What is the recommended treatment and dosage for Zosyn (piperacillin/tazobactam) in patients with bacterial infections?

Zosyn (Piperacillin/Tazobactam) Treatment Guidelines

Standard Dosing

For most bacterial infections in adults, administer piperacillin/tazobactam 3.375 g (3 g piperacillin/0.375 g tazobactam) intravenously every 6 hours, totaling 13.5 g daily. 1

Adult Dosing by Indication

Nosocomial Pneumonia (Hospital-Acquired/Ventilator-Associated):

• 4.5 g (4 g piperacillin/0.5 g tazobactam) IV every 6 hours (total 18 g daily), typically combined with an aminoglycoside 1, 2
• Duration: 7-14 days 3, 2
• Infuse over 30 minutes 1

Complicated Intra-Abdominal Infections:

• 3.375 g IV every 6 hours 1
• Duration: 5-7 days after adequate source control 2
• For polymicrobial infections, this provides excellent coverage against mixed aerobic-anaerobic flora 3, 4

Severe Skin and Soft Tissue Infections/Necrotizing Fasciitis:

• 3.375 g IV every 6-8 hours PLUS vancomycin 15 mg/kg every 12 hours for empiric coverage of MRSA and polymicrobial pathogens 3
• Duration: 5-10 days, extending if infection has not improved 2
• For necrotizing infections, surgical debridement is mandatory alongside antibiotics 3

Complicated Urinary Tract Infections:

• 3.375 g IV every 6 hours 1
• Duration: 5-7 days 3
• Clinical cure rates of 86% demonstrated in trials 5

Community-Acquired Pneumonia:

• 3.375 g IV every 6 hours 1
• Duration: 7-14 days 2

Pediatric Dosing (≥2 Months of Age, Normal Renal Function)

Ages 2-9 Months:

• Appendicitis/Peritonitis: 90 mg/kg (80 mg piperacillin/10 mg tazobactam) IV every 8 hours 1
• Nosocomial Pneumonia: 90 mg/kg IV every 6 hours 1

Ages >9 Months (up to 40 kg):

• Appendicitis/Peritonitis: 112.5 mg/kg (100 mg piperacillin/12.5 mg tazobactam) IV every 8 hours 1
• Nosocomial Pneumonia: 112.5 mg/kg IV every 6 hours 1

Alternative pediatric dosing from guidelines: 60-75 mg/kg/dose of piperacillin component every 6 hours IV 3

Renal Dose Adjustments

Creatinine Clearance ≤40 mL/min requires dose reduction 1:

• Consult FDA label for specific adjustments based on degree of impairment
• Dialysis patients require modified dosing 1

Administration

• Infuse over 30 minutes for both adults and pediatrics 1
• If co-administering with aminoglycosides, reconstitute and administer separately; Y-site co-administration possible under specific conditions 1
• For extended infusion in critically ill patients or high MIC organisms, consider 3-4 hour infusions 3

Key Clinical Considerations

Combination Therapy:

• Nosocomial pneumonia: Always combine with aminoglycoside initially 1, 2
• Necrotizing infections: Combine with vancomycin or linezolid for MRSA coverage 3
• Febrile neutropenia: Combination with amikacin shows superior efficacy versus ceftazidime plus amikacin 4, 6

Resistant Organisms:

• For carbapenem-resistant Pseudomonas aeruginosa susceptible to piperacillin/tazobactam: 3-4 g IV every 6 hours 3
• Beta-lactam/beta-lactamase inhibitors may be considered when susceptibility testing confirms susceptibility 3

Safety Profile

Common Adverse Events:

• Gastrointestinal symptoms (most commonly diarrhea) and skin reactions 4, 7
• Higher incidence when combined with aminoglycosides versus monotherapy 4
• Most adverse effects are mild-to-moderate severity 7, 6

Serious Warnings:

• Discontinue immediately if: anaphylaxis, Stevens-Johnson syndrome, toxic epidermal necrolysis, progressive rashes, or signs of hemophagocytic lymphohistiocytosis occur 1
• Rhabdomyolysis: Monitor for signs/symptoms; discontinue if observed 1
• Hematologic effects: Monitor during prolonged therapy for bleeding, leukopenia, neutropenia 1
• Neuromuscular excitability/seizures: Higher risk with elevated doses, especially in renal impairment; closely monitor patients with seizure disorders 1
• Nephrotoxicity: Independent risk factor for renal failure in critically ill patients 1

Contraindications:

• History of allergic reactions to penicillins, cephalosporins, or beta-lactamase inhibitors 1

Spectrum of Activity

Piperacillin/tazobactam provides broad-spectrum coverage against:

• Most Gram-positive and Gram-negative aerobic bacteria 4
• Anaerobic bacteria 4
• Beta-lactamase-producing pathogens 4, 6
• Particularly effective for polymicrobial infections involving mixed aerobic-anaerobic flora 3, 4, 6

This makes it especially valuable for intra-abdominal infections, febrile neutropenia, and necrotizing soft tissue infections where polymicrobial etiology is common 4, 6.