Antibiotic · Beta-lactam · Penicillin
Piperacillin-tazobactam (Zosyn)
Also called Zosyn, pip-tazo, piperacillin
Indications
- Intra-abdominal infection, adults and children 2 months and up (label)
- Nosocomial pneumonia, 4.5 g every 6 h with an aminoglycoside, and moderate community-acquired pneumonia (label)
- Skin and skin-structure and female pelvic infections (label)
- Empiric sepsis therapy covering Pseudomonas, enteric gram-negative rods and anaerobes, often with vancomycin
- Extended or continuous infusion to lengthen time above the MIC (off-label)
Dosing
| Where | Dose |
|---|---|
| Antimicrobials | Piperacillin-tazobactam: Reduce at CrCl under 40; extended infusion common |
On the quick cards
- Sepsis, source unknownEmpiric Antibiotics: Broad coverage until the source declares itself
- AntimicrobialsRenal Dosing: Adjust, or no change
Mechanism of action
Piperacillin is a ureidopenicillin that inhibits cell-wall synthesis (label) by binding penicillin-binding proteins and blocking peptidoglycan cross-linking; like other beta-lactams it kills in proportion to the time its level stays above the MIC. Tazobactam has little activity of its own but inhibits Ambler class A beta-lactamases, with variable activity against others (label), protecting piperacillin from many penicillinases and ESBLs. It does not induce chromosomal beta-lactamases at recommended doses (label), and it inhibits AmpC poorly.
Pharmacology
- Infectious: ceftriaxone-resistant E. coli or Klebsiella bacteremia had 30-day mortality 12.3% vs 3.7% with meropenem (MERINO 2018), so carbapenems are preferred for ESBL bloodstream infection
- Renal: slower renal recovery than other beta-lactams in critically ill patients, and more AKI with vancomycin (label); stage 3 AKI 7.5% vs 7.0% with cefepime (ACORN 2023)
- GI: diarrhea 11.3% (label); C. difficile
- CNS: neuromuscular excitability or seizures with high doses or renal impairment (label)
- Hematologic: bleeding with abnormal clotting tests, leukopenia and neutropenia with long courses (label)
Pharmacokinetics
| Half-life | 0.7–1.2 h for both (label) |
|---|---|
| Protein binding | About 30% each (label) |
| Metabolism | Piperacillin to a minor active desethyl metabolite; tazobactam to one inactive metabolite (label) |
| Elimination | Urine: 68% of piperacillin and 80% of tazobactam unchanged (label) |
| Renal dosing | CrCl 20–40: 2.25 g every 6 h; under 20: every 8 h; higher for nosocomial pneumonia (label) |
| Dialysis | Hemodialysis removes 30–40%: 2.25 g every 12 h plus 0.75 g after each session (label) |
| Infusion | Over 30 min per label; 4-h extended infusion off-label |
Chemistry
- Piperacillin: derived from ampicillin, with a 4-ethyl-2,3-dioxopiperazine carboxamido side chain that extends gram-negative and Pseudomonas activity; sodium salt C₂₃H₂₆N₅NaO₇S, MW 539.5 (label)
- Tazobactam: a penicillanic acid sulfone with a triazole group; sodium salt MW 322.3; fixed 8:1 ratio (label)
- Sodium 2.84 mEq (65 mg) per gram of piperacillin, 11.17 mEq per 4.5 g dose (label)
Adverse effects and cautions
In the one-pagers
- Acute Kidney InjuryNephrotoxins and ICU causes: Adding piperacillin-tazobactam raises creatinine, partly pseudo-AKI; ACORN 2023 found no AKI difference vs cefepime
- Bleeding, Reversal, HIT and DICThrombocytopenia in the ICU, including ITP: Common drug culprits: vancomycin, piperacillin and other β-lactams, TMP-SMX, quinine, carbamazepine, phenytoin; GP IIb/IIIa inhibitors can drop counts within hours. ITP is a diagnosis of exclusion; ASH 2019 suggests treating newly diagnosed adults with platelets under 30,000, using prednisone (no more than 6 weeks) or dexamethasone 40 mg daily for 4 days
- CEN Pediatric Emergencies: Ingestions, GI, Head Injury and FracturesIntussusception, malrotation and Hirschsprung enterocolitis: Most neonates pass meconium within 24 h; most with Hirschsprung disease have not passed it by 48 h (Merck). Up to 20% of term infants with the disease develop Hirschsprung-associated enterocolitis, mostly before surgery but also in the first year after: fever (temperature instability in neonates), distension, explosive or bloody diarrhea
- CEN: Genitourinary, Gynecologic and Early-Pregnancy EmergenciesUTI, pyelonephritis and special groups: Empiric choice (IDSA 2025): Third- or fourth-generation cephalosporin, piperacillin-tazobactam or fluoroquinolone; avoid a drug the last isolate resisted and fluoroquinolones after use in the past 12 months; narrow to the culture
- CEN: Musculoskeletal and Wound EmergenciesSoft-tissue infection in depth: Empiric antibiotics: vancomycin or linezolid plus piperacillin-tazobactam or a carbapenem, or ceftriaxone plus metronidazole. For documented group A streptococci, penicillin plus clindamycin: clindamycin suppresses streptococcal toxin and cytokine production, and penicillin stays alongside it for reliable streptococcal coverage. Continue antibiotics until no further
- Oncologic EmergenciesNeutropenic fever: Antipseudomonal β-lactam within 60 min of triage (ASCO/IDSA 2018): cefepime, piperacillin-tazobactam or meropenem
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Sources
- FDA label: Zosyn in Galaxy containers (Pfizer, 2022)
- Harris 2018 (MERINO trial)
- Qian 2023 (ACORN trial)
For education and exam preparation only. Follow your institution’s protocols. Typical adult values for study. Follow the order, the label and your institution's protocols.