Does Zosyn (piperacillin/tazobactam) cover Gram-positive cocci?

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Last updated: April 13, 2025View editorial policy

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From the Guidelines

Yes, Zosyn (piperacillin-tazobactam) does cover gram-positive cocci, including methicillin-susceptible Staphylococcus aureus (MSSA) and other streptococci, as indicated in the 2024 guidelines by the WHO 1.

Key Points

  • Zosyn is a broad-spectrum antibiotic combination that consists of piperacillin, an extended-spectrum penicillin, and tazobactam, a beta-lactamase inhibitor.
  • This combination is effective against many gram-positive cocci, but it does not cover methicillin-resistant Staphylococcus aureus (MRSA) or Enterococcus faecium.
  • The typical dosing for adults with normal renal function is 3.375g or 4.5g IV every 6 hours, with adjustments needed for patients with renal impairment, as suggested by various guidelines including those from the Infectious Diseases Society of America 1.
  • Zosyn works by inhibiting bacterial cell wall synthesis, with tazobactam protecting piperacillin from degradation by certain beta-lactamases.

Clinical Use

  • While Zosyn provides good gram-positive coverage, it's particularly valued for its broad activity against gram-negative organisms, including Pseudomonas aeruginosa, making it useful for mixed infections or empiric therapy when both gram-positive and gram-negative coverage is needed, as seen in the management of hospital-acquired and ventilator-associated pneumonia 1.
  • For specific infections such as necrotizing fasciitis, Zosyn (piperacillin-tazobactam) can be used in combination with other antibiotics like clindamycin and vancomycin, as recommended by the WHO guidelines 1.

Important Considerations

  • The choice of antibiotic should always consider the local resistance patterns and the specific infection being treated.
  • Guidelines such as those from the Infectious Diseases Society of America and the WHO should be consulted for the most up-to-date recommendations on antibiotic use.

From the FDA Drug Label

Antimicrobial Activity Piperacillin and tazobactam has been shown to be active against most isolates of the following microorganisms, both in vitro and in clinical infections [see Indications and Usage (1)] Aerobic bacteria Gram-positive bacteria Staphylococcus aureus (methicillin susceptible isolates only)

The following in vitro data are available, but their clinical significance is unknown At least 90 percent of the following bacteria exhibit an in vitro minimum inhibitory concentration (MIC) less than or equal to the susceptible breakpoint for piperacillin and tazobactam against isolates of similar genus or organism group However, the efficacy of piperacillin and tazobactam for injection in treating clinical infections caused by these bacteria has not been established in adequate and well-controlled clinical trials Aerobic bacteria Gram-positive bacteria Enterococcus faecalis (ampicillin or penicillin-susceptible isolates only) Staphylococcus epidermidis (methicillin susceptible isolates only) Streptococcus agalactiae† Streptococcus pneumoniae† (penicillin-susceptible isolates only) Streptococcus pyogenes† Viridans group streptococci†

Zosyn (piperacillin/tazobactam) has activity against certain Gram-positive cocci, including:

  • Staphylococcus aureus (methicillin susceptible isolates only)
  • Streptococcus agalactiae
  • Streptococcus pneumoniae (penicillin-susceptible isolates only)
  • Streptococcus pyogenes
  • Viridans group streptococci
  • Enterococcus faecalis (ampicillin or penicillin-susceptible isolates only)
  • Staphylococcus epidermidis (methicillin susceptible isolates only) 2

From the Research

Zosyn Coverage Against Gram-Positive Cocci

  • Zosyn, a combination of piperacillin and tazobactam, has been studied for its effectiveness against various gram-positive cocci, including methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-intermediate Staphylococcus aureus (VISA) 3, 4.
  • The combination of piperacillin/tazobactam with vancomycin has been shown to have synergistic effects against MRSA and VISA, with enhanced antimicrobial activity compared to vancomycin alone 3, 4.
  • Piperacillin/tazobactam has been found to be active against oxacillin-susceptible Staphylococcus spp., with MIC50 values ranging from 0.12-0.5 μg/ml 5.
  • The combination of meropenem/piperacillin/tazobactam has also been evaluated against clinical isolates of Staphylococcus aureus, Staphylococcus epidermidis, and vancomycin-resistant Enterococcus spp., with promising results 6.
  • Piperacillin-tazobactam has a wide spectrum of activity that includes gram-positive organisms such as staphylococci and streptococci, as well as many gram-negative aerobic and anaerobic bacteria 7.

Specific Coverage Against Gram-Positive Cocci

  • MRSA: The combination of piperacillin/tazobactam with vancomycin has been shown to be effective against MRSA, with synergistic effects and enhanced antimicrobial activity 3, 4.
  • VISA: The combination of piperacillin/tazobactam with vancomycin has also been found to be effective against VISA, with enhanced antimicrobial activity compared to vancomycin alone 3.
  • Vancomycin-resistant Enterococcus spp.: The combination of meropenem/piperacillin/tazobactam has been evaluated against clinical isolates of vancomycin-resistant Enterococcus spp., with promising results 6.
  • Staphylococcus epidermidis: The combination of meropenem/piperacillin/tazobactam has been found to be effective against clinical isolates of Staphylococcus epidermidis 6.

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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