UpToDate
Official reprint from UpToDate®
www.uptodate.com ©2016 UpToDate®

Microbiology, epidemiology and treatment of Haemophilus influenzae

Author
Sylvia Yeh, MD
Section Editor
Daniel J Sexton, MD
Deputy Editor
Anna R Thorner, MD

INTRODUCTION

Haemophilus influenzae colonizes the human respiratory tract and is transmitted from person to person via airborne droplets and direct contact with respiratory secretions [1].

H. influenzae has encapsulated (serotypes a through f) and nonencapsulated forms (nontypeable). The most important serotype is H. influenzae serotype b (Hib), which was a frequent cause of bacteremia, meningitis, and other invasive infections prior to the routine use of Hib conjugate vaccines in children [2]. Other capsular serotypes and unencapsulated H. influenzae strains can also cause disease, mainly mucosal infections (sinusitis, otitis, bronchitis, and pneumonia), but occasionally cause more invasive infections.

The bacteriology, epidemiology, and treatment of H. influenzae are reviewed here. H. influenzae infections in children and prevention of H. influenzae are discussed separately. (See "Prevention of Haemophilus influenzae type b infection".)

MICROBIOLOGY

H. influenzae are small, pleomorphic gram-negative rods that are oxidase positive, facultatively anaerobic, and nonmotile. In clinical specimens obtained from patients who have received beta-lactam antibiotics, H. influenzae can appear as filamentous rods. In vitro growth requires a CO2-enriched atmosphere, hemin (factor X), and nicotinamide adenine dinucleotide (NAD, factor V); therefore, isolation from clinical specimens on solid medium requires the use of chocolate agar or other X and V factor supplemented media. H. influenzae appear as transparent or slightly opaque colonies on solid media.

Capsule — The presence or absence of a polysaccharide capsule is an important distinguishing characteristic of H. influenzae species. The polysaccharide capsule can be serologically classified into six serotypes (a through f), while H. influenzae lacking a polysaccharide capsule are considered to be nontypeable [3]. The type b capsule consists of a ribosyl and ribitol phosphate polymer and is the primary antigenic constituent of polysaccharide and polysaccharide conjugate H. influenzae serotype b (Hib) vaccines [2].

           

