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Clinical bacteriology and immunology in acute otitis media in children

  • Review Article
  • Published:
Journal of Infection and Chemotherapy

Abstract

Acute otitis media (AOM) is the most common disease seen in childhood. Streptococcus pneumoniae, non-typeable Haemophilus influenzae (NTHi), and Moraxella catarrhalis are the most frequent pathogens of all AOM episodes. The high prevalence of drug-resistant pathogens such as penicillin-resistant S. pneumoniae (PRSP) and betalactamase producing or nonproducing ampicillin-resistant H. influenzae (BLPAR or BLNAR) is causing serious clinical problems worldwide. PRSP and BLNAR have become important risk factors for intractable clinical outcome of AOM. PRSP causes a three times higher incidence of intractable AOM than susceptible strains. BLNAR strains show penicillin-binding protein gene mutation and are not only resistant to ampicillin, but also have reduced susceptibility to cephalosporin. The resistant H. influenzae pathogen has shown clonal dissemination in Japan in ways different from those of penicillin-resistant S. pneumoniae. Protection against AOM due to these pathogens may depend on pathogen-specific antibodies. Pneumococcal capsular polysaccharides (PCPs) are type specific and poorly immunogenic in children younger than 2 years old. Approximately 50% of otitis-prone children showed subnormal levels of anti-PCP IgG2 antibody. In our immunological study in children with otitis media, however, otitis-prone children were not unusually vulnerable to infections except those resulting in otitis media. This fact seems to refute the presence of a broad immunological deficit in these children. Some pathogen-specific antibodies may be directed against protein immunogens such as pneumococcal surface protein A (PspA) of S. pneumoniae, P6 of NTHi, and UspA of M. catarrhalis. The levels of antibody to P6 of NTHi in healthy children were significantly higher than those in the otitis-prone children after the age of 18 months. In general, individual antibody levels in otitis-prone individuals did not have an age-dependent rise. The failure to develop a good antibody response to common antigens such as PspA and P6 may enable the pathogen to cause persistent or recurrent disease.

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References

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

    PubMed  CAS  Google Scholar 

  2. Hotomi M, Billal DS, Shimada J, Suzumoto M, Yamauchi K, Fujihara K, et al. High prevalence of Streptococcus pneumoniae with mutations in pbp1a, pbp2x, and pbp2b genes of penicillin binding proteins in the nasopharynx among children in Japan. ORL J Otorhinolaryngol Relat Spec 2006;68:139–145.

    PubMed  CAS  Google Scholar 

  3. Foxwell AR, Kyd JM, Cripps AW. Nontypeable Haemophilus influenzae: pathogenesis and prevention. Microbiol Mol Biol Rev 1998;62:294–308.

    PubMed  CAS  Google Scholar 

  4. Barcus VA, Ghanker K, Yeo M, Coffey TJ, Dowson CG. Genetics of high-level penicillin resistance in clinical isolates of Streptococcus pneumoniae. FEMS Microbiol Lett 1995;126:299–303.

    Article  PubMed  CAS  Google Scholar 

  5. Kell CM, Sharma UK, Dowson CG, Town C, Balganesh TS, Spratt BG. Deletion analysis of the essentiality of penicillin-binding proteins 1A, 2B, 2X of Streptococcus pneumoniae. FEMS Microbiol Lett 1993;106:171–175.

    Article  PubMed  CAS  Google Scholar 

  6. Markiewicz Z, Tomaz A. Variation in penicillin-binding protein patterns of penicillin-resistant clinical isolates of pneumococci. J Clin Microbiol 1989;27:405–410.

    PubMed  CAS  Google Scholar 

  7. Munoz RC, Dowson CG, Daniels M, Coffey TJ, Martin C, Hakenbeck R, et al. Genetics of resistance to third-generation cephalosporins in clinical isolates of Streptococcus pneumoniae. Mol Microbiol 1992;6:2461–2465.

    PubMed  CAS  Google Scholar 

  8. Reid AJ, Simpson IN, Harder PH, Aymes SGB. Ampicillin resistance in Haemophilus influenzae: identification of resistance mechanism. J Antimicrobiol Chemother 1987;20:645–656.

    Article  CAS  Google Scholar 

  9. Vega R, Sadoff HL, Patterson MJ. Mechanism of ampicillin resistance in Haemophilus influenzae type B. Antimicrob Agent Chemother 1976;9:164–168.

    CAS  Google Scholar 

  10. Medeiros AA, Levesque R, Jacoby GA. An animal source for the ROB-1 beta-lactamase of Haemophilus influenzae type b. Antimicrob Agent Chemother 1986;29:212–215.

    CAS  Google Scholar 

  11. Mendelman PM, Chaffin DO, Kalaizoglou G. Penicillin binding proteins and ampicillin resistance in Haemophilus influenzae. J Antimicrob Chemother 1990;25:525–534.

