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# Piperacillin/Tazobactam
## Overview
Piperacillin/tazobactam is an extended-spectrum penicillin-class antibiotic combined with a beta-lactamase inhibitor.
## Primary Indications
* Complicated intra-abdominal infections
* Complicated skin and skin-structure infections
* Community-acquired pneumonia
* Nosocomial pneumonia
* Febrile neutropenia (empiric treatment)
* Various other serious infections caused by susceptible organisms, including those involving *Pseudomonas aeruginosa*.
## Adult Dosing
* **Standard Dose:** 3.375 grams (piperacillin 3 g / tazobactam 0.375 g) intravenously every 6 hours.
* **High Dose (for severe infections, nosocomial pneumonia, or *Pseudomonas*):** 4.5 grams (piperacillin 4 g / tazobactam 0.5 g) intravenously every 6 or 8 hours.
* **Continuous Infusion:** Dosing can be administered via continuous infusion, often at higher daily doses (e.g., 13.5 grams over 24 hours), which may improve outcomes in certain severe infections. Specific protocols vary.
## Pediatric Dosing
Dosing is based on piperacillin component. Administered intravenously.
* **Patients 2 months and older:**
* **General Infections:** 240 mg/kg/day divided into 4 doses (60 mg/kg per dose).
* **Serious Infections (including *Pseudomonas*):** 300 mg/kg/day divided into 4 doses (75 mg/kg per dose).
* **Maximum Dose:** Generally not to exceed 16 grams/day for piperacillin component in children weighing over 40 kg. Refer to specific guidelines for exact maximums.
* **Neonates/Infants < 2 months:** Dosing is not well established and requires careful consideration of gestational and postnatal age.
## Dose Adjustments
* **Renal Impairment:**
* CrCl > 40 mL/min: No dose adjustment needed.
* CrCl 20-40 mL/min: Reduce dose frequency to every 8 hours (for q6h regimens) or every 12 hours (for q8h regimens).
* CrCl < 20 mL/min: Reduce dose frequency to every 12 hours (for q6h regimens) or every 12-18 hours (for q8h regimens).
* Consider intermittent versus continuous infusion adjustments based on renal function.
* **Hepatic Impairment:** No dose adjustment is typically needed, but caution is advised.
## Contraindications
* Hypersensitivity to piperacillin, tazobactam, other penicillinase-resistant penicillins, or any component of the formulation.
* History of immediate and severe allergic reaction to beta-lactam antibiotics.
## Adverse Effects
* **Common:** Diarrhea, nausea, vomiting, rash, headache, insomnia, constipation, elevated liver enzymes.
* **Serious:** *Clostridioides difficile*-associated diarrhea, hypersensitivity reactions (including anaphylaxis), seizures (especially with high doses or renal impairment), neutropenia, thrombocytopenia, interstitial nephritis, Stevens-Johnson syndrome/toxic epidermal necrolysis.
## Key Drug Interactions
* **Probenecid:** May increase and prolong piperacillin/tazobactam serum concentrations.
* **Neuromuscular blocking agents (e.g., vecuronium):** Penicillins can prolong the neuromuscular blockade.
* **Warfarin:** May decrease the effect of warfarin. Monitor INR closely.
* **Aminoglycosides:** While often used together, in vitro data suggest potential antagonism. However, clinical significance is debated. Avoid coadministration in the same IV line.
## Monitoring
* Renal function (BUN, creatinine)
* Liver function tests (AST, ALT)
* Complete blood count (CBC) with differential (especially during prolonged therapy)
* Electrolytes
* Signs and symptoms of infection (clinical response)
* Signs of hypersensitivity reactions
## Clinical Pearls
* Piperacillin/tazobactam has broad-spectrum activity, including against many Gram-positive, Gram-negative (including *Pseudomonas aeruginosa*), and anaerobic bacteria.
* Dosing frequency is often tied to renal function and severity of illness.
* For severe infections or *Pseudomonas* coverage, consider the higher dose regimens (4.5 g every 6 or 8 hours) or continuous infusion.
* Administer over at least 30 minutes for intermittent infusion.
* Reconstituted solutions are generally stable for 24 hours at room temperature or 48 hours refrigerated.
* Electrolyte disturbances (e.g., hyperkalemia) can occur, particularly with high doses or in renal impairment.
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*Please verify current prescribing information and institutional protocols for definitive dosing and management.*
