Antibiotics and infection

Infection and Antibiotics

Inflammation

Acute Inflammation

  • Increased vascular permeability leading to the migration of:
    • Neutrophils initially.
    • Monocytes later.
  • Phagocytosis: These cells phagocytose foreign material.
  • Leucocytes: Minimal in acute infection.

Chronic Infection

  • Causes:
    • Resistant organisms exhibiting a low-grade immune reaction.
    • Persistent non-degradable toxins (e.g., silica).
    • Immune-mediated reactions.
  • Predominant cells:
    • Mononuclear cells:
      • Macrophages (the main cell).
      • Lymphocytes.
      • Plasma cells.
    • Fibroblasts.
    • Eosinophils (in immune reactions).

Macrophage Stimulation

  • Two mechanisms:
    1. Secretion of gamma interferon by T cells (lymphocytes).
    2. Secretion of endotoxin by microbes.

Consequences of Chronic Macrophage Activity

  • Secretion of multiple growth factors and proteases:
    • Leads to tissue destruction, neovascularisation, and fibroblast proliferation.
    • Stimulation of lymphocytes further increases gamma interferon production, creating a vicious cycle that stimulates macrophages.

Bacteriology

Bacterial Characteristics

  • Prokaryotic: Bacteria have no nucleus.
  • No mitochondria or lysosomes.
  • They do have a cell wall.

Gram Staining

  • Based on the ability of bacterial cell walls to retain stains.
    • Gram-positive bacteria: Retain blue stain (crystal violet idium).
    • Gram-negative bacteria: Retain pink stain (safranin).

Bacterial Shapes

  • Cocci: Spherical bacteria.
  • Bacilli: Rod-shaped bacteria.

Bacteriology of Periprosthetic Infections

Staphylococcus Species

  • Staphylococcus Aureus:
    • Coagulase-positive.
    • Produces fibrin from fibrinogen, promoting clotting and protecting against phagocytosis, making it very virulent.
  • Staphylococcus Epidermidis:
    • Coagulase-negative, generally less virulent.
    • However, in the presence of a Biofilm, its virulence increases.

Glycocalyx and Biofilm

  • Glycocalyx:
    • A protective layer (protein or polysaccharide) secreted by bacteria.
    • Provides resistance to phagocytosis and enhances adhesion to foreign materials (e.g., metal implants).
  • Biofilm:
    • A community of bacteria encased in a glycocalyx.
    • More resistant to phagocytosis and better at adhering to foreign materials.
    • Biofilm formation takes around 4 weeks.

MRSA (Methicillin Resistant Staphylococcus Aureus)

  • MRSA is a strain of Staphylococcus Aureus resistant to Beta-Lactam antibiotics, including Methicillin.
  • Resistance:
    • MRSA produces a penicillin-binding protein that reduces the action of antibiotics.
    • MRSA is not necessarily more virulent but much harder to treat due to its resistance.

Antibiotics

Beta-Lactam Antibiotics

  • Bactericidal: Inhibit bacterial cell wall synthesis by binding to penicillin-binding proteins (PBPs).
  • Examples:
    • Penicillins.
    • Cephalosporins (4 generations):
      • 1st Generation: Cephazolin.
      • 2nd Generation: Cefuroxime.
      • 3rd Generation: Ceftriaxone.
      • 4th Generation: Cefpirone.

Co-Amoxiclav

  • A combination of penicillin and a beta-lactamase inhibitor (clavulanic acid) that prevents beta-lactamase from deactivating the antibiotic.

Aminoglycosides

  • Bactericidal: Inhibit protein synthesis by binding to the 30S subunit of ribosomal RNA.
  • Predominantly effective against Gram-negative bacteria.
  • Examples: Gentamicin, Tobramycin.

Macrolides

  • Inhibit protein synthesis by binding to the 50S subunit of ribosomal RNA.
  • Examples: Erythromycin, Clindamycin.

Quinolones

  • Inhibit DNA gyrase.
  • Example: Ciprofloxacin.

Glycopeptides

  • Inhibit cell wall synthesis.
  • Provide good coverage for both Gram-positive and Gram-negative bacteria.
  • Examples: Teichoplanin, Vancomycin.

Rifampicin

  • Bactericidal: Inhibits RNA transcription.

Tetracyclines

  • Bacteriostatic: Inhibit protein synthesis by binding to the 30S subunit of ribosomal RNA.
  • Examples: Tetracycline, Doxycycline.

Antibiotic Use in Specific Situations

Prophylaxis

  • Administered within 1 hour of the incision.
  • Limited to 24 hours to prevent resistance.
  • Typically, 1st generation cephalosporins (e.g., Cephazolin) are used, particularly when hardware is involved.

Open Fractures (BAPRAS Guidelines)

  • Augmentin 1.2g IV 8-hourly or Cefuroxime 1.5mg 8-hourly until the wound is closed or up to 72 hours max.
  • If using Cefuroxime, add Gentamicin during debridement.
  • For penicillin-allergic patients, use Clindamycin 600mg QDS.
  • In gross contamination, consider adding Metronidazole.

Chronic Infection

  • Commonly caused by Staphylococcus Aureus or Staphylococcus Epidermidis in hardware-related cases.
  • Biofilm and glycocalyx formation require antibiotics with good bone penetration.
  • Clindamycin is recommended for osteomyelitis.

Antibiotic Resistance

Modes of Resistance

  1. Intrinsic Resistance:
    • Due to structural or metabolic properties that make bacterial cell walls resistant.
  2. Acquired Resistance:
    • Occurs when resistant strains develop from previously sensitive populations, mediated by plasmids and transposons.

Typical Bacteria in Specific Situations

Condition Organism(s)
Cellulitis Staphylococcus Aureus
Necrotizing Fasciitis Group A Streptococcus, Polymicrobial
Gas Gangrene Clostridia
Marine Infections Mycobacterium Marinum, Vibro Vulnificus
Rose Thorn Inoculation Sporothrix Schenckii
Human Bite Eikenella Corrodens, Staphylococcus Aureus
Cat Bite Pasteurella Multocida, Staphylococcus Aureus
Dog Bite Pasteurella Multocida, Strep Viridans, Staphylococcus Aureus
Pig Bite Polymicrobial
Periprosthetic Infection Staphylococcus Aureus, Coagulase-negative Staphylococcus (Epidermidis)
Open Fracture Staphylococcus, Streptococcus, Anaerobic bacteria
Shoe Puncture Pseudomonas
Meat Handling Brucella
Sickle Cell Salmonella
IV Drug Abuse Pseudomonas
Fungal Nail Bed Trichophyton Rubrum

Bacterial Classification by Gram Stain and Shape

Gram-Positive Gram-Negative
Cocci Cocci
Staphylococcus Aureus Neisseria
Enterococcus
Streptococcus
Bacilli Bacilli
Clostridia Pseudomonas
Actinomyces E. Coli, Salmonella, Klebsiella
Eikenella
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