Zosyn - Drug Monograph

Introduction

Zosyn (piperacillin/tazobactam) is an intravenous broad-spectrum antibiotic combination medication consisting of piperacillin, an extended-spectrum penicillin, and tazobactam, a beta-lactamase inhibitor. This combination extends the antibacterial spectrum of piperacillin to include beta-lactamase-producing strains of bacteria that would otherwise be resistant. Zosyn is widely used in hospital settings for the treatment of moderate to severe infections.

Mechanism of Action

Piperacillin exerts bactericidal activity by binding to penicillin-binding proteins (PBPs) and inhibiting bacterial cell wall synthesis. Tazobactam irreversibly binds to and inhibits many beta-lactamases, including those produced by many gram-positive and gram-negative aerobic and anaerobic bacteria. This protection allows piperacillin to maintain its antibacterial activity against beta-lactamase-producing organisms.

Indications

FDA-approved indications include:

• Intra-abdominal infections
• Skin and skin structure infections
• Community-acquired pneumonia (moderate severity only)
• Nosocomial pneumonia
• Gynecological infections
• Sepsis

Zosyn is also commonly used off-label for:

• Complicated urinary tract infections
• Febrile neutropenia
• Bone and joint infections

Dosage and Administration

• CrCl >40 mL/min: No adjustment needed
• CrCl 20-40 mL/min: 2.25 g every 6 hours
• CrCl <20 mL/min: 2.25 g every 8 hours
• Hemodialysis: 2.25 g every 12 hours (administer after dialysis)

• IV infusion over 30 minutes
• Reconstitute with appropriate diluent according to manufacturer instructions
• Compatible with most IV solutions including NS, D5W, LR

Pharmacokinetics

Contraindications

• History of severe hypersensitivity reactions to penicillins, cephalosporins, or other beta-lactam antibiotics
• History of drug-induced immune thrombocytopenia with Zosyn

Warnings and Precautions

• Hypersensitivity reactions: Serious and occasionally fatal anaphylactic reactions reported
• Clostridium difficile-associated diarrhea: May range from mild diarrhea to fatal colitis
• Bleeding manifestations: Has been associated with manifestations of bleeding
• Leukopenia/neutropenia: Reversible leukopenia/neutropenia may occur
• Seizures: May occur, especially in patients with renal impairment
• Nephrotoxicity: Monitor renal function during therapy
• Electrolyte imbalances: Contains 2.79 mEq sodium per gram of piperacillin

Drug Interactions

• Probenecid: Decreases renal clearance of piperacillin
• Heparin: May increase risk of bleeding
• Oral anticoagulants: May enhance anticoagulant effect
• Methotrexate: May decrease methotrexate clearance
• Vecuronium: May prolong neuromuscular blockade
• Aminoglycosides: Physical incompatibility; administer separately

Adverse Effects

• Diarrhea (7-11%)
• Headache (2-8%)
• Constipation (1-7%)
• Nausea (4-7%)
• Insomnia (3-7%)
• Rash (2-4%)

• Anaphylaxis
• Stevens-Johnson syndrome
• Toxic epidermal necrolysis
• Blood dyscrasias
• Interstitial nephritis
• Hepatitis
• Seizures
• Pseudomembranous colitis

Monitoring Parameters

• Complete blood count with differential (weekly)
• Renal function tests (baseline and periodically)
• Liver function tests (baseline and periodically)
• Coagulation parameters in at-risk patients
• Signs and symptoms of infection
• Signs of hypersensitivity reactions
• Electrolytes in patients receiving high doses
• Diarrhea evaluation for C. difficile

Patient Education

• Report any signs of allergic reaction immediately (rash, itching, swelling, difficulty breathing)
• Inform healthcare providers of all medications being taken
• Complete the full course of therapy even if feeling better
• Report severe diarrhea, especially if containing blood or mucus
• Report unusual bleeding or bruising
• Inform healthcare providers of any history of kidney disease
• Notify healthcare provider if pregnant, planning pregnancy, or breastfeeding

References

1. Zosyn [package insert]. Philadelphia, PA: Wyeth Pharmaceuticals Inc; 2022. 2. Liu C, Bayer A, Cosgrove SE, et al. Clinical practice guidelines by the Infectious Diseases Society of America for the treatment of methicillin-resistant Staphylococcus aureus infections in adults and children. Clin Infect Dis. 2011;52(3):e18-e55. 3. Tamma PD, Aitken SL, Bonomo RA, Mathers AJ, van Duin D, Clancy CJ. Infectious Diseases Society of America 2022 Guidance on the Treatment of Extended-Spectrum β-lactamase Producing Enterobacterales (ESBL-E), Carbapenem-Resistant Enterobacterales (CRE), and Pseudomonas aeruginosa with Difficult-to-Treat Resistance (DTR-P. aeruginosa). Clin Infect Dis. 2022;75(2):187-212. 4. Gilbert DN, Chambers HF, Saag MS, et al. The Sanford Guide to Antimicrobial Therapy. 52nd ed. Antimicrobial Therapy, Inc; 2022. 5. Lexicomp Online. Piperacillin/Tazobactam. Wolters Kluwer Clinical Drug Information, Inc. 2023.