Zosyn (Piperacillin-Tazobactam) Dosing
For adult patients with most infections, administer Zosyn 3.375 g intravenously every 6 hours (totaling 13.5 g daily), while nosocomial pneumonia requires 4.5 g every 6 hours plus an aminoglycoside (totaling 18 g daily). 1
Standard Adult Dosing by Indication
Non-Pneumonia Infections
- Intra-abdominal infections, skin/soft tissue infections, female pelvic infections, and community-acquired pneumonia: 3.375 g IV every 6 hours 1
- This provides 12.0 g piperacillin and 1.5 g tazobactam daily 1
- Infuse over 30 minutes 1
Nosocomial Pneumonia
- Initial empiric therapy: 4.5 g IV every 6 hours PLUS an aminoglycoside 1
- This provides 16.0 g piperacillin and 2.0 g tazobactam daily 1
- The aminoglycoside combination is essential for adequate gram-negative coverage in this setting 1
Pediatric Dosing (≥2 Months Old, ≤40 kg)
Ages 2-9 Months
- Appendicitis/peritonitis: 90 mg/kg (80 mg piperacillin/10 mg tazobactam) IV every 8 hours 1
- Nosocomial pneumonia: 90 mg/kg IV every 6 hours 1
Ages >9 Months
- Appendicitis/peritonitis: 112.5 mg/kg (100 mg piperacillin/12.5 mg tazobactam) IV every 8 hours 1
- Nosocomial pneumonia: 112.5 mg/kg IV every 6 hours 1
- Infuse over 30 minutes 1
Renal Impairment Dosing
For creatinine clearance ≤40 mL/min, reduce dosing frequency based on degree of impairment. 1 The FDA label specifies dose reductions are mandatory in this population, though specific adjustments vary by creatinine clearance level 1. Hemodialysis patients require additional dosing modifications 1.
Critical Administration Considerations
Aminoglycoside Compatibility
- Reconstitute, dilute, and administer Zosyn and aminoglycosides separately 1
- Y-site co-administration is permissible only under specific conditions with amikacin and gentamicin at defined concentrations 1, 2
- The reformulated product (approved 2005) allows Y-site compatibility with amikacin and gentamicin at specific doses/concentrations 2
Diluent Options
- Reformulated Zosyn is compatible with Lactated Ringer's solution for admixture preparation 2
- This expanded compatibility provides additional administration flexibility 2
Infusion Requirements
- Always infuse over 30 minutes for both adults and pediatrics 1
- Available as premixed frozen solutions: 2.25 g in 50 mL, 3.375 g in 50 mL, and 4.5 g in 100 mL 1
Critical Safety Warnings
Nephrotoxicity Risk
In critically ill patients, Zosyn is an independent risk factor for renal failure and delayed renal recovery compared to other beta-lactams. 1 Alternative treatment options should be prioritized in the critically ill population; if Zosyn is unavoidable, monitor renal function closely 1. The combination of Zosyn plus vancomycin significantly increases acute kidney injury risk (risk ratio 1.79) compared to alternative gram-negative agents plus vancomycin 3.
Hematologic Monitoring
- Monitor for thrombocytopenia, particularly in patients with renal impairment 1, 4
- Rapid-onset thrombocytopenia can occur within 36 hours of initiation, with platelet counts dropping precipitously 4
- Prolonged therapy requires hematologic monitoring for bleeding, leukopenia, and neutropenia 1
Neurologic Precautions
- Higher doses, especially with renal impairment, increase risk of neuromuscular excitability and seizures 1
- Closely monitor patients with seizure disorders or renal dysfunction 1
Drug Interactions
- Avoid probenecid co-administration unless benefit outweighs risk, as it prolongs piperacillin and tazobactam half-lives 1
- Monitor tobramycin levels in hemodialysis patients, as Zosyn significantly reduces tobramycin concentrations 1
- Monitor coagulation parameters when combined with heparin or oral anticoagulants 1