1887

Chapter 14 : Otitis Media

Author: Lauren O. Bakaletz1
VIEW AFFILIATIONS HIDE AFFILIATIONS
Affiliations: 1: Division of Molecular Medicine, College of Medicine and Public Health, The Ohio State University, and Children's Research Institute, Columbus, OH 43205
Content Type: Monograph
Publication Year: 2002

Category: Clinical Microbiology

MyBook is a cheap paperback edition of the original book and will be sold at uniform, low price.

Preview this chapter:
Preview Magnify
Zoom in
Zoomout

Otitis Media, Page 1 of 2

| /docserver/preview/fulltext/10.1128/9781555817947/9781555812447_Chap14-1.gif /docserver/preview/fulltext/10.1128/9781555817947/9781555812447_Chap14-2.gif

Abstract:

In all areas of the world, upper respiratory tract (URT) infections and their complicating sequelae are the leading causes of acute infectious morbidity. Otitis media (OM), or inflammation of the middle ear, is one of these complicating sequelae of URT infections and is indeed a major health care concern of childhood. This chapter discusses OM’s etiologic agents, animal models, and mechanisms of pathogenesis. Multiple mechanisms have been identified that serve as contributing factors in the synergistic relationship between the URT viruses and the primary bacterial pathogens of OM, and while each of these is a highly specific effect, all fall within the general category of compromise of airway defenses. The chapter reviews some of these mechanisms, such as viral effects on bacterial adherence and/or colonization, antibiotic efficacy, host immune functions, and rheological properties of mucus and mucociliary transport. We are continually adapting our treatment regimens for OM on the basis of newly acquired information and our improved understanding of the molecular mechanisms behind the pathogenesis of middle ear infections. Some of the ways this increased understanding has led to changes in our approaches to treat and/or prevent OM are reviewed. Good clinical evidence exists to believe that by eradicating the predisposing viral infection, one could have a significant effect on prevention of bacterial OM. Vaccine or treatment strategies that effectively inhibit the initial establishment of infection in the middle ear cleft will be particularly important in this regard.

Citation: Bakaletz L. 2002. Otitis Media, p 259-298. In Brogden K, Guthmiller J (ed), Polymicrobial Diseases. ASM Press, Washington, DC. doi: 10.1128/9781555817947.ch14

Key Concept Ranking

Infection and Immunity
0.47523966
Tumor Necrosis Factor alpha
0.43312988
Influenza B virus
0.4185895
0.47523966
Highlighted Text: Show | Hide
Loading full text...

Full text loading...

Figures

Otitis Media
[com.pub2web.rdf.cci.facet.ContentItem[id=http://asm.metastore.ingenta.com/content/author/10.1128/9781555817947.chap14-1,webId=/content/author/10.1128/9781555817947.chap14-1,properties={foaf_givenname=Lauren O., foaf_name=Lauren O. Bakaletz, foaf_surname=Bakaletz, pub_isAffiliatedWith=[com.pub2web.rdf.cci.facet.ContentItem[id=http://asm.metastore.ingenta.com/content/affiliation/10.1128/9781555817947.chap14-aff1]]}]]
Citation: Bakaletz L. 2002. Otitis Media, p 259-298. In Brogden K, Guthmiller J (ed), Polymicrobial Diseases. ASM Press, Washington, DC. doi: 10.1128/9781555817947.ch14
/content/10.1128/9781555817947.chap14.fig14-1
FIGURE 1

Number of patients per month with AOM ( = 4,524) (a) and respiratory virus infections (b to f ) during a 6-year study in the Turku University Hospital (Turku, Finland). (b) All virus infections ( = 961); (c) respiratory syncytial virus ( = 472); (d) adenovirus (= 197); (e) parainfluenza virus types 1, 2, and 3 (= 176); (f ) influenza A (unshaded) and influenza B (gray) viruses ( = 116). (Reprinted from [ ] with permission of the publisher.)

10.1128/9781555817947/fig14-1_thmb.gif
10.1128/9781555817947/fig14-1.gif
Image of FIGURE 1
FIGURE 1

Number of patients per month with AOM ( = 4,524) (a) and respiratory virus infections (b to f ) during a 6-year study in the Turku University Hospital (Turku, Finland). (b) All virus infections ( = 961); (c) respiratory syncytial virus ( = 472); (d) adenovirus (= 197); (e) parainfluenza virus types 1, 2, and 3 (= 176); (f ) influenza A (unshaded) and influenza B (gray) viruses ( = 116). (Reprinted from [ ] with permission of the publisher.)

Citation: Bakaletz L. 2002. Otitis Media, p 259-298. In Brogden K, Guthmiller J (ed), Polymicrobial Diseases. ASM Press, Washington, DC. doi: 10.1128/9781555817947.ch14
Permissions and Reprints Request Permissions
Download as Powerpoint
/content/10.1128/9781555817947.chap14.fig14-2
FIGURE 2

(A) Cumulative percentage of 38 ears (19 chinchillas) developing OME after i.n. inoculation of type 7F All ears with effusion yielded pneumococci on culture. (B) Cumulative percentage of 72 ears (36 chinchillas) developing OME and without effusion after i.n. inoculation of type 7F and influenza A virus. Symbols: ●, animals with pneumococcal OME; Δ, animals with pneumococcal and other culture-positive OME (other bacteria included [1 ear] and species [1 ear]); □, animals with culturepositive as well as sterile OME; ○, animals with all types of OME and OM without effusion. (Both panels are reprinted from [ ] with permission of the publisher.)

10.1128/9781555817947/fig14-2_thmb.gif
10.1128/9781555817947/fig14-2.gif
Image of FIGURE 2
FIGURE 2

(A) Cumulative percentage of 38 ears (19 chinchillas) developing OME after i.n. inoculation of type 7F All ears with effusion yielded pneumococci on culture. (B) Cumulative percentage of 72 ears (36 chinchillas) developing OME and without effusion after i.n. inoculation of type 7F and influenza A virus. Symbols: ●, animals with pneumococcal OME; Δ, animals with pneumococcal and other culture-positive OME (other bacteria included [1 ear] and species [1 ear]); □, animals with culturepositive as well as sterile OME; ○, animals with all types of OME and OM without effusion. (Both panels are reprinted from [ ] with permission of the publisher.)

Citation: Bakaletz L. 2002. Otitis Media, p 259-298. In Brogden K, Guthmiller J (ed), Polymicrobial Diseases. ASM Press, Washington, DC. doi: 10.1128/9781555817947.ch14
Permissions and Reprints Request Permissions
Download as Powerpoint
/content/10.1128/9781555817947.chap14.fig14-3
FIGURE 3

Adherence of NTHI to chinchilla eustachian tube floor (a) or roof (b) mucus during AV infection. Symbols: ●, pharyngeal; ▪, mid-Eustachian tube; ▲, tympanic portion; *, significant difference compared with same day, same portion of ET roof, µ 0.05.) (c) Adherence of NTHI to chinchilla middle ear mucosal epithelium during adenovirus infection. (All panels are reprinted from [ ] with permission of the publisher.) Error bars indicate deviations.

10.1128/9781555817947/fig14-3_thmb.gif
10.1128/9781555817947/fig14-3.gif
Image of FIGURE 3
FIGURE 3

Adherence of NTHI to chinchilla eustachian tube floor (a) or roof (b) mucus during AV infection. Symbols: ●, pharyngeal; ▪, mid-Eustachian tube; ▲, tympanic portion; *, significant difference compared with same day, same portion of ET roof, µ 0.05.) (c) Adherence of NTHI to chinchilla middle ear mucosal epithelium during adenovirus infection. (All panels are reprinted from [ ] with permission of the publisher.) Error bars indicate deviations.

Citation: Bakaletz L. 2002. Otitis Media, p 259-298. In Brogden K, Guthmiller J (ed), Polymicrobial Diseases. ASM Press, Washington, DC. doi: 10.1128/9781555817947.ch14
Permissions and Reprints Request Permissions
Download as Powerpoint
/content/10.1128/9781555817947.chap14.fig14-4
FIGURE 4

Histographic representation of number of A549 cells ( axis) expressing red fluorescence of PKH-26-labeled NTHI ( axis), as determined by flow cytometry (A549:NTHI = 1:100). (A) Background fluorescence of RSV-exposed (multiplicity of infection = 1, 24 h) or control A549 cells; (B and C) fluorescence of NTHI and NTHI attached to control or pRSV-exposed A549 cells. (Reprinted from [ ] with permission of the publisher.)

10.1128/9781555817947/fig14-4_thmb.gif
10.1128/9781555817947/fig14-4.gif
Image of FIGURE 4
FIGURE 4

Histographic representation of number of A549 cells ( axis) expressing red fluorescence of PKH-26-labeled NTHI ( axis), as determined by flow cytometry (A549:NTHI = 1:100). (A) Background fluorescence of RSV-exposed (multiplicity of infection = 1, 24 h) or control A549 cells; (B and C) fluorescence of NTHI and NTHI attached to control or pRSV-exposed A549 cells. (Reprinted from [ ] with permission of the publisher.)

Citation: Bakaletz L. 2002. Otitis Media, p 259-298. In Brogden K, Guthmiller J (ed), Polymicrobial Diseases. ASM Press, Washington, DC. doi: 10.1128/9781555817947.ch14
Permissions and Reprints Request Permissions
Download as Powerpoint
/content/10.1128/9781555817947.chap14.fig14-5
FIGURE 5

Comparison of nasopharyngeal carriage of nontypeable and in normal (□) and otitis-prone (▨) children during health (A) and during upper respiratory tract illness (B). , < 0.05; , < 0.001 ( ). (Reprinted from the [ ] with permission of the publisher.)

10.1128/9781555817947/fig14-5_thmb.gif
10.1128/9781555817947/fig14-5.gif
Image of FIGURE 5
FIGURE 5

Comparison of nasopharyngeal carriage of nontypeable and in normal (□) and otitis-prone (▨) children during health (A) and during upper respiratory tract illness (B). , < 0.05; , < 0.001 ( ). (Reprinted from the [ ] with permission of the publisher.)

