Is Zosyn (piperacillin-tazobactam) effective against Proteus species in patients with urinary tract infections?

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Last updated: January 31, 2026View editorial policy

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Zosyn Coverage Against Proteus Species

Yes, Zosyn (piperacillin-tazobactam) provides effective coverage against Proteus species, including both Proteus mirabilis and Proteus vulgaris, with demonstrated clinical efficacy in urinary tract infections. 1, 2

Microbiological Activity

  • Piperacillin-tazobactam demonstrates robust in vitro activity against Proteus mirabilis with an MIC90 of 1.56 mcg/mL and against Proteus vulgaris with an MIC90 of 3.13 mcg/mL, showing 4- to 64-fold greater potency than piperacillin alone or other beta-lactam/beta-lactamase inhibitor combinations. 2

  • The FDA-approved drug label specifically lists Proteus mirabilis and Proteus vulgaris among organisms for which at least 90% of isolates exhibit MICs at or below the susceptible breakpoint, though it notes these are not beta-lactamase producing bacteria and are therefore susceptible to piperacillin alone. 1

Clinical Evidence in Urinary Tract Infections

  • In a clinical trial of 217 patients with complicated UTIs treated with piperacillin-tazobactam 4g/500mg every 8 hours, the overall pathogen eradication rate was 82%, with 86% of clinically evaluable patients cured or improved. 3

  • Piperacillin-tazobactam has demonstrated effectiveness across multiple clinical trials for complicated urinary tract infections, with clinical and bacteriological response rates of 85% and 73% respectively at study endpoint. 3, 4

Guideline Recommendations

  • For healthcare-associated complicated UTIs where Proteus species are commonly encountered, guidelines recommend piperacillin-tazobactam as part of empirical therapy regimens, particularly for postoperative infections caused by more resistant flora. 5

  • The European Association of Urology guidelines identify Proteus spp. among the most common species found in complicated UTI cultures, and piperacillin-tazobactam is included in recommended empirical treatment algorithms for these infections. 5

Important Clinical Considerations

  • Proteus species are frequently involved in healthcare-associated infections and can develop multidrug resistance, including ESBL production, which may compromise piperacillin-tazobactam efficacy in some isolates. 5, 6

  • For ESBL-producing Proteus isolates specifically, piperacillin-tazobactam may retain activity against ESBL-producing E. coli but effectiveness varies, and carbapenem therapy should be considered for severe infections or confirmed ESBL producers. 7, 6

  • Local susceptibility patterns should guide empirical therapy selection, as resistance mechanisms in Proteus can include loss of porins, reduced PBP expression, or acquisition of resistance genes affecting multiple antibiotic classes. 6

Dosing for Proteus Infections

  • The standard dosing regimen is piperacillin-tazobactam 4.5g (4g piperacillin/0.5g tazobactam) IV every 6-8 hours for complicated UTIs, with treatment duration of 7-14 days depending on clinical response and underlying complicating factors. 5, 3

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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