Antimicrobial therapies

Question 1

What are the 4 distinct mechanism of antibiotic resistance?

Answer 1

Altered target site (acquisition of alternative gene or a gene that encodes for target modifying enzyme)
Inactivation of antibiotic (enzymatic degradation of antibiotic)
altered metabolism (increased production of enzyme substrate can out-compete antibiotic inhibitor. Or bacteria can switch to other metabolic pathways)
Decreased drug accumulation (reduced penetration of a.b,. into bacterial cell due to decreased permeability and/or increased a.b. efflux from cell. So a.b. conc is not high enough to be effective)

Question 2

Sources of antibiotic resistance genes

Answer 2

Plasmids – extra-chromosomal circular DNA, often multiple copy. Often carry mutliple AB res genes – selection for one maintains resistance to all.
Transposons. Integrate into chromosomal DNA. Allow transfer of genes from plasmid to chromosome and vice versa.
Naked DNA. DNA from dead bacteria released into environment.

Question 3

Non-genetic mechanisms of resistance/treatment failure

Answer 3

Biofilm
Intracellular location
Slow growth
Spores
Persisters

Question 4

Other reasons for treatment failure

Answer 4

Inappropriate choice for organism
Poor penetration of AB into target site
Inappropriate dose (half life)
Inappropriate administration (oral vs IV)
Presence of AB resistance within commensal flora e.g. secretion of beta-lactamase

Question 5

Risk-factors for HAI

Answer 5

High number of ill people! (immunosuppression)
Crowded wards
Presence of pathogens
Broken skin – surgical wound/IV catheter
Indwelling devices - intubation
AB therapy may suppress normal flora
Transmission by staff – contact with multiple patients

Question 6

2 methods for overcoming resistance

Answer 6

Modification of existing medications to e.g. Prevent cleavage (beta-lactams) or enhance efficacy. E.g. Methicillin.
Combinations of antibiotic + inhibitor of e.g. Beta-lactamase. E.g. Augmentin (combination of small molecule beta lactamase inhibitor with a beta lactam antibiotic)

Question 7

Pseudomonas aeruginosa

Answer 7

Gram-negative

Cystic fibrosis, burn wound infections. Survives on abiotic surfaces.

Question 8

E. Coli (ESBL)

Answer 8

Gram-negative

GI infect., neonatal meningitis, septicaemia, UTI

Question 9

Acinetobacter baumannii (MDRAB)

Answer 9

Gram-negative

Opportunistic, wounds, UTI, pneumonia (VAP). Survives on abiotic surfaces.

Question 10

Staphylococcus aureus (MRSA, VISA

Answer 10

Gram-positive

Wound and skin infect. pneumonia, septicaemia, infective endocarditis.

Question 11

Clostridium difficle

Answer 11

Gram-positive

Pseudomembranous colitis, antibiotic-associated diarrhoea.

Question 12

Enterococcus spp (VRE)

Answer 12

Gram-positive

UTI, bacteraemia, infective endocarditis.