What is the recommended dose of piperacillin/tazobactam (Pip/Taz) in neonates?

From the Guidelines

Piperacillin/tazobactam dosing for neonates should be based on both gestational and postnatal age, with specific dosing recommendations provided for different age groups, as outlined in the most recent guidelines 1.

Key Considerations

• For neonates with a gestational age of 30-34 weeks, the recommended dose is 5 mg/kg/dose IV q36 h for postnatal age ≤14 days, and 5 mg/kg/dose IV q24 h for postnatal age >14 days.
• For neonates with a gestational age of 35 weeks, the recommended dose is 4 mg/kg/dose IV q24 h for postnatal age ≤7 days, and 5 mg/kg/dose IV q24 h for postnatal age >7 days.

Administration and Monitoring

• Piperacillin/tazobactam should be administered as an intravenous infusion over 30 minutes.
• Dose adjustments are necessary for neonates with significant renal impairment.
• Monitor renal function during therapy, especially in premature neonates who are at higher risk for drug accumulation.

Rationale

The dosing recommendations are based on the immature renal function in premature neonates, which gradually matures with postnatal age 1. The medication provides broad-spectrum coverage against many gram-positive, gram-negative, and anaerobic bacteria, making it useful for serious infections including sepsis, pneumonia, and complicated intra-abdominal infections in neonates.

Comparison with Other Guidelines

While other guidelines, such as those from 2010 1, provide general recommendations for antibiotic dosing in pediatric patients, the most recent guidelines 1 provide specific dosing recommendations for piperacillin/tazobactam in neonates based on gestational and postnatal age.

From the FDA Drug Label

Pediatric Patients by Indication and Age: See Table below (2. 5) 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 dose of piperacillin/tazobactam for neonates is not explicitly stated in the provided table, which only includes recommendations for patients 2 months of age and older. However, according to the second drug label 2, after intravenous administration of 50 mg/kg (5-minute infusion) in neonates, the mean plasma concentration of piperacillin extrapolated to time zero was 141 μg/mL. In premature neonates, the mean elimination half-life has been reported to range from 147 to 258 minutes following administration of a single intravenous dose of 75 mg/kg. In one study in neonates, the mean elimination half-life ranged from 127 to 217 minutes following a single intravenous dose of 50 mg/kg. Therefore, a conservative approach would be to consider a dose of 50 mg/kg for neonates, but the exact dosing regimen is unclear and should be determined based on individual patient needs and clinical judgment.

From the Research

Piperacillin/Tazobactam Dosing in Neonates

• The optimal dosing regimen for piperacillin/tazobactam in neonates is not well established, but several studies have investigated this topic 3, 4, 5, 6, 7.
• A study published in 2022 found that a model-based dosing regimen of 90 mg/kg every 8 hours was effective and well-tolerated in neonates with early-onset sepsis 4.
• Another study published in 2019 found that a dose of 75 mg/kg every 4 hours infused over 0.5 hours was optimal for infants aged 2 to 6 months 3.
• A simulation study published in 2017 found that a dose of 100 mg/kg every 6 hours as a 3-hour infusion reached the pharmacodynamic target at MICs of 32 mg/L in infants aged 2 to 6 months 5.
• A study published in 2007 found that a dose of 80/10 mg/kg every 8 hours was recommended for pediatric patients aged 2-9 months, due to immature renal function 6.
• A study published in 2017 found that a loading dose followed by a continuous infusion was recommended for treatment of severe infections in children >2 months of age 7.

Key Findings

• The optimal dosing regimen for piperacillin/tazobactam in neonates may vary depending on factors such as age, weight, and renal function 3, 4, 5, 6, 7.
• Model-based dosing regimens may be effective and well-tolerated in neonates with early-onset sepsis 4.
• Extended infusions may be beneficial in achieving optimal pharmacodynamic targets 3, 5, 7.
• Further studies are needed to establish evidence-based dosing regimens for piperacillin/tazobactam in neonates 3, 4, 5, 6, 7.