Does Zosyn Cover Haemophilus influenzae Type B?
Yes, Zosyn (piperacillin/tazobactam) provides excellent coverage against Haemophilus influenzae type b, with all strains typically inhibited at MICs ≤0.5 μg/mL, well below the susceptibility breakpoint. 1
FDA-Approved Indication
The FDA label explicitly lists Haemophilus influenzae as a covered pathogen for multiple indications 1:
- Nosocomial pneumonia: Piperacillin/tazobactam is FDA-approved for moderate to severe nosocomial pneumonia caused by piperacillin/tazobactam-susceptible H. influenzae 1
- Community-acquired pneumonia: FDA-approved for moderate severity CAP caused by beta-lactamase producing isolates of H. influenzae 1
Microbiological Activity
Piperacillin/tazobactam demonstrates potent activity against all resistance phenotypes of H. influenzae, including the most challenging strains 2:
- Beta-lactamase producing strains: The tazobactam component inhibits plasmid-mediated beta-lactamases (TEM-1, TEM-2, SHV-1) that confer ampicillin resistance 3
- BLNAR strains (beta-lactamase-negative ampicillin-resistant): All BLNAR isolates tested showed MICs ≤0.5 μg/mL, despite CLSI's disclaimer suggesting these should be considered resistant 2
- BLPACR strains (beta-lactamase-positive amoxicillin-clavulanate-resistant): Even these highly resistant strains remain susceptible, with all MICs ≤0.5 μg/mL 2
In surveillance studies, piperacillin/tazobactam inhibited 100% of H. influenzae isolates (including 39.2% that were ampicillin-resistant) at ≤0.25 μg/mL 4. This makes it the most potent beta-lactam tested against all classes of H. influenzae 2.
Clinical Efficacy
Pediatric clinical studies demonstrate excellent outcomes 5:
- Clinical efficacy of 95% (19/20 cases) in children with lower respiratory tract infections caused by H. influenzae, including resistant strains 5
- The single treatment failure occurred in a patient with severe concurrent RSV infection, not due to antimicrobial resistance 5
Important Clinical Considerations
The CLSI disclaimer about BLNAR strains being "considered resistant" to piperacillin/tazobactam is not supported by microbiological or clinical data 2. This disclaimer was adapted without presentation of supporting evidence, and subsequent research demonstrates all BLNAR strains remain fully susceptible 2.
Disk diffusion testing: A zone diameter ≥21 mm indicates susceptibility for H. influenzae 3, 2. The MIC breakpoint is ≤16/2 μg/mL for susceptible 3.
Comparison to Other Agents
While carbapenems like meropenem also provide excellent H. influenzae coverage 6, piperacillin/tazobactam offers equivalent activity with a narrower spectrum, making it preferable for antimicrobial stewardship when H. influenzae is the primary concern 4. The combination was more active than ticarcillin-clavulanate against H. influenzae in head-to-head comparisons 7.