Piperacillin-Tazobactam (Piptaz) Dosing and Indications in Children
For children 2 months to 6 years with serious infections, administer piperacillin-tazobactam 100 mg/kg/dose (based on piperacillin component) every 6 hours as a 3-hour infusion, or use a loading dose of 75 mg/kg followed by continuous infusion of 300 mg/kg/24 hours to achieve optimal therapeutic targets against resistant organisms. 1, 2
FDA-Approved Indications in Pediatric Patients
Piperacillin-tazobactam is FDA-approved for children ≥2 months of age for the following infections: 3
- Intra-abdominal infections (appendicitis and/or peritonitis)
- Nosocomial pneumonia
- Skin and skin structure infections (approved in adults, but used off-label in children)
Age-Specific Dosing Recommendations
Neonates (Postmenstrual Age-Based)
- PMA ≤30 weeks: 100 mg/kg/dose IV every 8 hours 1, 4
- PMA >30 weeks: 80 mg/kg/dose IV every 6 hours 1, 4
Infants and Children ≥2 Months
Standard FDA-approved dosing: 3
Ages 2-9 months:
- Appendicitis/peritonitis: 90 mg/kg (80 mg piperacillin/10 mg tazobactam) every 8 hours
- Nosocomial pneumonia: 90 mg/kg every 6 hours
Ages >9 months to 40 kg:
- Appendicitis/peritonitis: 112.5 mg/kg (100 mg piperacillin/12.5 mg tazobactam) every 8 hours
- Nosocomial pneumonia: 112.5 mg/kg every 6 hours
Maximum daily dose: 24,000 mg/day (based on piperacillin component) 1, 4, 3
Optimized Dosing for Critically Ill Children
Standard intermittent dosing regimens frequently fail to achieve therapeutic targets in critically ill children, particularly against organisms with MICs ≥16 mg/L. 2
Evidence-Based Optimal Regimens
- 75 mg/kg/dose every 4 hours infused over 0.5 hours (for MICs up to 16 mg/L)
- 100 mg/kg/dose every 6 hours as a 3-hour infusion (achieves targets at MICs up to 32 mg/L)
For children >6 months to 6 years: 5, 6, 2
- 130 mg/kg/dose every 8 hours infused over 4 hours (for MICs up to 16 mg/L)
- 100 mg/kg/dose every 4 hours over 2 hours (alternative for severe infections)
- Loading dose of 75 mg/kg followed by continuous infusion of 300 mg/kg/24 hours (optimal for critically ill patients)
Pharmacodynamic Target
The therapeutic goal is maintaining free piperacillin concentrations above the MIC for ≥50% of the dosing interval (50% fT>MIC). 5, 7, 6 For critically ill patients, targeting 60% fT>MIC at MIC >16 mg/L is recommended. 2
Administration Guidelines
- Infusion duration: Administer over 30 minutes for standard dosing 3
- Extended infusions: 2-4 hour infusions significantly improve probability of target attainment, especially against Pseudomonas aeruginosa and resistant organisms 5, 7, 2
- Continuous infusion: Requires loading dose of 75 mg/kg, then 300 mg/kg/24 hours for children >2 months 2
- Compatibility: Piperacillin-tazobactam and aminoglycosides must be reconstituted, diluted, and administered separately; Y-site co-administration possible under specific conditions 3
Special Populations and Dose Adjustments
Renal Impairment
Dosage reduction required when creatinine clearance ≤40 mL/min and in dialysis patients. 3 Close monitoring of renal function is essential in critically ill patients, as piperacillin-tazobactam is an independent risk factor for renal failure in this population. 3
Concomitant Furosemide
Furosemide administration increases piperacillin clearance; consider dose adjustment or extended infusions. 5
Common Pitfalls and Caveats
Standard dosing inadequacy: Traditional 0.5-hour infusions of 240-300 mg/kg/day fail to achieve therapeutic targets at MICs ≥16 mg/L in children >6 months. 6 This risks treatment failure against resistant organisms.
Age-related clearance: Piperacillin clearance increases with age; older children (>6 months) require higher doses or extended infusions compared to younger infants. 5, 7, 2
Critical illness considerations: Critically ill children have altered pharmacokinetics requiring either extended infusions or continuous infusion strategies. 2 Standard intermittent dosing is insufficient for severe infections.
Infusion site reactions: Extended infusions (3-4 hours) carry risk of site infiltration; monitor IV access carefully. 5
Nephrotoxicity monitoring: In critically ill patients, alternative antibiotics should be considered when possible; if piperacillin-tazobactam is necessary, monitor renal function closely throughout treatment. 3
Hypersensitivity: Contraindicated in patients with penicillin, cephalosporin, or beta-lactamase inhibitor allergies. 3 Severe cutaneous reactions (Stevens-Johnson syndrome, toxic epidermal necrolysis) require immediate discontinuation. 3
Safety Profile
Most common adverse events (incidence >5%): diarrhea, constipation, nausea, headache, and insomnia. 3 In pediatric studies, 49% experienced ≥1 adverse event, with only 3 cases (site infiltrations) definitively related to extended infusions. 5
Hematological effects including bleeding, leukopenia, and neutropenia may occur with prolonged therapy; monitor complete blood counts. 3