Piperacillin–Tazobactam
1️⃣ Introduction
Piperacillin–Tazobactam (PIPTAZ) is a broad-spectrum β-lactam/β-lactamase inhibitor combination It combines:
- Piperacillin → Extended-spectrum ureidopenicillin
- Tazobactam → β-lactamase inhibitor
Important:
It does NOT cover:
- ESBL-producing organisms
- AmpC β-lactamases (Enterobacter, Serratia)
- Carbapenemases (KPC, NDM)
3️⃣ Spectrum of Activity
Gram-Positive Coverage
- Streptococcus spp.
- Enterococcus faecalis (not E. faecium)
- MSSA (but not MRSA)
Gram-Negative Coverage
- Enterobacteriaceae (non-ESBL)
- Pseudomonas aeruginosa
- Haemophilus influenzae
- Neisseria spp.
Anaerobic Coverage
- Bacteroides fragilis
- Clostridium spp.
No coverage:
- MRSA
- VRE
- ESBL organisms
- Atypicals
Clinical Indications
Severe Sepsis / Septic Shock
Empiric therapy for:
- Intra-abdominal sepsis
- Urosepsis
- Biliary sepsis
Hospital-Acquired Pneumonia (HAP) / Ventilator-Associated Pneumonia (VAP)
- Anti-pseudomonal coverage
Febrile Neutropenia-Monotherapy option
Diabetic Foot Infection-Polymicrobial coverage
5️⃣ Pharmacokinetics
|
Parameter |
Value |
|
Route |
IV only |
|
Elimination |
Renal (glomerular filtration + tubular secretion) |
|
CSF penetration |
Poor (unless inflamed meninges) |
Time-dependent killing → efficacy depends on %T>MIC
Extended Infusion 3–4 hours every 6 hours Preferred in ICU
Why?
- Maximizes %T>MIC
- Better outcomes in severe sepsis
- Especially useful for Pseudomonas
Continuous Infusion Strategy
Used in:
- Septic shock
- High MIC organisms
7️⃣ Renal Dose Adjustment needed
8️⃣ Adverse Effects
Common
- Diarrhea
- Rash
- Nausea
🔴 Acute Kidney Injury (AKI)
- Especially when combined with vancomycin
- Risk higher than vancomycin alone
🔴 Electrolyte disturbances
- Hypokalemia
🔴 Hematologic
- Thrombocytopenia
- Neutropenia (prolonged use)
🔴 Neurotoxicity
- Seizures (rare; high dose + renal failure)