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# Piperacillin/Tazobactam
## Overview
Piperacillin/tazobactam is a combination of an extended-spectrum penicillin antibiotic (piperacillin) and a beta-lactamase inhibitor (tazobactam).
## Primary Indications
* **Complicated intra-abdominal infections:** Often in combination with metronidazole.
* **Complicated skin and skin structure infections:** Including diabetic foot infections.
* **Community-acquired pneumonia:** Especially when healthcare-associated pneumonia is suspected.
* **Nosocomial pneumonia.**
* **Bacterial infections** in febrile neutropenic patients (when suspected to be due to piperacillin-susceptible organisms).
## Adult Dosing
* **Complicated intra-abdominal infections, complicated skin and skin structure infections, community-acquired pneumonia, nosocomial pneumonia:**
* 3.375 grams (piperacillin 3 g/tazobactam 0.375 g) intravenously every 6 hours.
* Alternatively, 4.5 grams (piperacillin 4 g/tazobactam 0.5 g) intravenously every 8 hours.
* **Maximum daily dose:** 18 grams (piperacillin 16 g/tazobactam 2 g) intravenously per day.
* **Febrile neutropenic patients:**
* 4.5 grams (piperacillin 4 g/tazobactam 0.5 g) intravenously every 6 hours.
* **Duration:** Typically 7 days, or until neutrophil count is >500/mm³ and fever has resolved for at least 2 days.
## Pediatric Dosing
Dosing is weight-based and depends on indication and patient weight. Consult specific institutional guidelines or pediatric infectious disease resources.
* **Children < 12 years:** Dosing varies by indication.
* Commonly: 80 mg piperacillin / 10 mg tazobactam per kg per dose intravenously every 6 hours.
* For children weighing > 50 kg who require pediatric dosing, administer as per adult dosing.
* **Children ≥ 12 years:** Administer as per adult dosing.
## Dose Adjustments
* **Renal Impairment (CrCl ≤ 40 mL/min):**
* Dose and/or frequency reduction is required.
* **For 3.375 g every 6 hours:** Administer 2.25 g every 6 hours.
* **For 4.5 g every 6 hours:** Administer 3.375 g every 6 hours.
* **For 4.5 g every 8 hours:** Administer 3.375 g every 8 hours.
* **For 4.5 g every 6 hours (febrile neutropenia):** Administer 3.375 g every 6 hours.
* Intermittent hemodialysis: Administer the recommended dose every 8 hours, plus an additional dose after each hemodialysis session.
* **Hepatic Impairment:** No specific dose adjustment recommended, but caution is advised.
## Contraindications
* Known serious allergy to piperacillin, tazobactam, other penicillins, or beta-lactamase inhibitors.
## Adverse Effects
* **Common:** Diarrhea, nausea, vomiting, rash, headache, insomnia, constipation, dizziness, fever.
* **Serious:** Hypersensitivity reactions (anaphylaxis), *Clostridioides difficile*-associated diarrhea, seizures (especially with high doses or renal impairment), neutropenia, thrombocytopenia, leukopenia, eosinophilia, elevated liver enzymes, interstitial nephritis.
## Key Drug Interactions
* **Probenecid:** May increase and prolong piperacillin/tazobactam plasma concentrations.
* **Neuromuscular blocking agents:** May prolong the neuromuscular blockade.
* **Warfarin:** May alter the anticoagulant response. Monitor INR closely.
* **Methotrexate:** Piperacillin may reduce methotrexate clearance. Monitor methotrexate levels.
* **Aminoglycosides:** Consider concurrent administration for synergistic activity against certain pathogens, but avoid co-administration in the same IV infusion bag.
## Monitoring
* **Renal function:** Baseline and periodically during therapy, especially in patients with renal impairment or those receiving nephrotoxic agents.
* **Hepatic function:** Baseline and periodically during therapy.
* **Complete blood count:** Monitor for hematologic changes, especially with prolonged therapy.
* **Signs and symptoms of infection:** Clinical response to therapy.
* **Signs and symptoms of hypersensitivity reactions.**
* ***Clostridioides difficile* infection:** Monitor for diarrhea.
## Clinical Pearls
* Piperacillin/tazobactam is a broad-spectrum antibiotic active against many Gram-positive, Gram-negative, and anaerobic bacteria, including *Pseudomonas aeruginosa*.
* Tazobactam protects piperacillin from degradation by many beta-lactamases.
* The 3.375 g and 4.5 g formulations contain piperacillin and tazobactam in an 8:1 ratio.
* Infuse over at least 30 minutes to minimize the risk of infusion-related reactions.
* Do not add piperacillin/tazobactam to lipid-containing solutions or to solutions containing only albumin.
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*This information is intended for healthcare professionals. Always consult the official prescribing information and relevant institutional protocols for complete details and to ensure patient safety.*