Subscribers log in here

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information or to purchase a personal subscription, click below on the option that best describes you:
Literature review current through: Nov 2016. | This topic last updated: Mon Aug 24 00:00:00 GMT+00:00 2015.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2016 UpToDate, Inc.
References
Top
  1. Ward JI, Zangwill KM. Haemophilus influenzae vaccines. In: Vaccines, 3rd ed, Plotkin SA, Orienstein WA (Eds), WB Saunders Company, Philadelphia 1999.
  2. Eskola J, Käyhty H, Takala AK, et al. A randomized, prospective field trial of a conjugate vaccine in the protection of infants and young children against invasive Haemophilus influenzae type b disease. N Engl J Med 1990; 323:1381.
  3. St Geme JW 3rd, Takala A, Esko E, Falkow S. Evidence for capsule gene sequences among pharyngeal isolates of nontypeable Haemophilus influenzae. J Infect Dis 1994; 169:337.
  4. Segada LM, Carlone GM, Gheesling LL, Lesse AJ. Characterization of P1-deficient isogenic mutant of Haemophilus influenzae biogroup aegyptius associated with Brazilian purpuric fever. Microb Pathog 2000; 28:145.
  5. Quentin R, Musser JM, Mellouet M, et al. Typing of urogenital, maternal, and neonatal isolates of Haemophilus influenzae and Haemophilus parainfluenzae in correlation with clinical source of isolation and evidence for a genital specificity of H. influenzae biotype IV. J Clin Microbiol 1989; 27:2286.
  6. Wallace RJ Jr, Baker CJ, Quinones FJ, et al. Nontypable Haemophilus influenzae (biotype 4) as a neonatal, maternal, and genital pathogen. Rev Infect Dis 1983; 5:123.
  7. Rao VK, Krasan GP, Hendrixson DR, et al. Molecular determinants of the pathogenesis of disease due to non-typable Haemophilus influenzae. FEMS Microbiol Rev 1999; 23:99.
  8. Krasan GP, Cutter D, Block SL, St Geme JW 3rd. Adhesin expression in matched nasopharyngeal and middle ear isolates of nontypeable Haemophilus influenzae from children with acute otitis media. Infect Immun 1999; 67:449.
  9. Kubiet M, Ramphal R, Weber A, Smith A. Pilus-mediated adherence of Haemophilus influenzae to human respiratory mucins. Infect Immun 2000; 68:3362.
  10. St Geme JW 3rd. Insights into the mechanism of respiratory tract colonization by nontypable Haemophilus influenzae. Pediatr Infect Dis J 1997; 16:931.
  11. Whisnant JK, Rogentine GN, Mann DL, Robbins JB. Human cell-surface structures related to Haemophilus influenzae type B disease. Lancet 1971; 2:895.
  12. Miragliotta G, Colucci M, Semeraro N, et al. Platelet injury and stimulation of leukocyte procoagulant activity in vitro by a lipopolysaccharide from Haemophilus influenzae type b. Microbiologica 1981; 4:173.
  13. Plaut AG. The IgA1 proteases of pathogenic bacteria. Annu Rev Microbiol 1983; 37:603.
  14. Moxon ER. Molecular basis of invasive Haemophilus influenzae type b disease. J Infect Dis 1992; 165 Suppl 1:S77.
  15. Aniansson G, Alm B, Andersson B, et al. Nasopharyngeal colonization during the first year of life. J Infect Dis 1992; 165 Suppl 1:S38.
  16. Shapiro ED, Ward JI. The epidemiology and prevention of disease caused by Haemophilus influenzae type b. Epidemiol Rev 1991; 13:113.
  17. Krasinski K, Nelson JD, Butler S, et al. Possible association of mycoplasma and viral respiratory infections with bacterial meningitis. Am J Epidemiol 1987; 125:499.
  18. Takala AK, Meurman O, Kleemola M, et al. Preceding respiratory infection predisposing for primary and secondary invasive Haemophilus influenzae type b disease. Pediatr Infect Dis J 1993; 12:189.
  19. Mäkelä PH, Takala AK, Peltola H, Eskola J. Epidemiology of invasive Haemophilus influenzae type b disease. J Infect Dis 1992; 165 Suppl 1:S2.
  20. MacNeil JR, Cohn AC, Farley M, et al. Current epidemiology and trends in invasive Haemophilus influenzae disease--United States, 1989-2008. Clin Infect Dis 2011; 53:1230.
  21. Wenger JD, Hightower AW, Facklam RR, et al. Bacterial meningitis in the United States, 1986: report of a multistate surveillance study. The Bacterial Meningitis Study Group. J Infect Dis 1990; 162:1316.
  22. Cochi SL, Broome CV. Vaccine prevention of Haemophilus influenzae type b disease: past, present and future. Pediatr Infect Dis 1986; 5:12.
  23. Ward JI, Fraser DW, Baraff LJ, Plikaytis BD. Haemophilus influenzae meningitis. A national study of secondary spread in household contacts. N Engl J Med 1979; 301:122.
  24. Recommendations for use of Haemophilus b conjugate vaccines and a combined diphtheria, tetanus, pertussis, and Haemophilus b vaccine. Recommendations of the advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep 1993; 42:1.
