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# Piperacillin/Tazobactam
## Overview
Piperacillin/tazobactam is a combination penicillin-class antibacterial and beta-lactamase inhibitor. Piperacillin targets a broad spectrum of gram-positive and gram-negative bacteria, including Pseudomonas aeruginosa, while tazobactam inhibits beta-lactamase enzymes, extending piperacillin's spectrum to include many beta-lactamase producing organisms.
## Primary Indications
* Complicated intra-abdominal infections
* Complicated skin and skin structure infections
* Community-acquired pneumonia
* Nosocomial pneumonia
* Febrile neutropenia (empiric treatment)
## Adult Dosing
* **Standard Dosing:** 3.375 grams (3g piperacillin/0.375g tazobactam) every 6 hours or 4.5 grams (4g piperacillin/0.5g tazobactam) every 8 hours, administered intravenously over at least 30 minutes.
* **Severe/Nosocomial Infections:** Dosing may be increased to 4.5 grams every 6 hours in severe infections, particularly those due to Pseudomonas aeruginosa or suspected resistant organisms. Maximum daily dose is generally 18 grams.
Dosing frequency and duration depend on the type and severity of infection and the patient's clinical response. Specific dosing for febrile neutropenia may be guided by institutional protocols.
## Pediatric Dosing
Dosing is based on piperacillin component. Administered intravenously over 30 minutes.
* **Patients 2 months to 12 years:**
* **General Infections:** 100 mg piperacillin/12.5 mg tazobactam per kg per dose every 8 hours.
* **Pseudomonas aeruginosa Infections:** 100 mg piperacillin/12.5 mg tazobactam per kg per dose every 6 hours.
* **Maximum Dose:** 4.5 grams (4g piperacillin/0.5g tazobactam) per dose.
* **Patients < 2 months:** Dosing is not well established and typically based on institutional guidelines and severity of illness, often lower doses and/or more frequent administration.
## Dose Adjustments
* **Renal Impairment (CrCl < 40 mL/min):** Reduce dose frequency.
* For 3.375g q6h: Administer 2.25g every 6 hours or 3.375g every 8 hours.
* For 4.5g q8h: Administer 3.375g every 8 hours or 4.5g every 12 hours.
* For 4.5g q6h: Administer 3.375g every 6 hours or 4.5g every 8 hours.
* Hemodialysis: Administer a dose after each dialysis session.
* **Hepatic Impairment:** No specific dose adjustment recommended, but caution is advised.
## Contraindications
* Hypersensitivity to piperacillin, tazobactam, other penicillins, or beta-lactamase inhibitors.
* History of cholestatic jaundice/hepatic dysfunction associated with piperacillin/tazobactam therapy.
## Adverse Effects
Common: Diarrhea, rash, nausea, vomiting, headache, insomnia, fever, injection site reactions.
Serious: *Clostridioides difficile*-associated diarrhea, hypersensitivity reactions (including anaphylaxis), seizures (especially with high doses or renal impairment), neutropenia, thrombocytopenia, interstitial nephritis, hepatic enzyme elevations.
## Key Drug Interactions
* **Probenecid:** May increase and prolong piperacillin serum concentrations.
* **Neuromuscular blocking agents:** Piperacillin may prolong the effect of vecuronium.
* **Warfarin:** May decrease the efficacy of warfarin. Monitor INR closely.
* **Methotrexate:** Piperacillin may decrease methotrexate levels; monitor methotrexate levels.
## Monitoring
* Renal function (especially in elderly or those with pre-existing renal disease).
* Liver function tests.
* Complete blood count (CBC) for hematologic abnormalities (neutropenia, thrombocytopenia) with prolonged therapy.
* Signs and symptoms of infection.
* Monitor for *C. difficile*-associated diarrhea.
## Clinical Pearls
* Administer IV slowly over at least 30 minutes to minimize infusion-related reactions.
* Reconstitute and dilute according to manufacturer instructions.
* Avoid coadministration with aminoglycosides in vitro due to inactivation of piperacillin; however, coadministration in vivo is common and often beneficial. Separate administration if possible.
* Adjust dose in renal impairment.
* Tazobactam is primarily cleared by the kidneys.
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*Disclaimer: This information is intended for clinical use and does not replace the need to consult the official prescribing information for the most current and complete details.*
