ceftolozane-tazobactam
Brand: Zerbaxa
Prototype: ceftazidime-avibactam
Drug Class: beta-lactam/beta-lactamase inhibitor combination
Drug Family: antibiotic
Subclass: novel anti-pseudomonal beta-lactam/BLI
Organ Systems: infectious-disease
Mechanism of Action
Ceftolozane binds multiple PBPs of Pseudomonas aeruginosa with high affinity; tazobactam is a beta-lactamase inhibitor that expands coverage to ESBL-producing organisms; uniquely potent against multidrug-resistant Pseudomonas.
penicillin-binding proteins (PBPs)AmpC/ESBL beta-lactamases
Indications
- complicated UTI due to MDR Pseudomonas
- complicated intra-abdominal infection (with metronidazole)
- hospital-acquired/VAP due to MDR Pseudomonas
Contraindications
- cephalosporin or penicillin hypersensitivity
Adverse Effects
Common
- nausea
- headache
- diarrhea
- elevated LFTs
Serious
- C. difficile colitis
- anaphylaxis
- renal impairment
- atrial fibrillation (rare)
Pharmacokinetics (ADME)
| Absorption | IV only |
| Distribution | widely distributed; both components have similar Vd |
| Metabolism | minimal; tazobactam undergoes hydrolysis to inactive M1 metabolite |
| Excretion | renal (ceftolozane ~95% unchanged; tazobactam mainly as M1 metabolite) |
| Half-life | ceftolozane 3 h; tazobactam 1 h |
| Onset | immediate (IV) |
| Peak | end of 1-hour infusion |
| Duration | 8 hours |
| Protein Binding | ceftolozane 16–21%; tazobactam 30% |
| Vd | moderate |
Drug Interactions
| Drug / Agent | Mechanism | Severity |
|---|---|---|
| nephrotoxic agents | additive nephrotoxicity | moderate |
Nursing Considerations
- Administer IV over 60 minutes (standard dose) or 3 hours (extended infusion) to optimize pharmacodynamic target attainment against MDR Pseudomonas.
- Renal dose adjustment is critical; monitor CrCl closely and adjust doses accordingly — underdosing leads to treatment failure against Pseudomonas.
- Obtain cultures and sensitivities before initiating therapy; this agent is reserved for MDR or extensively drug-resistant Pseudomonas.
- Monitor hepatic enzymes and renal function throughout course.
Clinical Pearls
- Ceftolozane-tazobactam is active against many MDR Pseudomonas aeruginosa strains but does NOT have activity against Klebsiella pneumoniae carbapenemases (KPC); ceftazidime-avibactam is preferred for KPC producers.
- Extended infusion (3-hour infusion) increases the pharmacodynamic target attainment for pathogens with higher MICs, a strategy used for severe Pseudomonas infections.
Safety Profile
Pregnancy insufficient-data
Lactation use-with-caution
Renal Adjustment Required
Hepatic Adjustment Not required
TDM Not required
Guideline Update pending
Concordance Terms
Cross-referenced clinical concepts — click any term to see all content where it appears.