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Drug Reference

piperacillin/tazobactam

penicillin/beta-lactamase inhibitor combination· Brands: Tazocin, ZosynIV

Mechanism of action
Piperacillin is a broad-spectrum penicillin that inhibits bacterial cell wall synthesis by binding to penicillin-binding proteins (PBPs). Tazobactam is a beta-lactamase inhibitor that protects piperacillin from degradation by many beta-lactamases, extending its spectrum to include some beta-lactamase-producing organisms. The combination has activity against many Gram-positive, Gram-negative, and anaerobic bacteria.
Pharmacokinetics
Piperacillin and tazobactam are both poorly absorbed orally, so they are given intravenously. After IV administration, both distribute widely into body fluids and tissues, including peritoneal fluid, bile, and urine. Piperacillin is metabolized to a minor degree, and tazobactam is metabolized to a single inactive metabolite. Both are eliminated primarily by the kidney, with piperacillin undergoing both glomerular filtration and tubular secretion. Tazobactam is also renally excreted. Dosage adjustments are needed in renal impairment.
Indications & dosing

Hospital-acquired pneumonia (including ventilator-associated pneumonia)

Severe infection: 4.5 g q6h; q8h may be used in less severe cases.

  • adult · IV: 4.5 g q6h · Severe infection: 4.5 g q6h; q8h may be used in less severe cases.

Community-acquired pneumonia (requiring IV therapy)

For severe CAP; if non-severe, 4.5 g q8h may be used.

  • adult · IV: 4.5 g q6h · For severe CAP; if non-severe, 4.5 g q8h may be used.

Complicated intra-abdominal infections

In combination with appropriate empirical antimicrobial therapy if local resistance is high.

  • adult · IV: 4.5 g q6h · In combination with appropriate empirical antimicrobial therapy if local resistance is high.

Complicated urinary tract infections (including pyelonephritis)

For severe infection, q6h may be used; adjust dose in renal impairment.

  • adult · IV: 4.5 g q8h · For severe infection, q6h may be used; adjust dose in renal impairment.

Complicated skin and soft tissue infections

For severe infections; q8h for moderate infections.

  • adult · IV: 4.5 g q6h · For severe infections; q8h for moderate infections.

Febrile neutropenia (empirical therapy)

Initial empirical therapy; adjust according to cultures.

  • adult · IV: 4.5 g q6h · Initial empirical therapy; adjust according to cultures.

Bacteraemia (empirical therapy)

Source control and de-escalate when possible.

  • adult · IV: 4.5 g q6h · Source control and de-escalate when possible.
Contraindications & precautions
  • Known hypersensitivity to penicillins or other beta-lactam antibiotics · Includes anaphylaxis, severe cutaneous reactions, or other type I hypersensitivity.
  • Known hypersensitivity to tazobactam or any component of the formulation · Cross-reactivity with other beta-lactams may occur.
  • History of severe allergic reaction to cephalosporins or other beta-lactams · Exercise caution; cross-reactivity is possible. Desensitisation may be considered if treatment essential.
  • Dose adjustment and monitoring of renal function are required in patients with moderate to severe renal impairment (creatinine clearance <40 mL/min).
  • Monitor serum electrolytes, particularly sodium, due to the high sodium content of piperacillin.
  • Use with caution in patients with a history of allergy to cephalosporins or other beta-lactams, as cross-reactivity may occur.
  • Monitor for signs of superinfection, particularly Clostridium difficile-associated diarrhoea, especially with prolonged therapy.
  • Caution in patients with a history of seizures or CNS disorders; dosages may need adjustment, especially in renal impairment.
Adverse effects
  • Diarrhoea
  • Nausea
  • Headache
  • Rash
  • Anaphylaxisserious
  • Pseudomembranous colitis (Clostridium difficile-associated diarrhoea)serious
  • Seizuresserious
  • Hepatotoxicity (elevated liver transaminases, cholestatic jaundice)serious
  • Acute kidney injury (interstitial nephritis)serious
  • Neutropenia and thrombocytopeniaserious
Renal & hepatic adjustment
  • eGFR 0–20: CrCl <20 mL/min: reduce dose to 2.25 g IV every 8 h.
  • eGFR 20–40: CrCl 20-40 mL/min: reduce dose to 3.375 g IV every 8 h.
  • eGFR 40+: CrCl >40 mL/min: no dose adjustment required.
Monitoring, pregnancy & toxicity
  • Renal function (serum creatinine, creatinine clearance) · At baseline and at least every 2-3 days in patients with renal impairment or prolonged therapy
  • Serum electrolytes (especially potassium) · Periodically during therapy
  • Blood counts (leukocytes, platelets) · Periodically, especially in prolonged therapy
  • Liver function tests (AST, ALT) · Baseline and periodically
  • Signs of anaphylaxis or hypersensitivity · During infusion
  • Signs of superinfection (e.g., candidiasis) · Throughout therapy
  • Pregnancy: Piperacillin/tazobactam is generally considered safe in pregnancy, with no evidence of teratogenicity in animal studies. It crosses the placenta. Use only if clearly indicated, and when the potential benefit outweighs the potential risk to the fetus.
  • Toxicity: Hypersensitivity reactions (e.g., rash, pruritus, anaphylaxis) · Withdraw the drug; treat anaphylaxis with adrenaline, antihistamines, and corticosteroids. Seek immediate specialist advice.
  • Toxicity: Clostridioides difficile-associated diarrhoea · Evaluate for C. difficile; discontinue piperacillin/tazobactam if possible; treat with oral vancomycin or fidaxomicin.
  • Toxicity: Neurotoxicity (e.g., seizures) at high doses or in renal impairment · Reduce dose or discontinue; consider valproate or benzodiazepines for seizures.
  • Toxicity: Hypokalaemia · Monitor serum potassium; supplement potassium chloride if needed.
Clinical notes
This combination is used for moderate to severe infections, including pneumonia, complicated urinary tract infections, intra-abdominal infections, and skin and soft tissue infections, particularly those caused by beta-lactamase-producing organisms. It is also used for febrile neutropenia when an anti-pseudomonal beta-lactam is needed. Doses are adjusted based on renal function. Common adverse effects include diarrhoea, nausea, headache, and rash. Hypersensitivity reactions are important, especially in patients with a history of penicillin allergy. Regional susceptibility patterns vary, so local guidelines should be consulted.

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BNF; local formulary