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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. 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
* Hospital-acquired pneumonia
* Febrile neutropenia (empiric treatment)
* Various other serious bacterial infections
## Adult Dosing
* **Complicated Intra-abdominal Infections, Complicated Skin and Skin Structure Infections, Community-Acquired Pneumonia, Hospital-Acquired Pneumonia:** Typically 3.375 grams IV every 6 hours or 4.5 grams IV every 6 or 8 hours.
* **Febrile Neutropenia:** Typically 4.5 grams IV every 6 or 8 hours.
* **Dosing duration:** Varies based on indication and clinical response, often 7 to 14 days.
* **Maximum daily dose:** Generally 18 grams per day (4.5 grams every 6 hours).
* **Dosing Interval:** Standard is every 6 or 8 hours, but prolonged infusions (e.g., over 30 minutes) are often used, especially at higher doses, to achieve target concentrations.
## Pediatric Dosing
* **Neonates and Infants (0-1 month):** Dosing is complex and depends on gestational and postnatal age. Consult specific pediatric guidelines. A common starting point may be 100 mg piperacillin/12.5 mg tazobactam per kg per day divided into 3 or 4 doses.
* **Children (1 month to 12 years):** Dosing is typically based on piperacillin component:
* **Complicated Intra-abdominal Infections, Complicated Skin and Skin Structure Infections:** 100 mg piperacillin/12.5 mg tazobactam per kg per dose IV every 8 hours.
* **Hospital-Acquired Pneumonia, Febrile Neutropenia:** 100 mg piperacillin/12.5 mg tazobactam per kg per dose IV every 6 or 8 hours.
* **Maximum dose:** Generally 4.5 grams per dose, not to exceed 18 grams per day.
* **Children 12 years and older:** Dosed as adults.
* **Dosing interval and duration:** Varies based on indication and clinical response.
## Dose Adjustments
* **Renal Impairment:**
* CrCl > 40 mL/min: No adjustment needed.
* CrCl 20-40 mL/min: Reduce dose frequency to every 8 hours (if on a 6-hour regimen) or every 12 hours (if on an 8-hour regimen).
* CrCl < 20 mL/min: Reduce dose frequency to every 12 hours and consider reducing the dose by 25-50%.
* **Hemodialysis:** Administer dose every 12 hours and supplement with one additional dose during or after each hemodialysis session.
* **Hepatic Impairment:** No specific dose adjustments are typically recommended, but caution is advised.
## Contraindications
* Hypersensitivity to piperacillin, tazobactam, other penicillins, cephalosporins, or beta-lactams.
* History of cholestatic jaundice or hepatic dysfunction associated with piperacillin/tazobactam.
## Adverse Effects
* **Common:** Diarrhea, nausea, vomiting, rash, pruritus, headache, insomnia.
* **Serious:**
* Hypersensitivity reactions (including anaphylaxis)
* Clostridioides difficile-associated diarrhea (CDAD)
* Hepatotoxicity (cholestatic jaundice)
* Hematologic effects (neutropenia, thrombocytopenia, anemia)
* Seizures (especially with high doses or renal impairment)
* Interstitial nephritis
## Key Drug Interactions
* **Probenecid:** May increase and prolong serum concentrations of piperacillin/tazobactam.
* **Neuromuscular blocking agents (e.g., vecuronium):** Piperacillin can prolong the neuromuscular blockade.
* **Warfarin:** May decrease the effect of warfarin, requiring increased monitoring of INR.
* **Methotrexate:** Piperacillin may decrease methotrexate clearance, increasing toxicity risk.
## Monitoring
* Renal function (BUN, creatinine)
* Liver function tests (AST, ALT, bilirubin)
* Complete blood count (CBC) with differential and platelet count
* Electrolytes
* Signs and symptoms of infection (temperature, white blood cell count, clinical improvement)
* Signs and symptoms of hypersensitivity reactions
## Clinical Pearls
* Piperacillin/tazobactam is reconstituted and further diluted for IV infusion. Standard infusion times are 30 minutes. Prolonged infusion may be beneficial for certain pathogens or in critical illness.
* Monitor for signs of superinfection, including fungal infections.
* Consider the potential for additive neuromuscular blockade with other agents.
* Dosing for very young infants and critically ill patients may require specific protocol-based adjustments or consultation with infectious disease specialists.
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*Please verify the most current prescribing information and institutional protocols before administering this medication.*
