What is the dosing for Zosyn (piperacillin/tazobactam) antibiotics?

From the Guidelines

The recommended dosing for Zosyn (piperacillin/tazobactam) antibiotics is 3.375 g every 6 hours or 4.5 g every 8 hours.

Key Considerations

• The dosing strategy for β-lactams, such as piperacillin/tazobactam, 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.
• The simplest way to increase T > MIC is to use increased frequency of dosing (given an identical total daily dose), such as dosing piperacillin/tazobactam at 3.375 g every 6 hours instead of 4.5 g every 8 hours 1.
• Extended infusion of β-lactams, such as piperacillin/tazobactam, over several hours may be more effective than intermittent rapid infusion, particularly for relatively resistant organisms and in critically ill patients with sepsis 1.

Specific Dosing Recommendations

• For complicated intra-abdominal infection, the recommended dose is 3.375 g every 6 hours or 4.5 g every 8 hours 1.
• For infections due to carbapenem-resistant Pseudomonas aeruginosa (CRPA) or difficult-to-treat P. aeruginosa (DTR-PA), the recommended dose is 3.375-4.5 g every 6 hours 1.
• For critically ill patients, a loading dose of piperacillin/tazobactam may be necessary to rapidly achieve therapeutic drug levels, followed by continuous or extended infusion to maintain optimal T > MIC 1.

From the FDA Drug Label

2 DOSAGE AND ADMINISTRATION

2.1 Dosage in Adult Patients with Indications Other Than Nosocomial Pneumonia The usual total daily dosage of piperacillin and tazobactam for injection for adult patients with indications other than nosocomial pneumonia is 3.375 g every six hours [totaling 13.5 g (12 g piperacillin and 1. 5 g tazobactam)], to be administered by intravenous infusion over 30 minutes. 2.2 Dosage in Adult Patients with Nosocomial Pneumonia Initial presumptive treatment of adult 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 and 2 g tazobactam)], administered by intravenous infusion over 30 minutes. 2. 3 Dosage in Adult Patients with Renal Impairment In adult patients with renal impairment (creatinine clearance ≤ 40 mL/min) and dialysis patients (hemodialysis and CAPD), the intravenous dose of piperacillin and tazobactam for injection should be reduced based on the degree of renal impairment The recommended daily dosage of piperacillin and tazobactam for injection for patients with renal impairment administered by intravenous infusion over 30 minutes is described in Table 1

The dosing for Zosyn (piperacillin/tazobactam) antibiotics is as follows:

• Adult patients with indications other than nosocomial pneumonia: 3.375 g every 6 hours, totaling 13.5 g per day
• Adult patients with nosocomial pneumonia: 4.5 g every 6 hours, totaling 18 g per day, plus an aminoglycoside
• Patients with renal impairment: dosage reduction based on creatinine clearance, as described in Table 1 2 Key considerations include:
• Renal function: dosage adjustments necessary for patients with creatinine clearance ≤ 40 mL/min
• Hemodialysis: additional dose of 0.75 g piperacillin and tazobactam for injection after each dialysis session on hemodialysis days
• Pediatric patients: dosage described in Table 2 for patients with appendicitis and/or peritonitis or nosocomial pneumonia aged 2 months of age and older, weighing up to 40 kg, and with normal renal function 2

From the Research

Dosing Strategies for Zosyn (Piperacillin/Tazobactam)

• The dosing strategy for piperacillin/tazobactam can significantly impact clinical outcomes, with extended or continuous infusion showing higher clinical cure rates and lower mortality rates compared to conventional intermittent infusion 3.
• A study using Monte Carlo simulation found that prolonged infusions of 4.5 g or 3.375 g every 6-8 hours achieved similar or better probability of target attainment (PTA) compared to standard regimens, supporting the use of a single piperacillin/tazobactam strength to simplify dosing 4.

Specific Dosing Recommendations

• For patients with normal renal function, optimal dosing regimens based on the piperacillin component were 75 mg/kg/dose every 4 hours infused over 0.5 hours in infants ages 2 to ≤6 months and 130 mg/kg/dose every 8 hours infused over 4 hours in children ages >6 months to 6 years against bacteria with MICs up to 16 mg/liter 5.
• Extended-infusion piperacillin/tazobactam therapy (3.375 g intravenously for 4 hours every 8 hours) was associated with improved outcomes, including lower 14-day mortality rates and shorter hospital stays, compared to intermittent-infusion therapy in critically ill patients with Pseudomonas aeruginosa infection 6.

Real-World Evidence and Clinical Implications

• A retrospective cohort study found that piperacillin-tazobactam dose reduction in early phase septic shock was associated with worsened clinical outcomes, including fewer 28-day norepinephrine-free days and higher rates of in-hospital mortality/hospice disposition 7.
• These findings suggest that clinicians should avoid piperacillin/tazobactam dose reduction in early phase septic shock and instead use normal dosing regimens (≥27 g cumulative 48-hour dose) to improve clinical outcomes.