Citation: Bakaletz L. 2002. Otitis Media, p 259-298. In Brogden K, Guthmiller J (ed), Polymicrobial Diseases. ASM Press, Washington, DC. doi: 10.1128/9781555817947.ch14
Permissions and Reprints Request Permissions
Download as Powerpoint
/content/10.1128/9781555817947.chap14.fig14-6
FIGURE 6

Anatomy of the Eustachian tube and middle ear system. (Reprinted from [ ] with permission of the publisher.)

10.1128/9781555817947/fig14-6_thmb.gif
10.1128/9781555817947/fig14-6.gif
Image of FIGURE 6
FIGURE 6

Anatomy of the Eustachian tube and middle ear system. (Reprinted from [ ] with permission of the publisher.)

Citation: Bakaletz L. 2002. Otitis Media, p 259-298. In Brogden K, Guthmiller J (ed), Polymicrobial Diseases. ASM Press, Washington, DC. doi: 10.1128/9781555817947.ch14
Permissions and Reprints Request Permissions
Download as Powerpoint
/content/10.1128/9781555817947.chap14.fig14-7
FIGURE 7

Eustachian tube lumen on day 5 (a and b) and day 10 (c and d) after i.n. influenza virus inoculation showing mucoid secretions and cellular debris (hematoxylin and eosin stain; original magnification, ×400). (Reprinted from [ ] with permission of the publisher.)

10.1128/9781555817947/fig14-7_thmb.gif
10.1128/9781555817947/fig14-7.gif
Image of FIGURE 7
FIGURE 7

Eustachian tube lumen on day 5 (a and b) and day 10 (c and d) after i.n. influenza virus inoculation showing mucoid secretions and cellular debris (hematoxylin and eosin stain; original magnification, ×400). (Reprinted from [ ] with permission of the publisher.)

Citation: Bakaletz L. 2002. Otitis Media, p 259-298. In Brogden K, Guthmiller J (ed), Polymicrobial Diseases. ASM Press, Washington, DC. doi: 10.1128/9781555817947.ch14
Permissions and Reprints Request Permissions
Download as Powerpoint
/content/10.1128/9781555817947.chap14.fig14-8
FIGURE 8

Occurrence of AOM after the onset of URI in 250 episodes. Bar, number of cases on each day; line, cumulative force of morbidity. (Reprinted from [ ] with permission of the publisher.)

10.1128/9781555817947/fig14-8_thmb.gif
10.1128/9781555817947/fig14-8.gif
Image of FIGURE 8
FIGURE 8

Occurrence of AOM after the onset of URI in 250 episodes. Bar, number of cases on each day; line, cumulative force of morbidity. (Reprinted from [ ] with permission of the publisher.)

Citation: Bakaletz L. 2002. Otitis Media, p 259-298. In Brogden K, Guthmiller J (ed), Polymicrobial Diseases. ASM Press, Washington, DC. doi: 10.1128/9781555817947.ch14
Permissions and Reprints Request Permissions
Download as Powerpoint
/content/10.1128/9781555817947.chap14.fig14-9
FIGURE 9

Ciliary beat frequency of chinchilla Eustachian tube epithelium at sites near the tympanic or pharyngeal orifice following inoculation of influenza A virus. *, significant difference ( ≤ 0.01) from control. Error bars indicate standard deviations. (A) Transbullar inoculation; (B) i.n. inoculation. (Reprinted from [ ] with permission of the publisher.)

10.1128/9781555817947/fig14-9_thmb.gif
10.1128/9781555817947/fig14-9.gif
Image of FIGURE 9
FIGURE 9

Ciliary beat frequency of chinchilla Eustachian tube epithelium at sites near the tympanic or pharyngeal orifice following inoculation of influenza A virus. *, significant difference ( ≤ 0.01) from control. Error bars indicate standard deviations. (A) Transbullar inoculation; (B) i.n. inoculation. (Reprinted from [ ] with permission of the publisher.)

Citation: Bakaletz L. 2002. Otitis Media, p 259-298. In Brogden K, Guthmiller J (ed), Polymicrobial Diseases. ASM Press, Washington, DC. doi: 10.1128/9781555817947.ch14
Permissions and Reprints Request Permissions
Download as Powerpoint
/content/10.1128/9781555817947.chap14.fig14-10
FIGURE 10

Light micrographs of chinchilla Eustachian tube epithelium after i.n. inoculation of influenza A virus (original magnification, ×64). (A) Two days postinoculation, tympanic site. (B) At 4 days, pharyngeal site. Note focal loss of ciliated cells. (C) At 10 days, pharyngeal site. Note short, regenerating cilia. (D) At 28 days, pharyngeal site. Note normal appearance of epithelium. (Reprinted from [ ] with permission of the publisher.)

10.1128/9781555817947/fig14-10_thmb.gif
10.1128/9781555817947/fig14-10.gif
Image of FIGURE 10
FIGURE 10

Light micrographs of chinchilla Eustachian tube epithelium after i.n. inoculation of influenza A virus (original magnification, ×64). (A) Two days postinoculation, tympanic site. (B) At 4 days, pharyngeal site. Note focal loss of ciliated cells. (C) At 10 days, pharyngeal site. Note short, regenerating cilia. (D) At 28 days, pharyngeal site. Note normal appearance of epithelium. (Reprinted from [ ] with permission of the publisher.)

Citation: Bakaletz L. 2002. Otitis Media, p 259-298. In Brogden K, Guthmiller J (ed), Polymicrobial Diseases. ASM Press, Washington, DC. doi: 10.1128/9781555817947.ch14
Permissions and Reprints Request Permissions
Download as Powerpoint
/content/10.1128/9781555817947.chap14.fig14-11
FIGURE 11

(A) Change over time in ciliary activity of Eustachian tube mucosal epithelium after i.n. inoculation of AV type 1. Data represent means and standard deviations of at least 30 readings. (B) Change over time in ability of Eustachian tube to transport dye after i.n. inoculation of AV type 1. (Both panels are reprinted from [ ] with permission of the publisher.)

10.1128/9781555817947/fig14-11_thmb.gif
10.1128/9781555817947/fig14-11.gif
Image of FIGURE 11
FIGURE 11

(A) Change over time in ciliary activity of Eustachian tube mucosal epithelium after i.n. inoculation of AV type 1. Data represent means and standard deviations of at least 30 readings. (B) Change over time in ability of Eustachian tube to transport dye after i.n. inoculation of AV type 1. (Both panels are reprinted from [ ] with permission of the publisher.)

Citation: Bakaletz L. 2002. Otitis Media, p 259-298. In Brogden K, Guthmiller J (ed), Polymicrobial Diseases. ASM Press, Washington, DC. doi: 10.1128/9781555817947.ch14
Permissions and Reprints Request Permissions
Download as Powerpoint
/content/10.1128/9781555817947.chap14.fig14-12
FIGURE 12

Cross-sections in mid-Eustachian tube 14 days after intranasal inoculation. (a) Note many vacuolated epithelial cells (vac) and those demonstrating late stages of intranuclear inclusions typical of AV. (b) Note marked goblet cell (*) hyperplasia. Bars = 50 µm. (Reprinted from [ ] with permission of the publisher.)

10.1128/9781555817947/fig14-12_thmb.gif
10.1128/9781555817947/fig14-12.gif
Image of FIGURE 12
FIGURE 12

Cross-sections in mid-Eustachian tube 14 days after intranasal inoculation. (a) Note many vacuolated epithelial cells (vac) and those demonstrating late stages of intranuclear inclusions typical of AV. (b) Note marked goblet cell (*) hyperplasia. Bars = 50 µm. (Reprinted from [ ] with permission of the publisher.)

Citation: Bakaletz L. 2002. Otitis Media, p 259-298. In Brogden K, Guthmiller J (ed), Polymicrobial Diseases. ASM Press, Washington, DC. doi: 10.1128/9781555817947.ch14
Permissions and Reprints Request Permissions
Download as Powerpoint
/content/10.1128/9781555817947.chap14.fig14-13
FIGURE 13

(A) Percentage of nasal lavage specimens that were culture positive for NTHI in AV-compromised chinchillas that received either saline (shamimmunized) or antisera directed against one of two adhesin-based immunogens [LB1 or LPD-LB1 (f)] by passive transfer prior to i.n. challenge with either of two strains of NTHI (86-028NP or 1885MEE). (B) Percentage of ears that developed OM within each cohort of animals depicted in A. (Both panels are reprinted from [ ] with permission of the publisher.)

10.1128/9781555817947/fig14-13a_thmb.gif
10.1128/9781555817947/fig14-13a.gif
Image of FIGURE 13
FIGURE 13

(A) Percentage of nasal lavage specimens that were culture positive for NTHI in AV-compromised chinchillas that received either saline (shamimmunized) or antisera directed against one of two adhesin-based immunogens [LB1 or LPD-LB1 (f)] by passive transfer prior to i.n. challenge with either of two strains of NTHI (86-028NP or 1885MEE). (B) Percentage of ears that developed OM within each cohort of animals depicted in A. (Both panels are reprinted from [ ] with permission of the publisher.)

