Antibiotic Therapy for Musculoskeletal Infections

Mechanism

Antibiotics are categorised according to their mechanism of action, namely:

  1. cell wall active
  2. ribosomal active
  3. RNA active
  4. DNA active
  5. antimetabolites
  6. reducing compounds

Cell Wall Active Antibiotics

Penicillins

  • Active against
    • S. pyogenes, S. agalactiae
    • Good anaerobic spectrum = Clostridia except Bacteroides
    • Increasing resistance from S. pneumoniae
  • Side effects
    • Hypersensitivity reactions namely anaphylaxis, bronchospasm, hives
    • Potential interstitial nephritis, Coombs positive haemolytic anaemia
  • Parenteral penicillinase resistant penicillins
    • methicillin, nafcillin, isoxazolyl penicillins (flucloxacillin, dicloxacillin, cloxacillin) are resistant to Staph beta lactamase
  • Aminopenicillins = ampicillin, amoxycillin
    • Active against Enterococci & highly susceptible E. coli + Proteus
    • Not stable to beta lactamase
  • Ticarcillin
    • Active against Pseudomonas, Enterobacter, Serratia but not Klebsiella
    • Side effect of platelet dysfunction
  • Extended spectrum penicillins = piperacillin + mezlocillin
    • Act in synergy with aminoglycosides against Pseudomonas

Beta Lactamase Inhibitors

  • Clavulanic acid, sulbactam, tazobactam inhibit beta lactamase produced by
  • gram positives notably S. aureus + S. epi
  • gram negatives namely E. coli, most Klebsiella + Bacteroides
  • Beta lactamase is situated in periplasmic space & is chromosome + plasmid induced
  • Clavulanic acid + amoxycillin = Augmentin
  • Clavulanic acid + Ticarcillin = Timentin
  • Tazobactam + piperacillin = Zosyn

Cephalosporins

Divided into generations

GenerationAgentsActivity
1stCephalothin, cefazolin, cephapirinStaph aureus, Staph epidermidis and streptococci, limited gram negative cover. Cefazolin has the longest half life of the group
2ndCefoxitin, cefotetan, cefuroximeAnaerobes and, to a lesser extent, gram negatives
3rdCeftriaxone, cefotaxime, ceftazidimeBeta lactamase resistant, gram positives (except enterococci) and Enterobacter
4thCefepimeGram positives and Pseudomonas
  • Generally safe, with occasional rash, phlebitis and diarrhoea
  • 3 to 7% cross reactivity in penicillin allergic patients
  • Type 1 immediate hypersensitivity with bronchospasm, hives or rash
  • Coombs positive anaemia in 3%
  • Abnormal liver function tests in 1 to 7%
  • Antibiotic associated colitis

Other Beta Lactam Antibiotics

  • Aztreonam iv use only, active against Enterobacter + Pseudomonas
  • Imipenem active against S. aureus, S. epi, Strep

Vancomycin

  • Antibiotic of choice in penicillin + cephalosporin allergy
  • Active against S. aureus, MRSA, S. epi, Enterococci
  • Vancomycin resistant Enterococci (VRE) reported
  • Adverse effects
  • Red man syndrome = head + neck + trunk flushing & hypotension when infusion given over <1 hour
  • Nephrotoxicity, ototoxicity, neutropaenia, thrombocytopaenia

Ribosomal Active Antibiotics

Clindamycin

  • Active against
    • Bacteroides but not Clostridia (except C. perfringens)
    • S. aureus, coagulase negative Staph, Strep
  • Good bone + abscess penetration
  • Adverse effects = diarrhoea + pseudomembranous colitis in 8% (C. difficile)

Macrolides

  • Erythromycin, clarithromycin, roxythromycin work at ribosomal level & are bacteriostatic
  • Active against Strep, Mycoplasma, Listeria, Legionella, Chlamydia
  • Adverse effects = generally safe but GIT upset
  • Induces hepatic cytochrome P450 complexes = ↑drug metabolism

Tetracyclines

  • 3 groups
  • short acting = tetracycline
  • intermediate acting = demeclocycline
  • long acting = doxycycline, minocycline (minocycline + rifampicin for MRSA)
  • Active against uncommon diseases mycoplasma, rickettsia, Lyme disease
  • Adverse effects = GIT upset, hepatotoxicity, teeth discolouration, photosensitivity

Aminoglycosides

  • Gentamicin, tobramycin, amikacin, netilmicin
  • Active against aerobic gram negatives
  • Adverse effects = nephrotoxicity, ototoxicity (hearing loss, tinnitus, vestibular problems, gait disturbance)

RNA Active Antibiotics (Rifampicin)

  • Most active antistaphylococcal agent known
  • Rifampicin alone rapidly produces rifampicin resistant subpopulation
  • Fusidic acid or cotrimoxazole or minocycline + rifampicin for MRSA
  • Adverse effects = orange body fluids, GIT upset, hepatitis
  • Must be taken on empty stomach
  • Induces hepatic microsomal enzymes

DNA Active Antibiotics (Fluoroquinolones)

  • 2nd generation quinolones = ciprofloxacin active against gram negatives. No activity against Strep + anaerobes
  • Oral ciprofloxacin provides excellent serum concentrations
  • Adverse effects = tendonitis with Achilles tendon rupture, photosensitivity but overall toxicity is low

Antimetabolites

  • Cotrimoxazole is active against gram negatives
  • Adverse effects = GIT upset, acute haemolytic anaemia, aplastic anaemia, thrombocytopaenia, hypersensitivity (erythema multiforme + nodosum, urticaria)

Reducing Compounds (Metronidazole)

  • Lead to toxic free radical formation
  • Active against all anaerobes (anaerobes lack protective superoxide dismutase + catalase)
  • Good absorption + tissue penetration
  • Adverse effects = metallic taste, pseudomembranous colitis, disulfiram reaction with alcohol

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