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# Piperacillin-Tazobactam
## Overview
Piperacillin-tazobactam is a combination antibiotic consisting of piperacillin, a broad-spectrum penicillin antibiotic, and tazobactam, a beta-lactamase inhibitor. Tazobactam protects piperacillin from degradation by many beta-lactamase enzymes, thereby extending its spectrum of activity to include many beta-lactamase-producing bacteria.
## Primary Indications
* Complicated intra-abdominal infections
* Complicated skin and skin-structure infections (including diabetic foot infections)
* Community-acquired pneumonia
* Nosocomial pneumonia
* Febrile neutropenia (in combination with an aminoglycoside, though monotherapy is sometimes used)
## Adult Dosing
* **Standard Dose:** 3.375 grams every 6 hours or 4.5 grams every 6 or 8 hours intravenously (IV).
* 3.375 g vial contains 3g piperacillin and 0.375g tazobactam.
* 4.5 g vial contains 4g piperacillin and 0.5g tazobactam.
* **Duration:** Typically 7 to 14 days, depending on the severity and type of infection.
## Pediatric Dosing
* **Patients weighing > 2 kg with normal renal function:**
* **2 months to < 12 years:** 100 mg piperacillin component/kg/dose every 8 hours.
* **12 years and older:** Dosing as per adult recommendations.
* **Maximum Dose:** Do not exceed the maximum adult dose.
* **Note:** Dosing for neonates and infants < 2 months is not well-established due to immature renal and hepatic function.
## Dose Adjustments
* **Renal Impairment (CrCl < 20 mL/min):** Reduce dose frequency.
* **3.375 g every 6 hours:** Administer every 8 hours.
* **4.5 g every 6 or 8 hours:** Administer every 8 or 12 hours, respectively.
* **Hemodialysis:** Administer the usual recommended dose after each dialysis session. Supplemental doses may be needed.
* **Hepatic Impairment:** No dose adjustment is generally required.
## Contraindications
* Hypersensitivity to piperacillin, tazobactam, other penicillin antibiotics, or any component of the formulation.
* History of immediate or severe allergic reaction to a beta-lactam antibiotic.
## Adverse Effects
* **Common:** Diarrhea, nausea, vomiting, rash, headache, insomnia, constipation, abdominal pain, rash, pruritus.
* **Serious:**
* *Clostridioides difficile*-associated diarrhea (CDAD).
* Hypersensitivity reactions (anaphylaxis).
* Seizures (more common with high doses or renal impairment).
* Hepatotoxicity.
* Hematologic effects (e.g., neutropenia, thrombocytopenia, eosinophilia).
* Superinfection.
## Key Drug Interactions
* **Probenecid:** May increase and prolong piperacillin-tazobactam serum concentrations.
* **Neuromuscular blocking agents (e.g., vecuronium):** Piperacillin may prolong the effect of vecuronium.
* **Warfarin:** May decrease the effect of warfarin; monitor INR closely.
* **Methotrexate:** Piperacillin may decrease methotrexate clearance; monitor methotrexate levels.
* **Aminoglycosides:** Concurrent use may result in inactivation of the aminoglycoside; administer separately if used together.
## Monitoring
* Renal function (CrCl).
* Liver function tests (LFTs).
* Complete blood count (CBC) with differential and platelets.
* Signs and symptoms of infection, including fever and inflammatory markers.
* Signs and symptoms of hypersensitivity reactions.
* Stool for *C. difficile* if diarrhea occurs.
## Clinical Pearls
* The 4.5 g formulation (4g piperacillin/0.5g tazobactam) is often preferred for more severe infections or when targeting organisms with reduced susceptibility.
* Consider patient-specific factors, local resistance patterns, and infection severity when determining dose and duration.
* Tazobactam itself has minimal antibacterial activity.
* Ensure adequate hydration and electrolytes, especially in patients with prolonged diarrhea or vomiting.
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*Please verify current prescribing information and institutional protocols before administering any medication.*
