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# Piperacillin/Tazobactam (Zosyn)
## Overview
Piperacillin/tazobactam is an extended-spectrum penicillin combined with a beta-lactamase inhibitor. It is bactericidal.
## Primary Indications
* Complicated intra-abdominal infections
* Complicated skin and skin structure infections
* Community-acquired pneumonia
* Hospital-acquired pneumonia (including ventilator-associated pneumonia)
* Empirical treatment of febrile neutropenia
* Nosocomial infections caused by piperacillin-resistant *Pseudomonas aeruginosa*
## Adult Dosing
* **Standard Dose:** 3.375 grams (3g piperacillin/0.375g tazobactam) every 6 hours intravenously.
* **Higher Dose:** 4.5 grams (4g piperacillin/0.5g tazobactam) every 6 or 8 hours intravenously. The 8-hour interval is often used for *Pseudomonas* coverage or more severe infections.
* **Maximum Dose:** Generally not to exceed 18 grams per day (16g piperacillin/2g tazobactam).
Dosing frequency and duration depend on the indication, severity of illness, and pathogen susceptibility. Specific protocols may dictate exact dosing regimens.
## Pediatric Dosing
Dosing is weight-based and varies by indication and age. Consult specific pediatric guidelines or institutional protocols. Common regimens include:
* **Neonates and Infants (up to 12 weeks):** 50 mg piperacillin/6.25 mg tazobactam per kg per dose every 8 to 12 hours.
* **Children 12 weeks to < 1 year:** 75 mg piperacillin/9.375 mg tazobactam per kg per dose every 6 hours.
* **Children 1 to < 2 years:** 100 mg piperacillin/12.5 mg tazobactam per kg per dose every 6 hours.
* **Children 2 to < 12 years (or weighing < 40 kg):** 2.4 g piperacillin/0.3 g tazobactam (3.0 g total) every 6 hours.
* **Children 12 years and older (or weighing ≥ 40 kg):** Dosing for adults is typically used.
Maximum pediatric doses should not exceed adult maximums.
## Dose Adjustments
* **Renal Impairment (CrCl < 20 mL/min):** Reduce dose frequency. For standard 3.375g q6h dosing, consider 2.25g q6h or 3.375g q8h. For higher 4.5g q6h dosing, consider 3.375g q6h or 4.5g q8h.
* **End-Stage Renal Disease (ESRD):** For intermittent therapy, administer a loading dose of 2.25g or 3.375g (depending on regimen) then 2.25g every 8 hours. For continuous infusion, consult specific guidelines.
* **Hepatic Impairment:** No dose adjustment is generally required.
## Contraindications
* Hypersensitivity to piperacillin, tazobactam, other penicillins, or cephalosporins.
* History of cholestatic jaundice or hepatic dysfunction associated with piperacillin/tazobactam.
## Adverse Effects
* **Common:** Diarrhea, nausea, vomiting, rash, headache, insomnia, rash, pruritus, fever, eosinophilia, elevated liver enzymes.
* **Serious:** *Clostridioides difficile*-associated diarrhea (CDAD), hypersensitivity reactions (including anaphylaxis), seizures (especially with high doses or renal impairment), neutropenia, thrombocytopenia, interstitial nephritis, serum sickness.
## Key Drug Interactions
* **Probenecid:** May increase and prolong piperacillin/tazobactam plasma concentrations.
* **Neuromuscular Blocking Agents (e.g., vecuronium):** Piperacillin may prolong the neuromuscular blockade.
* **Warfarin:** May decrease the effect of warfarin, increasing INR. Monitor INR closely.
* **Aminoglycosides:** Concurrent use can lead to physical inactivation of piperacillin/tazobactam. Avoid co-administration in the same IV line. If co-administration is necessary, separate administration times and flush lines.
## Monitoring
* Renal function (BUN, creatinine)
* Liver function tests (AST, ALT, bilirubin)
* Complete blood count (CBC) with differential and platelets
* Signs and symptoms of hypersensitivity reactions
* Signs and symptoms of CDAD
* Culture and sensitivity results to guide therapy duration.
## Clinical Pearls
* Reconstitute and further dilute for IV infusion.
* Administer as a slow IV infusion over 30 minutes to minimize infusion reactions.
* For febrile neutropenia, often given in combination with an aminoglycoside.
* The beta-lactamase inhibitor tazobactam extends the spectrum of piperacillin to cover many beta-lactamase producing bacteria, including some strains of *Staphylococcus aureus*, *Haemophilus influenzae*, *Moraxella catarrhalis*, *E. coli*, *Klebsiella* spp., and *Bacteroides* spp.
* Piperacillin is active against *Pseudomonas aeruginosa*.
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**Disclaimer:** This information is intended for healthcare professionals. Always consult the most current prescribing information, institutional protocols, and relevant literature for complete and up-to-date guidance before prescribing or administering any medication.