  25. Band JD, Fraser DW, Ajello G. Prevention of Hemophilus influenzae type b disease. JAMA 1984; 251:2381.
  26. Fleming DW, Leibenhaut MH, Albanes D, et al. Secondary Haemophilus influenzae type b in day-care facilities. Risk factors and prevention. JAMA 1985; 254:509.
  27. Makintubee S, Istre GR, Ward JI. Transmission of invasive Haemophilus influenzae type b disease in day care settings. J Pediatr 1987; 111:180.
  28. Osterholm MT, Pierson LM, White KE, et al. The risk of subsequent transmission of Hemophilus influenzae type B disease among children in day care. Results of a two-year statewide prospective surveillance and contact survey. N Engl J Med 1987; 316:1.
  29. Murphy TV, Clements JF, Breedlove JA, et al. Risk of subsequent disease among day-care contacts of patients with systemic Hemophilus influenzae type B disease. N Engl J Med 1987; 316:5.
  30. Centers for Disease Control and Prevention (CDC). Progress toward eliminating Haemophilus influenzae type b disease among infants and children--United States, 1987-1997. MMWR Morb Mortal Wkly Rep 1998; 47:993.
  31. Oh SY, Griffiths D, John T, et al. School-aged children: a reservoir for continued circulation of Haemophilus influenzae type b in the United Kingdom. J Infect Dis 2008; 197:1275.
  32. Watt JP, Wolfson LJ, O'Brien KL, et al. Burden of disease caused by Haemophilus influenzae type b in children younger than 5 years: global estimates. Lancet 2009; 374:903.
  33. Heath PT, Booy R, Azzopardi HJ, et al. Non-type b Haemophilus influenzae disease: clinical and epidemiologic characteristics in the Haemophilus influenzae type b vaccine era. Pediatr Infect Dis J 2001; 20:300.
  34. Adam HJ, Richardson SE, Jamieson FB, et al. Changing epidemiology of invasive Haemophilus influenzae in Ontario, Canada: evidence for herd effects and strain replacement due to Hib vaccination. Vaccine 2010; 28:4073.
  35. Bender JM, Cox CM, Mottice S, et al. Invasive Haemophilus influenzae disease in Utah children: an 11-year population-based study in the era of conjugate vaccine. Clin Infect Dis 2010; 50:e41.
  36. Resman F, Ristovski M, Ahl J, et al. Invasive disease caused by Haemophilus influenzae in Sweden 1997-2009; evidence of increasing incidence and clinical burden of non-type b strains. Clin Microbiol Infect 2011; 17:1638.
  37. Lee YC, Kelly DF, Yu LM, et al. Haemophilus influenzae type b vaccine failure in children is associated with inadequate production of high-quality antibody. Clin Infect Dis 2008; 46:186.
  38. St Geme JW 3rd. Molecular and cellular determinants of non-typeable Haemophilus influenzae adherence and invasion. Cell Microbiol 2002; 4:191.
  39. Murphy TF, Faden H, Bakaletz LO, et al. Nontypeable Haemophilus influenzae as a pathogen in children. Pediatr Infect Dis J 2009; 28:43.
  40. Howard AJ, Dunkin KT, Millar GW. Nasopharyngeal carriage and antibiotic resistance of Haemophilus influenzae in healthy children. Epidemiol Infect 1988; 100:193.
  41. Spinola SM, Peacock J, Denny FW, et al. Epidemiology of colonization by nontypable Haemophilus influenzae in children: a longitudinal study. J Infect Dis 1986; 154:100.
  42. Trottier S, Stenberg K, Svanborg-Edén C. Turnover of nontypable Haemophilus influenzae in the nasopharynges of healthy children. J Clin Microbiol 1989; 27:2175.
  43. Faden H, Duffy L, Williams A, et al. Epidemiology of nasopharyngeal colonization with nontypeable Haemophilus influenzae in the first 2 years of life. J Infect Dis 1995; 172:132.
  44. Faden H, Waz MJ, Bernstein JM, et al. Nasopharyngeal flora in the first three years of life in normal and otitis-prone children. Ann Otol Rhinol Laryngol 1991; 100:612.
  45. Kuklinska D, Kilian M. Relative proportions of Haemophilus species in the throat of healthy children and adults. Eur J Clin Microbiol 1984; 3:249.
  46. Farley MM, Stephens DS, Brachman PS Jr, et al. Invasive Haemophilus influenzae disease in adults. A prospective, population-based surveillance. CDC Meningitis Surveillance Group. Ann Intern Med 1992; 116:806.
  47. Sáez-Llorens X. Pathogenesis of acute otitis media. Pediatr Infect Dis J 1994; 13:1035.
  48. Hasegawa K, Kobayashi R, Takada E, et al. High prevalence of type b beta-lactamase-non-producing ampicillin-resistant Haemophilus influenzae in meningitis: the situation in Japan where Hib vaccine has not been introduced. J Antimicrob Chemother 2006; 57:1077.
  49. García-Cobos S, Campos J, Lázaro E, et al. Ampicillin-resistant non-beta-lactamase-producing Haemophilus influenzae in Spain: recent emergence of clonal isolates with increased resistance to cefotaxime and cefixime. Antimicrob Agents Chemother 2007; 51:2564.
