Antimicrobials and Antimicrobial Resistance

We don’t ______ antibiotic resistant bacteria- bacteria are constantly mutating and we _______ growth of bacteria with mutations that enhance survival in the presence of that antibiotic.

induce; selectively encourage

What is constitutive resistance?

bacteria are resistant to antibiotic because they lack the uptake system or targets of the antibiotic

What type of resistance is unrelated to previous antibiotic exposure?

constitutive

What is acquired resistance?

bacteria become resistant to antibiotics by mutation resulting in alteration of uptake systems or targets of antibiotics

What type of resistance is dependent on prior exposure?

acquired

What are the three basic mechanisms of acquired resistance?

1. Alter the target of the drug

2. Alter uptake of drug

3. Inactive the drug

What are ways a bacteria could alter the target of the drug?

• modify the target site

• reduce significance of the target site

How could a bacteria alter uptake of a drug?

• inhibit uptake (decrease pore size)

• increase excretion (tetracyclines)

How could bacteria inactivate a drug?

• synthesis of inactivating enzymes

• some bacteria produce beta-lactamase enzyme that destroys or deactivates the beta-lactam antimicrobials

What is the difference between multi-antibiotic resistant and cross-resistance?

multi-antibiotic: multiple DIFFERENT resistance mechanisms = different classes

cross-resistance: resistance due to a COMMON mechanism - so that resistance to one antibiotic implies resistance to others = same class

What are two ways multi-antibiotic resistance could occur?

• common when R-plasmids exchanged (conjugation)

• constant use of drugs eliminates sensitive cells

True or false: cross-resistance is unidirectional.

true

How could an organisms be resistant to several Beta-lactams?

production of Beta-lactamase

What are the two basic mechanisms by which bacteria ACQUIRE resistance?

• changes in DNA via MUTATION

• Acquisition of DNA

What form of acquired resistance is lethal?

mutations

What is selective advantage?

mutations that are not lethal, but increase in population until they may become dominant type

What is selective pressure?

antibiotic resistance only confers selective advantage IF antibiotics are present

What mechanism of acquired resistance generates genetic diversity?

genetic transfer (acquisition of DNA)

What is genetic transfer a critical mechanism for?

bacterial adaptation to changing environments and host conditions

What are the two relevant mechanisms of genetic transfer?

transduction and conjugation

What is transduction?

transfer of DNA following bacteriophage infection → bacteriophage DNA is integrated into bacterial chromosome

What is conjugation?

inter-bacterial DNA transfer through sex pilus

What can plasmids encode?

• pili genes

• exotoxins

• MULTIPLE antibiotic resistance genes (R plasmids)

True or false: plasmids usually encode factors not ESSENTIAL for growth and replication.

true

How are plasmids transferred?

transferred vertically during bacterial division and horizontally during conjugation

What is the basis for selecting antibiotic that is effective against the bacteria?

• gram related spectra

• historical data

• in vitro sensitivity and antibiotic sensitivity testing

What is this an example of?

synergism between two antimicrobial agents

What are strategies for limiting antibacterial resistance?

• Effective surveillance systems for the collection of data at the local and national level and monitor

• Ideally treatment should be based on antimicrobial susceptibility test results

• Strict adherence to drug withdrawal periods in food-producing animals

• Maintain high concentration of drug in patient for sufficient time

• Use antimicrobials only when necessary

• Use antimicrobial agents in combination

What are the routes of administration in prescribing antimicrobial drugs?

• topical

• oral route

• IM

• IV

What are safety and side effect considerations when prescribing antimicrobial drugs?

toxicity and allergies