What is the frequency of administration for Zosyn (piperacillin/tazobactam)?

From the Guidelines

Zosyn (piperacillin-tazobactam) should be administered every 6 hours for most adult patients with normal renal function, with standard dosing being 3.375g or 4.5g IV every 6 hours, as recommended by the most recent guidelines 1. The dosing frequency of Zosyn is crucial in maintaining adequate blood levels to effectively kill bacteria.

• For patients with normal renal function, the standard dosing is 3.375g or 4.5g IV every 6 hours 1.
• For patients with renal impairment, the dosing interval needs to be extended based on creatinine clearance:
  • For creatinine clearance 20-40 mL/min, dosing is typically every 8 hours.
  • For clearance less than 20 mL/min, dosing is extended to every 12 hours. Extended infusion protocols, where the drug is administered over 3-4 hours instead of the standard 30 minutes, are increasingly used to maximize time-dependent bacterial killing and improve outcomes, particularly for serious infections 1.
• For critically ill patients or those with severe infections like pneumonia or sepsis, higher doses may be used, such as 16g/d, as suggested by experts 1. The frequency of Zosyn administration is based on the drug's half-life and pharmacokinetic properties, and monitoring renal function during therapy is important as dosing adjustments may be needed if kidney function changes during treatment 1.
• It is essential to note that the optimal dosing strategy for β-lactams, such as Zosyn, involves optimizing the time that the plasma concentration of the drug is above the pathogen minimum inhibitory concentration (MIC) relative to the dosing interval (T > MIC) 1.
• A minimum T > MIC of 60% is generally sufficient to allow a good clinical response in mild to moderate illness, but optimal response in severe infections, including sepsis, may be achieved with a T > MIC of 100% 1.

From the FDA Drug Label

Adult Patients With Indications Other Than Nosocomial Pneumonia; The usual daily dosage of piperacillin and tazobactam for injection for adults is 3.375 g every six hours totaling 13.5 g (12 g piperacillin/ 1.5 g tazobactam). Adult Patients with Nosocomial Pneumonia: Initial presumptive treatment of patients with nosocomial pneumonia should start with piperacillin and tazobactam for injection at a dosage of 4.5 g every six hours plus an aminoglycoside, totaling 18 g (16 g piperacillin/2 g tazobactam). Pediatric Patients by Indication and Age: Recommended Dosage of piperacillin and tazobactam for injection for Pediatric Patients 2 months of Age and Older, Weighing up to 40 Kg and With Normal Renal Function Age Appendicitis and /or Peritonitis Nosocomial Pneumonia 2 months to 9 months 90 mg/kg (80 mg piperacillin/10 mg tazobactam) every 8 (eight) hours 90 mg/kg (80 mg piperacillin/10 mg tazobactam) every 6 (six) hours Older than 9 months 112.5 mg/kg (100 mg piperacillin/12.5 mg tazobactam) every 8 (eight) hours 112.5 mg/kg (100 mg piperacillin/12.5 mg tazobactam) every 6 (six) hours

The frequency of administering Zosyn (piperacillin and tazobactam) is:

• Every 6 hours for adult patients with nosocomial pneumonia and for pediatric patients older than 9 months with nosocomial pneumonia, and for pediatric patients 2 months to 9 months with nosocomial pneumonia.
• Every 6 hours for adult patients with indications other than nosocomial pneumonia.
• Every 8 hours for pediatric patients 2 months to 9 months with appendicitis and/or peritonitis, and for pediatric patients older than 9 months with appendicitis and/or peritonitis. 2

From the Research

Administration Frequency of Zosyn (Piperacillin/Tazobactam)

The administration frequency of Zosyn (Piperacillin/Tazobactam) can vary depending on the specific infection being treated and the patient's renal function.

• According to the study 3, Piperacillin/Tazobactam is effective and well-tolerated in patients with lower respiratory tract infections, intra-abdominal infections, skin and soft tissue infections, and febrile neutropenia.
• The study 4 used Monte Carlo simulation to calculate pharmacodynamic target attainment for Piperacillin-Tazobactam 3.375 g q6h and 4.5 g q8h, indicating that the 3.375 g q6h regimen achieved greater than 90% likelihood of achieving bactericidal exposure in serum and blister fluid.
• The study 5 compared Piperacillin-Tazobactam 4.5 g every 6 hours with Meropenem 1 g every 8 hours for the treatment of bloodstream infections caused by AmpC β-lactamase-producing Enterobacter spp, Citrobacter freundii, Morganella morganii, Providencia spp, or Serratia marcescens.
• The study 6 evaluated the efficacy and safety of Imipenem/Cilastatin/Relebactam versus Piperacillin/Tazobactam in adults with hospital-acquired or ventilator-associated bacterial pneumonia, with Piperacillin/Tazobactam administered at 4 g/500 mg intravenously every 6 hours for 7-14 days.
• The study 7 planned to compare Meropenem with Piperacillin-Tazobactam for the definitive treatment of bloodstream infections due to ceftriaxone non-susceptible Escherichia coli and Klebsiella spp, with Piperacillin-Tazobactam administered at 4.5 g every 6 hours.

Key Findings

• Piperacillin/Tazobactam can be administered every 6 hours for the treatment of various infections, including lower respiratory tract infections, intra-abdominal infections, skin and soft tissue infections, and febrile neutropenia 3.
• The 3.375 g q6h regimen of Piperacillin-Tazobactam achieved greater than 90% likelihood of achieving bactericidal exposure in serum and blister fluid 4.
• Piperacillin-Tazobactam 4.5 g every 6 hours was compared with Meropenem 1 g every 8 hours for the treatment of bloodstream infections caused by AmpC β-lactamase-producing bacteria 5.
• Piperacillin/Tazobactam was administered at 4 g/500 mg intravenously every 6 hours for 7-14 days in the treatment of hospital-acquired or ventilator-associated bacterial pneumonia 6.