Antimicrobial Resistance

Question 1

Sulphonamide Antibiotic

Answer 1

Bacteriostatic
Synthetic
Used for UTIs,RTIs,bactaraemia and prophylaxis for HIV+
Some host toxicity

Question 2

Beta-lactams mechanism and examples

Answer 2

Interferes with the synthesis of peptidoglycan component of bacterial cell wall
Binds to penicillin-binding proteins
These catalyse a number of steps in peptidoglycan synthesis

Penicillin & methicillin

Question 3

What is an antibiotic

Answer 3

An antimicrobial agent produced by a microorganism that kills or inhibits other microorganisms

Question 4

Reasons for increased mortality, morbidity and cost from AB res.

Answer 4

Increased time to effective therapy
Requirement for additional approaches (surgery)
Use of expensive therapy (newer drugs)
Use of more toxic drugs
Use of less effective ‘second choice’ antibiotics

Question 5

Aminoglycosides mechanism and examples

Answer 5

Bactericidal-targets protein synthesis, RNA proofreading causing damage to cell membrane
Toxicity has limited use, but AB resistance has led to increase usage

Gentamicin,streptomycin

Question 6

Rifmapicin mechanism

Answer 6

Bactericidal
Targets RpoB sunbunit of RNA polymerase
Frequent spontaneous resistance

Question 7

Vancomycin mechanism

Answer 7

Bactericidal
Targets Lipid II components of cell wall biosynthesis, as well as wall cross linking via D-ala residues
Toxicity has limited use but other AB res. Has led to increase usage

Question 8

Linezolid mechanism

Answer 8

Bacteriostatic
Inhibits initiation of protein synthesis by binding to 50S rRNA subunit
Gram+ spectrum of activity

Question 9

Daptomycin mechanism

Answer 9

Bactericidal
Targets bacterial cell membrane
Gram+
Toxicity limits dose

Question 10

4 AB res. Mechanisms

Answer 10

Altered target site
Inactivation of antibiotic
Altered metabolism
Decreased drug accumulation

Question 11

Altered target site

Answer 11

Acquisition of alternative gene or a gene that encodes a target modifying enzyme

Question 12

Inactivation of antibiotic

Answer 12

Enzymatic degradation or alteration rendering antibiotic ineffective

Question 13

Altered metabolism

Answer 13

Increased production of enzyme substrate can out-compete antibiotic inhibitor

Question 14

Decreased drug accumulation

Answer 14

Reduced penetration of AB into bacterial cell and/or increased efflux of AB out of the cell - drug does not reach conc. required to be effective

Question 15

Macrolides mechanism and examples

Answer 15

Gram+ and some gram-
Targets 50S ribosomal subunits preventing amino-acyl transfer and thus truncation of polypeptides

Question 16

Quinolones

Answer 16

Synthetic, broad spectrum, Bactericidal
Target DNA gyrase in Gm -ve and topoisomerase IV in Gm+ve

Question 17

Sources of antibiotic resistance

Answer 17

Plasmids- Extra chromosomal circular DNA
Transposons- Integrate into chromosomal DNA which allows transfer of genes from plasmid to chromosome and vice versa
Naked DNA - released by dead bacteria into environment

Question 18

Spread of AB resistance genes

Answer 18

Transformation - uptake of extracellular DNA
Conjugation - pilus mediated DNA transfer
Transduction - phage (infection) mediated DNA transfer

Question 19

Other reasons for treatment failure

Answer 19

Inappropriate choice of AB
Poor penetration of AB into target site
Inappropriate dose
Inappropriate administration (IV vs Oral)
Presence of AB resistance within commensal flora

Question 20

Why are hospitals such strong selection pressures for AB resistance

Answer 20

Large numbers of infected people
High doses of AB

Question 21

Risk factors for HAI

Answer 21

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 22

Addressing resistance

Answer 22

Prescribing strategies – tighter controls, temporary withdrawal of certain classes. Restriction of ABs for certain serious infections
•Reduce use of broad-spectrum antibiotics
•Quicker identification of infections caused by resistant strains
•Combination therapy
•Knowledge of local strains/resistance patterns

Question 23

Overcoming resistance

Answer 23

•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.