What is Haemophilus (H.) influenzae and how is it treated?

Haemophilus Influenzae: Overview and Treatment

Haemophilus influenzae is a gram-negative bacterium that can cause various respiratory infections and invasive diseases, with treatment typically involving beta-lactam antibiotics for susceptible strains or alternative agents for resistant strains.

Characteristics and Classification

• H. influenzae is a small, pleomorphic, facultatively anaerobic gram-negative bacillus with complex nutritional requirements, characterized by its need for both hemin (X factor) and NAD (V factor) for growth 1
• The bacterium can be either encapsulated (typeable, serotypes a-f) or unencapsulated (nontypeable) 1
• Nontypeable strains typically cause upper respiratory tract infections such as otitis media, sinusitis, and acute exacerbations of chronic bronchitis 1, 2
• Invasive disease caused by H. influenzae can produce several clinical syndromes, including meningitis, bacteremia, epiglottitis, or pneumonia 1

Clinical Significance

• H. influenzae is present as a commensal organism in the nasopharynx of most healthy adults, from where it can spread to cause both systemic and respiratory tract infections 2
• Nontypeable H. influenzae (NTHi) is a significant respiratory pathogen in children, often associated with pneumonia and acute otitis media 3
• H. influenzae is a major bacterial pathogen in acute exacerbations of chronic bronchitis and also causes otitis media and sinusitis, particularly in elderly persons 4
• H. influenzae infections frequently occur as secondary infections following viral or other bacterial infections 3

Laboratory Diagnosis

• Laboratory confirmation requires isolation of H. influenzae from a normally sterile site (e.g., blood, cerebrospinal fluid, joint fluid, pleural fluid, or pericardial fluid) 1
• The organism grows poorly on ordinary blood agar but grows well on chocolate agar 5
• A probable case of invasive H. influenzae can be diagnosed with detection of H. influenzae type b antigen in cerebrospinal fluid 1

Antimicrobial Resistance

• Beta-lactamase production is the primary mechanism of resistance to ampicillin and amoxicillin, with prevalence ranging from 30-40% in the United States 1, 4
• Beta-lactamase-negative ampicillin-resistant (BLNAR) strains exist due to alterations in penicillin-binding proteins (PBPs) 3a and 3b 1
• H. influenzae has intrinsically poor susceptibility to macrolides and azalides due to efflux pumps mediated by acrAB genes 1

Treatment Recommendations

First-line Treatment

• For susceptible (beta-lactamase-negative) H. influenzae infections, high-dose amoxicillin (80-90 mg/kg/day in 2 divided doses) is the recommended first-line treatment 1, 6
• For beta-lactamase-producing H. influenzae, high-dose amoxicillin-clavulanate (90 mg/kg/day of amoxicillin with 6.4 mg/kg/day of clavulanate in 2 divided doses) is recommended 1
• Essentially all H. influenzae isolates, including beta-lactamase-producing strains, are susceptible to high-dose amoxicillin-clavulanate 1

Alternative Treatments

• For patients with penicillin allergy, alternative treatments include:
  • Cefdinir (14 mg/kg/day in 1 or 2 doses) 1
  • Cefuroxime (30 mg/kg/day in 2 divided doses) 1
  • Cefpodoxime (10 mg/kg/day in 2 divided doses) 1
• For treatment failures, options include:
  • Ceftriaxone (50 mg IM or IV per day for 1 or 3 days) 1
  • Clindamycin (30-40 mg/kg/day in 3 divided doses) plus a third-generation cephalosporin 1

Impact of Vaccination

• The Haemophilus influenzae type b (Hib) vaccine has dramatically reduced invasive H. influenzae type b disease, including meningitis and pneumonia 1
• The Hib vaccine has not affected mucosal diseases (otitis media, sinusitis) which are largely caused by nontypeable H. influenzae 1

Clinical Considerations

• Treatment should be continued for a minimum of 48 to 72 hours beyond the time that the patient becomes asymptomatic 6
• For respiratory infections where H. influenzae is suspected but not confirmed, empiric therapy should cover both H. influenzae and S. pneumoniae 1
• In patients with chronic obstructive pulmonary disease (COPD), H. influenzae can cause airway inflammation and colonization, requiring targeted therapy 2
• Treatment of respiratory tract infections with H. influenzae is often only partially successful, with ongoing infection and inflammation 2

Monitoring and Follow-up

• For patients who fail initial amoxicillin therapy for bacterial infections, second-line options include amoxicillin-clavulanate or ceftriaxone 7
• If a patient with suspected bacterial infection fails to respond to initial treatment within 48-72 hours, they should be reassessed 7