What is the highest recommended dosage of Zosyn (piperacillin/tazobactam)?

Highest Recommended Dosage of Zosyn (Piperacillin/Tazobactam)

The highest recommended dosage of Zosyn (piperacillin/tazobactam) for adults with serious infections is 4.5 grams administered intravenously every 6 hours, with a maximum daily dose of 18 grams of piperacillin component (24 grams per day total). 1, 2

Adult Dosing Guidelines

Standard Dosing for Serious Infections

• For serious infections such as septicemia, nosocomial pneumonia, and complicated intra-abdominal infections: 3.375-4.5g IV every 6-8 hours 1
• For necrotizing infections of skin, fascia, and muscle: 3.37g every 6-8 hours IV 1
• For mixed infections requiring broad coverage: 4.5g IV every 6 hours 1
• Maximum daily dose: 18g of piperacillin component (24g total daily dose) 2

Dosing Based on Infection Type

• Hospital-acquired pneumonia/ventilator-associated pneumonia: 4.5g IV every 6 hours 1
• Complicated intra-abdominal infections: 3.375-4.5g IV every 6 hours 1
• Skin and soft tissue infections: 3.37g IV every 6-8 hours 1

Special Population Considerations

Renal Impairment Dosing Adjustments

• CrCl >40 mL/min: No dosage adjustment necessary 2
• CrCl 20-40 mL/min: For serious systemic infections, reduce to 3g every 8 hours (12g/day) 2
• CrCl <20 mL/min: For serious systemic infections, reduce to 4g every 12 hours (8g/day) 2
• Hemodialysis patients: Maximum 6g/day (2g every 8 hours) plus 1g additional dose after each dialysis session 2

Pediatric Dosing

• Neonates with postmenstrual age >30 weeks: 80 mg/kg/dose of piperacillin component IV every 6 hours 1
• Children: 240-300 mg/kg/day of piperacillin component IV in 3-4 divided doses 1
• Maximum pediatric dose: 4000 mg per dose 1

Administration Methods

Standard Administration

• Intravenous administration as a 20-30 minute infusion 2
• For serious infections, IV route should be used rather than IM 2

Extended/Prolonged Infusion

• Extended infusion over 3-4 hours may improve pharmacodynamic target attainment, particularly for resistant organisms 3, 4
• For critically ill patients, a loading dose followed by continuous infusion may optimize drug exposure 5

Clinical Considerations

Pharmacodynamic Optimization

• Prolonged infusions of 4.5g every 6 hours (over 3 hours) achieve better target attainment than standard short infusions 3, 4
• For Pseudomonas aeruginosa infections, higher doses and extended infusions may be needed to achieve therapeutic targets 3

Combination Therapy

• When combined with aminoglycosides for severe infections, both drugs should be used in full therapeutic doses 2
• Reformulated Zosyn allows Y-site co-administration with certain aminoglycosides (amikacin and gentamicin) at specific doses and concentrations 6

Important Precautions

• Do not mix with aminoglycosides in the same syringe or infusion bottle as this can result in inactivation of the aminoglycoside 2
• Monitor renal function during therapy, especially with high doses or prolonged treatment 2
• For patients with both renal failure and hepatic insufficiency, serum level monitoring may be necessary to guide dosage adjustments 2

Remember that while the maximum recommended dose is 4.5g every 6 hours (18g piperacillin daily), the actual dosing should be tailored based on the severity of infection, pathogen susceptibility, and patient's renal function.