Principles of Antimicrobial Therapy

Why are heavy metals antimicrobial?

mercury binds to (and damages) many proteins non-specifically (both ours and microbial ones)

so antimicrobial (yay!) but also toxic (noooo!)

What is the principle one which every antimicrobial works?

to be more toxic to the microbe than to us :)

what different types of treatments require antimicrobials?

bacterial (antibiotics)

fungal

viral

and helminth/protozoan

*different types of microbials are required for each

therapeutic dose

amount of medication required to produce the desired effect in treating the disease

toxic dose

specific quantity of a substance that can cause harmful effects to the host

therapeutic index

calculated from the ratio of the toxic dose to the therapeutic dose

higher therapeutic index = safer drug

what is the easiest way to make a highly effective and safe drug?

to target cell processes that humans do have

ex: many antimicrobials target the cell wall (create pores for lysis) because human cells do not have cell walls

Penicillin

first antibiotic that is selectively toxic for bacteria

targets crosslinking of cell wall on bacteria

• weakened cell wall → lysising

modification to penicillin helps target other bacteria and change how we can administer it

Bacteriostatic

keep bacteria from growing (when drug is gone bacteria will resume growth)

bacericidal

kill bacteria

ex: penicillin

60:40 rule

cure is 60% immune system and 40% antibiotic

fully functioning immune system will provide optimal outcome for antimicrobial therapy

pharmacokinetics (PK)

what the body does to the drug

Pharmacodynamics (PD)

what the drug does to the pathogen

Questions to ask to figure out what drug to use:

1. What do we know about the bacteria?

   • what is this bacteria and what antibiotics is it susceptible to?

   • PD understanding

   • culture and antibiotic sensitivity data

     • if there is not antibiotic sensitivity data, choose drug that would typically kill the organism

2. What do we know about the host?

   • PK understanding

   • how sick are they?

   • immunosuppressed?

   • are there host factors that might alter pharmacokinetics?

     • obesity, renal or hepatic impairment

3. What kind of infection is it? Where does the drug need to go?

   • ex: meningitis needs to get all the way to the central nervous system but for intestinal infections, absorption may not be required and for intracellular pathogens antibiotic must get inside mammalian cells

4. What do we know about how the drug behaves?

   a. route of administration needed

   b. distribution (circulatory system, diffusion into tissues)

   c. removal (metabolism or excretion)

   d. next dose?

Should antimicrobials be used in combination?

yes if:

• we don’t know whats causing the infection but know we need to kill it

• more than one kind of microbe is causing the infection (polymicrobial)

• prevents emergence of resistance through mutation

• synergy (two antibiotics will work better when combined)

• combining will allow reduction of dose of a toxic antimicrobial

antibiotic synergy

one makes the other work better

antibiotic indifference

antibiotics don’t affect one another

Antibiotic antagonism

one inhibits the other

Benefits of Antibiotics

shorter, less severe infections

cure infections

prevent infections (prophylactic)

reduced morbidity and mortality

Drawbacks of Antibiotics

side effects

allergies

emergence of resistance

secondary infections