Citation: Bakaletz L. 2002. Otitis Media, p 259-298. In Brogden K, Guthmiller J (ed), Polymicrobial Diseases. ASM Press, Washington, DC. doi: 10.1128/9781555817947.ch14
Permissions and Reprints Request Permissions
Download as Powerpoint

References

/content/book/10.1128/9781555817947.chap14
1. Abramson, J. S.,, G. S. Giebink,, E. L. Mills,, and P. G. Quie. 1981. Polymorphonuclear leukocyte dysfunction during influenza virus infection in chinchillas. J. Infect. Dis. 143: 836– 845.
2. Abramson, J. S.,, and J. G. Wheeler. 1994. Virus-induced neutrophil dysfunction: role in the pathogenesis of bacterial infections. Pediatr. Infect. Dis. J. 13: 643– 652.
3. Alsarraf, R.,, C. J. Jung,, J. Perkins,, C. Crowley,, N. W. Alsarraf,, and G. A. Gates. 1999. Measuring the indirect and direct costs of acute otitis media. Arch. Otolaryngol. Head Neck Surg. 125: 12– 18.
4. Anderson, L. J. 2000. Respiratory syncytial virus vaccines for otitis media. Vaccine 19( Suppl. 1): S59– S65.
5. Arola, M.,, O. Ruuskanen,, T. Ziegler,, J. Mertsola,, K. Nanto-Salonen,, A. Putto-Laurila,, M. K. Viljanen,, and P. Halonen. 1990. Clinical role of respiratory virus infection in acute otitis media. Pediatrics. 86: 848– 855.
6. Arola, M.,, T. Ziegler,, H. Puhakka,, O. P. Lehtonen,, and O. Ruuskanen. 1990. Rhinovirus in otitis media with effusion. Ann. Otol. Rhinol. Laryngol. 99: 451– 453.
7. Arola, M.,, T. Ziegler,, and O. Ruuskanen. 1990. Respiratory virus infection as a cause of prolonged symptoms in acute otitis media. J. Pediatr. 116: 697– 701.
8. Arva, E.,, and B. Andersson. 1999. Induction of phagocyte-stimulating and Th1-promoting cytokines by in vitro stimulation of human peripheral blood mononuclear cells with Streptococcus pneumoniae. Scand. J. Immunol. 49: 417– 423.
9. Arva, E.,, and B. Andersson. 1999. Induction of phagocyte-stimulating cytokines by in vitro stimulation of human peripheral blood mononuclear cells with Haemophilus influenzae. Scand. J. Immunol. 49: 411– 416.
10. Aul, J. J.,, K. W. Anderson,, R. M. Wadowsky,, W. J. Doyle,, L. A. Kingsley,, J. C. Post,, and G. D. Ehrlich. 1998. Comparative evaluation of culture and PCR for the detection and determination of persistence of bacterial strains and DNAs in the Chinchilla laniger model of otitis media. Ann. Otol. Rhinol. Laryngol. 107: 508– 513.
11. Bakaletz, L.,, S. R. Griffith,, and D. J. Lim,. 1988. Effect of prostaglandin E2 and bacterial endotoxin on the rate of dye transport in the chinchilla eustachian tube, p. 99– 102. In D. J. Lim,, C. D. Bluestone,, J. O. Klein,, and J. D. Nelson (ed.), Proceedings of the Fourth International Symposium on Recent Advances in Otitis Media. B. C. Decker Inc., Toronto, Ontario, Canada..
12. Bakaletz, L. O. 1995. Viral potentiation of bacterial superinfection of the respiratory tract. Trends Microbiol. 3: 110– 114.
13. Bakaletz, L. O.,, R. L. Daniels,, and D. J. Lim. 1993. Modeling adenovirus type 1-induced otitis media in the chinchilla: effect on ciliary activity and fluid transport function of eustachian tube mucosal epithelium. J. Infect. Dis. 168: 865– 872. ( Erratum, 168:1605, 1993.).
14. Bakaletz, L. O.,, T. M. Hoepf,, T. F. De- Maria,, and D. J. Lim. 1988. The effect of antecedent influenza A virus infection on the adherence of Hemophilus influenzae to chinchilla tracheal epithelium. Am. J. Otolaryngol. 9: 127– 134.
15. Bakaletz, L. O.,, and K. A. Holmes. 1997. Evidence for transudation of specific antibody into the middle ears of parenterally immunized chinchillas after an upper respiratory tract infection with adenovirus. Clin. Diagn. Lab. Immunol. 4: 223– 225.
16. Bakaletz, L. O.,, B. J. Kennedy,, L. A. Novotny,, G. Dequesne,, J. Cohen,, and Y. Lobet. 1999. Protection against development of otitis media induced by nontypeable Haemophilus influenzae by both active and passive immunization in a chinchilla model of virus-bacterium superinfection. Infect. Immun. 67: 2746– 2762.
17. Bakaletz, L. O.,, D. M. Murwin,, and J. M. Billy. 1995. Adenovirus serotype 1 does not act synergistically with Moraxella (Branhamella) catarrhalis to induce otitis media in the chinchilla. Infect. Immun. 63: 4188– 4190.
18. Bakaletz, L. O.,, G. J. White,, J. C. Post,, and G. D. Ehrlich. 1998. Blinded multiplex PCR analyses of middle ear and nasopharyngeal fluids from chinchilla models of single- and mixedpathogen- induced otitis media. Clin. Diagn. Lab. Immunol. 5: 219– 224.
19. Baldwin, R. L. 1993. Effects of otitis media on child development. Am. J. Otol. 14: 601– 604.
20. Belshe, R. B.,, P. M. Mendelman,, J. Treanor,, J. King,, W. C. Gruber,, P. Piedra,, D. I. Bernstein,, F. G. Hayden,, K. Kotloff,, K. Zangwill,, D. Iacuzio,, and M. Wolff. 1998. The efficacy of live attenuated, cold-adapted, trivalent, intranasal influenza virus vaccine in children. N. Engl. J. Med. 338: 1405– 1412.
21. Berman, S.,, R. Roark,, and D. Luckey. 1994. Theoretical cost effectiveness of management options for children with persisting middle ear effusions. Pediatrics 93: 353– 363.
22. Black, S.,, H. Shinefield,, B. Fireman,, E. Lewis,, P. Ray,, J. R. Hansen,, L. Elvin,, K. M. Ensor,, J. Hackell,, G. Siber,, F. Malinoski,, D. Madore,, I. Chang,, R. Kohberger,, W. Watson,, R. Austrian,, K. Edwards, and the Northern California Kaiser Permanente Vaccine Study Center Group. 2000. Efficacy, safety and immunogenicity of heptavalent pneumococcal conjugate vaccine in children. Pediatr. Infect. Dis. J. 19: 187– 195.
23. Bluestone, C. D. 1996. Pathogenesis of otitis media: role of eustachian tube. Pediatr. Infect. Dis. J. 15: 281– 291.
24. Bright, R. A.,, R. M. Moore, Jr.,, L. L. Jeng,, C. M. Sharkness,, S. E. Hamburger,, and P. M. Hamilton. 1993. The prevalence of tympanostomy tubes in children in the United States, 1988. Am. J. Public Health 83: 1026– 1028.
25. Brook, I.,, and A. E. Gober. 1999. Resistance to antimicrobials used for therapy of otitis media and sinusitis: effect of previous antimicrobial therapy and smoking. Ann. Otol. Rhinol. Laryngol. 108: 645– 647.
26. Buchman, C. A.,, W. J. Doyle,, D. Skoner,, P. Fireman,, and J. M. Gwaltney. 1994. Otologic manifestations of experimental rhinovirus infection. Laryngoscope 104: 1295– 1299.
27. Buchman, C. A.,, W. J. Doyle,, D. P. Skoner,, J. C. Post,, C. M. Alper,, J. T. Seroky,, K. Anderson,, R. A. Preston,, F. G. Hayden,, P. Fireman, et al. 1995. Influenza A virus-induced acute otitis media. J. Infect. Dis. 172: 1348– 1351.
28. Budhani, R. K.,, and J. K. Struthers. 1998. Interaction of Streptococcus pneumoniae and Moraxella catarrhalis: investigation of the indirect pathogenic role of beta-lactamase-producing moraxellae by use of a continuous-culture biofilm system. Antimicrob. Agents Chemother. 42: 2521– 2526.
29. Canafax, D. M.,, Z. Yuan,, T. Chonmaitree,, K. Deka,, H. Q. Russlie,, and G. S. Giebink. 1998. Amoxicillin middle ear fluid penetration and pharmacokinetics in children with acute otitis media. Pediatr. Infect. Dis. J. 17: 149– 156.
30. Cantekin, E. I.,, E. M. Mandel,, C. D. Bluestone,, H. E. Rockette,, J. L. Paradise,, S. E. Stool,, T. J. Fria,, and K. D. Rogers. 1983. Lack of efficacy of a decongestant-antihistamine combination for otitis media with effusion (“secretory” otitis media) in children. Results of a double-blind, randomized trial. N. Engl. J. Med. 308: 297– 301.
31. Carson, J. L.,, A. M. Collier,, and S. S. Hu. 1985. Acquired ciliary defects in nasal epithelium of children with acute viral upper respiratory infections. N. Engl. J. Med. 312: 463– 468.
32. Casselbrant, M. L.,, E. M. Mandel,, P. A. Fall,, H. E. Rockette,, M. Kurs-Lasky,, C. D. Bluestone,, and R. E. Ferrell. 1999. The heritability of otitis media: a twin and triplet study. JAMA 282: 2125– 2130.
33. Cassell, G. H. 1997. New and Reemerging Infectious Diseases: a Global Crisis and Immediate Threat to the Nation’s Health: the Role of Research. American Society for Microbiology, Washington, D.C..
34. Cassell, G. H.,, G. L. Archer,, T. R. Beam,, M. J. Gilchrist,, D. Goldmann,, D. C. Hooper,, R. N. Jones,, S. H. Kleven,, J. Lederberg,, S. B. Levy,, D. H. Lein,, R. C. Moellering,, T. F. O’Brien,, B. Osburn,, M. Osterholm,, D. M. Shlaes,, M. Terry,, S. A. Tolin,, and A. Tomasz. 1994. Report of the ASM Task Force on Antibiotic Resistance. American Society for Microbiology, Washington, D.C..
35. Chartrand, S. A.,, and A. Pong. 1998. Acute otitis media in the 1990s: the impact of antibiotic resistance. Pediatr. Ann. 27: 86– 95.
36. Chonmaitree, T.,, V. M. Howie,, and A. L. Truant. 1986. Presence of respiratory viruses in middle ear fluids and nasal wash specimens from children with acute otitis media. Pediatrics 77: 698– 702.
37. Chonmaitree, T.,, M. J. Owen,, and V. M. Howie. 1990. Respiratory viruses interfere with bacteriologic response to antibiotic in children with acute otitis media. J. Infect. Dis. 162: 546– 549.
38. Chonmaitree, T.,, M. J. Owen,, J. A. Patel,, D. Hedgpeth,, D. Horlick,, and V. M. Howie. 1992. Effect of viral respiratory tract infection on outcome of acute otitis media. J. Pediatr. 120: 856– 862.
39. Chonmaitree, T.,, M. J. Owen,, J. A. Patel,, D. Hedgpeth,, D. Horlick,, and V. M. Howie. 1992. Presence of cytomegalovirus and herpes simplex virus in middle ear fluids from children with acute otitis media. Clin. Infect. Dis. 15: 650– 653.
40. Chonmaitree, T.,, J. A. Patel,, M. A. Lett- Brown,, T. Uchida,, R. Garofalo,, M. J. Owen,, and V. M. Howie. 1994. Virus and bacteria enhance histamine production in middle ear fluids of children with acute otitis media. J. Infect. Dis. 169: 1265– 1270.