    Article  PubMed  CAS  Google Scholar 

  12. Mendelman PM, Chaffin DO, Stull TL, Rubens CE, Mack KD, Selanser RK. Characterization of non-beta-lactamase-mediated ampicillin resistance in Haemophilus influenzae. Antimicrob Agents Chemother 1984;26:235–244.

    PubMed  CAS  Google Scholar 

  13. Parr TR Jr, Bryan LE. Mechanism of resistance of an ampicillin-resistant, beta-lactamase-negative clinical isolate of Haemophilus influenzae type b to beta-lactam antibiotic. Antimicrob Agents Chemother 1984;25:747–753.

    PubMed  CAS  Google Scholar 

  14. Clairoux N, Picard M, Brochu A, Rousseau N, Gourde P, Beauchamp D, et al. Molecular basis of non-β-lactamase-mediated resistance to β-lactam antibiotics in strains of Haemophilus influenzae. Antimicrob Agents Chemother 1992;36:1504–1513.

    PubMed  CAS  Google Scholar 

  15. Hotomi M, Fujihara K, Billal DS, Suzuki K, Nishimura T, Baba S, et al. Genetic characteristics and clonal dissemination of β-lactamase non-producing ampicillin resistant (BLNAR) Haemophilus influenzae isolated from the upper respiratory tract in Japan. Antimicrob Agents Chemother 2007;51:3969–3976.

    Article  PubMed  CAS  Google Scholar 

  16. Jae-Hoon S, Jung S, Ko KS. Hogh prevalence of antimicrobial resistance among clinical Streptococcus pneumoniae isolates in Asia (an ANSORP study). Antimicrob Agents Chemother 2004;48:2101–2107.

    Article  CAS  Google Scholar 

  17. Hotomi M, Billal DS, Shimada J, Suzumoto M, Yamauchi K, Fujihara K, et al. An increase of macrolide resistant Streptococcus pneumoniae expressing mefE or ermB gene in the nasopharynx among children with otitis media. Laryngoscope 2005;115:317–320.

    Article  PubMed  Google Scholar 

  18. Farrell DJ, File TM, Jenkins SG. Prevalence and antibacterial susceptibility of mef(A)-positive macrolide-resistant Streptococcus pneumoniae over 4 years (2000 to 2004) of the PROTEKT US study. J Clin Microb 2007;45:290–293.

    Article  CAS  Google Scholar 

  19. Doern GV, Brueggemann AB, Pierce G, Horry HP Jr, Rauch A. Antibiotic resistance among clinical isolates of Haemophilus influenzae in the United States in 1994 and 1995 and detection of beta-lactamase-positive strains resistant to amoxicillin-clavulanate: results of a national multicenter surveillance study. Antimicrob Agents Chemother 1997;41:292–297.

    PubMed  CAS  Google Scholar 

  20. Doern GV, Jones RN,. Pfaller MA, Kugler K. Haemophilus influenzae and Moraxella catarrhalis from patients with community-acquired respiratory tract infections: antimicrobial susceptibility patterns from the SENTRY Antimicrobial Surveillance Program (United States and Canada, 1997). Antimicrob Agents Chemother 1999;43:385–389.

    PubMed  CAS  Google Scholar 

  21. Thomas WJ, McReynolds JW, Mock CR, Bailey DW. Ampicillin-resistant Haemophilus influenzae meningitis. Lancet 1974;23:313.

    Article  Google Scholar 

  22. Qin L, Watanabe H, Asoh N, Watanabe K, Oishi K, Mizota T, et al. Antimicrobial susceptibilities and genetic characteristics of Haemophilus influenzae isolated from patients with respiratory tract infections between 1987 and 2000, including beta-lactamase-negative ampicillin-resistant strains. Epidemiol Infect 2006;6:1–4.

    Google Scholar 

  23. Jasen WT, Varel A, Beistma M, Herhoof J, Milatovic D. Longitudinal European surveillance study of antibiotic resistance of Haemophilus influenzae. J Antimicrob Chemother 2006;58:873–877.

    Article  Google Scholar 

  24. Hotomi M, Fugihara K, Sakai A, Billal DS, Shimada J, Suzumoto M, et al. Antimicrobial resistance of Haemophilus influenzae isolated from the nasopharynx of Japanese children with acute otitis media. Acta Otolaryngol 2006;126:240–247.

    Article  PubMed  CAS  Google Scholar 

  25. Bruyn GAW, Zegers BJM, van Furth R. Mechanisms of host defense against infection with Streptococcus pneumoniae. Clin Infect Dis 1992;14:251–262.

    PubMed  CAS  Google Scholar 

  26. Douglas R, Paton J, Duncan SJ, Hansman DJ. Antibody response to pneumococcal vaccination in children younger than five years of age. J Infect Dis 1983;148:131–137.

