What are the clinical manifestations and treatment options for Haemophilus (H.) influenzae infections?

Clinical Features of Haemophilus influenzae Infection

H. influenzae causes a spectrum of respiratory and invasive infections in adults, with nontypeable strains (NTHi) now predominating since Hib vaccination, primarily affecting patients with predisposing conditions such as chronic lung disease, immunocompromise, CSF leaks, or ENT infections. 1, 2, 3

Key Clinical Syndromes

Invasive Disease Manifestations

Meningitis:

• Uncommon in adults (4% of bacterial meningitis cases), with median age 61 years and female predominance (59%) 3
• 79% caused by nontypeable strains (NTHi) in contemporary series 3
• Predisposing factors present in most cases: otitis/sinusitis (49%), immunocompromise (25%), CSF leak (17%) 3
• Mortality 4%, unfavorable outcomes 17% at discharge 3
• Poor prognostic indicators: concurrent pneumonia (OR 5.8), immunocompromise (OR 6.0), seizures on admission (OR 10.7) 3
• Should be particularly suspected in alcoholics, head trauma patients (especially with CSF rhinorrhea), splenectomy patients, and those with hypogammaglobulinemia 4

Pneumonia:

• Type b H. influenzae pneumonia affects predominantly older adults: 60% are >50 years old, 30-40% are alcoholics, 30-40% have chronic pulmonary disease 5
• Distinctive radiographic pattern: multilobular, maculate, diffuse, usually bilateral involvement 5
• High mortality rate of 30-40% for type b bacteremic pneumonia 5
• Nontypeable strains cause less severe, non-bacteremic pneumonia with lower mortality and less extensive involvement 5
• Has distinctive appearance on Gram stain (pleomorphic gram-negative coccobacilli) 4

Other Invasive Infections:

• Epiglottitis: H. influenzae is the most frequent etiologic agent of acute epiglottitis in adults 4
• Rare manifestations include purulent pericarditis, endocarditis, septic arthritis, obstetrical/gynecologic infections, urinary/biliary tract infections, and cellulitis 4

Respiratory Tract Colonization and Infection

Chronic Obstructive Pulmonary Disease (COPD):

• NTHi plays an important role in acute exacerbations of COPD 5, 6
• Colonizes bronchi causing ongoing airway inflammation, particularly in COPD patients 6
• Treatment often only partially successful with persistent infection and inflammation 6

Acute Sinusitis:

• H. influenzae, along with S. pneumoniae, is a major etiologic factor in acute sinusitis 4

Upper Respiratory Infections:

• Affects ear, nose, and throat structures 7

Microbiological Characteristics

Growth Requirements:

• Requires both X factor (hemin) and V factor (NAD) for growth 2, 4
• Grows poorly on ordinary blood agar unless streaked with S. aureus 4
• Grows well on chocolate agar 4
• Critical diagnostic pitfall: Frequently missed because chocolate agar often not used for adult specimens and organism may be overgrown by other bacteria 4

Classification:

• Encapsulated (typeable, serotypes a-f) versus unencapsulated (nontypeable) 2
• Small, pleomorphic, facultatively anaerobic gram-negative coccobacillus 2, 8
• Adheres to respiratory epithelial cells via fimbriae 8

Antimicrobial Resistance Patterns

β-lactamase Production:

• 30-40% of U.S. isolates produce β-lactamase, conferring ampicillin/amoxicillin resistance 2
• Geographic variation in UK: 2-17% β-lactamase production 1
• Mediated by R-factors or plasmids 5

Macrolide Susceptibility:

• Intrinsically poor susceptibility to macrolides due to efflux pumps (acrAB genes) 2
• Macrolides (except clarithromycin) have poor in vivo activity against H. influenzae 1
• Clarithromycin demonstrates superior activity compared to azithromycin 9, 2

Treatment Recommendations

First-Line Therapy:

• Co-amoxiclav 625 mg three times daily orally is the preferred agent for non-severe infections 1, 9
• Doxycycline 200 mg loading dose, then 100 mg once daily is an equally preferred alternative 1, 9
• For severe pneumonia requiring IV therapy: co-amoxiclav 1.2 g three times daily IV or cefuroxime 1.5 g three times daily IV 1, 9

Alternative Therapy:

• Clarithromycin 500 mg twice daily is the preferred macrolide when needed (superior H. influenzae coverage versus other macrolides) 9, 2
• Fluoroquinolones (levofloxacin or moxifloxacin) provide coverage but should be reserved for specific circumstances 1

Critical Treatment Pitfall:

• Do not use azithromycin as first-line empiric therapy when H. influenzae is suspected 9
• Ampicillin/amoxicillin alone should only be used for confirmed β-lactamase-negative isolates 7
• For serious infections with ampicillin-resistant organisms or penicillin allergy, chloramphenicol was historically the best choice 4

Diagnostic Confirmation

Laboratory Diagnosis:

• Isolation from normally sterile sites (blood, CSF, joint/pleural/pericardial fluid) confirms invasive disease 1, 2
• Detection of H. influenzae type b antigen in CSF indicates probable invasive disease 1, 2
• Blood cultures frequently not obtained in adults, contributing to underdiagnosis 4
• Laboratories should routinely subculture blood cultures onto chocolate agar 4

Transmission and Prevention

Epidemiology:

• Present as commensal in nasopharynx of most healthy adults 6
• Nasopharyngeal carriage very common; carriers usually harbor unencapsulated strains 8
• Secondary infection risk in children exposed to type b cases: approximately 2.1% 5
• Adults in close contact with infected children should be warned of secondary infection risk 5

Vaccination Impact:

• Hib vaccine dramatically reduced invasive H. influenzae type b disease (meningitis, pneumonia) 2
• Nontypeable strains now predominate in adult disease 3