41. Chonmaitree, T.,, J. A. Patel,, T. Sim,, R. Garofalo,, T. Uchida,, V. M. Howie,, and M. J. Owen. 1996. Role of leukotriene B4 and interleukin- 8 in acute bacterial and viral otitis media. Ann. Otol. Rhinol. Laryngol. 105: 968– 974.
42. Chung, M. H.,, R. Enrique,, D. J. Lim,, and T. F. De Maria. 1994. Moraxella (Branhamella) catarrhalis-induced experimental otitis media in the chinchilla. Acta Otolaryngol. 114: 415– 422.
43. Chung, M. H.,, S. R. Griffith,, K. H. Park,, D. J. Lim,, and T. F. DeMaria. 1993. Cytological and histological changes in the middle ear after inoculation of influenza A virus. Acta Otolaryngol. (Stockholm) 113: 81– 87.
44. Clemans, D. J.,, R. J. Bauer,, J. A. Hanson,, M. V. Hobbs,, J. W. St. Geme III, C. F. Marrs, and J. R. Gilsdorf. 2000. Induction of proinflammatory cytokines from human respiratory epithelial cells after stimulation by nontypeable Haemophilus influenzae. Infect. Immun. 68: 4430– 4440.
45. Clements, D. A.,, L. Langdon,, C. Bland,, and E. Walter. 1995. Influenza A vaccine decreases the incidence of otitis media in 6- to 30- monthold children in day care. Arch. Pediatr. Adolesc. Med. 149: 1113– 1117.
46. Cohen, R.,, E. Bingen,, E. Varon,, F. de La Rocque,, N. Brahimi,, C. Levy,, M. Boucherat,, J. Langue,, and P. Geslin. 1997. Change in nasopharyngeal carriage of Streptococcus pneumoniae resulting from antibiotic therapy for acute otitis media in children. Pediatr. Infect. Dis. J. 16: 555– 560.
47. Cohen, R.,, C. Levy,, M. Boucherat,, J. Langue,, E. Autret,, P. Gehanno,, and F. de La Rocque. 2000. Five vs. ten days of antibiotic therapy for acute otitis media in young children. Pediatr. Infect. Dis. J. 19: 458– 463.
48. Costerton, J. W. 1999. Introduction to biofilm. Int. J. Antimicrob. Agents 11: 217– 221, 237– 239.
49. Costerton, J. W.,, P. S. Stewart,, and E. P. Greenberg. 1999. Bacterial biofilms: a common cause of persistent infections. Science 284: 1318– 1322.
50. Culpepper, L.,, and J. Froom. 1997. Routine antimicrobial treatment of acute otitis media: is it necessary? JAMA 278: 1643– 1645.
51. Dagan, R.,, E. Leibovitz,, G. Cheletz,, A. Leiberman,, and N. Porat. 2001. Antibiotic treatment in acute otitis media promotes superinfection with resistant Streptococcus pneumoniae carried before initiation of treatment. J. Infect. Dis. 183: 880– 886.
52. Daly, K. A.,, J. E. Brown,, B. R. Lindgren,, M. H. Meland,, C. T. Le,, and G. S. Giebink. 1999. Epidemiology of otitis media onset by six months of age. Pediatrics 103: 1158– 1166.
53. De, B. K.,, J. S. Sampson,, E. W. Ades,, R. C. Huebner,, D. L. Jue,, S. E. Johnson,, M. Espina,, A. R. Stinson,, D. E. Briles,, and G. M. Carlone. 2000. Purification and characterization of Streptococcus pneumoniae palmitoylated pneumococcal surface adhesin A expressed in Escherichia coli. Vaccine 18: 1811– 1821.
54. DeMaria, T. F. 1989. Animal models for nontypable Haemophilus influenzae otitis media. Pediatr. Infect. Dis. J. 8: S40– S42.
55. DeMaria, T. F.,, J. M. Billy,, and D. G. Danahey. 1996. Growth factors during endotoxin- induced otitis media. Acta Otolaryngol. (Stockholm) 116: 854– 856.
56. Derecola, A.,, D. L. Butler,, R. L. Kaplan,, L. A. Miller,, and J. A. Poupard. 1999. A 5-year surveillance study of 44,691 isolates of Haemophilus influenzae project Beta-Alert 1993-1997. Antimicrob. Agents Chemother. 43: 185– 186.
57. Dowell, S. F.,, S. M. Marcy,, W. R. Phillips,, M. A. Gerber,, and B. Schwartz. 1998. Otitis media: principles of judicious use of antimicrobial agents. Pediatrics 101: 165– 171.
58. Doyle, W. J. 1989. Animal models of otitis media: other pathogens. Pediatr. Infect. Dis. J. 8: S45– S47.
59. Doyle, W. J.,, D. P. Skoner,, F. Hayden,, C. A. Buchman,, J. T. Seroky,, and P. Fireman. 1994. Nasal and otologic effects of experimental influenza A virus infection. Ann. Otol. Rhinol. Laryngol. 103: 59– 69.
60. Doyle, W. J.,, D. P. Skoner,, M. White,, F. Hayden,, A. P. Kaplan,, M. A. Kaliner,, Y. Shibayama,, and P. Fireman. 1996. Pattern of nasal secretions during experimental influenza virus infection. Rhinology 34: 2– 8.
61. El Ahmer, O. R.,, M. W. Raza,, M. M. Ogilvie,, D. M. Weir,, and C. C. Blackwell. 1999. Binding of bacteria to HEp-2 cells infected with influenza A virus. FEMS Immunol. Med. Microbiol. 23: 331– 341.
62. Eskola, J.,, T. Kilpi,, A. Palmu,, J. Jokinen,, J. Haapakoski,, E. Herva,, A. Takala,, H. Kayhty,, P. Karma,, R. Kohberger,, G. Siber,, and P. H. Makela. 2001. Efficacy of a pneumococcal conjugate vaccine against acute otitis media. N. Engl. J. Med. 344: 403– 409.
63. Faden, H. 2001. The microbiologic and immunologic basis for recurrent otitis media in children. Eur J Pediatr. 160: 407– 413.
64. Faden, H.,, J. Bernstein,, L. Brodsky,, J. Stanievich,, and P. L. Ogra. 1992. Effect of prior antibiotic treatment on middle ear disease in children. Ann. Otol. Rhinol. Laryngol. 101: 87– 91.
65. Faden, H.,, G. Doern,, J. Wolf,, and M. Blocker. 1994. Antimicrobial susceptibility of nasopharyngeal isolates of potential pathogens recovered from infants before antibiotic therapy: implications for the management of otitis media. Pediatr. Infect. Dis. J. 13: 609– 612.
66. Faden, H.,, L. Duffy,, R. Wasielewski,, J. Wolf,, D. Krystofik,, Y. Tung, and Tonawanda/ Williamsville Pediatrics. 1997. Relationship between nasopharyngeal colonization and the development of otitis media in children. J. Infect. Dis. 175: 1440– 1445.
67. Faden, H.,, L. Duffy,, A. Williams,, D. A. Krystofik,, and J. Wolf. 1995. Epidemiology of nasopharyngeal colonization with nontypeable Haemophilus influenzae in the first 2 years of life. J. Infect. Dis. 172: 132– 135.
68. Faden, H. S. 1997. Immunology of the middle ear: role of local and systemic antibodies in clearance of viruses and bacteria. Ann. N. Y. Acad. Sci. 830: 49– 60.
69. Fainstein, V.,, D. M. Musher,, and T. R. Cate. 1980. Bacterial adherence to pharyngeal cells during viral infection. J. Infect. Dis. 141: 172– 176.
70. Fireman, P. 1990. The role of antihistamines in otitis. J. Allergy Clin. Immunol. 86: 638– 641.
71. Foxwell, A. R.,, J. M. Kyd,, and A. W. Cripps. 1998. Nontypeable Haemophilus influenzae: pathogenesis and prevention. Microbiol. Mol. Biol. Rev. 62: 294– 308.
72. Froom, J.,, L. Culpepper,, M. Jacobs,, R. A. DeMelker,, L. A. Green,, L. van Buchem,, P. Grob,, and T. Heeren. 1997. Antimicrobials for acute otitis media? A review from the International Primary Care Network. BMJ 315: 98– 102.
73. Gates, G. A. 1999. Otitis media: the pharyngeal connection. JAMA 282: 987– 989.
74. Gazagne, L.,, C. Delmas,, E. Bingen,, and H. Dabernat. 1998. Molecular epidemiology of ampicillin-resistant non-beta-lactamase-producing Haemophilus influenzae. J. Clin. Microbiol. 36: 3629– 3635.
75. Gentile, D.,, W. Doyle,, T. Whiteside,, P. Fireman,, F. G. Hayden,, and D. Skoner. 1998. Increased interleukin-6 levels in nasal lavage samples following experimental influenza A virus infection. Clin. Diagn. Lab. Immunol. 5: 604– 608.
76. Giebink, G. S. 1989. The microbiology of otitis media. Pediatr. Infect. Dis. J. 8: S18– S20.
77. Giebink, G. S. 1997. Vaccination against middle- ear bacterial and viral pathogens. Ann. N. Y. Acad. Sci. 830: 330– 352.
78. Giebink, G. S.,, I. K. Berzins,, S. C. Marker,, and G. Schiffman. 1980. Experimental otitis media after nasal inoculation of Streptococcus pneumoniae and influenza A virus in chinchillas. Infect. Immun. 30: 445– 450.
79. Giebink, G. S.,, E. L. Mills,, J. S. Huff,, K. L. Cates,, S. K. Juhn,, and P. G. Quie. 1979. Polymorphonuclear leukocyte dysfunction in children with recurrent otitis media. J. Pediatr. 94: 13– 18.
80. Giebink, G. S.,, M. L. Ripley,, and P. F. Wright. 1987. Eustachian tube histopathology during experimental influenza A virus infection in the chinchilla. Ann. Otol. Rhinol. Laryngol. 96: 199– 206.
81. Giebink, G. S.,, and P. F. Wright. 1983. Different virulence of influenza A virus strains and susceptibility to pneumococcal otitis media in chinchillas. Infect. Immun. 41: 913– 920.
82. Glezen, W. P. 2000. Prevention of acute otitis media by prophylaxis and treatment of influenza virus infections. Vaccine 19( Suppl. 1): S56-– S58.
83. Gooch, W. M., 3rd, E. Blair, A. Puopolo, R. Z. Paster, R. H. Schwartz, H. C. Miller, H. L. Smyre, R. Yetman, G. G. Giguere, and J. J. Collins. 1996. Effectiveness of five days of therapy with cefuroxime axetil suspension for treatment of acute otitis media. Pediatr. Infect. Dis. J. 15: 157– 164.
84. Green, M., and Wald, E. R. 1996. Emerging resistance to antibiotics: impact on respiratory infections in the outpatient setting. Ann. Allergy Asthma Immunol. 77: 167– 173.
85. Gwaltney, J. M., Jr. 1971. Virology of middle ear. Ann. Otol. Rhinol. Laryngol. 80: 365– 370.
86. Hakansson, A.,, A. Kidd,, G. Wadell,, H. Sabharwal,, and C. Svanborg. 1994. Adenovirus infection enhances in vitro adherence of Streptococcus pneumoniae. Infect. Immun. 62: 2707– 2714.
87. Hament, J. M.,, J. L. Kimpen,, A. Fleer,, and T. F. Wolfs. 1999. Respiratory viral infection predisposing for bacterial disease: a concise review. FEMS Immunol. Med. Microbiol. 26: 189– 195.
88. Harsten, G.,, K. Prellner,, B. Lofgren,, and O. Kalm. 1991. Serum antibodies against respiratory tract viruses in episodes of acute otitis media. J. Laryngol. Otol. 105: 337– 340.
