What is the recommended antibiotic coverage for Haemophilus (H) influenzae infections?

Antibiotic Coverage for Haemophilus influenzae Infections

For H. influenzae infections, amoxicillin-clavulanate is the preferred first-line oral antibiotic, while ceftriaxone or cefotaxime are the preferred agents for severe or invasive infections requiring parenteral therapy. 1

Critical Context: Beta-Lactamase Production

• 18-42% of H. influenzae strains produce β-lactamase, rendering plain amoxicillin or ampicillin ineffective 1, 2
• Never use plain ampicillin or amoxicillin empirically without documented susceptibility testing 1, 3
• Always assume β-lactamase production when selecting empiric therapy 3

First-Line Treatment by Severity

Non-Severe Infections (Outpatient)

Preferred oral regimens:

• Amoxicillin-clavulanate 625 mg PO three times daily (or 90 mg/kg/day in children, divided twice daily with 14:1 ratio to minimize diarrhea) 1, 4
• Doxycycline 200 mg loading dose, then 100 mg PO twice daily (equally preferred alternative) 1, 4

Alternative oral regimens for penicillin allergy:

• Clarithromycin 500 mg PO twice daily (preferred macrolide due to superior H. influenzae activity compared to azithromycin) 1, 4
• Respiratory fluoroquinolones: levofloxacin 750 mg PO once daily or moxifloxacin 400 mg PO once daily 1, 4

Severe/Invasive Infections (Inpatient)

Preferred parenteral regimens:

• Ceftriaxone 1-2 g IV once daily (2 g IV every 12 hours for meningitis) 1, 3, 5
• Cefotaxime 1-2 g IV every 6-8 hours (2 g IV every 6 hours for meningitis) 1, 3, 6

Alternative parenteral regimens:

• Amoxicillin-clavulanate 1.2 g IV every 8-12 hours 1
• Cefuroxime 750 mg-1.5 g IV every 8 hours 1, 7
• Levofloxacin 500 mg IV once daily (if β-lactams contraindicated) 1

Site-Specific Recommendations

Community-Acquired Pneumonia (Pediatric)

Fully immunized children (inpatient):

• Ampicillin or penicillin G (if local resistance minimal) 4
• Ceftriaxone or cefotaxime (if not fully immunized or significant local resistance) 4

Outpatient (≥5 years):

• Amoxicillin 90 mg/kg/day in 2 doses (maximum 4 g/day) 4

Acute Otitis Media (Pediatric)

• High-dose amoxicillin-clavulanate (90 mg/kg/day amoxicillin component with 6.4 mg/kg/day clavulanate, 14:1 ratio, divided twice daily) 4
• This formulation provides superior eradication of S. pneumoniae (96%) and adequate H. influenzae coverage 4

Acute Bacterial Rhinosinusitis (Adult)

Mild disease without recent antibiotic use:

• Amoxicillin-clavulanate 1.75-4 g/250 mg daily (calculated efficacy 90-91% clinical, 97-99% bacteriologic) 4

Moderate disease or recent antibiotic use:

• Amoxicillin-clavulanate 4 g/250 mg daily 4
• Respiratory fluoroquinolones (92% clinical, 100% bacteriologic efficacy) 4

Meningitis

• Ceftriaxone 2 g IV once daily or cefotaxime 2 g IV every 6 hours for 10-14 days 1, 3, 6
• Third-generation cephalosporins achieve CSF concentrations 10-100 fold higher than MIC within 24-48 hours 5
• CSF sterilization typically occurs within 24-48 hours 5, 8

Treatment Duration

• Non-severe infections: 7 days 1, 2
• Severe pneumonia or systemic infections: 10-14 days 1, 3, 2
• Meningitis: 10-14 days 3, 6
• Streptococcus pyogenes co-infection: minimum 10 days to prevent acute rheumatic fever 9

Common Pitfalls to Avoid

• Do not assume all macrolides are equivalent: Clarithromycin has clinically superior activity against H. influenzae compared to azithromycin or erythromycin 1
• Macrolides have poor intrinsic activity against H. influenzae due to efflux pumps, with >98% resistance in some studies 3
• Do not use plain amoxicillin empirically in areas with β-lactamase production rates of 18-42% 1, 2
• Monitor local antibiograms: β-lactamase production and fluoroquinolone resistance vary significantly by region 3, 2

Treatment Failure Algorithm

If no improvement after 48-72 hours:

1. Switch to broader-spectrum agent (ceftriaxone if not already used) 2
2. Check local antimicrobial resistance patterns 2
3. Reevaluate diagnosis and consider additional pathogens 2
4. Consider imaging for complications (parapneumonic effusion, abscess) 4

Special Populations

Penicillin allergy with anaphylaxis history:

• Respiratory fluoroquinolone (levofloxacin or moxifloxacin) for severe infections 1, 3
• Doxycycline for non-severe infections 1, 3

Children <5 years (preschool) with pneumonia:

• Amoxicillin 90 mg/kg/day in 2 doses (outpatient) 4
• Ampicillin or ceftriaxone/cefotaxime (inpatient) 4

Adults with cardiopulmonary disease or smoking history:

• β-lactam plus macrolide combination OR antipneumococcal fluoroquinolone monotherapy to cover both typical and atypical pathogens 3, 2