Antibiotics

Definition

  • Used for prophylaxis, open fractures, infection treatment and local delivery
  • Biofilm bacteria on implants resist antibiotics
  • Debridement or implant removal often needed

Classification

  • Time-dependent killing with beta-lactams and vancomycin
  • Concentration-dependent killing with aminoglycosides and quinolones

Penicillins

  • Bind penicillin-binding proteins and inhibit peptidoglycan cross-linking
  • Benzylpenicillin covers streptococci and clostridia, including gas gangrene
  • Flucloxacillin is beta-lactamase stable, first choice for MSSA, and can cause cholestatic jaundice
  • MRSA resists all beta-lactams except ceftaroline, as mecA encodes PBP2a
  • Penicillin and cephalosporin cross-reactivity is low, depending on side chain similarity

Cephalosporins

  • First generation (cefazolin) covers Gram-positives including MSSA and is the standard prophylactic agent
  • Third generation for Gram-negatives and gonococcal arthritis, ceftazidime for Pseudomonas
  • No activity against enterococci

Aminoglycosides

  • Bind the 30S subunit, bactericidal with a post-antibiotic effect
  • Cover aerobic Gram-negatives including Pseudomonas, no anaerobic activity
  • Synergistic with beta-lactams against staphylococci and enterococci
  • Nephrotoxicity, irreversible ototoxicity and neuromuscular blockade, reduced by once daily dosing and levels

Vancomycin

  • Binds D-alanyl-D-alanine, Gram-positive only, including MRSA and coagulase-negative staphylococci
  • Less effective than flucloxacillin or cefazolin against MSSA
  • Rapid infusion causes histamine flushing, nephrotoxicity is the main adverse effect

Quinolones

  • Oral bioavailability and bone penetration suit step-down, with rifampicin for staphylococcal implant infection
  • Achilles rupture, QT prolongation and aortic aneurysm

Management

Prophylaxis

  • Cefazolin within 60 minutes before incision and before tourniquet, weight-adjusted
  • Redose for long surgery or major blood loss, stop by 24 hours
  • Vancomycin for MRSA colonisation or immediate beta-lactam hypersensitivity, started earlier
  • Open fractures need antibiotics ideally within an hour of injury

Antibiotic loaded cement

  • Antibiotic must be heat stable, water soluble, powdered and broad spectrum
  • Gentamicin, tobramycin and vancomycin most used, liquid antibiotics weaken cement
  • Most elution occurs from the surface in the first days
  • Low dose premixed cement in primary arthroplasty lowers revision for infection on registry data
  • High dose hand-mixed cement for beads and spacers is too weak for definitive fixation
  • Large spacers risk renal toxicity

Reviewed by Professor Phong Tran, Head of Orthopaedic Surgery, Western Health. Last updated 10 October 2026.