Piperacillin + Tazobactam

• Approved indications:
• Treatment of moderate to severe infections caused by susceptible bacteria, including:
• Intra-abdominal infections (e.g., peritonitis, abscess)
• Skin and soft tissue infections
• Complicated urinary tract infections (including pyelonephritis)
• Community-acquired and hospital-acquired pneumonia
• Septicemia and bacteremia
• Gynecological infections
• Bone and joint infections
• Febrile neutropenia (as empiric therapy)
• Important off-label uses:
• Severe infections caused by multidrug-resistant Gram-negative organisms (as per susceptibility)
• Empiric treatment in critically ill patients with suspected polymicrobial infections

• Route: Intravenous (IV) infusion; intramuscular (IM) use limited.
• Adults:
• Usual dose: 3.375 g (piperacillin 3 g + tazobactam 0.375 g) every 6 hours IV over 30 minutes.
• Severe infections: Dose may increase up to 4.5 g (piperacillin 4 g + tazobactam 0.5 g) every 6 to 8 hours.
• Maximum dose: up to 18 g piperacillin per day.
• Pediatrics:
• IV dosing based on body weight, commonly 80–100 mg/kg (piperacillin component) every 6–8 hours.
• Adjustments according to severity and site of infection.
• Elderly:
• Use standard dosing unless renal impairment present; adjust dose as per renal function.
• Renal impairment:
• Dose adjustment required based on creatinine clearance:
• ClCr 20–40 mL/min: extend dosing interval to every 8–12 hours.
• ClCr <20 mL/min: extend dosing interval to every 12–24 hours; avoid IM use.
• Hepatic impairment:
• No significant dosage adjustment needed.

Piperacillin is a broad-spectrum ureidopenicillin antibiotic that inhibits bacterial cell wall synthesis by binding to penicillin-binding proteins (PBPs), leading to cell lysis and death. Tazobactam is a beta-lactamase inhibitor that irreversibly inhibits many beta-lactamases produced by bacteria, preventing the enzymatic degradation of piperacillin and thereby extending its spectrum of activity against beta-lactamase-producing organisms. Together, they provide synergistic bactericidal activity against a wide range of Gram-positive, Gram-negative, and anaerobic bacteria.

• Absorption: Not applicable (administered IV/IM); poor oral absorption.
• Distribution: Widely distributed into body tissues and fluids including lungs, bile, bone, and abscesses; volume of distribution approx. 0.16 L/kg.
• Metabolism: Minimal hepatic metabolism; tazobactam partially metabolized.
• Elimination: Primarily renal excretion of unchanged drug; both piperacillin and tazobactam are eliminated via kidneys.
• Half-life:
• Piperacillin: ~0.7 to 1.2 hours
• Tazobactam: ~0.7 to 1.2 hours
• Onset: Rapid after IV infusion.
• Steady state: Achieved within 24–48 hours with multiple dosing.

• Pregnancy: FDA category B; animal studies show no risk, but controlled human data are limited. Use only if clearly needed.
• Lactation: Piperacillin and tazobactam are excreted in breast milk in small amounts; caution advised during breastfeeding.

• Combination antibiotic: Extended-spectrum penicillin + beta-lactamase inhibitor

• Known hypersensitivity to piperacillin, tazobactam, penicillins, or beta-lactam antibiotics
• History of severe allergic reactions (e.g., anaphylaxis) to beta-lactams
• Cross-reactivity caution with cephalosporins and carbapenems

• Use with caution in patients with a history of penicillin allergy or hypersensitivity reactions
• Monitor for signs of hypersensitivity reactions, including anaphylaxis
• Risk of Clostridioides difficile-associated diarrhea and superinfection with prolonged use
• Monitor renal function regularly; dose adjustment required in renal impairment
• Caution in patients with hepatic dysfunction or seizure history
• May cause electrolyte disturbances (e.g., sodium load); monitor electrolytes in high doses
• Use carefully in patients with bleeding disorders due to platelet dysfunction risk

• Common:
• Gastrointestinal: diarrhea, nausea, vomiting
• Injection site reactions
• Rash, urticaria
• Serious but less common:
• Hypersensitivity reactions including anaphylaxis
• Clostridioides difficile-associated diarrhea
• Hematologic: neutropenia, thrombocytopenia, eosinophilia
• Hepatic enzyme elevations
• Electrolyte imbalance
• Rare:
• Seizures (particularly in renal impairment or overdose)
• Stevens-Johnson syndrome, toxic epidermal necrolysis

• May increase anticoagulant effects of warfarin and increase bleeding risk
• Enhanced nephrotoxicity with aminoglycosides
• Possible reduced efficacy of oral contraceptives (theoretical)
• Increased risk of seizures with concomitant penicillins and probenecid or imipenem
• Sodium load may interact with sodium-restricted diets or drugs affecting electrolyte balance

• Recent guidelines emphasize using piperacillin-tazobactam as empiric therapy for hospital-acquired infections and multidrug-resistant organisms, especially Pseudomonas aeruginosa
• Recommendations to adjust dosing in renal impairment to reduce toxicity
• Newer dosing strategies include extended or continuous infusions to optimize pharmacodynamics in critically ill patients
• Ongoing surveillance for resistance patterns recommended

• Store at 20°C to 25°C (68°F to 77°F)
• Protect from moisture and light
• After reconstitution, store solution refrigerated at 2°C to 8°C (36°F to 46°F) and use within 24 hours
• Do not freeze reconstituted solution
• Use aseptic technique to prepare and administer