Will Zosyn (piperacillin/tazobactam) cover gram-negative organisms?

Zosyn Coverage of Gram-Negative Organisms

Yes, Zosyn (piperacillin/tazobactam) provides excellent coverage against most gram-negative organisms, including Pseudomonas aeruginosa, making it an effective broad-spectrum antibiotic for serious infections.

Spectrum of Activity Against Gram-Negative Organisms

Piperacillin/tazobactam has demonstrated activity against the following gram-negative pathogens:

• Enterobacteriaceae family:

  • Escherichia coli
  • Klebsiella pneumoniae
  • Proteus mirabilis
  • Morganella morganii
  • Serratia marcescens
  • Citrobacter species

• Non-fermenters:

  • Pseudomonas aeruginosa
  • Acinetobacter baumannii (though resistance is increasing)

• Other gram-negatives:

  • Haemophilus influenzae
  • Neisseria gonorrhoeae

According to the FDA drug label, piperacillin/tazobactam has been shown to be active against most isolates of these gram-negative bacteria both in vitro and in clinical infections 1.

Mechanism of Action

Piperacillin is a beta-lactam antibiotic that exerts bactericidal activity by inhibiting septum formation and cell wall synthesis of susceptible bacteria. Tazobactam is a beta-lactamase inhibitor that protects piperacillin from degradation by certain beta-lactamases, particularly:

• Molecular class A enzymes
• Richmond-Sykes class III (Bush class 2b & 2b') penicillinases
• Some cephalosporinases 1

This combination allows piperacillin to maintain activity against many beta-lactamase-producing gram-negative organisms that would otherwise be resistant to piperacillin alone.

Clinical Applications

Piperacillin/tazobactam is recommended in several clinical guidelines for infections likely to involve gram-negative pathogens:

1. Hospital-acquired pneumonia (HAP)/Ventilator-associated pneumonia (VAP):

   • Recommended as an antipseudomonal agent for empiric therapy in patients at risk for gram-negative infections 2

2. Intra-abdominal infections:

   • Effective for complicated intra-abdominal infections, particularly when Pseudomonas coverage is needed 2

3. Febrile neutropenia:

   • Recommended as monotherapy for high-risk patients requiring inpatient management with IV broad-spectrum antibiotic therapy 2

Limitations and Resistance Concerns

Despite its broad gram-negative coverage, there are important limitations to consider:

• ESBL-producing organisms: While piperacillin/tazobactam has activity against some ESBL-producing Enterobacteriaceae, carbapenems are generally more reliable for these pathogens 2

• AmpC beta-lactamase producers: Limited activity against organisms that hyperproduce AmpC beta-lactamases (some Enterobacter, Citrobacter, and Serratia species) 3

• Carbapenemase-producing organisms: Not effective against carbapenemase-producing Enterobacteriaceae (CRE) or carbapenem-resistant Pseudomonas aeruginosa

Enterococcal Coverage

An additional benefit of piperacillin/tazobactam is its activity against Enterococcus faecalis (but not reliably against E. faecium), which distinguishes it from many other antibiotics used for gram-negative coverage such as cephalosporins and carbapenems 4, 1.

Dosing Considerations

Standard dosing for serious infections in adults with normal renal function is 3.375g or 4.5g IV every 6-8 hours. Dose adjustments are required for patients with renal impairment (CrCl <40 mL/min) 1.

Conclusion

Zosyn (piperacillin/tazobactam) provides reliable coverage against most clinically important gram-negative pathogens, including Pseudomonas aeruginosa. Its broad spectrum of activity makes it suitable for empiric therapy in many serious infections, particularly healthcare-associated infections where resistant gram-negative pathogens are a concern.