V - Microbiology & Infection - Principles of infection control and TDM

Question 1

How does the site to be treated effect selection of microbial control methods?

Answer 1

• Choice of antimicrobial method depends on nature of site to be treated- so for e.g. inside the body, oral.etc.
• say you wanted to treat an oral disease you wouldn’t also target the skin as well
• the same compound can be used for different components/targets e.g. disinfectants and
  antiseptics

Question 2

How does the relative susceptibility of microorganisms effect selection of microbial control methods?

Answer 2

• Microbes fall under a continuum from most susceptible to most resistant to antimicrobial agents
• So, if we know an area is likely to be infected by a specific organism then we should use methods
  to target that organism

Question 3

How do the environmental conditions of microorganisms effect selection of microbial control methods?

Answer 3

• Changing conditions will change the activity
• We can target the growth of that microorganism by changing temperature [higher temperature is favourable for growth] or changing pH which could also change activity [low pH is favourable]
• We can’t change all conditions. A compound may go through a range of environmental conditions. For example, if you have an oral preparation it will go to the acidic nature of the stomach then goes to intestine which has a more neutral or alkali pH.
• These changing conditions may change the activity of your compound [the antimicrobial]
• The above variables are examples of how to target growth of microorganisms

Question 4

There are various methods for evaluating disinfectants and antiseptics. What is the phenol coefficient test?

Answer 4

– Efficacy of various disinfectants and antiseptics calculated by ratio that compares a given agents ability to control microbes to that of phenol
– Compares the activity of compound against the activity of phenol. More active=higher number for e.g. alcohol
– Outdated but still used

Question 5

There are various methods for evaluating disinfectants and antiseptics. What is the Use-dilution test?

Answer 5

– Several metal cylinders dipped into broth cultures of (different) bacteria, dried at 37C, then the contaminated cylinders immersed into different dilutions of disinfectants and then inspected for growth of microorganism
– If the microorganisms grow, then growth hasn’t been inhibited
– But if they don’t grow then that concentration has been effective
– Commonly used in the US

Question 6

There are various methods for evaluating disinfectants and antiseptics. What is the Kelsey-Sykes Capacity test?

Answer 6

– Suspension of bacterium added to suitable concentration of chemical being tested. At predetermined times, samples of mixtures moved into growth medium and observed for growth or to see if there’s been inhibition
– Agar plates will have a neutralising agent to stop the disinfectant [test reagent] from working

Question 7

There are various methods for evaluating disinfectants and antiseptics. What is the In Use test?

Answer 7

– Swabs taken from actual objects before and after application of disinfectant or antiseptic. Swabs then inoculated into appropriate growth media and observed for growth
– This method is better than the other 3 but is more time consuming.
– It is used subsequent to any of the other 3 tests
– You need both tests to see if you have the correct concentration of antimicrobial

Question 8

What is therapeutic drug monitoring and why is it used?

Answer 8

• TDM can be viewed as arena of multidisciplinary service
• It is used to ensure the antibiotic level is always above the MIC of the organism you want to treat
• Regular testing for TDM= time consuming but can be v effective
• TDM commonly utilized during therapy of variety of drugs, e.g. antituberculotic chemotherapy
• 3 common PK and PD parameters associated with efficacy of antimicrobials:
  1) What is the max concentration (Cmax) in relation to the MIC [ratio of Cmax to MIC]
  2) The AUC that is above MIC
  3) How long is your drug concentration above MIC
• Antibiotic drugs that have intracellular activity- (1) + (2) are the important parameters
• Antibiotic drugs that have activity on cell wall-( 3) is the important parameter

Question 9

What are some considerations that need to be acknowledged when prescribing antibiotics?

Answer 9

• Malabsorption states, e.g. other disease states may result in severe wasting of patients
• Pharmacokinetic drug interactions, e.g. (i) inducers of cytochrome P-450 enzyme, particularly
  isoform enzymes of CYP3A subfamily (ii) inhibition of absorption of other drugs. CYP3A- most common- 30% found in liver and 70% found in gut wall- these areas are targeted by many drugs as an inducer or inhibitor of the enzyme. Rifampicin is an antimicrobial- the most potent inducer of CYP450 enzyme [compared to other antibiotics.
• Drug-disease interactions, e.g. renal problems, liver problems

Question 10

What is sepsis? Why do we have to therapeutically monitor its treatment?

Answer 10

• At increased risk for severe infection - extensive use of invasive devices [e.g. cannulas, catheters] and weakened physical condition
• Serious infections incite systemic inflammatory response syndrome (SIRS). Infections provoking SIRS produce the syndrome sepsis
• Mortality rate approx. 20-30%
• 40-50% of critically ill patients will develop an infection so we have to keep an eye on them. They are often immunocompromised or have an affected organ.
• If the infection hasn’t been recognised, then it can infect the whole body which will lead to
  Sepsis > Septic shock > Severe hypotension > Death
• Sepsis is a whole-body inflammation and is a natural part of the immune system
• As it has a high mortality rate (30%) it is v important to identify it early on
• Severe sepsis=organ failure
• In sepsis you give them a broad spectrum antibiotic ASAP as we don’t know what the causative organism is
• Therefore, TDM is important here too