What is the recommended treatment and dosage for infections using Zosyn (piperacillin/tazobactam)?

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Zosyn (Piperacillin/Tazobactam) Treatment and Dosage Recommendations

For adult patients with infections, Zosyn (piperacillin/tazobactam) should be administered at a dose of 3.375 g every 6 hours intravenously for most infections, or 4.5 g every 6 hours for nosocomial pneumonia, with dosage adjustments required for renal impairment. 1

Adult Dosing Recommendations

Standard Dosing

  • Most infections: 3.375 g IV every 6 hours (totaling 13.5 g/day) administered over 30 minutes 1
  • Nosocomial pneumonia: 4.5 g IV every 6 hours (totaling 18 g/day) plus an aminoglycoside 1
  • Treatment duration: 7-10 days for most infections; 7-14 days for nosocomial pneumonia 1

Renal Impairment Dosing

Creatinine Clearance Standard Infections Nosocomial Pneumonia
>40 mL/min 3.375 g q6h 4.5 g q6h
20-40 mL/min 2.25 g q6h 3.375 g q6h
<20 mL/min 2.25 g q8h 2.25 g q6h
Hemodialysis 2.25 g q12h* 2.25 g q8h*
CAPD 2.25 g q12h 2.25 g q8h

*Additional 0.75 g dose should be administered following each hemodialysis session 1

Pediatric Dosing

For children 2 months and older, weighing up to 40 kg:

Age Appendicitis/Peritonitis Nosocomial Pneumonia
2-9 months 90 mg/kg (80/10) IV q8h 90 mg/kg (80/10) IV q6h
>9 months 112.5 mg/kg (100/12.5) IV q8h 112.5 mg/kg (100/12.5) IV q6h

Children >40 kg should receive adult dosing 1

Indications

Zosyn is FDA-approved for the treatment of:

  1. Intra-abdominal infections (appendicitis, peritonitis) 1
  2. Nosocomial pneumonia 1
  3. Skin and skin structure infections (cellulitis, abscesses, diabetic foot infections) 1
  4. Female pelvic infections (postpartum endometritis, PID) 1
  5. Community-acquired pneumonia (moderate severity) 1

Specific Clinical Scenarios

Skin and Soft Tissue Infections

  • For complicated skin/soft tissue infections, Zosyn is effective as monotherapy at 3.375 g every 6 hours or 4.5 g every 8 hours IV 2
  • For necrotizing infections, Zosyn can be used as part of broad-spectrum coverage (often combined with vancomycin or linezolid for MRSA coverage) 2

Intra-abdominal Infections

  • Zosyn is effective as monotherapy for most intra-abdominal infections 2, 1
  • For healthcare-associated or nosocomial infections, consider local resistance patterns 2

Nosocomial Pneumonia

  • Higher dosing (4.5 g every 6 hours) plus an aminoglycoside is recommended 1
  • Continue aminoglycoside in patients with confirmed Pseudomonas aeruginosa 1

Multidrug-Resistant Organisms

  • For carbapenem-resistant Pseudomonas aeruginosa (CRPA) susceptible to piperacillin/tazobactam: 3.375-4.5 g IV q6h 2
  • For difficult-to-treat Pseudomonas, combination therapy may be needed 2

Administration Considerations

  • Administer by IV infusion over 30 minutes 1
  • For patients with high MIC pathogens, prolonged infusion of β-lactams is recommended 2
  • Consider infectious disease consultation for management of infections caused by multidrug-resistant organisms 2

Common Pitfalls and Caveats

  1. Renal dosing: Failure to adjust dosing in renal impairment can lead to toxicity 1
  2. Resistance concerns: Local antibiograms should guide therapy, especially for healthcare-associated and nosocomial infections 2
  3. Inadequate dosing: Underdosing may lead to treatment failure, particularly with high-MIC pathogens 2
  4. Combination therapy: For severe infections or suspected Pseudomonas, combination therapy may be necessary 1
  5. Duration: Avoid unnecessarily prolonged courses; 7-10 days is typically sufficient for most infections 1

For infections caused by suspected or confirmed multidrug-resistant organisms, infectious disease consultation is strongly recommended to optimize therapy and improve outcomes 2.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

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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