001;50:783-784.

19. Centers for Disease Control and Prevention. Limited supply of pneumococcal conjugate vaccine: suspension of recommendation for fourth dose. MMWR Morb Mortal Wkly Rep. 2004;53:108-109.

20. CDC National Immunization Survey. Estimated vaccination coverage with individual vaccines and selected vaccination series by 24 months of age by state and immunization action plan area US, Q3/2003-Q4/2004. Available at: http://www2a.cdc.gov/nip/coverage/nis/nis_iap.asp?fmt=v&rpt=tab09_24mo_iap_0304&qtr=Q3/2003-Q2/2004. Accessed September 20, 2005.

21. Whitney CG, Farley MM, Hadler J, et al. Decline in invasive pneumococcal disease after the introduction of protein-polysaccharide conjugate vaccine. N Engl J Med. 2003;348:1737-1746.

22. Black S, Shinefield H, Baxter R, et al. Postlicensure surveillance for pneumococcal invasive disease after use of heptavalent pneumococcal vaccine in Northern California Kaiser Permanente. Pediatr Infect Dis J. 2004;23:485-489.

23. Pichichero ME, Casey JR. Acute otitis media: Making sense of recent guidelines on antimicrobial treatment. J Fam Pract. 2005;54:313-332.

24. Block SL, Harrison CJ. Diagnosis and Management of Acute Otitis Media, 3rd ed. In press.

Key Points and Recommendations

Widespread use of the 7-valent pneumococcal conjugate vaccine has resulted in a shift in frequency of causative bacterial pathogens responsible for recurrent and persistent acute otitis media (AOM); disease management practice should encompass this change (SOR: B).
High-dose amoxicillin is the first choice for antibiotic therapy in uncomplicated bacterial AOM, although β-lactamase–producing pathogens are increasingly common primary causative agents, and amoxicillin is susceptible to β-lactamase (SOR: B).
Adding clavulanate to amoxicillin increases resistance to and improves effectiveness against β-lactamase–producing pathogens. Specific third-generation cephalosporins also should be included as antibiotic choices because of excellent activity against β-lactamase–producing pathogens and because of compliance advantages, such as better taste, less frequent dosing, and even shorter duration of therapy (SOR: B).

Since the approval of the 7-valent pneumococcal conjugate vaccine (PCV-7) for use in children younger than 24 months in February 2000, occurrences of acute otitis media (AOM) and the frequency of recurrent AOM have declined. Based on results from early clinical trials, PCV-7 may reduce total AOM by 6% to 8%, recurrent AOM by 10% to 26%, and tympanostomy tube placements by 24%.^1,2

Acute otitis media occurs most frequently in children between the ages of 6 months and 18 months. By the end of their first year, approximately 86% of children will experience at least 1 episode of AOM.³

The condition remains a leading reason for visits to pediatricians and family physicians in the United States.⁴ It accounted for 16 million visits in 2000.⁴ This is a decrease from almost 25 million visits in 1995, prior to use of PCV-7. Additionally, AOM is associated with significant costs: In 1995, the direct and indirect costs of AOM were estimated to be about $3 billion.⁵

Changes in pathogen frequency for AOM in the ERA of PCV-7

The true impact of PCV-7 on management practice is not characterized by the modest reduction in incidence of uncomplicated AOM but in the PCV-7–associated shift in causative pathogens. Pre-PCV-7, 40% to 50% of cases of AOM in young children were caused by Streptococcus pneumoniae, 20% to 30% by Haemophilus influenzae, and 10% to 15% by Moraxella catarrhalis.⁶ In studies conducted prior to 2000, diagnostic tympanocentesis isolated S pneumoniae from 25% to 55% of all middle ear aspirates from children with AOM.^6-8

FAST TRACK

Amoxicillin is ineffective against β-lactamase–positive strains of Haemophilus influenzae

Conversely, 1 study published in 2001 and 2 studies published in 2004 appear to document a reverse trend with the advent of the conjugate pneumococcal vaccine.^9,10 Compared with children studied in an earlier era, those vaccinated with PCV-7 may be more likely to have H influenzae isolates. These studies will be described in detail below.

Bacterial AOM: initial antibiotic therapy and specific pathogens

Current guidelines recommend amoxicillin (45 mg/kg/day) or high-dose amoxicillin (80-90 mg/kg/day) as initial therapy in presumed or documented bacterial AOM.⁵ Although amoxicillin is effective against pneumococcus and β-lactamase–negative strains of H influenzae, it is ineffective against β-lactamase–positive strains of H influenzae.⁹ Significant initial failures may point to a changing pathogen per population frequency. A 2004 review assessed children with continued (persistence of infection detected within 30 days after treatment completion) or refractory (clinical failure while receiving antimicrobial therapy) AOM who have received high-dose amoxicillin as initial empiric therapy. The authors noted that the rate of infection due to H influenzae has increased from 43% among those treated prior to the licensure of PCV-7 to 57% among those who received 2 or more doses of PCV-7.¹⁰

Evidence from the medical literature

Three studies provide the major evidence concerning the pathogen shift associated with the adoption of the PCV-7 conjugate vaccine:

The Finnish Otitis Media Vaccine Trial²
A published collection of clinical trial results from a rural practice in Kentucky in which 94% of children were immunized with PCV-7⁹
A prospective study conducted in a suburban community-based private practice in Rochester, NY that evaluated children with persistent or nonresponsive AOM.¹⁰

The Finnish Otitis Media Vaccine Trial

In this trial, 1662 infants received either the PCV-7 vaccine or a control vaccine at ages 2, 4, 6, and 12 months and were monitored from ages 6.5 months to 24 months.² An overall 6.9% reduction in episodes of clinical AOM were diagnosed (n=1251) in PCV-7–vaccinated children compared with the control group (n=1345). This suggested that fewer AOM cases were caused by the S pneumoniae vaccine serotypes than nonvaccine serotypes. The bacteriologic findings in the samples of middle ear fluid taken during 93% of the visits for AOM (TABLE 1) show a 34% reduction in culture-confirmed episodes in the PCV-7–vaccinated group, a decrease of more than 50% in pneumococcal AOM episodes caused by vaccine or vaccine cross-reactive serotypes, a 33% increase in infections caused by other pneumococcal serotypes, and an 11% increase in the proportion of AOM cases due to H influenzae.²