Antimicrobials, Their Resistance and Stewardship

Question 1

What are antimicrobials?

Answer 1

Agents active against microbes: antibacterial, antifungal, antiviral or antiprotozoal.

Question 2

What are antibiotics and what are antibacterials?

Answer 2

An antibiotic is an agent derived from another living creature that is anti-bacterial.
Antibacterial agents are: bactericidal or bacteriostatic, on a spectrum of broad to narrow, have mechanisms of action with a target site and a chemical structure, as part of an antibacterial class.

Question 3

What are good features of an antimicrobial?

Answer 3

Selectively toxic with few adverse effects, can reach the site of infection, is available orally/as an IV formulation, has a long half life (for infrequent dosing) and no interference with other drugs.

Question 4

What are the different classes of antibiotics (with examples)?

Answer 4

Those that affect cell wall synthesis - beta-lactams, glycopeptides.
Protein synthesis - tetracyclines, amino glycosides, macrolides.
Nucleic acid synthesis - quinolones.
(More rare) cell membrane function - polymixins.

Question 5

Penicillin is an example of which type of antibiotic, how does it work?

Answer 5

A cell wall antibiotic. It binds to penicillin-binding protein, so it is unable to do its job of forming cross links between side chains of amino acids. The cell wall is a peptidoglycan - linked amino acids acting as a mesh.

Question 6

How does vancomycin work, what type of antibiotic is it?

Answer 6

It targets cell wall synthesis by sitting on the side chain of amino acid to block penicillin-binding protein, so no cross links can be made.

Question 7

Apart from targeting cell wall synthesis (as with penicillin and vancomycin), can can antibiotics target bacteria?

Answer 7

In protein synthesis they can interact with the pathway and with nucleic acid synthesis, quinolone inhibit 2 replications enzymes, including one which supercoils.

Question 8

What are the 3 types of antibiotic resistance?

Answer 8

Intrinsic - no target or access for drug (usually permanent).
Acquired - new genetic material gained/mutates (usually permanent).
Adaptive - organisms response to a stress (e.g. A subinhibitory level of antibiotic), that’s usually reversible.

Question 9

What are the mechanisms of antibiotic resistance?

Answer 9

Drug inactivating enzymes - beta-lactamases, aminoglycoside enzymes,
Altered target - target enzyme gets lower affinity for antibacterial e.g. MRSA,
Altered uptake - decreased permeability or increased efflux (pump developed).

Question 10

What’s the genetic basis of antibiotic resistance?

Answer 10

Chromosomal gene mutation then horizontal gene transfer. After an antibiotic is administered, all susceptible organisms are killed and bacteria with the mutated gene conferring resistance becomes the dominant strain. Resistance gene could reside in chromosome, plasmid or transposon (fragment) - each can get incorporated into the previous in horizontal gene transfer via conjugation, injection by bacteriophages, transduction or transformation - free DNA gets through porin.

Question 11

How has antibiotic choosing changed with developing antibiotic resistance?

Answer 11

Originally the empiric/best choice drug was used, but now the antibiotics activity may be assessed with disc sensitivity testing.

Question 12

What is the Minimum Inhibitory Concentration and how is it found out?

Answer 12

Can give a numeric value of the effect of an antibiotic against a specific organism.
Test tubes with doubling dilutions are incubated with positive and negative controls and any growth is observed.

Question 13

Beta-lactams are one of the largest groups of antibiotics. They include ________, with some beta-lactamase ___________ combinations. Also includes Cephalosporins, which are better as with standing _________-___________. Also includes Carbapenems which are ___________ spectrum and Monobactams.

Answer 13

Penicillin
Combinations
Beta-lactamases
Broad

Question 14

Aside from beta-lactate, the other type of antibiotic to target cell wall synthesis are _____________, which include Vancomycin, which needs therapeutic drug monitoring as it has a narrow ___________ __________ (so could become toxic quickly). It also includes Teicoplanin.

Answer 14

Glycopeptides

Therapeutic window

Question 15

Tetracyclines are a type of antibiotic that target _________ synthesis. Tetracycline and doxycycline should not be used in children

Answer 15

Protein
12
Teeth and bones
Gentamicin 
Negative 
Macrolides

Question 16

What are the 3 types of antibiotic known to target folic acid and so DNA synthesis? In combination, 2 are known as Co-trimoxazole.

Answer 16

Quinilones as well as Trimethoprim and Sulphonamides. The later 2 make Cotrimaxazole.
Trimethoprim is used alone in the U.K. For ITUs and has activity against MRSA.

Question 17

What are the 2 types of antifungals?

Answer 17

Azoles inhibit cell membrane synthesis and Polyenes inhibit function.

