Hospital acquired infection and antibiotic resistance

Question 1

What is Prontosil?

Answer 1

First example of an effective and safe anti-bacterial therapeutic

Question 2

What are the main features of Prontosil?

Answer 2

Bacteriostatic
Synthetic
Used to treat UTI’s, RTI’s, bacteraemia and prophylaxis for HIV+ individuals
Sometimes used together with Trimethoprim- work better together
Becoming more common due to resistance to other anti-bacterials

Question 3

What was the issues with Prontosil?

Answer 3

Only effective with Gram-positive bacteria (single outer membrane)

Question 4

Why is it difficult to develop drugs against Gram-negative bacteria?

Answer 4

To get a drug across the outer layer it must be hydrophilic

And hydrophobic for the inner layer

Question 5

What was the issue with early penicillin?

Answer 5

Excreted from the body very rapidly WH

Question 6

What is a Beta-lactam?

Answer 6

Most commonly prescribed type of antibiotic
E.g pencilling and methicillin
Has a characteristic Beta-lactam ring
Chemically mimic components of peptidoglycan cell wall
Competitive inhibitor of enzymes involved in cell wall synthesis

Question 7

What is an antibiotic? (strictly speaking)

Answer 7

Agent produces by microorganism the kills or inhibits another microorganism
However many are semi-synthetic or synthetic

Question 8

What are the 4 types of antibiotic?

Answer 8

Antimicrobial
Bactericidal
Bacteriostatic
Antiseptic

Question 9

Why did antibiotic discoveries slow down?

Answer 9

Economic factors

Already so many, why spend money acquiring more?

Question 10

What did Flemming predict?

Answer 10

Resistance primarily due to misuse

Question 11

What are the main features of resistance?

Answer 11

Constantly changing landscape- problems we face today are not what we will face tomorrow
Countries that use the most antibiotics have the most resistance
Resistance usually emerges soon after the new arrival of the new AB

Question 12

Why is the market for antibiotics different from any other type of drug?

Answer 12

Newest drugs are kept sparingly for the most severe of cases- small market
Older drugs are in more demand

Question 13

How does resistance come about?

Answer 13

Evolution by natural selection

Routine use of antibiotics provides selection pressure

Question 14

What were the misconception at the dawn of the antibiotic era?

Answer 14

Resistance against more than one class of antibiotics would not occur at the same time
Horizontal gene transfer would not occur
Resistance organisms would be significantly less ‘fit’

Question 15

What are the consequences of resistance?

Answer 15

Increased mortality, morbidity and cost
Increased time for effective therapy, requirement for additional approaches
Use of expensive therapy
More toxic drugs

Question 16

Name some gram-negative resistant bacteria

Answer 16

Pseudomonas aeruginosa
E. coli
Salmonella
Acinetobacter

Question 17

Name some gram-positive resistant bacteria

Answer 17

Staphylococcus aureus
Streptococcus pneumonias
Clostridium difficle
Myobacterium tuberculosis

Question 18

What are Aminoglycosides?

Answer 18

E.g. Gentamicin, streptomycin
Bactericidal 
Targets proteins synthesis, RNA proofreading and causes damage to cell membrane
Toxic- limited use 
Increasing due to resistance to others

Question 19

What is Rifampicin?

Answer 19

Bactericidal
Targets RpoB subunit of RNA polymerase
Spontaneous resistance frequent
Makes secretions go red

Question 20

What is Vancomycin?

Answer 20

Bactericidal
Targets lipid II components of cell wall biosynthesis
Toxic
Increasing use due to resistance to others

Question 21

What is Linezolid?

Answer 21

Bacteriostatic
Inhibits the imitation of protein synthesis
Gram-positive

Question 22

What is Daptmycin?

Answer 22

Bactericidla
Targets cell membrane
Gram positive
Toxicity limits dose

Question 23

What principle do antibiotic works on?

Answer 23

Selective toxicity

Question 24

What are the 4 mechanisms of antibiotic resistance?

Answer 24

Altered target site
Inactivation of antibiotic
Altered metabolism
Decreased drug accumulation

Question 25

How does the altered target site mechanism work?

Answer 25

Gene encodes a target-modifying enzyme e.g MRSA encodes alternative enzyme with low affinity for Beta-lactams Streptococcus pneumoniae encodes enzyme that methylates the AB target site

Question 26

How does the inactivation of antibiotic mechanism work?

Answer 26

Enzymatic degradation or altering rendering antibiotic ineffective

Question 27

How does the altered metabolism mechanism work?

Answer 27

Increased production of enzyme substrate can out-compete antibiotic inhibitor Bacteria south to other metabolic pathways

Question 28

How does the decreased drug accumulation mechanism work?

Answer 28

Reduced penetration of AB into bacterial cell Increased efflux of AB out of cell Drug does not reach concentration to be effective

Question 29

What macrocolides?

Answer 29

E.g. erythromycin, azithromycin Gram-positive and some gram-negative Targets ribosomal sub-unit preventing amino-acyl transfer

Question 30

What are quinolones?

Answer 30

Synthetic, broad spectrum, bactericidal Target DNA gyrase in GM-ve Toposomerase on GM+ve

Question 31

What are the sources of antibiotic resistance genes?

Answer 31

Plasmids Transposons Naked DNA

Question 32

What are transposons?

Answer 32

They integrate into chromosomal DNA allowing transfer of genes from plasmin to chromosome and vice versa

Question 33

What are the non-genetic mechanisms of resistance?

Answer 33

``` Biofilm Intracellular location Slow growth Spores Persisters ```

Question 34

What are other reasons for failure of antibiotics?

Answer 34

Wrong for organism Poor penetration to target site Wrong dose Wrong administration

Question 35

Why do hospitals provide strong elective pressure for AB resistance?

Answer 35

Large number so infected people receiving high doses of antibiotics Strong selective pressure

Question 36

What are some risk factors for HAI?

Answer 36

``` High no. of immunosuppressed Crowded wards Presence of pathogens Broken skin AB therapy may suppress normal flora Transmission by staff with contact with multiple patients ```

Question 37

What can be done to address resistance?

Answer 37

``` Prescribing strategies Reduce broad-spectrum use Quicker identification Combination therapy Knowledge of strains and resistance patterns ```