What bacterial coverage does Zosyn (piperacillin/tazobactam) provide?

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Last updated: June 18, 2025View editorial policy

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From the Guidelines

Zosyn (piperacillin/tazobactam) provides broad-spectrum coverage against many gram-positive, gram-negative, and anaerobic bacteria, including Streptococci, methicillin-sensitive Staphylococcus aureus, Enterococcus faecalis, Enterobacteriaceae, Pseudomonas aeruginosa, and anaerobes like Bacteroides fragilis. The combination of piperacillin and tazobactam works by inhibiting bacterial cell wall synthesis and protecting piperacillin from degradation by beta-lactamase enzymes, respectively 1. This makes Zosyn particularly useful for treating complicated intra-abdominal infections, pneumonia, skin/soft tissue infections, and febrile neutropenia.

  • Key coverage includes:
    • Streptococci (including S. pneumoniae)
    • Methicillin-sensitive Staphylococcus aureus (but not MRSA)
    • Enterococcus faecalis
    • Many Enterobacteriaceae (including E. coli, Klebsiella, Proteus, Enterobacter)
    • Pseudomonas aeruginosa
    • Anaerobes like Bacteroides fragilis
  • The standard adult dose is typically 3.375g or 4.5g IV every 6-8 hours, with adjustments needed for renal impairment, as recommended by guidelines such as those from the Infectious Diseases Society of America 1.
  • Zosyn does not cover MRSA, most Acinetobacter species, Stenotrophomonas maltophilia, or organisms producing certain extended-spectrum beta-lactamases (ESBLs) or carbapenemases.
  • It is essential to note that the use of Zosyn should be guided by local antimicrobial susceptibility patterns and the specific clinical context, including the severity of the infection and the presence of any underlying conditions that may affect the patient's response to treatment 1.

From the FDA Drug Label

Piperacillin and tazobactam has been shown to be active against most isolates of the following microorganisms both in vitro and in clinical infections: Aerobic bacteria Gram-positive bacteria Staphylococcus aureus (methicillin susceptible isolates only) Gram-negative bacteria Acinetobacter baumannii Escherichia coli Haemophilus influenzae (excluding beta-lactamase negative, ampicillin-resistant isolates) Klebsiella pneumoniae Pseudomonas aeruginosa (given in combination with an aminoglycoside to which the isolate is susceptible) Anaerobic bacteria Bacteroides fragilis group (B. fragilis, B. ovatus, B. thetaiotaomicron, and B. vulgatus)

Zosyn (piperacillin/tazobactam) provides coverage against a variety of Gram-positive and Gram-negative aerobic and anaerobic bacteria, including:

  • Staphylococcus aureus (methicillin susceptible isolates only)
  • Acinetobacter baumannii
  • Escherichia coli
  • Haemophilus influenzae (excluding beta-lactamase negative, ampicillin-resistant isolates)
  • Klebsiella pneumoniae
  • Pseudomonas aeruginosa (given in combination with an aminoglycoside to which the isolate is susceptible)
  • Bacteroides fragilis group (B. fragilis, B. ovatus, B. thetaiotaomicron, and B. vulgatus) 2

From the Research

Bacterial Coverage of Zosyn (Piperacillin/Tazobactam)

Zosyn, a combination of piperacillin and tazobactam, provides broad-spectrum antibacterial coverage against various Gram-positive and Gram-negative bacteria, including:

  • Methicillin-susceptible staphylococci 3
  • Streptococcus pneumoniae 4
  • Haemophilus influenzae 4
  • Enterococci 4
  • Bacteroides fragilis group 3, 4
  • Many Enterobacteriaceae, such as Escherichia coli and Klebsiella species 3, 4
  • Pseudomonas aeruginosa 5, 4

Limitations of Coverage

However, Zosyn may not be effective against:

  • Extended-spectrum beta-lactamase (ESBL) producing Klebsiella species and some high-level TEM and SHV beta-lactamase producing E. coli and Klebsiella species 4
  • Some Enterobacter species that are derepressed hyperproducing mutants 4
  • Penicillinase-producing Staphylococcus aureus 3

Key Points

  • Piperacillin/tazobactam has excellent activity against many Gram-positive and Gram-negative bacteria, making it a suitable option for monotherapy in mixed anerobic infections and mixed respiratory infections 4
  • The combination of piperacillin and tazobactam improves the activity of piperacillin against staphylococci, TEM and SHV beta-lactamase producing Gram-negative bacteria, and anaerobes 4
  • Zosyn may be used in combination with an aminoglycoside to provide Gram-positive and Gram-negative coverage in febrile episodes in immunosuppressed patients 4

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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