piperacillin-tazobactam
Brand: Zosyn
Prototype: penicillin-g
Drug Class: antibiotic
Drug Family: antibiotic
Subclass: antipseudomonal penicillin + beta-lactamase inhibitor
Organ Systems: infectious-disease
Mechanism of Action
Piperacillin is an extended-spectrum penicillin with antipseudomonal activity; tazobactam is a beta-lactamase inhibitor protecting piperacillin from class A and some class C enzymes; broad spectrum includes Pseudomonas aeruginosa, most enterobacteriaceae, anaerobes, and streptococci.
penicillin-binding proteins (PBPs)class A and C beta-lactamases
Indications
- hospital-acquired pneumonia
- complicated intra-abdominal infections
- complicated urinary tract infections
- complicated skin and soft tissue infections
- sepsis (empiric broad-spectrum therapy)
- febrile neutropenia (in combination with aminoglycoside or fluoroquinolone)
Contraindications
- penicillin allergy
- severe penicillin anaphylaxis
Adverse Effects
Common
- diarrhea
- nausea
- rash
- electrolyte abnormalities (hypokalemia — piperacillin contains sodium)
Serious
- Clostridioides difficile colitis
- hepatotoxicity (elevated LFTs)
- neurotoxicity (high doses, renal failure — encephalopathy, seizures)
- thrombocytopenia and platelet dysfunction (especially prolonged courses)
Pharmacokinetics (ADME)
| Absorption | IV only (oral absorption is poor) |
| Distribution | Protein binding 16–48%; Vd ~0.2 L/kg |
| Metabolism | Minimal; both components excreted largely unchanged |
| Excretion | Renal; tazobactam requires dose adjustment for CrCl <40 mL/min |
| Half-life | Piperacillin: 1 hour; tazobactam: 1 hour |
| Onset | End of infusion (30–60 min infusion typical; extended infusion 3–4h maximizes PD target attainment) |
| Peak | End of infusion |
| Duration | 6–8 hours (q6h or q8h dosing); extended infusion over 4h improves time>MIC |
| Protein Binding | 16–48% |
| Vd | ~0.2 L/kg |
Drug Interactions
| Drug / Agent | Mechanism | Severity |
|---|---|---|
| methotrexate | piperacillin inhibits methotrexate tubular secretion; methotrexate toxicity | major |
| aminoglycosides | physically incompatible in IV line; separate infusions; synergistic antibiotic effect | moderate |
| vecuronium/neuromuscular blockers | piperacillin may potentiate neuromuscular blockade | moderate |
Nursing Considerations
- Do not mix piperacillin-tazobactam in the same IV line as aminoglycosides (gentamicin, tobramycin, amikacin) — they are physically incompatible and the aminoglycoside will be inactivated
- Extended infusion (4-hour infusion) achieves better pharmacodynamic target attainment against Pseudomonas and other less-susceptible organisms — used in some institutions for severe infections
- Monitor renal function, electrolytes (Na, K), CBC with platelets, and LFTs on prolonged courses (>7–10 days)
- Each 3.375 g vial contains 4.69 mEq (108 mg) sodium — relevant in fluid-restricted patients (HF, ESRD)
Clinical Pearls
- Extended-infusion piperacillin-tazobactam (4-hour infusion instead of 30-minute) exploits its time-dependent pharmacodynamics to increase the percentage of time drug concentrations exceed the MIC, improving outcomes in critically ill patients with resistant organisms
- Piperacillin-tazobactam does NOT reliably cover MRSA, ESBL-producing organisms, or Acinetobacter; empiric coverage must account for local antibiogram and patient risk factors
Safety Profile
Pregnancy generally-safe
Lactation safe
Renal Adjustment Required
Hepatic Adjustment Not required
TDM Not required
Concordance Terms
Cross-referenced clinical concepts — click any term to see all content where it appears.