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