89. Hayden, F. G. 2000. Influenza virus and rhinovirus- related otitis media: potential for antiviral intervention. Vaccine 19( Suppl. 1): S66– S70.
90. Hayden, F. G.,, J. J. Treanor,, R. S. Fritz,, M. Lobo,, R. F. Betts,, M. Miller,, N. Kinnersley,, R. G. Mills,, P. Ward,, and S. E. Straus. 1999. Use of the oral neuraminidase inhibitor oseltamivir in experimental human influenza: randomized controlled trials for prevention and treatment. JAMA 282: 1240– 1246.
91. Heikkinen, T. 2000. The role of respiratory viruses in otitis media. Vaccine 19( Suppl. 1): S51– S55.
92. Heikkinen, T. 2000. Role of viruses in the pathogenesis of acute otitis media. Pediatr. Infect. Dis. J. 19: S17– S22, S22– S23.
93. Heikkinen, T. 1994. Temporal development of acute otitis media during upper respiratory tract infection. Pediatr. Infect. Dis. J. 13: 659– 661.
94. Heikkinen, T.,, and T. Chonmaitree. 2000. Viral-bacterial synergy in otitis media: implications for management. Curr. Infect. Dis. Rep. 2: 154– 159.
95. Heikkinen, T.,, F. Ghaffar,, A. O. Okorodudu,, and T. Chonmaitree. 1998. Serum interleukin- 6 in bacterial and nonbacterial acute otitis media. Pediatrics 102: 296– 299.
96. Heikkinen, T.,, O. Ruuskanen,, M. Waris,, T. Ziegler,, M. Arola,, and P. Halonen. 1991. Influenza vaccination in the prevention of acute otitis media in children. Am. J. Dis. Child. 145: 445– 448.
97. Heikkinen, T.,, M. Thint,, and T. Chonmaitree. 1999. Prevalence of various respiratory viruses in the middle ear during acute otitis media. N. Engl. J. Med. 340: 260– 264.
98. Henderson, F. W.,, A. M. Collier,, M. A. Sanyal,, J. M. Watkins,, D. L. Fairclough,, W. A. Clyde, Jr.,, and F. W. Denny. 1982. A longitudinal study of respiratory viruses and bacteria in the etiology of acute otitis media with effusion. N. Engl. J. Med. 306: 1377– 1383.
99. Hendolin, P. H.,, A. Markkanen,, J. Ylikoski,, and J. J. Wahlfors. 1997. Use of multiplex PCR for simultaneous detection of four bacterial species in middle ear effusions. J. Clin. Microbiol. 35: 2854– 2858.
100. Hendolin, P. H.,, L. Paulin,, and J. Ylikoski. 2000. Clinically applicable multiplex PCR for four middle ear pathogens. J. Clin. Microbiol. 38: 125– 132.
101. Hirano, T.,, Y. Kurono,, I. Ichimiya,, M. Suzuki,, and G. Mogi. 1999. Effects of influenza A virus on lectin-binding patterns in murine nasopharyngeal mucosa and on bacterial colonization. Otolaryngol. Head Neck Surg. 121: 616– 621.
102. Hotomi, M.,, T. Tabata,, H. Kakiuchi,, and M. Kunimoto. 1993. Detection of Haemophilus influenzae in middle ear of otitis media with effusion by polymerase chain reaction. Int. J. Pediatr. Otorhinolaryngol. 27: 119– 126.
103. Hu, W. G.,, J. Chen,, F. M. Collins,, and X. X. Gu. 1999. An aerosol challenge mouse model for Moraxella catarrhalis. Vaccine 18: 799– 804.
104. Hunter, L. L.,, R. H. Margolis,, and G. S. Giebink. 1994. Identification of hearing loss in children with otitis media. Ann. Otol. Rhinol. Laryngol. Suppl. 163: 59– 61.
105. Infante-Rivard, C.,, and A. Fernandez. 1993. Otitis media in children: frequency, risk factors, and research avenues. Epidemiol. Rev. 15: 444– 465.
106. Jakab, G. J. 1982. Viral-bacterial interactions in pulmonary infection. Adv. Vet. Sci. Comp. Med. 26: 155– 171.
107. Jero, J.,, and P. Karma. 1997. Bacteriological findings and persistence of middle ear effusion in otitis media with effusion. Acta Oto-Laryngol. Suppl. 529: 22– 66.
108. Jiang, Z.,, N. Nagata,, E. Molina,, L. O. Bakaletz,, H. Hawkins,, and J. A. Patel. 1999. Fimbria-mediated enhanced attachment of nontypeable Haemophilus influenzae to respiratory syncytial virus-infected respiratory epithelial cells. Infect. Immun. 67: 187– 192.
109. Johnson, I. J.,, T. Brooks,, D. A. Hutton,, J. P. Birchall,, and J. P. Pearson. 1997. Compositional differences between bilateral middle ear effusions in otitis media with effusion: evidence for a different etiology? Laryngoscope 107: 684– 689.
110. Johnson, M.,, G. Leonard,, and D. L. Kreutzer. 1997. Murine model of interleukin- 8-induced otitis media. Laryngoscope 107: 1405– 1408.
111. Jossart, G. H.,, D. M. Canafax,, G. R. Erdmann,, M. J. Lovdahl,, H. Q. Russlie,, S. K. Juhn,, and G. S. Giebink. 1994. Effect of Streptococcus pneumoniae and influenza A virus on middle ear antimicrobial pharmacokinetics in experimental otitis media. Pharm. Res. 11: 860– 864.
112. Jung, T. T. 1988. Arachidonic acid metabolites in otitis media pathogenesis. Ann. Otol. Rhinol. Laryngol. 132( Suppl.): 14– 18.
113. Jung, T. T.,, D. M. Smith,, S. K. Juhn,, and J. M. Gerrard. 1980. Effect of prostaglandin on the composition of chinchilla middle ear effusion. Ann. Otol. Rhinol. Laryngol. 89( Suppl.): 153– 160.
114. Kaplan, B.,, T. L. Wandstrat,, and J. R. Cunningham. 1997. Overall cost in the treatment of otitis media. Pediatr. Infect. Dis. J. 16: S9– S11.
115. Karalus, R.,, and A. Campagnari. 2000. Moraxella catarrhalis: a review of an important human mucosal pathogen. Microb. Infect. 2: 547– 559.
116. Kawana, M.,, C. Kawana,, and G. S. Giebink. 1992. Penicillin treatment accelerates middle ear inflammation in experimental pneumococcal otitis media. Infect. Immun. 60: 1908– 1912.
117. Kennedy, B. J.,, L. A. Novotny,, J. A. Jurcisek,, Y. Lobet,, and L. O. Bakaletz. 2000. Passive transfer of antiserum specific for immunogens derived from a nontypeable Haemophilus influenzae adhesin and lipoprotein D prevents otitis media after heterologous challenge. Infect. Immun. 68: 2756– 2765.
118. Klein, B. S.,, F. R. Dollete,, and R. H. Yolken. 1982. The role of respiratory syncytial virus and other viral pathogens in acute otitis media. J. Pediatr. 101: 16– 20.
119. Klein, J. O.,, and D. W. Teele. 1976. Isolation of viruses and mycoplasmas from middle ear effusions: a review. Ann. Otol. Rhinol. Laryngol. 85: 140– 144.
120. Kodama, S.,, S. Suenaga,, T. Hirano,, M. Suzuki,, and G. Mogi. 2000. Induction of specific immunoglobulin A and Th2 immune responses to P6 outer membrane protein of nontypeable Haemophilus influenzae in middle ear mucosa by intranasal immunization. Infect. Immun. 68: 2294– 2300.
121. Koivunen, P.,, T. Kontiokari,, M. Niemela,, T. Pokka,, and M. Uhari. 1999. Time to development of acute otitis media during an upper respiratory tract infection in children. Pediatr. Infect. Dis. J. 18: 303– 305.
122. Korppi, M.,, M. Leinonen,, M. Koskela,, P. H. Makela,, and K. Launiala. 1989. Bacterial coinfection in children hospitalized with respiratory syncytial virus infections. Pediatr. Infect. Dis. J. 8: 687– 692.
123. Korppi, M.,, M. Leinonen,, P. H. Makela,, and K. Launiala. 1991. Mixed infection is common in children with respiratory adenovirus infection. Acta Paediatr. Scand. 80: 413– 417.
124. Kozyrskyj, A. L.,, G. E. Hildes-Ripstein,, S. E. Longstaffe,, J. L. Wincott,, D. S. Sitar,, T. P. Klassen,, and M. E. Moffatt. 1998. Treatment of acute otitis media with a shortened course of antibiotics: a meta-analysis. JAMA 279: 1736– 1742.
125. Kurono, Y.,, M. Yamamoto,, K. Fujihashi,, S. Kodama,, M. Suzuki,, G. Mogi,, J. R. McGhee,, and H. Kiyono. 1999. Nasal immunization induces Haemophilus influenzae-specific Th1 and Th2 responses with mucosal IgA and systemic IgG antibodies for protective immunity. J. Infect. Dis. 180: 122– 132.
126. Kvaerner, K. J.,, P. Nafstad,, J. Hagen,, I. W. Mair,, and J. J. Jaakkola. 1997. Early acute otitis media: determined by exposure to respiratory pathogens. Acta Otolaryngol. Suppl. 529: 14– 18.
127. Kyd, J. M.,, and A. W. Cripps. 1999. Killed whole bacterial cells, a mucosal delivery system for the induction of immunity in the respiratory tract and middle ear: an overview. Vaccine 17: 1775– 1781.
128. LaMarco, K. L.,, W. F. Diven,, and R. H. Glew. 1986. Experimental alteration of chinchilla middle ear mucosae by bacterial neuraminidase. Ann. Otol. Rhinol. Laryngol. 95: 304– 308.
129. Liederman, E. M.,, J. C. Post,, J. J. Aul,, D. A. Sirko,, G. J. White,, C. A. Buchman,, and G. D. Ehrlich. 1998. Analysis of adult otitis media: polymerase chain reaction versus culture for bacteria and viruses. Ann. Otol. Rhinol. Laryngol. 107: 10– 16.
130. Linder, T. E.,, R. L. Daniels,, D. J. Lim,, and T. F. DeMaria. 1994. Effect of intranasal inoculation of Streptococcus pneumoniae on the structure of the surface carbohydrates of the chinchilla eustachian tube and middle ear mucosa. Microb. Pathog. 16: 435– 441.
131. Linder, T. E.,, D. J. Lim,, and T. F. De- Maria. 1992. Changes in the structure of the cell surface carbohydrates of the chinchilla tubotympanum following Streptococcus pneumoniae-induced otitis media. Microb. Pathog. 13: 293– 303.
132. Luce, B. R.,, K. M. Zangwill,, C. S. Palmer,, P. M. Mendelman,, L. Yan,, M. C. Wolff,, I. Cho,, S. M. Marcy,, D. Iacuzio,, and R. B. Belshe. 2001. Cost-effectiveness analysis of an intranasal influenza vaccine for the prevention of influenza in healthy children. Pediatrics 108: E24.
133. Mackowiak, P. A. 1978. Microbial synergism in human infections (first of two parts) N. Engl. J. Med. 298: 21– 26.
134. Mah, T. F.,, and G. A. O’Toole. 2001. Mechanisms of biofilm resistance to antimicrobial agents. Trends Microbiol. 9: 34– 39.
135. Mandel, E. M.,, H. E. Rockette,, C. D. Bluestone,, J. L. Paradise,, and R. J. Nozza. 1987. Efficacy of amoxicillin with and without decongestant-antihistamine for otitis media with effusion in children. Results of a double-blind, randomized trial. N. Engl. J. Med. 316: 432– 437.
