Lecture 38: Antimicrobials and antimicrobial resistance

In this year, over 20% of S. aureus hospital isolates were penicillin resistant (PRSA)

1945

In what year was MRSA observed?

1961

In what year was VRSA (vancomycin resistant S. aureus) observed?

2002

How can bacterial resistance be selectively encouraged?

Over prescribing antibiotic, not completing full antibiotic course

What is constitutive resistance?

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

Obligate anaerobes are uniformly resistant to what?

aminoglycosides

Why do aminoglycosides not work in obligate anaerobes?

Entry requires active transport system that is not active in anaerobes

Is constitutive resistance related to previous antibiotic exposure?

No

What is acquired resistance?

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

What are the three mechanisms of acquired resistance (how does the bacteria resist the drug)?

alter the target of the drug, alter uptake of the drug, inactivate the drug

How do bacteria alter the target of the drug?

Modify the target site, reduce significance of the target site

What is an example of reducing significance of drug target sites by developing alternative pathways?

resistance to sulfonamides via alternative folic acid synthesis pathway

What does multi-antibiotic resistance imply?

Multiple different resistance mechanisms, resistance against different classes

What is cross-resistance?

resistance due to a common mechanism, resistance against one class

True/false: If a bacteria is resistant to amikacin (newer), resistance to gentamicin (older, same class) is implied

True

Cross resistance is _______ - newer aminoglycosides have greater stability to destruction by enzymes than older

unidirectional

What can an organism produce to be resistant to several beta-lactams?

extended spectrum beta lactamases (ESBL)

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

changes in DNA via mutation, acquisition of DNA

Most DNA mutations are ________

lethal

If a mutation is not lethal, what are the 3 possibilities?

Selective disadvantage, no advantage, selective advantage

What is selective pressure in the context of antibiotic resistance?

Antibiotic resistance only confers selective advantage if antibiotics are present

What is the goal of genetic transfer?

Generate genetic diversity

What are the two relevant mechanisms of DNA transfer?

Transduction and conjugation

What is transduction?

transfer of DNA following bacteriophage infection

What is conjugation?

Inter-bacterial DNA transfer through sex pilus

How can conjugation transfer multiple antibiotic resistance genes?

R plasmids

What genus uses transferable drug resistance?

Salmonella

Is penicillin used against gram positive or negative organisms?

positive

Is gentamicin used for gram positive or negative organisms?

negative

What is the basis for antibiotic selection?

gram related spectra, historical data, in vitro sensitivity and antibiotic sensitivity testing

What does the E-test determine?

Exact minimum inhibitory concentration of an antimicrobial against a pathogen

When using the broth dilution method of AST, what shows bacterial growth?

turbidity

How can you tell if a bacteria is resistant to an antibiotic using disk diffusion (Kirby-Bauer procedure)?

there will be an empty circle around the antibiotic disk

Disk diffusion

E-test