Principles of anti- infective therapy

Question 1

what is the antimicrobial infection

Answer 1

1. disrupt cell wall
2. disrupt cell membrane
3. inhibit proteins synthesis
4. dna interference
5. Metabolic pathway interference

Question 2

Mechanisms of bacteria to resist antibiotics

Answer 2

1. Decrease amount of drug availability ( by either efflux or impermeability )
2. Destroy the drug( enzymatic inactivation )
3. Prevent drug binding (alter binding site)

Question 3

List the types of terminological resistance in microbes

Answer 3

1. Intrinsic ( already within the bac) Vs acquired resistance ( acquired for eg mutation )

wild type organisms are defined as organisms that have the

2. chromosomal resistance : resistance is activated by switching on of a gene ( can be acquired or intrinsic )and mobile resistance through plasmids
3. Constitutive resistance ( part of genetic make up) and inducible(Activated by stimulus )
4. Heteroresistance ( 1 cell forms a colony ,some will be resistant to an antimicrobe while some will not)

Question 4

How does resistance of antimicrobial emerge

Answer 4

1. Mutation (spontaneous due to selective pressure eg changing target site )
2. Acquisition of resistance mechanism from mobile genetic elements
   * transformation (uptake of DNA from environment)
   * transduction ( transfer of genetic material from virus
   * Conjugation : direct transfer of genetic material from one bacterium to another through direct contact of pilli

Question 5

How do microbes determine resistance

Answer 5

1. Absolute fitness more important than relative fitness for emergence of resistance
2. Fitness id not fixed but dependent on ecological parameter eg immunity
3. compettitive suppression ( suspetiable microbes are more fit than resistant microbes= cost of resistance)
4. Competitive release

relative fitness is how one is fit compared to another ,it does not matter we need absolute resistance

Question 6

the 90/60 rule

Answer 6

9-% ofpatients treated with an agent which tests susceptible will respond

60% of patients treated with an agent which tests resistant will respond

Question 7

How to derive an MIC

reference methods

Answer 7

Test an organism to a series of two fold dilution of the antimicrobial agent using a dilution method

agar dilution or liquid broth

Question 8

How to derive an MIC other than the reference

antimicrobial testing

Answer 8

1. Zone sizes correlate with MIC
2. A range of zone sizes are then categorized into resistant ,intermediate or susceptible ,which is the interpretation of the AST result
   * you cannot use zone size to determine MIC
3. Gradient diffusion method
   * bind simplicity of diffusion disk with determination of an MIC
   * good correlation with reference method although there are limitations
4. Automated methods
   * software derived based on assessment of growth

Question 9

what is antimicrobial stewardship

Answer 9

Coordinated interventions to improve and measures the appropriates of antibiotics by promoting selection of optimal drugs regimen including dosing ,duration of therapy and route of administration

Question 10

benefits of antimicrobial stewardship

Answer 10

• improved patient outcome
• reduced adverse events eg C. difficile infection
• improvement in rates of antibiotics susceptibility to targeted antibiotics
• optimization of resource utilization across the continuum of care

Question 11

what are the focus in AMS

Answer 11

1. Reduce unnecessary antimicrobial therapy
   * good diagnosis ,be sure illness is caused by microbe
   * duration = shorter is better
   * dual cover ,when using combination of microbial ,make sure they work synergistically and that they do not the same thing
2. Appropriate use of antimicrobial agents
   * choice ,know your drugs
   * dose optimization
3. strengthening of antimicrobial resistance surveillance data to better inform interventions
4. policies and protocol

Question 12

What are the pharmacokinetic parameters in antimicrobial prescribing

Answer 12

1Absorption = oral vs IV

2. Distribution = Vd
3. metabolism= side effects and optimizing drug ,optimal therapy
4. elimination= clearance : hepatic or renal

Question 13

what are the pharmacodynamics patterns of microbial activity

Answer 13

1. time- dependent killing and minimal to moderate persistent effects
2. Time- dependent killing and prolonged persistent effects
3. Concentration -dependent killing and prolonged persistent effects