136. Matsuda, K.,, H. Tsutsumi,, Y. Okamoto,, and C. Chiba. 1995. Development of interleukin 6 and tumor necrosis factor alpha activity in nasopharyngeal secretions of infants and children during infection with respiratory syncytial virus. Clin. Diagn. Lab. Immunol. 2: 322– 324.
137. McBride, T. P.,, W. J. Doyle,, F. G. Hayden,, and J. M. Gwaltney, Jr. 1989. Alterations of the eustachian tube, middle ear, and nose in rhinovirus infection. Arch. Otolaryngol. Head Neck Surg. 115: 1054– 1059.
138. McIntosh, K.,, P. Halonen,, and O. Ruuskanen. 1993. Report of a workshop on respiratory viral infections: epidemiology, diagnosis, treatment, and prevention. Clin. Infect. Dis. 16: 151– 164.
139. McLinn, S.,, and D. Williams. 1996. Incidence of antibiotic-resistant Streptococcus pneumoniae and beta-lactamase-positive Haemophilus influenzae in clinical isolates from patients with otitis media. Pediatr. Infect. Dis. J. 15: S3-– S9.
140. Melhus, A.,, and A. F. Ryan. 2000. Expression of cytokine genes during pneumococcal and nontypeable Haemophilus influenzae acute otitis media in the rat. Infect. Immun. 68: 4024– 4031.
141. Michon, F.,, P. C. Fusco,, C. A. Minetti,, M. Laude-Sharp,, C. Uitz,, C. H. Huang,, A. J. D’Ambra,, S. Moore,, D. P. Remeta,, I. Heron,, and M. S. Blake. 1998. Multivalent pneumococcal capsular polysaccharide conjugate vaccines employing genetically detoxified pneumolysin as a carrier protein. Vaccine 16: 1732– 1741.
142. Miura, M.,, H. Takahashi,, I. Honjo,, S. Hasebe,, and M. Tanabe. 1997. Influence of the upper respiratory tract infection on tubal compliance in children with otitis media with effusion. Acta Otolaryngol. 117: 574– 577.
143. Miyamoto, N.,, and L. O. Bakaletz. 1997. Kinetics of the ascension of NTHi from the nasopharynx to the middle ear coincident with adenovirus-induced compromise in the chinchilla. Microb. Pathog. 23: 119– 126.
144. Miyamoto, N.,, and L. O. Bakaletz. 1996. Selective adherence of non-typeable Haemophilus influenzae (NTHi) to mucus or epithelial cells in the chinchilla eustachian tube and middle ear. Microb. Pathog. 21: 343– 356.
145. Narkio-Makela, M.,, J. Jero,, and S. Meri. 1999. Complement activation and expression of membrane regulators in the middle ear mucosa in otitis media with effusion. Clin. Exp. Immunol. 116: 401– 409.
146. Nelson, C. T.,, E. O. Mason, Jr.,, and S. L. Kaplan. 1994. Activity of oral antibiotics in middle ear and sinus infections caused by penicillin- resistant Streptococcus pneumoniae: implications for treatment. Pediatr. Infect. Dis. J. 13: 585– 589.
147. Noah, T. L.,, F. W. Henderson,, I. A. Wortman,, R. B. Devlin,, J. Handy,, H. S. Koren,, and S. Becker. 1995. Nasal cytokine production in viral acute upper respiratory infection of childhood. J. Infect. Dis. 171: 584– 592.
148. Ogra, P. L.,, H. Faden,, and R. C. Welliver. 2001. Vaccination strategies for mucosal immune responses. Clin. Microbiol. Rev. 14: 430– 445.
149. Ohashi, Y.,, Y. Nakai,, Y. Esaki,, H. Ikeoka,, and H. Koshimo. 1988. Effects of bacterial endotoxin on ciliary activity in the tubotympanum. Ann. Otol. Rhinol. Laryngol. 97: 298– 301.
150. Ohashi, Y.,, Y. Nakai,, Y. Esaki,, Y. Ohno,, Y. Sugiura,, and H. Okamoto. 1991. Influenza A virus-induced otitis media and mucociliary dysfunction in the guinea pig. Acta Otolaryngol. Suppl. 486: 135– 148.
151. Okamoto, Y.,, K. Kudo,, K. Ishikawa,, E. Ito,, K. Togawa,, I. Saito,, I. Moro,, J. A. Patel,, and P. L. Ogra. 1993. Presence of respiratory syncytial virus genomic sequences in middle ear fluid and its relationship to expression of cytokines and cell adhesion molecules. J. Infect. Dis. 168: 1277– 1281.
152. Okamoto, Y.,, K. Kudo,, K. Shirotori,, M. Nakazawa,, E. Ito,, K. Togawa,, J. A. Patel,, and P. L. Ogra. 1992. Detection of genomic sequences of respiratory syncytial virus in otitis media with effusion in children. Ann. Otol. Rhinol. Laryngol. 157( Suppl.): 7– 10.
153. Paap, C. M. 1996. Management of otitis media with effusion in young children. Ann. Pharmacother. 30: 1291– 1297.
154. Paradise, J. L.,, H. E. Rockette,, D. K. Colborn,, B. S. Bernard,, C. G. Smith,, M. Kurs-Lasky,, and J. E. Janosky. 1997. Otitis media in 2253 Pittsburgh-area infants: prevalence and risk factors during the first two years of life. Pediatrics 99: 318– 333.
155. Park, K.,, L. O. Bakaletz,, J. M. Coticchia,, and D. J. Lim. 1993. Effect of influenza A virus on ciliary activity and dye transport function in the chinchilla eustachian tube. Ann. Otol. Rhinol. Laryngol. 102: 551– 558.
156. Patel, J.,, H. Faden,, S. Sharma,, and P. L. Ogra. 1992. Effect of respiratory syncytial virus on adherence, colonization and immunity of non-typable Haemophilus influenzae: implications for otitis media. Int. J. Pediatr. Otorhinolaryngol. 23: 15– 23.
157. Patel, J. A.,, B. Reisner,, N. Vizirinia,, M. Owen,, T. Chonmaitree,, and V. Howie. 1995. Bacteriologic failure of amoxicillin-clavulanate in treatment of acute otitis media caused by nontypeable Haemophilus influenzae. J. Pediatr. 126: 799– 806.
158. Persson, C. G.,, I. Erjefalt,, U. Alkner,, C. Baumgarten,, L. Greiff,, B. Gustafsson,, A. Luts,, U. Pipkorn,, F. Sundler,, C. Svensson,, and P. Wollmer. 1991. Plasma exudation as a first line respiratory mucosal defence. Clin. Exp. Allergy 21: 17– 24.
159. Pichichero, M. E. 1998. Changing the treatment paradigm for acute otitis media in children JAMA 279: 1748– 1750.
160. Pichichero, M. E.,, and C. L. Pichichero. 1995. Persistent acute otitis media: I. Causative pathogens. Pediatr. Infect. Dis. J. 14: 178– 183.
161. Pitkaranta, A.,, J. Jero,, E. Arruda,, A. Virolainen,, and F. G. Hayden. 1998. Polymerase chain reaction-based detection of rhinovirus, respiratory syncytial virus, and coronavirus in otitis media with effusion. J. Pediatr. 133: 390– 394.
162. Pitkaranta, A.,, A. Virolainen,, J. Jero,, E. Arruda,, and F. G. Hayden. 1998. Detection of rhinovirus, respiratory syncytial virus, and coronavirus infections in acute otitis media by reverse transcriptase polymerase chain reaction. Pediatrics 102: 291– 295.
163. Plotkowski, M. C.,, E. Puchelle,, G. Beck,, J. Jacquot,, and C. Hannoun. 1986. Adherence of type I Streptococcus pneumoniae to tracheal epithelium of mice infected with influenza A/PR8 virus. Am. Rev. Respir. Dis. 134: 1040– 1044.
164. Poolman, J. T.,, L. Bakaletz,, A. Cripps,, P. A. Denoel,, A. Forsgren,, J. Kyd,, and Y. Lobet. 2000. Developing a nontypeable Haemophilus influenzae (NTHi) vaccine. Vaccine 19( Suppl 1): S108– S115.
165. Post, J. C.,, J. J. Aul,, G. J. White,, R. M. Wadowsky,, T. Zavoral,, R. Tabari,, B. Kerber,, W. J. Doyle,, and G. D. Ehrlich. 1996. PCR-based detection of bacterial DNA after antimicrobial treatment is indicative of persistent, viable bacteria in the chinchilla model of otitis media. Am. J. Otolaryngol. 17: 106– 111.
166. Post, J. C.,, M. Ehrlich,, and G. D. Ehrlich. 2000. Otitis media with effusion as a bacterial biofilm disease, p. 1– 37. In New Paradigms in Infectious Disease: Applications to Otitis Media, October 13-15, 2000, Pittsburgh, Pa..
167. Post, J. C.,, R. A. Preston,, J. J. Aul,, M. Larkins-Pettigrew,, J. Rydquist-White,, K. W. Anderson,, R. M. Wadowsky,, D. R. Reagan,, E. S. Walker,, L. A. Kingsley, et al. 1995. Molecular analysis of bacterial pathogens in otitis media with effusion. JAMA 273: 1598– 1604.
168. Post, J. C.,, G. J. White,, J. J. Aul,, T. Zavoral,, R. M. Wadowsky,, Y. Zhang,, R. A. Preston,, and G. D. Ehrlich. 1996. Development and validation of a multiplex PCR-based assay for the upper respiratory tract bacterial pathogens Haemophilus influenzae, Streptococcus pneumoniae, and Moraxella catarrhalis. Mol. Diagn. 1: 29– 39.
169. Potera, C. 1999. Forging a link between biofilms and disease. Science 283: 1837– 1839.
170. Rayner, M. G.,, Y. Zhang,, M. C. Gorry,, Y. Chen,, J. C. Post,, and G. D. Ehrlich. 1998. Evidence of bacterial metabolic activity in culture- negative otitis media with effusion. JAMA 279: 296– 299.
171. Reisinger, K.,, F. Hayden,, R. Whitley,, R. Dutkowski,, D. Ipe,, R. Mills,, and P. Ward. 2000. Oral oseltamivir is effective and safe in the treatment of children with acute influenza. Clin. Microbiol. Infect. 6( Suppl. 1): 250.
172. Richter, S. S.,, P. L. Winokur,, A. B. Brueggemann,, H. K. Huynh,, P. R. Rhomberg,, E. M. Wingert,, and G. V. Doern. 2000. Molecular characterization of the beta-lactamases from clinical isolates of Moraxella (Branhamella) catarrhalis obtained from 24 U.S. medical centers during 1994-1995 and 1997-1998. Antimicrob. Agents Chemother. 44: 444– 446.
173. Ruohola, A.,, T. Heikkinen,, J. Jero,, T. Puhakka,, T. Juven,, M. Narkio-Makela,, H. Saxen,, and O. Ruuskanen. 1999. Oral prednisolone is an effective adjuvant therapy for acute otitis media with discharge through tympanostomy tubes. J. Pediatr. 134: 459– 463.
174. Ruohola, A.,, T. Heikkinen,, M. Waris,, T. Puhakka,, and O. Ruuskanen. 2000. Intranasal fluticasone propionate does not prevent acute otitis media during viral upper respiratory infection in children. J. Allergy Clin. Immunol. 106: 467– 471.
175. Ruuskanen, O.,, M. Arola,, T. Heikkinen,, and T. Ziegler. 1991. Viruses in acute otitis media: increasing evidence for clinical significance. Pediatr. Infect. Dis. J. 10: 425– 427.
176. Ruuskanen, O.,, M. Arola,, A. Putto-Laurila,, J. Mertsola,, O. Meurman,, M. K. Viljanen,, and P. Halonen. 1989. Acute otitis media and respiratory virus infections. Pediatr. Infect. Dis. J. 8: 94– 99.
