What is Zosyn (Piperacillin-Tazobactam) Used to Treat?
Zosyn is a broad-spectrum beta-lactam/beta-lactamase inhibitor combination used to treat moderate-to-severe bacterial infections including intra-abdominal infections, nosocomial pneumonia, skin and soft tissue infections, complicated urinary tract infections, female pelvic infections, community-acquired pneumonia, and febrile neutropenia. 1
FDA-Approved Indications
Intra-Abdominal Infections
- Appendicitis complicated by rupture or abscess and peritonitis caused by beta-lactamase producing Escherichia coli or Bacteroides fragilis group organisms 1
- Effective for polymicrobial intra-abdominal infections with aerobic and anaerobic bacteria 2
- The 2017 World Society of Emergency Surgery guidelines recommend piperacillin/tazobactam as an option for severe intra-abdominal infections due to its broad-spectrum activity including anti-Pseudomonas effect and anaerobic coverage 3
Nosocomial Pneumonia
- Moderate-to-severe nosocomial pneumonia caused by beta-lactamase producing Staphylococcus aureus, Acinetobacter baumannii, Haemophilus influenzae, Klebsiella pneumoniae, and Pseudomonas aeruginosa 1
- Critical caveat: When P. aeruginosa is suspected or confirmed, Zosyn must be combined with an aminoglycoside 1, 3
- Dosing for nosocomial pneumonia is higher: 4.5 grams every 6 hours (totaling 18 grams daily) for 7-14 days 1
Skin and Soft Tissue Infections
- Uncomplicated and complicated skin infections including cellulitis, cutaneous abscesses, and ischemic/diabetic foot infections caused by beta-lactamase producing S. aureus 1
- Effective for polymicrobial skin infections involving both aerobic and anaerobic organisms 4
Female Pelvic Infections
- Postpartum endometritis and pelvic inflammatory disease caused by beta-lactamase producing E. coli 1
- Effective for gynecological infections with mixed aerobic-anaerobic flora 2
Community-Acquired Pneumonia
- Moderate severity community-acquired pneumonia caused by beta-lactamase producing H. influenzae 1
- Clinical trials demonstrated superior efficacy compared to ticarcillin/clavulanic acid for community-acquired pneumonia 2
Complicated Urinary Tract Infections
- Pyelonephritis and complicated UTIs with 86% cure/improvement rates in clinical trials 5
- Most commonly treats E. coli (47% of cases), P. aeruginosa (13%), and enterococci (8%) 5
Febrile Neutropenia
- Empiric treatment of febrile episodes in neutropenic patients, particularly when combined with an aminoglycoside 2, 6
- Significantly more effective than ceftazidime plus amikacin for empirical treatment of febrile neutropenia 2
Standard Dosing Regimens
For Most Infections (Non-Pneumonia)
- 3.375 grams every 6 hours (totaling 13.5 grams daily) administered by IV infusion over 30 minutes 1
- Duration: 7-10 days for most infections 1
For Nosocomial Pneumonia
- 4.5 grams every 6 hours (totaling 18 grams daily) plus an aminoglycoside, administered by IV infusion over 30 minutes 1
- Duration: 7-14 days 1
Optimized Administration in Critical Illness
- Extended or continuous infusions are recommended in critically ill patients to improve clinical outcomes 3
- Continuous infusion preceded by a loading dose achieves superior pharmacodynamic targets compared to intermittent boluses 3
- Particularly beneficial in patients with APACHE II scores ≥15-17 or SOFA scores ≥9 3
Antimicrobial Spectrum
Gram-Negative Coverage
- Broad activity against Enterobacteriaceae including E. coli, Klebsiella, and Proteus 2, 4
- Anti-pseudomonal activity against P. aeruginosa at lower concentrations than carbenicillin or ticarcillin 7
- Retains activity against broad-spectrum beta-lactamase-producing Enterobacteriaceae 4
Gram-Positive Coverage
- Active against methicillin-susceptible S. aureus (MSSA) 1, 2
- Does not cover methicillin-resistant S. aureus (MRSA) or penicillinase-producing staphylococci 7
Anaerobic Coverage
- Excellent activity against Bacteroides fragilis group and Clostridium difficile 7
- Provides comprehensive anaerobic coverage without requiring metronidazole 3
Critical Clinical Considerations
When to Use Combination Therapy
- Always combine with an aminoglycoside for nosocomial pneumonia caused by P. aeruginosa 1
- Combination therapy recommended for critically ill patients with septic shock, profound neutropenia, or suspected P. aeruginosa infection 6
- Monotherapy is appropriate for hemodynamically stable patients with community-acquired infections 6
Resistance Limitations
- Controversial use in ESBL-producing organisms, though may be effective in stable patients 3
- Not active against AmpC beta-lactamase-producing organisms 4
- Not effective against carbapenem-resistant Enterobacteriaceae 3
- Fluoroquinolone resistance patterns may make Zosyn preferable in many geographic regions 3
De-escalation Strategy
- Switch to narrower-spectrum oral agents at 48-72 hours once culture results confirm susceptibility and clinical stability is achieved 6
- Discontinue aminoglycoside after 3-5 days once clinical improvement is evident 6
- Oral fluoroquinolones (ciprofloxacin 750 mg twice daily or levofloxacin 750 mg daily) are appropriate de-escalation options for susceptible organisms 6
Important Safety Considerations
Nephrotoxicity Risk
- Zosyn combined with vancomycin (Z+V) carries significantly higher risk of acute kidney injury compared to alternative gram-negative agents plus vancomycin (risk ratio 1.79) 8
- This risk is particularly elevated in ICU populations 8
- Consider cefepime plus vancomycin as an alternative when nephrotoxicity is a concern 8
Tolerability Profile
- Generally well tolerated with low frequency of toxicity 7
- Most common adverse events are gastrointestinal symptoms (especially diarrhea) and skin reactions 2
- Higher incidence of adverse events when combined with aminoglycosides compared to monotherapy 2