Does piperacillin/tazobactam (Zosyn) effectively treat Streptococcus pneumoniae that is resistant to penicillin but susceptible to amoxicillin/clavulanate (Augmentin)?

Zosyn for Penicillin-Resistant, Augmentin-Susceptible S. pneumoniae

Yes, piperacillin/tazobactam (Zosyn) is effective against Streptococcus pneumoniae that is penicillin-resistant but amoxicillin/clavulanate-susceptible, and can be used for pneumonia caused by this organism.

Microbiological Activity

Piperacillin/tazobactam demonstrates robust activity against penicillin-resistant S. pneumoniae:

• Piperacillin/tazobactam inhibits all Streptococcus pneumoniae strains at ≤16 mcg/mL, including penicillin-resistant strains 1
• Against penicillin-intermediate and penicillin-resistant pneumococci, piperacillin shows MIC50 of 0.5 mcg/mL and MIC90 of 2 mcg/mL, demonstrating potent activity 2
• Piperacillin has low MICs against pneumococci and may be effective even against penicillin-resistant strains 3

Guideline-Based Recommendations

The major respiratory guidelines specifically address piperacillin/tazobactam for drug-resistant S. pneumoniae:

• The American Thoracic Society/Infectious Diseases Society of America guidelines list piperacillin/tazobactam as an active agent against drug-resistant S. pneumoniae (DRSP) when penicillin MIC is ≤2 mg/L 4
• These guidelines note that piperacillin/tazobactam is active against P. aeruginosa but also provides broader coverage than necessary for typical community-acquired pneumonia, making it appropriate when DRSP is suspected 4
• Piperacillin/tazobactam should not be used as primary therapy for uncomplicated CAP since it provides unnecessarily broad coverage, but is appropriate for severe CAP or when risk factors for resistant organisms exist 4

Clinical Context for Your Scenario

Your specific scenario describes an organism that is:

• Penicillin-resistant (meaning penicillin MIC >2 mg/L by older breakpoints)
• Augmentin-susceptible (meaning amoxicillin/clavulanate MIC in susceptible range)

This resistance pattern indicates:

• The organism has altered penicillin-binding proteins causing penicillin resistance 4
• Amoxicillin is more effective than penicillin against pneumococci in vitro, with MIC thresholds that are higher 4
• If the organism is susceptible to amoxicillin/clavulanate, it has intermediate-level resistance, not high-grade resistance 4

Treatment Algorithm

For pneumonia (not meningitis) caused by this organism:

1. First-line options (if susceptibility known):

   • High-dose amoxicillin/clavulanate (875 mg twice daily or 2g/125mg q12h formulation) 4
   • Ceftriaxone or cefotaxime (preferred parenteral agents) 4

2. Piperacillin/tazobactam is an acceptable alternative when:

   • Severe pneumonia requiring broad empiric coverage 4
   • Patient cannot tolerate preferred agents
   • Polymicrobial infection suspected 5

3. Avoid ceftazidime (8-16-fold less active than ceftriaxone) 6

Critical Caveats

• Do not confuse penicillin resistance with resistance to all beta-lactams—many penicillin-resistant strains remain susceptible to amoxicillin, ceftriaxone, and piperacillin/tazobactam 6
• The beta-lactamase inhibitor component (tazobactam) does not enhance activity against pneumococci, as pneumococcal resistance is due to altered PBPs, not beta-lactamase production 7
• For meningitis, different breakpoints apply and piperacillin/tazobactam would NOT be appropriate 4
• Clinical response to beta-lactams in pneumonia is preserved even with reduced in vitro susceptibility, as much higher drug levels are achieved in blood and alveoli compared to CSF 4

Practical Recommendation

If treating pneumonia empirically before susceptibilities are known, piperacillin/tazobactam provides adequate coverage for this resistance pattern 1, 5. However, once susceptibilities confirm amoxicillin/clavulanate susceptibility, de-escalate to the narrower-spectrum agent (oral amoxicillin/clavulanate for outpatients, or ceftriaxone/cefotaxime for hospitalized patients) to reduce selective pressure for resistance 4.