177. Ruuskanen, O.,, and T. Heikkinen. 1994. Viral-bacterial interaction in acute otitis media. Pediatr. Infect. Dis. J. 13: 1047– 1049.
178. Saidi, I. S.,, J. F. Biedlingmaier,, and P. Whelan. 1999. In vivo resistance to bacterial biofilm formation on tympanostomy tubes as a function of tube material. Otolaryngol. Head Neck Surg. 120: 621– 627.
179. Sanford, B. A.,, A. Shelokov,, and M. A. Ramsay. 1978. Bacterial adherence to virus-infected cells: a cell culture model of bacterial superinfection. J. Infect. Dis. 137: 176– 181.
180. Sarkkinen, H.,, O. Ruuskanen,, O. Meurman,, H. Puhakka,, E. Virolainen,, and J. Eskola. 1985. Identification of respiratory virus antigens in middle ear fluids of children with acute otitis media. J. Infect. Dis. 151: 444– 448.
181. Sarkkinen, H. K.,, P. E. Halonen,, P. P. Arstila,, and A. A. Salmi. 1981. Detection of respiratory syncytial, parainfluenza type 2, and adenovirus antigens by radioimmunoassay and enzyme immunoassay on nasopharyngeal specimens from children with acute respiratory disease. J. Clin. Microbiol. 13: 258– 265.
182. Sarkkinen, H. K.,, O. Meurman,, T. T. Salmi,, H. Puhakka,, and E. Virolainen. 1983. Demonstration of viral antigens in middle ear secretions of children with acute otitis media Acta Paediatr. Scand. 72: 137– 138.
183. Sato, K.,, C. L. Liebeler,, M. K. Quartey,, C. T. Le,, and G. S. Giebink. 1999. Middle ear fluid cytokine and inflammatory cell kinetics in the chinchilla otitis media model. Infect. Immun. 67: 1943– 1946.
184. Shaw, C. B.,, N. Obermyer,, S. J. Wetmore,, G. A. Spirou,, and R. W. Farr. 1995. Incidence of adenovirus and respiratory syncytial virus in chronic otitis media with effusion using the polymerase chain reaction. Otolaryngol. Head Neck Surg. 113: 234– 241.
185. Siegrist, C. A. 2000. Vaccination in the neonatal period and early infancy. Int. Rev. Immunol. 19: 195– 219.
186. Simoes, E. A.,, J. R. Groothuis,, D. A. Tristram,, K. Allessi,, M. V. Lehr,, G. R. Siber,, and R. C. Welliver. 1996. Respiratory syncytial virus-enriched globulin for the prevention of acute otitis media in high risk children. J. Pediatr. 129: 214– 219.
187. Sirakova, T.,, P. E. Kolattukudy,, D. Murwin,, J. Billy,, E. Leake,, D. Lim,, T. De- Maria,, and L. Bakaletz. 1994. Role of fimbriae expressed by nontypeable Haemophilus influenzae in pathogenesis of and protection against otitis media and relatedness of the fimbrin subunit to outer membrane protein A. Infect. Immun. 62: 2002– 2020.
188. Stenfors, L. E.,, and S. Raisanen. 1989. Presence of Branhamella catarrhalis alters the survival of Streptococcus pneumoniae and Haemophilus influenzae in middle ear effusion: an in vitro study. J. Laryngol. Otol. 103: 1030– 1033.
189. Stool, S. E.,, A. O. Berg,, S. Berman,, C. J. Carney,, J. R. Cooley,, L. Culpepper,, R. D. Eavey,, L. V. Feagans,, T. Finitzo,, E. M. Friedman,, J. A. Goertz,, A. J. Goldstein,, K. M. Grundfast,, D. G. Long,, L. L. Macconi,, L. Melton,, J. E. Roberts,, J. L. Sherrod,, and J. E. Sisk. 1994. Otitis Media with Effusion in Young Children. Clinical Practice Guideline, vol. 12. Agency for Health Care Policy and Research, Public Health Service, U.S. Department of Health and Human Services, Rockville, Md..
190. Sung, B. S.,, T. Chonmaitree,, L. D. Broemeling,, M. J. Owen,, J. A. Patel,, D. C. Hedgpeth,, and V. M. Howie. 1993. Association of rhinovirus infection with poor bacteriologic outcome of bacterial-viral otitis media. Clin. Infect. Dis. 17: 38– 42.
191. Sutbeyaz, Y.,, B. Yakan,, H. Ozdemir,, M. Karasen,, F. Doner,, and I. Kufrevioglu. 1996. Effect of SC-41930, a potent selective leukotriene B4 receptor antagonist, in the guinea pig model of middle ear inflammation. Ann. Otol. Rhinol. Laryngol. 105: 476– 480.
192. Suzuki, K.,, and L. O. Bakaletz. 1994. Synergistic effect of adenovirus type 1 and nontypeable Haemophilus influenzae in a chinchilla model of experimental otitis media. Infect. Immun. 62: 1710– 1718.
193. Swarts, J. D.,, J. Y. Westcott,, and K. H. Chan. 1997. Eicosanoid synthesis and inactivation in healthy and infected chinchilla middle ears. Acta Otolaryngol. (Stockholm) 117: 845– 850.
194. Teele, D. W.,, J. O. Klein,, C. Chase,, P. Menyuk,, B. A. Rosner, and the Greater Boston Otitis Media Study Group. 1990. Otitis media in infancy and intellectual ability, school achievement, speech, and language at age 7 years. J. Infect. Dis. 162: 685– 694.
195. Teele, D. W.,, J. O. Klein,, and B. Rosner. 1989. Epidemiology of otitis media during the first seven years of life in children in greater Boston: a prospective, cohort study. J. Infect. Dis. 160: 83– 94.
196. Tejani, N. R.,, T. Chonmaitree,, D. K. Rassin,, V. M. Howie,, M. J. Owen,, and A. S. Goldman. 1995. Use of C-reactive protein in differentiation between acute bacterial and viral otitis media. Pediatrics 95: 664– 669.
197. Tong, H. H.,, L. M. Fisher,, G. M. Kosunick,, and T. F. DeMaria. 2000. Effect of adenovirus type 1 and influenza A virus on Streptococcus pneumoniae nasopharyngeal colonization and otitis media in the chinchilla. Ann. Otol. Rhinol. Laryngol. 109: 1021– 1027.
198. Tong, H. H.,, J. N. Weiser,, M. A. James,, and T. F. DeMaria. 2001. Effect of influenza A virus infection on nasopharyngeal colonization and otitis media induced by transparent or opaque phenotype variants of Streptococcus pneumoniae in the chinchilla model. Infect. Immun. 69: 602– 606.
199. Turner, R. B. 2001. The treatment of rhinovirus infections: progress and potential. Antivir. Res. 49: 1– 14.
200. Turner, R. B.,, M. T. Wecker,, G. Pohl,, T. J. Witek,, E. McNally,, R. St George,, B. Winther,, and F. G. Hayden. 1999. Efficacy of tremacamra, a soluble intercellular adhesion molecule 1, for experimental rhinovirus infection: a randomized clinical trial. JAMA 281: 1797– 1804.
201. Ueyama, T.,, Y. Kurono,, K. Shirabe,, M. Takeshita,, and G. Mogi. 1995. High incidence of Haemophilus influenzae in nasopharyngeal secretions and middle ear effusions as detected by PCR. J. Clin. Microbiol. 33: 1835– 1838.
202. Uhari, M.,, J. Hietala,, and H. Tuokko. 1995. Risk of acute otitis media in relation to the viral etiology of infections in children. Clin. Infect. Dis. 20: 521– 524.
203. Underdown, B. J.,, and S. A. Plotkin. 1999. The induction of mucosal protection by parenteral immunization: a challenge to the mucosal immunity paradigm, p. 719– 728, Mucosal Immunology. Academic Press, Inc., New York, N.Y..
204. Unhanand, M.,, I. Maciver,, O. Ramilo,, O. Arencibia-Mireles,, J. C. Argyle,, G. H. Mc- Cracken, Jr.,, and E. J. Hansen. 1992. Pul- monary clearance of Moraxella catarrhalis in an animal model. J. Infect. Dis. 165: 644– 650.
205. Valiante, N. M.,, R. Rappuoli,, R. A. Insel,, P. McInnes,, and A. Hoeveler. 1999. The challenges of vaccinating the very young: lessons from a very old system of host defense. Vaccine. 17: 2757– 2762.
206. van Buchem, F. L.,, M. F. Peeters,, and M. A. van’t Hof. 1985. Acute otitis media: a new treatment strategy. Br. Med. J. 290: 1033– 1037.
207. vander Ven, L. T.,, G. P. van den Dobbelsteen,, B. Nagarajah,, H. van Dijken,, P. M. Dortant,, J. G. Vos,, and P. J. Roholl. 1999. A new rat model of otitis media caused by Streptococcus pneumoniae: conditions and application in immunization protocols. Infect. Immun. 67: 6098– 6103.
208. Virolainen, A.,, P. Salo,, J. Jero,, P. Karma,, J. Eskola,, and M. Leinonen. 1994. Comparison of PCR assay with bacterial culture for detecting Streptococcus pneumoniae in middle ear fluid of children with acute otitis media. J. Clin. Microbiol. 32: 2667– 2670.
209. Wadowsky, R. M.,, S. M. Mietzner,, D. P. Skoner,, W. J. Doyle,, and P. Fireman. 1995. Effect of experimental influenza A virus infection on isolation of Streptococcus pneumoniae and other aerobic bacteria from the oropharynges of allergic and nonallergic adult subjects. Infect. Immun. 63: 1153– 1157.
210. Wang, E. E.,, T. R. Einarson,, J. D. Kellner,, and J. M. Conly. 1999. Antibiotic prescribing for Canadian preschool children: evidence of overprescribing for viral respiratory infections. Clin. Infect. Dis. 29: 155– 160.
211. Warshauer, D.,, E. Goldstein,, T. Akers,, W. Lippert,, and M. Kim. 1977. Effect of influenza viral infection on the ingestion and killing of bacteria by alveolar macrophages. Am. Rev. Respir. Dis. 115: 269– 277.
212. Westman, E. B.,, A. Hermansson,, K. Prellner,, A. Melhus,, and S. Hellstrom,. 1994. Moraxella catarrhalis-induced purulent otitis media in the rat middle ear, p. 193– 195. In G. Mogi,, I. Honjo,, T. Ishii,, and T. Takasaka (ed.), Second Extraordinary International Symposium on Recent Advances in Otitis Media. Kugler Publications, Amsterdam, The Netherlands.
213. Willett, D. N.,, R. P. Rezaee,, J. M. Billy,, M. B. Tighe,, and T. F. DeMaria. 1998. Relationship of endotoxin to tumor necrosis factoralpha and interleukin-1 beta in children with otitis media with effusion. Ann. Otol. Rhinol. Laryngol. 107: 28– 33.
214. Williams, R. L.,, T. C. Chalmers,, K. C. Stange,, F. T. Chalmers,, and S. J. Bowlin. 1993. Use of antibiotics in preventing recurrent acute otitis media and in treating otitis media with effusion. A meta-analytic attempt to resolve the brouhaha. JAMA 270: 1344– 1351. ( Erratum, 271:430, 1994.).
215. Yellon, R. F.,, W. J. Doyle,, T. L. Whiteside,, W. F. Diven,, A. R. March,, and P. Fireman. 1995. Cytokines, immunoglobulins, and bacterial pathogens in middle ear effusions. Arch. Otolaryngol. Head Neck Surg. 121: 865– 869 ( Erratum, 121:1402).

