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# Piperacillin-Tazobactam
## Overview
Piperacillin-tazobactam is a combination of an extended-spectrum penicillin-class antibacterial agent and a beta-lactamase inhibitor. It is bactericidal.
## Primary Indications
* Complicated and uncomplicated intra-abdominal infections
* Complicated and uncomplicated skin and skin-structure infections
* Community-acquired pneumonia
* Nosocomial pneumonia
* Bacterial meningitis (limited data)
* Febrile neutropenia (empirical treatment)
* Other serious infections due to susceptible organisms, including those caused by *Pseudomonas aeruginosa*
## Adult Dosing
* **Standard Dose:** 3.375 g every 6 hours or 4.5 g every 6 or 8 hours intravenously (IV). The ratio is typically 8:1 (piperacillin:tazobactam).
* **Severe Infections/Nosocomial Pneumonia/Pseudomonas aeruginosa:** 4.5 g IV every 6 or 8 hours.
* **Maximum Dose:** Generally, not to exceed 18 g per day (as 4.5 g every 6 hours).
## Pediatric Dosing
Dosing varies significantly by indication, weight, and age. Consult specific guidelines.
* **Infants and Children ≥ 12 months:** Dosing is typically based on the piperacillin component, ranging from 80 mg/kg/day to 300 mg/kg/day, divided into 3 or 4 doses every 6 or 8 hours. Specific recommendations for complicated intra-abdominal infections, community-acquired pneumonia, and febrile neutropenia exist.
* **Children < 12 months:** Use is generally not recommended due to limited data, unless deemed essential by a clinician.
## Dose Adjustments
* **Renal Impairment (CrCl < 40 mL/min):** Reduce the frequency of administration.
* For 3.375 g q6h regimen: Administer 2.25 g q6h; if CrCl < 20 mL/min, consider 2.25 g q8h.
* For 4.5 g q6h or q8h regimen: Administer 3.375 g q6h or q8h; if CrCl < 20 mL/min, consider 3.375 g q12h.
* **Hepatic Impairment:** No specific dose adjustment is typically required, but caution is advised.
## Contraindications
* History of hypersensitivity to piperacillin, tazobactam, any other piperacillin/tazobactam component, or penicillins.
* History of severe hypersensitivity reaction (e.g., anaphylaxis) to any other beta-lactam antibacterial.
## Adverse Effects
* **Common:** Diarrhea, nausea, vomiting, rash, headache, insomnia, constipation, rash, pruritus, fever, elevated liver enzymes (AST, ALT).
* **Serious:** *Clostridioides difficile*-associated diarrhea, hypersensitivity reactions (including anaphylaxis), seizures (rare, particularly with high doses or renal impairment), neutropenia, thrombocytopenia, interstitial nephritis, hemolytic anemia.
## Key Drug Interactions
* **Probenecid:** May decrease renal excretion of piperacillin-tazobactam, leading to prolonged and higher serum concentrations.
* **Vecuronium:** Piperacillin may prolong the neuromuscular blockade of vecuronium.
* **Warfarin:** May decrease the anticoagulant effect of warfarin. Monitor INR closely.
* **Methotrexate:** May decrease serum methotrexate levels. Monitor methotrexate levels.
* **Aminoglycosides:** Pharmacodynamic antagonism may occur *in vitro* when used together. However, clinical data suggest synergistic or additive effects are possible *in vivo*, particularly in severe infections. Separate administration if given concurrently.
## Monitoring
* Renal function (BUN, creatinine)
* Liver function tests (AST, ALT)
* Complete blood count (CBC) with differential, especially in prolonged therapy
* Signs and symptoms of infection resolution
* Signs and symptoms of hypersensitivity reactions
* *Clostridioides difficile* testing if diarrhea develops
## Clinical Pearls
* Piperacillin-tazobactam provides broad-spectrum coverage, including *Pseudomonas aeruginosa*.
* Dosing depends on the severity of infection, renal function, and the presence of *Pseudomonas aeruginosa*.
* The duration of therapy should be guided by the severity of the infection and clinical response, typically 7-14 days for complicated infections.
* In patients with severe renal impairment (CrCl < 20 mL/min), consider extending the dosing interval to 12 hours for the 4.5 g dose.
* Reconstituted solutions are typically stable for 24 hours at room temperature or 48 hours under refrigeration.
* Administer IV over at least 30 minutes to reduce the risk of hypersensitivity reactions.
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This information is intended for healthcare professionals. Always consult the most current prescribing information and local institutional guidelines for complete details and to ensure patient safety.