    PubMed  CAS  Google Scholar 

  27. Koskela M. Serum antibodies to pneumococcal C polysaccharide in children: response to acute pneumococcal otitis media or to vaccination. Pediatr Infect Dis J 1987;6:519–526.

    Article  PubMed  CAS  Google Scholar 

  28. Yamanaka N, Faden H. Antibody response to outer membrane protein of nontypeable Haemophilus influenzae in otitis-prone children. J Pediatr 1993;122:212–218.

    Article  PubMed  CAS  Google Scholar 

  29. Samukawa T, Yamanaka N, Hollingshead SK, Klingman K, Faden H. Immune responses to specific antigens of Streptococcus pneumoniae and Moraxella catarrhalis in the respiratory tract. Infect Immun 2000;68:1569–1573.

    Article  PubMed  CAS  Google Scholar 

  30. Samukawa T, Yamanaka N, Hollingshead SK, Murphy TF, Faden H. Immune response to surface protein A of Streptococcus pneumoniae and high-molecular-weight outer membrane protein A of Moraxella catarrhalis in children with acute otitis media. J Infect Dis 2000;181:1842–1845.

    Article  PubMed  CAS  Google Scholar 

  31. Hotomi M, Yamanaka N, Saito T, Shimada J, Suzumoto M, Suetake M, et al. Antibody responses to the outer membrane protein P6 of non-typeable Haemophilus influenzae and pneumococcal capsular polysaccharides in otitis-prone children. Acta Otolaryngol (Stockholm) 1999;119:703–707.

    Article  CAS  Google Scholar 

  32. McDaniel LS, Sheffield JS, Swiatlo E, Yother J, Crain MJ, Briles DE. Molecular localization of variable and conserved regions of PspA and identification of additional PspA homologous sequences in Streptococcus pneumoniae. Microb Pathog 1992;13:261–269.

    Article  PubMed  CAS  Google Scholar 

  33. Crain MJ, Waltman WD 2nd, Turner JS, Yother J, Talkington DF, McDaniel LS, et al. Pneumococcal surface protein (PspA) is serologically highly variable and is expressed by all clinically important capsular serotypes of Streptococcus pneumoniae. Infect Immun 1990;58:3293–3299.

    PubMed  CAS  Google Scholar 

  34. Nahm MH, Guo Y, Russell MW, Briles DE. Intranasal immunization of mice with PspA (pneumococcal surface protein A) can prevent intranasal carriage, pulmonary infection, and sepsis with Streptococcus pneumoniae. J Infect Dis 1997;175:839–846.

    Article  PubMed  Google Scholar 

  35. Briles DE, Tart RC, Swiatlo E, Dillard JP, Smith P, Benton KA, et al. Pneumococcal diversity: considerations for new vaccine strategies with emphasis on pneumococcal surface protein A (PspA). Clin Microbiol Rev 1998;11:645–657.

    PubMed  CAS  Google Scholar 

  36. Gray BM, Concerse GM III, Dillon HC. Epidemiologic studies of Streptococcus pneumoniae in infants: acquisition, carriage, and infection during the first 24 months of life. J Infect Dis 1980;142:923–933.

    PubMed  CAS  Google Scholar 

  37. Johnson CE, Murdell-Panek D, Barenkamp SJ. Early recurrences of otitis media: reinfection or relapse? J Pediatr 1987;110:20–25.

    Article  PubMed  Google Scholar 

  38. Murphy TF, Nelson MB, Dudas KC, Mylotte JM, Apicella MA. Identification of a specific epitope of Haemophilus influenzae in a 16600-dalton outer membrane protein. J Infect Dis 1985;152:1300–1307.

    PubMed  CAS  Google Scholar 

  39. Murphy TF, Bartos LC, Campagnari AM, Nelson MB, Dudas KC, Apicella MA. Antigenic characterization of the P6 protein of non-typeable Haemophilus influenzae. Infect Immun 1986;54:774–779.

    PubMed  CAS  Google Scholar 

  40. Harabuchi Y, Murakata H, Goh M, Kodama H, Kataura A, Faden H, et al. Serum antibodies specific to CD outer membrane proteins of Moraxella catarrhalis, P6 outer membrane protein of non-typeable Haemophilus influenzae, and capsular polysaccharides of Streptococcus pneumoniae in children with otitis media with effusion. Acta Otolaryngol (Stockholm) 1998;118:826–832.

    Article  CAS  Google Scholar 

  41. Kodama H, Faden H. Cellular immunity to the P6 outer membrane protein of non-typeable Haemophilus influenzae. Infect Immun 1997;63:2467–2472.

    Google Scholar 

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Yamanaka, N., Hotomi, M. & Billal, D.S. Clinical bacteriology and immunology in acute otitis media in children. J Infect Chemother 14, 180–187 (2008). https://doi.org/10.1007/s10156-007-0599-3

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  • DOI: https://doi.org/10.1007/s10156-007-0599-3

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