Lecture 2 - Antibiotic Resistance Flashcards
First Antibiotic
- Discovered in 1929 by Fleming
- Accident, he forgot his plates
WWII
Penicillin
- Used to treat staphylococci and streptococci (1946)
- Effective because everything was caused by these bacteria
Resistance to Penicillin
- Recognized immediately
- 80% of all strains of Staphylococcus aureus
Streptococcus pyogenes (Group A strep) still treated with penicillin
Is not effective against
Gm-negatives (Salmonella, Shigella, Bordetella pertussis, Yersinia pestis, Pseudomonas) – why?
Antibiotic Therapy:
Effective chemotherapy
- Depends on selective toxicity
- Good against pathogen, does not effect the host
Antibiotic Therapy:
Exploit pathogen process
- Not seen in humans
- Cell wall, metabolism
Antibiotic Therapy:
Where?
- Site
- Organism
- Allergy to host?
Antibiotic Therapy:
Other Considerations
- Route of administration
- Monitor the therapy
- Adverse effects
- – GI tract, skin, haemopoietic system, renal system, liver
Three Major Mechanisms of Resistance
- Alteration in drug target
- Production of inactivating enzymes
- Decreased uptake of antibiotic
Antibiotic Resistance
Resistance occurs when a susceptible microorganism is no longer inhibited by an antibiotic agent
Antibiotic Resistance:
Why does this occur?
- Intrinsic
- Acquired
Antibiotic Resistance:
Intrinsic
- Characteristics of microorganism vis-à-vis
antibiotic’s mecanism of action (inherent or “natural”)
Antibiotic Resistance:
Acquired
- New or added (driven by two genetic processes in bacteria…mutation and selection (vertical evolution) and exchange of genetic material (horizontal evolution)
Chromosomal Mutations Lead to
1- Change it site of antibiotic target (but protein for bacterial still works fine!) 2- Regulatory genes ------ turn on alternative path ------ turn on efflux mechanisms 3- Change cell permeability
Post Antibiotic Era
- With current overuse of antibiotics, we are forcing bacteria to change (evolve) in order to survive