  50. Nakamura S, Yanagihara K, Seki M, et al. Clinical characteristics of pneumonia caused by beta-lactamase negative ampicillin resistant Haemophilus influenzae (BLNAR). Scand J Infect Dis 2007; 39:521.
  51. Falla TJ, Dobson SR, Crook DW, et al. Population-based study of non-typable Haemophilus influenzae invasive disease in children and neonates. Lancet 1993; 341:851.
  52. Winkelstein JA, Moxon ER. The role of complement in the host's defense against Haemophilus influenzae. J Infect Dis 1992; 165 Suppl 1:S62.
  53. Harabuchi Y, Faden H, Yamanaka N, et al. Nasopharyngeal colonization with nontypeable Haemophilus influenzae and recurrent otitis media. Tonawanda/Williamsville Pediatrics. J Infect Dis 1994; 170:862.
  54. Faden H, Stanievich J, Brodsky L, et al. Changes in nasopharyngeal flora during otitis media of childhood. Pediatr Infect Dis J 1990; 9:623.
  55. Long SS, Henretig FM, Teter MJ, McGowan KL. Nasopharyngeal flora and acute otitis media. Infect Immun 1983; 41:987.
  56. Michaels RH, Schultz WF. The frequency of Haemophilus influenzae infections: Analysis of racial and environmental factors. In: Haemophilus influenzae, Sell SH, Karson DT (Eds), Vanderbilt University Press, Nashville 1973. p.243.
  57. Petersen GM, Silimperi DR, Chiu CY, Ward JI. Effects of age, breast feeding, and household structure on Haemophilus influenzae type b disease risk and antibody acquisition in Alaskan Eskimos. Am J Epidemiol 1991; 134:1212.
  58. Hanna JN, Wild BE. Bacterial meningitis in children under five years of age in Western Australia. Med J Aust 1991; 155:160.
  59. Muñoz P, Miranda ME, Llancaqueo A, et al. Haemophilus species bacteremia in adults. The importance of the human immunodeficiency virus epidemic. Arch Intern Med 1997; 157:1869.
  60. Cordero E, Pachón J, Rivero A, et al. Haemophilus influenzae pneumonia in human immunodeficiency virus-infected patients. The Grupo Andaluz para el Estudio de las Enfermedades Infecciosas. Clin Infect Dis 2000; 30:461.
  61. Möller LV, Regelink AG, Grasselier H, et al. Multiple Haemophilus influenzae strains and strain variants coexist in the respiratory tract of patients with cystic fibrosis. J Infect Dis 1995; 172:1388.
  62. Powars D, Overturf G, Turner E. Is there an increased risk of Haemophilus influenzae septicemia in children with sickle cell anemia? Pediatrics 1983; 71:927.
  63. Chilcote RR, Baehner RL, Hammond D. Septicemia and meningitis in children splenectomized for hodgkin's disease. N Engl J Med 1976; 295:798.
  64. Farrand RJ. Recurrent haemophilus septicaemia and immunoglobulin deficiency. Arch Dis Child 1970; 45:582.
  65. Miravitlles M, Espinosa C, Fernández-Laso E, et al. Relationship between bacterial flora in sputum and functional impairment in patients with acute exacerbations of COPD. Study Group of Bacterial Infection in COPD. Chest 1999; 116:40.
  66. Murphy TF. Haemophilus influenzae in chronic bronchitis. Semin Respir Infect 2000; 15:41.
  67. Collins S, Ramsay M, Slack MP, et al. Risk of invasive Haemophilus influenzae infection during pregnancy and association with adverse fetal outcomes. JAMA 2014; 311:1125.
  68. Rello J, Rodriguez R, Jubert P, Alvarez B. Severe community-acquired pneumonia in the elderly: epidemiology and prognosis. Study Group for Severe Community-Acquired Pneumonia. Clin Infect Dis 1996; 23:723.
  69. Brown VM, Madden S, Kelly L, et al. Invasive Haemophilus influenzae disease caused by non-type b strains in Northwestern Ontario, Canada, 2002-2008. Clin Infect Dis 2009; 49:1240.
  70. Figueroa JE, Densen P. Infectious diseases associated with complement deficiencies. Clin Microbiol Rev 1991; 4:359.
  71. Zuckerman JM. Macrolides and ketolides: azithromycin, clarithromycin, telithromycin. Infect Dis Clin North Am 2004; 18:621.
  72. Mandell LA, Wunderink RG, Anzueto A, et al. Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults. Clin Infect Dis 2007; 44 Suppl 2:S27.
  73. Ladhani S, Slack MP, Heath PT, et al. Invasive Haemophilus influenzae Disease, Europe, 1996-2006. Emerg Infect Dis 2010; 16:455.
  74. Ohno A, Ishii Y, Kobayashi I, Yamaguchi K. Antibacterial activity and PK/PD of ceftriaxone against penicillin-resistant Streptococcus pneumoniae and beta-lactamase-negative ampicillin-resistant Haemophilus influenzae isolates from patients with community-acquired pneumonia. J Infect Chemother 2007; 13:296.
  75. Resman F, Ristovski M, Forsgren A, et al. Increase of β-lactam-resistant invasive Haemophilus influenzae in Sweden, 1997 to 2010. Antimicrob Agents Chemother 2012; 56:4408.