Chapter 10: AntiMicrobial Treatment (spectrum of activity of penicillin down to before antimalarial drugs)

Is this spectrum of penicillin G and V? is it susceptible to microbial counterattacks? How has it changed over the years and has it over limitations of the original drug?

• Original penicillin (G and V) was narrow-spectrum (GM +) and susceptible to microbial counterattacks

• Molecule has been altered and improved upon over the years

• Later penicillins overcome the limitations of the original molecule

What are the parts of the penicillin molecule and why are they important? What are of the molecule is always the same?

1. Beta-lactam ring: this is what attaches to the bacteria and does its functions

2. Side chain/Group R: changes the properties of the antibiotic depending on side chain (ex: pH, formulation, etc.)

3. Nucleus (BL ring and the rest of the molecule): is everything but the side chain and is always the same

Penicillins are always what types of molecules? What must be intact in order to function correctly?

• Penicillins are all Beta-lactams and have the ring

• The BL ring must be intact in order to attach to the bacteria and does its functions

What is penicillinase and what’s its other name? How does it arise in bacteria?

Penicillinase is an enzyme B-lactamase which breaks down the ring

• Came from horizontal gene transfer and resistance over time to penicillin drugs

What is the 3 point scheme for selected penicillin drugs?

1. Spectrum of action:

2. Use, Advantages:

3. Disadvantages:

What’s the 3 point scheme for Penicillin G?

1. Spectrum of action: Narrow (GM +)

2. Use, Advantages: best against sensitive bacteria

3. Disadvantages: Can be hydrolysis by penicillinase and requires injection

What’s the 3 point scheme for Penicillin V?

1. Spectrum of action: Narrow (GM+)

2. Use, Advantages: good intestine absorption

3. Disadvantages:Hydrolysis by penicillinase; oral drug

What’s the 3 point scheme for Methicillin?

1. Spectrum of action: Narrow (GM+)

2. Use, Advantages: not usually susceptible to penicillinase

3. Disadvantages: growing resistance

What’s the 3 point scheme for Ampicillin?

1. Spectrum of action: Broad (GM± pos./neg.)

2. Use, Advantages: works on GM-

3. Disadvantages: can be hydrolyzed by penicillinase

What’s the 3 point scheme for Amoxicillin?

1. Spectrum of action: Broad (GM± pos./Neg.)

2. Use, Advantages: gram neg. Infections; good absorption

3. Disadvantages: hydrolysis by penicillinase

Do bacteria behave differently in biofilms vs free-living? Do usual antimicrobial work on them if they are in a biofilm?

• Bacteria in biofilms behave differently than when they are free-living:

• Often unaffected by the same antimicrobials that work against them

What happens to antibiotics against the sticky extracellular material surrounding biofilms? What do bacteria express differently when in a biofilm compared to free-living bacteria?

• Antibiotics often cannot penetrate the sticky extracellular material surrounding biofilms

• Bacteria in biofilms express a different phenotype and have different antibiotic susceptibility profiles than free-living bacteria

What are the 4 targets for fungal infections?

1. Bind to fungal membranes, causing loss of selective permeability;

2. Interfere with sterol synthesis in fungi

3. Inhibit fungal cell wall synthesis

4. Inhibit enzyme critical for ergosterol synthesis