II. Pathophysiology

  1. Haemophilus Influenzae
    1. Facultatively anaerobic Gram Negative Rods (or coccobacilli) in family Pasteurellaceae
    2. Non-motile and Non-Spore forming
    3. Respiratory transmission
    4. Haemophilus is derived from the greek "blood loving"
      1. Cytochrome system within Haemophilus organisms require Hematin (or Factor X, from blood)
  2. Polysaccharide Capsule
    1. Capsule confers virulence and is composed of Polyribitol Ribose Phosphate (PRP)
    2. Six different capsule types (A, B, C, D, E, F)
    3. Capsule Type B (Hib)
      1. Capsule Type B is most important in humans (esp. in children) and the Hib Vaccine target (see below)
      2. Encapsulated Haemophilus Influenzae (esp. Hib) is a significant risk for Sepsis in Asplenic patients
      3. Haemophilus Influenzae Type B is associated with invasive disease in children (e.g. Bacterial Meningitis)
        1. Hib invasive disease has been dramatically reduced in the U.S. by Hib Vaccine
    4. Non-Encapsulated Strains (Non-Typeable Haemophilus Influenzae, NTHi)
      1. Non-Typeable strains colonize the upper respiratory tract of children and adults
      2. Responsible for most Haemophilus Influenzae infections in adults and vaccinated children
      3. Low virulence organisms (lacking a capsule)
      4. Includes strains previously classified as separate species (now considered non-typable H. Influenzae)
        1. Haemophilus aegyptius (causes Bacterial Conjunctivitis, Brazilian Purpuric Fever)
        2. Haemophilus haemolyticus (rare Immunocompromised infections, including endocarditis)
      5. Typically NTHi causes only local disease (e.g. Otitis Media, Acute Sinusitis)
        1. Invasive disease (e.g. Pneumonia) may occur in age over 65 years or Immunocompromised patients

III. Associated Conditions: Haemophilus Influenzae Infections

  1. Haemophilus Influenzae Type B or Hib (Non-Immunized Children)
    1. Haemophilus Influenzae Pneumonia
      1. Hib Vaccine has nearly eliminated Hib Pneumonia in Children
        1. NTHi in adults now predominates as a Bacterial Pneumonia cause (see below)
      2. Prior to Hib Vaccine, Hib Pneumonia in Children 0–4 years of age caused significant morbidity and mortality
        1. Developed countries: 6 per 100,000 cases (5% mortality)
        2. Developing Countries: 300 per 100,000 cases (13 to 24% mortality)
    2. Occult Bacteremia (Pediatric Fever Age Under 3 Years)
      1. Vaccines (Hib, PCV) have reduced Occult Bacteremia in febrile children <36 months from 12% to 2%
    3. Bacterial Meningitis
      1. Hib was the most common cause of Bacterial Meningitis in age 6 months to 3 years prior to Hib Vaccine
      2. Hib Meningitis was previously 10,000 cases/year (now rare in U.S. after 1987 Hib Vaccine introduction)
      3. Significant neurologic deficits persisted in 50% of Antibiotic treated children (of the 95% that survived)
    4. Septic Arthritis
      1. Hib was the most common cause of Septic Joint in infants prior to Hib Vaccine
      2. Hib now (post-Hib Vaccine) represents <3% of Septic Arthritis cases
    5. Acute Epiglottitis
      1. High mortality condition, now rare in children since Hib Vaccine introduction
      2. Hib Epiglottitis now rare in U.S., and more likely to occur in adults (waning Immunity)
  2. Non-Encapsulated Strains (Non-Typeable Haemophilus Influenzae, NTHi)
    1. Non-Invasive Disease (most common)
      1. Acute Otitis Media (children)
      2. Acute Sinusitis
      3. Acute Exacerbation of Chronic Bronchitis (COPD)
    2. Invasive Disease in Adults (age >65 years, lung disease, Immunocompromised status)
      1. Bacterial Pneumonia
        1. NTHi is among the top 2 causes of Bacterial Pneumonia in hospitalized patients (esp elderly)

IV. Management: Antibiotics

  1. General
    1. Beta-lactam resistance in Haemophilus Influenzae may approach 50% in some communities
    2. Empiric Antibiotics should cover Beta-Lactamase producers until culture sensitivity is returned
  2. Intravenous Antibiotics in Life-threatening Disease (e.g. Meningitis)
    1. Ceftriaxone
    2. Cefotaxime
  3. Oral Antibiotics in Non-Life Threatening Disease
    1. Amoxicillin Clavulanate (Augmentin)
    2. Cefprozil
    3. Cefuroxime
    4. Cefdinir
  4. Alternative Antibiotics (e.g. allergy)
    1. Levofloxacin
    2. Doxycycline
    3. Azithromycin or Clarithromycin (resistance is common)

V. Prevention

  1. Haemophilus influenzae B Vaccine (Hib Vaccine)
    1. Released in 1987, Hib Vaccine has reduced invasive Hib associated disease by 99%

VII. References

  1. Gladwin, Trattler and Mahan (2014) Clinical Microbiology, Medmaster, Fl, p. 96-7
  2. Sanford Guide, accessed 2/3/2025
  3. Oliver (2023) Clin Infect Dis 76(11):1889-95 +PMID: 36722332 [PubMed]

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