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# Piperacillin-Tazobactam
## Overview
Piperacillin-tazobactam is a combination antibiotic consisting of an extended-spectrum penicillin (piperacillin) and a beta-lactamase inhibitor (tazobactam). It is active against many Gram-positive, Gram-negative, and anaerobic bacteria.
## Primary Indications
* Complicated intra-abdominal infections
* Complicated skin and skin-structure infections
* Community-acquired pneumonia
* Nosocomial pneumonia
* Febrile neutropenia
## Adult Dosing
* **Standard Dose:** 3.375 grams every 6 hours or 4.5 grams every 8 hours intravenously (IV). Each dose contains 3 grams of piperacillin and 0.375 grams of tazobactam, or 4 grams of piperacillin and 0.5 grams of tazobactam, respectively.
* **Higher Doses for Severe Infections:** Higher doses, such as 4.5 grams every 6 hours IV, may be used for severe infections, particularly in the setting of febrile neutropenia or nosocomial pneumonia, depending on local protocols and susceptibility patterns.
* **Duration of Therapy:** Typically 7 to 14 days, but depends on the infection and clinical response.
## Pediatric Dosing
* **Children ≥ 2 months:** Dosing is based on piperacillin weight.
* **Mild to Moderate Infections:** 24.375 mg/kg (21.25 mg piperacillin/3.125 mg tazobactam) every 6 hours IV.
* **Severe Infections (e.g., Febrile Neutropenia):** 32.5 mg/kg (28.3 mg piperacillin/4.2 mg tazobactam) every 6 hours IV.
* **Maximum dose:** Does not exceed the adult maximum of 4.5 grams per dose.
* **Neonates:** Data is limited, and use is generally not recommended.
## Dose Adjustments
* **Renal Impairment:**
* CrCl ≥ 50 mL/min: No dose adjustment needed.
* CrCl 20-49 mL/min: 2.25 grams (2 grams piperacillin/0.25 grams tazobactam) every 6 hours or 3.375 grams (3 grams piperacillin/0.375 grams tazobactam) every 8 hours.
* CrCl < 20 mL/min: 2.25 grams (2 grams piperacillin/0.25 grams tazobactam) every 8 hours.
* **Hemodialysis:** Administer a supplemental dose after each hemodialysis session.
* **Hepatic Impairment:** No specific dose adjustment is generally recommended, but caution is advised.
## Contraindications
* Known hypersensitivity to piperacillin, tazobactam, other penicillins, or beta-lactamase inhibitors.
* History of severe allergic reaction (e.g., anaphylaxis) to a beta-lactam antibiotic.
## Adverse Effects
* **Common:** Diarrhea, rash, nausea, vomiting, headache, insomnia, constipation.
* **Serious:**
* Hypersensitivity reactions (including anaphylaxis)
* Clostridioides difficile-associated diarrhea (CDAD)
* Seizures (especially with high doses or renal impairment)
* Hepatotoxicity
* Hematologic changes (e.g., neutropenia, thrombocytopenia)
* Interstitial nephritis
## Key Drug Interactions
* **Probenecid:** May increase and prolong piperacillin-tazobactam serum concentrations.
* **Neuromuscular blocking agents:** May prolong neuromuscular blockade.
* **Warfarin:** May decrease the efficacy of warfarin; monitor INR closely.
* **Methotrexate:** May decrease methotrexate levels; monitor methotrexate levels.
## Monitoring
* Renal function (baseline and periodically)
* Liver function tests (periodically)
* Complete blood count (periodically, especially with prolonged therapy)
* Signs and symptoms of infection for clinical response
* Signs and symptoms of hypersensitivity reactions
* Electrolytes, particularly if co-administered with diuretics
## Clinical Pearls
* Piperacillin-tazobactam is a broad-spectrum agent often reserved for more serious or complicated infections due to its broad coverage and potential for resistance development.
* The addition of tazobactam extends the spectrum of activity to include many beta-lactamase-producing organisms.
* Ensure adequate hydration and monitor for signs of fluid overload, especially in patients with heart failure.
* When reconstituting, follow manufacturer guidelines for stability.
* Infusion-related reactions, such as phlebitis, can occur; consider using a central venous catheter for prolonged therapy or irritating solutions.
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*This information is intended for clinical use and does not replace comprehensive drug references. Always consult the current prescribing information and relevant guidelines for complete details before making any treatment decisions.*
