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

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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

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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.

TABLE 1

Finnish Otitis Media Vaccine Trial: Causes of AOM Episodes and Impact of PCV-7 Immunization on Incidence

CAUSE	PCV-7 EPISODES	CONTROL EPISODES	DIFFERENCE (%)
Culture-confirmed pneumococcus	271	414	34
Pneumococcal serotype in vaccine	107	250	57
Vaccine cross-reactive serotypes*	41	84	51
Other pneumococcal serotypes	125	95	33
Haemophilus influenzae	315	287	11
Moraxella catarrhalis	379	381	1
*6A, 9N, 18B, 19A, 23A.
AOM, acute otitis media; PCV-7, 7-valent pneumococcal conjugate vaccine.
Adapted with permission from Eskola J, et al. N Engl J Med. 2001;344:403-409. Copyright 2001 Massachusetts Medical Society. All rights reserved.

Study Results From a Rural Kentucky Practice

In this practice, data on isolates from middle ear fluid were collected in children with severe or refractory AOM aged 7 to 24 months.⁹ Data were obtained from 1992 to 1998, before the introduction of PCV-7, and from 2000 to 2003, following immunization with 3 or 4 doses of PCV-7 during the first 18 months of life.

As shown in TABLE 2, the pre-PCV-7 group of children (N=336; 1992-1998) had a proportion of 48% culture-confirmed pneumococcus vs a proportion of 31% in the PCV-7-vaccinated group (N=83; 2000-2003), a 17% decrease. The decrease in proportion of AOM episodes resulting from vaccine serotypes was 34%.

FAST TRACK

β-lactamase-positive organisms increased 56% following PCV-7 vaccine introduction compared with pre-PCV-7 rates

In this investigation, 28% of the pre-PCV-7 group and 34% of the post-PCV-7 group had received antibiotic therapy within the previous 3 days. Additionally, 59% and 76%, respectively, had received antibiotic therapy within the preceding 30 days. There were increases of 30% in vaccine cross-reactive serotypes and 45% in nonvaccine serotypes. Vaccine cross-reactive serotypes 6A and 19A accounted for most of the penicillin-nonsusceptible S pneumoniae strains in the vaccinated population.

Most impressive, however, in the post-PCV-7 group, was that gram-negative bacteria, mainly H influenzae, accounted for two thirds of AOM isolates, an increase from 41% in the pre-PCV-7 group to 56% in the vaccinated group. A 56% increase was noted in β-lactamase–positive organisms from the pre-PCV-7 group to the post-PCV-7 group. The combined H influenzae and M catarrhalis β-lactamase–producing organisms accounted for nearly half of all isolates.⁹

TABLE 2

Results From a Rural Kentucky Practice: Change in AOM Microbiology From Pre-PCV-7 (1992–1998) to Post-PCV-7 (2000–2003)

PATHOGEN	PRE-PCV-7 1992-1998 (N=336)		POST-PCV-7 2000-2003 (N=83)		CHANGE (%)	P VALUE
PATHOGEN	n	%	n	%	CHANGE (%)	P VALUE
Culture-confirmed pneumococcus	160	48	26	31	17	.007
Pneumococcal serotype in vaccine	236	70	30	36	34	.003
Vaccine cross-reactive serotypes*	27	8	27	32	24	.003
Other pneumococcal serotypes^†	74	22	27	32	10	NS
Haemophilus influenzae	137	41	46	32	15	.01
β-lactamase-positive	108	23	39	36	15	.007
Moraxella catarrhalis, β-lactamase-positive	31	9	9	11	2	NS
AOM, acute otitis media; n, total isolates; NS, nonsignificant; PCV-7, 7-valent pneumococcal conjugate vaccine.
*Includes 6A and 19A.
^†Nonvaccine serotypes in post-PCV-7 group: 1, 11A, 15A, 29, and 33F.
Adapted with permission from Block SL, et al. Pediatr Infect Dis J. 2004;23:829-833.

The Prospective Rochester, New York Study

Changes in pre- and post-PVC-7 patterns also were seen in a prospective study of 551 children with persistent or nonresponsive AOM (defined as nonresponders after 1 or 2 empiric antibiotic courses or failures after 48 hours of treatment). These children underwent tympanocentesis to identify bacterial isolates during the 9-year period from 1995 to 2003.¹⁰

From 1995 to 1997, enrollees received a standard dose of amoxicillin (40-50 mg/kg, divided into 3 doses daily) as initial empiric treatment. From 1998 to 2000 and 2001 to 2003, all children received high-dose amoxicillin (80-100 mg/kg, divided into twice-daily doses).

During the latter period, the children also were vaccinated with PCV-7, with 63% receiving the primary series of 3 doses and 10% receiving the booster dose. In this investigation, shortages in vaccine supply, discussed below, caused vaccination schedules to be compromised.

Study results (TABLE 3) show that in the post-PCV-7 group, there was a 13% decrease in the proportion of S pneumoniae isolates and a 14% increase in the proportion of H influenzae isolates compared with the pre-PCV-7 group (1998-2000 enrollees). An increase of 22% for β-lactamase–positive bacteria was also observed, along with a trend toward an increased proportion of penicillin-susceptible S pneumoniae isolates (58% vs 72%; P=.017) post-PCV-7.¹⁰ A 24% reduction (P=.009) in the frequency of the diagnosis of persistent or AOM treatment failure occurred in the period after PCV-7 vaccination. These changes were considered to be the result of the use of the conjugate pneumococcal vaccine rather than of the change in amoxicillin dosing.¹⁰

TABLE 3

The Prospective Rochester, New York Study: Pathogens Isolated in Persistent AOM and AOM Treatment Failure Pre- and Post-PCV-7

PATHOGEN	PRE-PCV-7 1998-2000 (N=204)		POST-PCV-7 2000-2003 (N=152)		CHANGE (%)	P VALUE
PATHOGEN	n	%	n	%	CHANGE (%)	P VALUE
Streptococcus pneumoniae*	50	44	28	31	13	.017
Penicillin nonsusceptible	12	24	4	14	10	NS
Haemophilus influenzae	49	43	51	57	14	.012
β-lactamase-positive	16	33	28	55	22	.044
Moraxella catarrhalis	6	5	1	1	4	NS
AOM, acute otitis media; N, total isolates; NS, nonsignificant; PCV-7, 7-valent pneumococcal conjugate vaccine.
*Pneumococcal serotyping was not done.
Adapted with permission from Casey JR, Pichichero ME. Pediatr Infect Dis J. 2004;23:824-828.

Pneumococcal serotype shifts

In addition to the change in causative pathogens, use of the conjugate pneumococcal vaccine appears to have led to a significant shift in the pneumococcal strains causing AOM. Studies at urban medical centers and in the Kentucky practice documented an increase in the proportion of nonvaccine serotypes, accounting for 32% to 38% of pneumococcal AOM.^10-12 A 33% increase was seen in the Finnish Trial.² These nonvaccine pneumococcal serotypes do not carry the same level of resistance seen with those serotypes included in PCV-7.