Question 18

Antiviral:
Aciclovir, when _____________, inhibits viral DNA polymerase.
Oseltamivir/Tamiflu ________ viral neuraminidase and there are specialists agents for ___, ___, ___, etc.

Answer 18

Phosphorylated
Inhibits
HIV, HBV, HCV

Question 19

Metronidazole is an antimicrobial active against which 2 types of microorganism?

Answer 19

Anaerobic Bactria and Protozoa.

Question 20

Most resistance is preexisting and large scale resistance will emerge soon after clinical use is approved; it does so inevitably and 1 strain may become resistant to many microbial. What type of exposure of bacteria to antimicrobials results in antimicrobial resistance?

Answer 20

All exposure of bacteria to antimicrobials result in antimicrobial existence, whether used wisely or inappropriately, then resistance is effectively irreversible.

Question 21

Currently, antimicrobial development is stalled. What are the consequences of antibacterial resistance?

Answer 21

Treatment failure, prophylaxis failure (e.g. Prior to surgery) as well as economic costs (increases healthcare and social costs).
The current ‘discovery void’ is leading to a post-antibiotic era in which common infections and minor injuries can kill.

Question 22

There is a massive current global burden of antimicrobial resistance, how so?

Answer 22

Resistant bacteria are more likely to be treated with inappropriate empirical antibiotics initially and result in longer hospital stays with higher mortality and costs.

Question 23

What are the definitions of the 3 types of resistance?

Answer 23

MDR - multi drug resistant - non susceptibility to at least 1 agent in 3 or more antimicrobial categories.
XDR - extensively drug resistant - only susceptible fully to 2 or fewer classes of antimicrobials.
PDR - pan drug resistant - non suceptibility to all agents in all microbial categories, can’t treat.

Question 24

The IDSA definition of Antimicrobial stewardship includes:
Appropriate ____ of antimicrobials, optimal clinical ___________, minimising toxicity and other _________ effects, reducing the _______ of healthcare for infections and limiting the selection for antimicrobial resistant ________.

Answer 24

Use
Outcomes
Adverse
Cost
Strains

Question 25

What are some of the elements of Antimicrobial stewardship?

Answer 25

MDT, relationships to other quality/safety teams, surveillance (process and outcome measures) and interventions (persuasive, restriction and structural).
MDT includes anyone who prescribes or is responsible for antimicrobial distribution: medical microbiologist, antimicrobial pharmacist, infection control nurse, hospital epidemiologist and information system specialist.

Question 26

Antimicrobial stewardship depends on the causal link between what?

Answer 26

Antibacterial use and resistance.

Question 27

What are the different types of evidence used in Antimicrobial stewardship to prove the relationship between antimicrobial use and resistance?

Answer 27

Laboratory - provides biological plausibility,
Ecological studies - relates levels of use and resistance in a population and
Individual level data - relates prior antibacterial use in individuals with subsequent presence of bacterial resistance (texted by culture or molecular means).

Question 28

What areas does Antimicrobial Stewardship overlap with?

Answer 28

Infection prevention and environmental decontamination.

Question 29

What really the 3 types of interventions?

Answer 29

Persuasive, restricted and structural.

Question 30

Give examples of /explain persuasive interventions.

Answer 30

Education, consensus, opinion leaders, reminders, audits and feedback.

Question 31

Describe restrictive interventions.

Answer 31

Restricted susceptibility reporting, formulary restriction, prior authorisation and automatic stop orders.

Question 32

Describe structural interventions.

Answer 32

Computerised records, rapid lab tests, expert systems and quality monitoring.

Question 33

What type of intervention should be used and is best?

Answer 33

The techniques aren’t exclusive, but initially restrictive interventions are superior to persuasive - this imbalance changes over time.

Question 34

What are process measures used for?

Answer 34

Antimicrobial use recorded in quantity e.g. In defined daily dose per 1000 beds, so rates can be compared using bench-marking or
looking at certain antimicrobial classes or appropriateness with adherence to guidelines.

Question 35

What are outcome measures used for?

Answer 35

Outcome measures are used to look at patient outcomes, emergence of resistance e.g. Clostridium difficile infection rate.

Question 36

What are the requirements for successful stewardship?

Answer 36

Long term appropriate resources, hospital leadership support and authority to change, integration into organisational patient safety - structures and processes.
It is effective.

Question 37

What are interventions aimed at?

Answer 37

Improving appropriate prescribing of antibiotics.

Question 38

What are some potential challenges or unintended consequences of Antimicrobial stewardship?

Answer 38

Mortality actually decreases, as does length of stay, but readmission risk may rise after intervention.