Antibiotics

Types

Fluroquinolones

Tetracyclines

Rifampin

Sulphonamides

Beta Lactams

Penicillins - these treat streptococci and clostridia for skin and soft tissue infection

Inhibit cell wall synthesis

Interferes with nucleic acid synthesis

Inhibits gyrase

Inhibits protein synthesis

Inhibits folate synthesis

How They Work

Bacteriostatic: Antibiotic prevents growth of bacteria by inhibiting protein synthesis or DNA replication

Kills >90% in 18-24 hours

Bactericidal: Antibiotic kills bacteria by inhibiting cell wall synthesis

Kills >99.9% in 18-24 hours

Useful if infection needs to be treated quickly e.g. meningitis

MIC = Lowest minimal inhibitory concentration

Concentration: Key is how high the conc is above the MIC - knockout punch. Fluroquinolones work this way

Time: Key is how long the conc remains above the MIC - sustained killing. Beta lactams work this way

Two determinants of antibacterial effects are the concentration and time that the antibiotic remains on the binding sites

Considerations

Site of infection

What is PH of site

Is the antibiotic lipid soluble?

Safety

Allergy, anaphylaxis

Side effects

Age

Renal and liver function

Pregnancy and breast feeding

Drug Interactions

Risk of C.diff - antibiotic induced diarrhoea

Resistance

Mechanisms of Resistance

  1. Destroying antibiotic - e.g. Beta lactamase enzyme hydrolyses beta lactam ring of penicillins
  1. Preventing antibiotic access - bacteria can modify their porin channel size and number
  1. Changing antibiotic target - bacteria changes binding site on a molecular level. E.g. MRSA - flucloxacillin can no longer bind to staphylococci
  1. Removing antibiotic from bacteria - efflux pumps in the bacterial membrane remove the antibiotic

Development of Resistance

Intrinsic: All subpopulation of a species will be equally resistant e.g. vancomycin cannot enter gram negative bacteria as their membrane is too large

Acquired: A bacteria which was previously susceptible obtains the ability to resist. Only certain strains of a species will be resistant

Spontaneous gene mutation

Horizontal gene transfer e.g conjugation, transduction, transformation

Clinically Important Examples

Gram Positive

MRSA = methicillin resistant staph.aureus

VRE = vancomycin-resistant enterococci

Gram Negative

B-lactamase producing bacteria e.g. E.coli

Bacteria that produce extended spectrum b-lactamases - these can destroy more than penicllin and amoxycillin

Cephalosporins - c.difficile and enterococci are resistant

Amoxicillin - used to treat enterococci for pneumonia, skin and soft tissue infections and UTIs

E.g. doxycycline which treats cellulitis and MRSA

E.g. ciprofloxacin which treats UTIs