Are Gram-negative bacilli covered by Zosyn (piperacillin-tazobactam) and Vancomycin?

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Last updated: May 25, 2025View editorial policy

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From the Guidelines

Zosyn (piperacillin-tazobactam) effectively covers most gram-negative bacilli, while vancomycin does not. Zosyn is active against many gram-negative organisms including Pseudomonas aeruginosa, Escherichia coli, Klebsiella species, Proteus species, and other Enterobacteriaceae, as supported by the most recent guidelines 1. The piperacillin component is a broad-spectrum penicillin, while tazobactam inhibits beta-lactamases that would otherwise break down piperacillin. Vancomycin, on the other hand, is primarily effective against gram-positive organisms and has minimal to no activity against gram-negative bacilli due to its inability to penetrate the outer membrane of gram-negative bacteria. When treating suspected infections involving both gram-positive and gram-negative organisms, the combination of Zosyn and vancomycin provides comprehensive coverage. Some key points to consider when using Zosyn and vancomycin include:

  • Typical Zosyn dosing is 3.375-4.5g IV every 6-8 hours (adjusted for renal function)
  • Vancomycin is typically dosed at 15-20mg/kg IV every 8-12 hours with levels monitored for efficacy and to prevent toxicity
  • The choice of empiric therapy should consider epidemiological features and the clinical course of infection, and consultation with an infectious diseases specialist is recommended 1. It's also important to note that vancomycin should only be used in patients with concerns about MRSA infection, as stated in the guidelines 1. Overall, the combination of Zosyn and vancomycin can provide effective coverage for a wide range of infections, but it's crucial to use these medications judiciously and with consideration of the potential risks and benefits.

From the FDA Drug Label

Vancomycin is not active in vitro against gram-negative bacilli, mycobacteria, or fungi The answer to whether gram-negative bacilli are covered by vancomycin is no.

  • Vancomycin does not have activity against gram-negative bacilli. Since the question also mentions Zosyn (which is not provided in the label), we cannot draw a conclusion about the combination of Zosyn and vancomycin for gram-negative bacilli based on this information alone 2.

From the Research

Coverage of Gram-Negative Bacilli by Zosyn and Vancomycin

  • Zosyn (piperacillin/tazobactam) has a broad spectrum of antibacterial activity that includes Gram-positive and Gram-negative aerobic and anaerobic bacteria 3, 4.
  • Gram-negative bacilli covered by Zosyn include many pathogens producing beta-lactamases, such as Enterobacteriaceae, Pseudomonas, and Klebsiella 3, 5, 6.
  • However, Zosyn may not be effective against all Gram-negative bacilli, particularly those harboring AmpC beta-lactamases or extended-spectrum beta-lactamases (ESBLs) 4, 5.
  • Vancomycin, on the other hand, is primarily effective against Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA) 7.
  • The combination of vancomycin and Zosyn may be used to cover a broader range of pathogens, including both Gram-positive and Gram-negative bacteria, but it also increases the risk of acute kidney injury 7.

Specific Gram-Negative Bacilli Covered by Zosyn

  • Zosyn has been shown to be effective against:
    • Pseudomonas aeruginosa 5
    • Klebsiella pneumoniae 5
    • Escherichia coli 5
    • Enterobacter spp. 5
    • Citrobacter spp. 5
  • However, its effectiveness against these pathogens may be reduced in the presence of certain resistance mechanisms, such as AmpC beta-lactamases or ESBLs 4, 5.

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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