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

Zosyn (Piperacillin/Tazobactam) Treatment Guidelines

Recommended Dosing

For most bacterial infections in adults, administer piperacillin/tazobactam 3.375 g IV every 6 hours (totaling 13.5 g daily) infused over 30 minutes for 7-10 days. 1

Standard Adult Dosing by Indication

• Intra-abdominal infections (appendicitis, peritonitis): 3.375 g IV every 6 hours for 7-10 days 1
• Skin and soft tissue infections (cellulitis, diabetic foot infections): 3.375 g IV every 6 hours for 7-10 days 1, 2
• Community-acquired pneumonia: 3.375 g IV every 6 hours for 7-10 days 1
• Complicated urinary tract infections: 3.375 g IV every 6 hours for 7-10 days 1
• Female pelvic infections: 3.375 g IV every 6 hours for 7-10 days 1

High-Dose Regimen for Nosocomial Pneumonia

For nosocomial pneumonia, use 4.5 g IV every 6 hours (totaling 18 g daily) plus an aminoglycoside for 7-14 days. 1, 2

• This higher dose is specifically indicated for moderate to severe hospital-acquired pneumonia 1
• Continue aminoglycoside therapy if Pseudomonas aeruginosa is isolated 1
• The Infectious Diseases Society of America supports this dosing for patients at high risk of mortality 2

Severe Necrotizing Infections

For necrotizing fasciitis and severe polymicrobial infections, administer piperacillin/tazobactam 3.37 g IV every 6-8 hours in combination with vancomycin. 3

• This combination provides coverage for both aerobic-anaerobic polymicrobial infections and community-acquired MRSA 3
• Pediatric dosing: 60-75 mg/kg/dose of the piperacillin component every 6 hours IV 3

Pediatric Dosing (≥2 Months of Age)

For Children Weighing ≤40 kg

• Ages 2-9 months: 90 mg/kg (80 mg piperacillin/10 mg tazobactam) every 8 hours for appendicitis/peritonitis; every 6 hours for nosocomial pneumonia 1
• Ages >9 months: 112.5 mg/kg (100 mg piperacillin/12.5 mg tazobactam) every 8 hours for appendicitis/peritonitis; every 6 hours for nosocomial pneumonia 1
• Children >40 kg: Use adult dosing 1

Alternative Pediatric Dosing from Guidelines

• General pediatric infections: 100-300 mg/kg/day IV divided into 3-4 doses, maximum 24,000 mg/day 3
• Neonatal dosing (postmenstrual age ≥30 weeks): 100 mg/kg/dose IV every 8 hours 3
• Neonatal dosing (postmenstrual age >30 weeks): 80 mg/kg/dose IV every 6 hours 3

Renal Dose Adjustments

Reduce dosing based on creatinine clearance to prevent drug accumulation. 1

Creatinine Clearance	Standard Infections	Nosocomial Pneumonia
>40 mL/min	3.375 g every 6 hours	4.5 g every 6 hours
20-40 mL/min	2.25 g every 6 hours	3.375 g every 6 hours
<20 mL/min	2.25 g every 8 hours	2.25 g every 6 hours
Hemodialysis	2.25 g every 12 hours + 0.75 g after each dialysis	2.25 g every 8 hours + 0.75 g after each dialysis
CAPD	2.25 g every 12 hours	2.25 g every 8 hours

1

Clinical Indications and Spectrum

FDA-Approved Indications

Piperacillin/tazobactam is approved for infections caused by beta-lactamase producing organisms including: 1

• Intra-abdominal: E. coli, B. fragilis group (including B. fragilis, B. ovatus, B. thetaiotaomicron, B. vulgatus) 1
• Nosocomial pneumonia: S. aureus, A. baumannii, H. influenzae, K. pneumoniae, P. aeruginosa 1
• Skin/soft tissue: S. aureus (including diabetic foot infections, cellulitis, cutaneous abscesses) 1
• Pelvic infections: E. coli (postpartum endometritis, pelvic inflammatory disease) 1
• Community-acquired pneumonia: H. influenzae 1

Guideline-Supported Uses

• Severe non-purulent cellulitis: Combine with vancomycin or linezolid for MRSA coverage 3, 2
• Necrotizing infections: Use with vancomycin for polymicrobial necrotizing fasciitis 3
• Complicated intra-abdominal infections: Particularly for nosocomial infections or Pseudomonas risk 2

Treatment Duration

• Skin and soft tissue infections: 5-10 days, extend if inadequate improvement 2
• Intra-abdominal infections: 5-7 days after adequate source control 2
• Nosocomial pneumonia: 7-14 days 2, 1
• Standard infections: 7-10 days 1

Safety Profile

Piperacillin/tazobactam is generally well tolerated with predominantly mild-to-moderate adverse effects. 4, 5

Common Adverse Events

• Gastrointestinal: Diarrhea is the most frequent adverse event 4, 5
• Dermatologic: Allergic skin reactions 5
• Laboratory abnormalities: Liver function test elevations are the most common laboratory changes 5

Important Safety Considerations

• Higher incidence of adverse events when combined with aminoglycosides compared to monotherapy 4
• Withdrawal rate due to adverse effects is low (approximately 3-4% in clinical trials) 5
• Safety profile comparable to other beta-lactam/beta-lactamase inhibitor combinations 5

Antimicrobial Stewardship

Reserve piperacillin/tazobactam for moderate to severe infections requiring broad-spectrum coverage. 2

• For less severe community-acquired infections, narrower spectrum agents are more appropriate 2
• Particularly valuable for polymicrobial infections involving aerobic and anaerobic beta-lactamase-producing bacteria 4, 6
• Consider de-escalation based on culture results and susceptibility testing 3

Clinical Efficacy Data

• Intra-abdominal infections: 86% cure/improvement rate in complicated UTI/pyelonephritis studies 7
• Skin and soft tissue infections: 93% clinical cure/improvement in European studies; 76% in more stringent US trials including diabetic foot infections 8
• Nosocomial pneumonia: Superior to ceftazidime when combined with aminoglycosides 6
• Febrile neutropenia: Superior to ceftazidime plus amikacin when combined with amikacin 4, 6