Tables

Otitis Media
[com.pub2web.rdf.cci.facet.ContentItem[id=http://asm.metastore.ingenta.com/content/author/10.1128/9781555817947.chap14-1,webId=/content/author/10.1128/9781555817947.chap14-1,properties={foaf_givenname=Lauren O., foaf_name=Lauren O. Bakaletz, foaf_surname=Bakaletz, pub_isAffiliatedWith=[com.pub2web.rdf.cci.facet.ContentItem[id=http://asm.metastore.ingenta.com/content/affiliation/10.1128/9781555817947.chap14-aff1]]}]]
Citation: Bakaletz L. 2002. Otitis Media, p 259-298. In Brogden K, Guthmiller J (ed), Polymicrobial Diseases. ASM Press, Washington, DC. doi: 10.1128/9781555817947.ch14
/content/10.1128/9781555817947.chap14.tab14-1
TABLE 1

Comparison of clinical and bacteriologic outcome of patients with AOM caused by bacteria alone or bacteria and virus

10.1128/9781555817947/tab14-1_thmb.gif
10.1128/9781555817947/tab14-1.gif
Generic image for table
TABLE 1

Comparison of clinical and bacteriologic outcome of patients with AOM caused by bacteria alone or bacteria and virus

Citation: Bakaletz L. 2002. Otitis Media, p 259-298. In Brogden K, Guthmiller J (ed), Polymicrobial Diseases. ASM Press, Washington, DC. doi: 10.1128/9781555817947.ch14
/content/10.1128/9781555817947.chap14.tab14-2
TABLE 2

Dye transport values for chinchillas injected transbullarly with influenza A/Alaska/6/77 virus

10.1128/9781555817947/tab14-2_thmb.gif
10.1128/9781555817947/tab14-2.gif
Generic image for table
TABLE 2

Dye transport values for chinchillas injected transbullarly with influenza A/Alaska/6/77 virus

Citation: Bakaletz L. 2002. Otitis Media, p 259-298. In Brogden K, Guthmiller J (ed), Polymicrobial Diseases. ASM Press, Washington, DC. doi: 10.1128/9781555817947.ch14
/content/10.1128/9781555817947.chap14.tab14-3
TABLE 3

Demographic information on 186 participants in influenza-OM trial

10.1128/9781555817947/tab14-3_thmb.gif
10.1128/9781555817947/tab14-3.gif
Generic image for table
TABLE 3

Demographic information on 186 participants in influenza-OM trial

Citation: Bakaletz L. 2002. Otitis Media, p 259-298. In Brogden K, Guthmiller J (ed), Polymicrobial Diseases. ASM Press, Washington, DC. doi: 10.1128/9781555817947.ch14
/content/10.1128/9781555817947.chap14.tab14-4
TABLE 4

Percentage of infants with AOM and SOM infections before, during, and after influenza season

10.1128/9781555817947/tab14-4_thmb.gif
10.1128/9781555817947/tab14-4.gif
Generic image for table
TABLE 4

Percentage of infants with AOM and SOM infections before, during, and after influenza season

Citation: Bakaletz L. 2002. Otitis Media, p 259-298. In Brogden K, Guthmiller J (ed), Polymicrobial Diseases. ASM Press, Washington, DC. doi: 10.1128/9781555817947.ch14

Back to top
This is a required field
Please enter a valid email address
Please check the format of the address you have entered.
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error