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

Bacterial Classification by Gram Stain and Shape