Extended-spectrum Beta-lactam / Beta-lactamase Inhibitor Pregnancy: Use only if clearly necessary — beta-lactams generally considered low risk in pregnancy

Piperacillin-Tazobactam (Polymicrobial Open Fracture Infections)

Brand names: Tazocin

Adult dose

Dose: 4.5 g IV every 6–8 hours

Route: Intravenous infusion over 30 minutes

Frequency: Every 6–8 hours

Max: 18 g/day (4.5 g every 6 hours for severe infections)

Reserve for heavily contaminated open fractures (Gustilo-Anderson type III) with polymicrobial contamination, established infection with MDR Gram-negative involvement, or where co-amoxiclav is inadequate. Extended infusion (4-hour infusion) improves pharmacodynamic target attainment for Pseudomonas with raised MIC.

Paediatric dose

Dose: 90 mg/kg

Route: IV

Frequency: Every 6–8 hours

Max: 4.5 g every 6 hours

Paediatric severe polymicrobial bone and soft tissue infections — specialist guidance; neonates: different dosing schedule (piperacillin component)

Dose adjustments

Renal

eGFR 20–40 mL/min: 4.5 g every 8 hours; eGFR <20 mL/min: 4.5 g every 12 hours; haemodialysis: supplemental dose after session

Hepatic

No dose adjustment required for hepatic impairment alone

Paediatric weight-based calculator

Patient weight (kg)

Paediatric severe polymicrobial bone and soft tissue infections — specialist guidance; neonates: different dosing schedule (piperacillin component)

Clinical pearls

Gustilo-Anderson classification: type III open fractures (extensive soft tissue damage, contamination) are at highest risk of polymicrobial infection including Pseudomonas aeruginosa — piperacillin-tazobactam covers most relevant pathogens including Pseudomonas
SMART/MERINO trial (NEJM 2018): piperacillin-tazobactam was inferior to meropenem for definitive treatment of Escherichia coli or Klebsiella ESBL-producing bacteraemia — for ESBL-E: use meropenem not piperacillin-tazobactam even if susceptibility testing shows sensitive
Hypokalaemia monitoring: piperacillin acts as a non-reabsorbable anion in the distal nephron, causing kalaemia loss — monitor potassium daily in prolonged high-dose courses; supplement if K+ <3.5 mmol/L
Incompatibility: piperacillin-tazobactam physically and chemically incompatible with aminoglycosides — must NOT be mixed in same infusion bag; administer separately through different IV lines or at different times
Antimicrobial stewardship: piperacillin-tazobactam is a Watch-category antibiotic (WHO AWaRe) — requires prescribing justification; involve microbiology for courses beyond initial empirical treatment

Contraindications

Penicillin hypersensitivity
Glandular fever / EBV (rash risk)

Side effects

C. difficile diarrhoea — broad spectrum disrupts gut flora significantly
Hypokalaemia — piperacillin chelates potassium; monitor K+ in high-dose prolonged use
Hyponatraemia — high sodium load (each 4.5 g contains ~54 mg sodium)
Elevated LFTs
Thrombocytopenia — rare
Hypersensitivity reactions

Interactions

Methotrexate — penicillins reduce renal tubular secretion; MTX toxicity risk
Warfarin — vitamin K-producing gut flora reduction; monitor INR
Aminoglycosides (tobramycin, gentamicin) — synergistic against Pseudomonas; however, DO NOT mix in same IV bag — physicochemical incompatibility; give through separate lines

Monitoring

Serum potassium daily (hypokalaemia risk)
Serum sodium (high sodium load)
Renal function
LFTs
C. difficile if diarrhoea develops

Reference: BNFc; BNF 90; MERINO Trial (NEJM 2018); BOAST Open Fracture Guidelines 2017; WHO AWaRe Classification; SPC Tazocin. Verify against your local formulary and the latest BNF before prescribing.

Curated clinical cross-links plus same-class fallbacks.

Calculators

Pathways