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# Piperacillin/Tazobactam
## Overview
Piperacillin/tazobactam is a combination antibiotic consisting of piperacillin, a broad-spectrum penicillinase-sensitive penicillin, and tazobactam, a beta-lactamase inhibitor.
## 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 (piperacillin 3 grams/tazobactam 0.375 grams) intravenously every 6 hours.
Maximum dose: 4.5 grams (piperacillin 4 grams/tazobactam 0.5 grams) intravenously every 6 or 8 hours, depending on indication and local protocols. Some guidelines suggest every 8 hours for severe infections or those due to *Pseudomonas aeruginosa*.
## Pediatric Dosing
Dosing varies by indication and patient age/weight. Typical dosing ranges from 80 mg/kg to 300 mg/kg per day of piperacillin component, divided into 3 or 4 doses. Tazobactam dose is typically 1/8th of the piperacillin dose.
* **Complicated Intra-abdominal Infections:** 100 mg/kg/day of piperacillin component, divided every 8 hours.
* **Complicated Skin and Skin Structure Infections:** 80 mg/kg/day of piperacillin component, divided every 8 hours.
* **Community-Acquired Pneumonia:** 100 mg/kg/day of piperacillin component, divided every 8 hours.
* **Febrile Neutropenia:** 300 mg/kg/day of piperacillin component, divided every 6 hours.
**Note:** Specific pediatric dosing, especially for infants and neonates, can be complex and may require expert consultation. Maximum daily dose of piperacillin should not exceed 16 g/day.
## Dose Adjustments
* **Renal Impairment (CrCl < 20 mL/min):** Reduce dose frequency. For standard 3.375 g dose every 6 hours, administer every 8 hours. For 4.5 g dose, administer every 8 hours.
* **Hemodialysis:** Administer the recommended dose at the end of dialysis. Additional supplemental doses may be required.
* **Hepatic Impairment:** No dose adjustment is typically needed.
## Contraindications
* Hypersensitivity to piperacillin, tazobactam, other penicillinase-resistant penicillins, or any component of the formulation.
* History of immediate or severe allergic reaction to a beta-lactam antibiotic.
## Adverse Effects
* **Common:** Diarrhea, rash, nausea, vomiting, headache, insomnia, eosinophilia, increased AST/ALT.
* **Serious:** *Clostridioides difficile*-associated diarrhea, hypersensitivity reactions (including anaphylaxis), seizures (especially at high doses or with renal impairment), neutropenia, thrombocytopenia, interstitial nephritis.
## Key Drug Interactions
* **Probenecid:** Increases piperacillin/tazobactam serum concentrations.
* **Warfarin:** May decrease INR. Monitor INR closely.
* **Methotrexate:** May decrease methotrexate clearance. Monitor methotrexate levels.
* **Neuromuscular Blocking Agents:** May prolong neuromuscular blockade.
* **Bacteriostatic Antibiotics:** May antagonize the bactericidal effect of piperacillin.
## Monitoring
* Renal function (CrCl) for dose adjustment.
* Liver function tests (AST/ALT).
* Complete blood count (CBC) for hematologic effects (neutropenia, thrombocytopenia).
* Signs and symptoms of hypersensitivity reactions.
* Signs and symptoms of *Clostridioides difficile*-associated diarrhea.
## Clinical Pearls
* Tazobactam broadens the spectrum of piperacillin to include many beta-lactamase producing bacteria, including some *Bacteroides* species, *Staphylococcus aureus*, *Escherichia coli*, *Haemophilus influenzae*, and *Klebsiella pneumoniae*. It does not reliably cover *Enterobacteriaceae* or *Pseudomonas aeruginosa* that produce extended-spectrum beta-lactamases (ESBLs) or carbapenemases.
* Duration of therapy depends on the severity and type of infection and clinical response, typically ranging from 7 to 14 days.
* Reconstituted solutions should be used within 24 hours if stored at room temperature or within 48 hours if refrigerated.
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*Disclaimer: This information is intended for clinical professionals and does not replace a thorough review of the current prescribing information and clinical guidelines. Always verify drug information with the most recent official sources.*
