What is a great alternative to Zosyn (piperacillin/tazobactam)?

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Last updated: March 25, 2025 • View editorial policy

From the Guidelines

Piperacillin-tazobactam (Zosyn) alternatives include carbapenems like meropenem, imipenem-cilastatin, or ertapenem, which are effective broad-spectrum antibiotics for serious infections, as recommended by recent guidelines 1. When considering alternatives to Zosyn, it's essential to maintain similar antimicrobial coverage, as Zosyn covers many gram-positive, gram-negative, and anaerobic bacteria. The choice of alternative antibiotic should be based on the specific infection, local resistance patterns, and patient factors like allergies and kidney function.

Key Considerations

  • Local resistance patterns: The prevalence of resistant organisms, such as ESBL-producing Enterobacteriaceae, should guide the choice of alternative antibiotic 1.
  • Patient factors: Allergies, kidney function, and severity of infection should be considered when selecting an alternative antibiotic.
  • Antimicrobial coverage: The alternative antibiotic should provide similar coverage to Zosyn, including gram-positive, gram-negative, and anaerobic bacteria.

Alternative Antibiotics

  • Carbapenems: Meropenem, imipenem-cilastatin, or ertapenem are effective broad-spectrum antibiotics for serious infections 1.
  • Cefepime plus metronidazole: This combination is suitable for mixed infections, including those caused by gram-negative and anaerobic bacteria 1.
  • Ceftriaxone with metronidazole: This combination is an alternative for less severe infections, providing coverage against gram-positive, gram-negative, and anaerobic bacteria 1.
  • Ampicillin-sulbactam (Unasyn) or amoxicillin-clavulanate (Augmentin): These antibiotics may be suitable for less severe infections, but their use should be guided by local resistance patterns and patient factors 1.

Recent Guidelines

The 2017 WSES guidelines for the management of intra-abdominal infections recommend considering the use of carbapenems, such as meropenem or imipenem-cilastatin, as alternative antibiotics to Zosyn 1. Additionally, the 2016 clinical practice guidelines by the Infectious Diseases Society of America and the American Thoracic Society recommend the use of carbapenems, such as meropenem or imipenem, as part of the initial empiric antibiotic therapy for hospital-acquired pneumonia 2.

From the FDA Drug Label

FORTAZ is indicated for the treatment of patients with infections caused by susceptible strains of the designated organisms in the following diseases:

  1. Lower Respiratory Tract Infections, including pneumonia, caused by Pseudomonas aeruginosa and other Pseudomonas spp.;
  2. Skin and Skin-Structure Infections caused by Pseudomonas aeruginosa;
  3. Urinary Tract Infections, both complicated and uncomplicated, caused by Pseudomonas aeruginosa;
  4. Bacterial Septicemia caused by Pseudomonas aeruginosa,
  5. Bone and Joint Infections caused by Pseudomonas aeruginosa,
  6. Gynecologic Infections, including endometritis, pelvic cellulitis, and other infections of the female genital tract caused by Escherichia coli.
  7. Intra-abdominal Infections, including peritonitis caused by Escherichia coli,
  8. Central Nervous System Infections, including meningitis, caused by Haemophilus influenzae and Neisseria meningitidis

A great alternative to Zosyn (piperacillin/tazobactam) is Ceftazidime (FORTAZ), as it has a similar spectrum of activity against various bacterial infections, including those caused by Pseudomonas aeruginosa, Escherichia coli, and other susceptible organisms 3.

  • Key points to consider when using Ceftazidime as an alternative to Zosyn include: + Similar indications for use, including lower respiratory tract infections, skin and skin-structure infections, and urinary tract infections + Effective against a range of bacterial organisms, including Pseudomonas aeruginosa and Escherichia coli + Can be used alone or in combination with other antibacterial drugs, such as aminoglycosides and vancomycin + Dosing depends on the severity of the infection and the patient's condition + Should only be used to treat infections proven or strongly suspected to be caused by susceptible bacteria 3

From the Research

Alternatives to Zosyn (Piperacillin/Tazobactam)

  • Meropenem is a broad-spectrum antibacterial agent that has shown similar efficacy to piperacillin/tazobactam in various infections, including complicated intra-abdominal infections, complicated skin and skin structure infections, and febrile neutropenia 4, 5.
  • Meropenem has also demonstrated greater efficacy than piperacillin/tazobactam in certain infections, such as nosocomial pneumonia 4.
  • Another alternative is doripenem, a broad-spectrum carbapenem antibiotic that has been shown to be non-inferior to piperacillin/tazobactam in the treatment of nosocomial pneumonia 6.
  • Ertapenem is also a carbapenem antibiotic that has been shown to have equivalent efficacy and safety compared to piperacillin/tazobactam in various infections, including complicated intra-abdominal infections, acute pelvic infection, and complicated skin and soft-structure infection 7.

Key Characteristics of Alternatives

  • Meropenem: broad-spectrum activity, stable against many beta-lactamases, and suitable for administration as an intravenous bolus or infusion 4, 5.
  • Doripenem: broad-spectrum activity, stable against many beta-lactamases, and non-inferior to piperacillin/tazobactam in certain infections 6.
  • Ertapenem: broad-spectrum activity, limited activity against certain nonfermentative Gram-negative bacteria, and suitable for once-daily dosing due to extensive protein binding 7.

Comparison of Alternatives

  • Meropenem and doripenem have similar efficacy and safety profiles compared to piperacillin/tazobactam, but meropenem has demonstrated greater efficacy in certain infections 4, 6.
  • Ertapenem has equivalent efficacy and safety compared to piperacillin/tazobactam, but its limited activity against certain nonfermentative Gram-negative bacteria may be a consideration in certain infections 7.

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.