T3-L9: Antibacterial Concepts and Stewardship

Question 1

Describe the relationship between drug concentrations and antibiotics.

Answer 1

Increasing the concentration of antibiotics increases the percentage of survival until a certain point in which increasing concentrations has no effect of efficacy.

There are intra-species variations in MIC values. Antibiotic treatment considers bacteria populations and the variation within it.

Question 2

Describe the relationship between mortality and AUC:MIC.

Answer 2

As AUC:MIC, where AUC is the area under the curve and so the total exposure of an antibiotic to an organism, increases the percentage of mortality decreases. AUC:MIC would be the pharmacodynamic target. After this has been achieved we get no additional efficiency benefit.

For different drugs and different bacteria the relationships may be more important. For some drugs we try and achieve high Cmax - we may give these daily once target a high Cmax. For others we just try and keep them above MIC and so dose them regularly.

Question 3

What is the probability of target attainment?

Answer 3

There is lots of variation between patients in how the antibiotics is distributed in the body and is cleared from the body (pharmacokinetics).

We describe the MIC and pharmacokinetics using probability distributions and determine the pharmacodynamic target. We can then estimate if we will achieve the target with the dose.

This is called the probability of target attainment (PTA).

Question 4

Give differences between oral and intravenous antibiotics.

Answer 4

• Oral antibiotics may be absorbed slower - in a patient with a serious acute infection it may be better with IV. IV may be used when the oral route is inappropriate as the patient may have issues with their bowels.
• Absorption of oral antibiotics can vary but we can vary the rate of IV absorption.
• Self-administration can only occur with the oral route.
• The oral route is cheaper.

However the efficacy of both is the same once the dress has reached systemic circulation.

Question 5

What strategies are used to determine antibiotic duration?

Answer 5

• Clinical response - more appropriate in the hospital than the community as you can monitor patients
  
  • Biomarker driven e.g. CRP, Procalcitonin
  • Imaging strategy - e.g. using X-ray to look for evidence of consolidation has cleared
  • Other factors includes evidence, clinical factors, social factors, costs and resources available.

Question 6

How do we know when to start antibiotics?

Answer 6

Should be started when the benefits out way the disadvantages.

- There are times when they should always be started e.g. sepsis 
- There are times when it should never be started such as when there is no evidence of infection but they are sick e.g. auto-inflammation
- The choice must be done within the context of an overall management plan

Question 7

Give benefits of starting antibiotic therapy early.

Answer 7

• Lower risk fo mortality and morbidity
• If clinically stable, narrow spectrum antibiotics may be administered and the response assessed
• If clinically stable, an oral antibiotic may be administered and the response assessed
• Prevent infection metastases

Question 8

Give disadvantages of starting antibiotic therapy early.

Answer 8

• May reduce the time available to do cultures - this means a reduced change of triggered therapy and getting a diagnosis
• May reduce the time to do investigations and so over-treatment is possible
• May increase the change of giving the wrong antibiotic or not enough leading to resistance
• Insufficient time to check for allergies
• Toxicity

Question 9

What is the therapeutic window?

Give an example of 2 common antibiotics with a narrow therapeutic window.

Answer 9

A concentration range where you can achieve efficiency. Any drug has a therapeutic window. Some have a narrow therapeutic window. In these patients we monitor their concentration very carefully to ensure they stay in that window. In terms of antibiotics we do this for vancomycin/teicoplanin and (glycopeptides) gentamicin particularly (aminoglycosides). Both are otoxic (toxic to the ear) and nephrotoxic). Efficacy can be reduced if sub-therapeutic levels are reached.

Question 10

What is antibiotic stewardship?

Answer 10

A lot of antibiotics when used are impropriate.

It is an interdisciplinary effort. It involved timely and optimal selection, dose and duration of an antimicrobial for the best clinical outcome for the treatment or prevention of infection. This is all done whilst maintaining minimal toxicity to the patient and having the minimum impact on resistance an other ecological adverse effects such as C. diff.

Question 11

Give interactions of the following antibiotics:

(a) Quinolones e.g. ciprofloxacin
(b) Macrolides e.g. clarithromycin
(c) Trimethoprim
(d) Glycopeptides e.g. teicoplanin
(e) Linezoid
(f) Aminoglycosides

Answer 11

(a) Alters phenytoin (a medicine used to treat epilepsy) concentrations
(b) Enhances anticoagulant effect, increases plasma phenytoin concentrations and increases plasma digoxin concentration.
(c) Hyperkalaemia with ACE inhibitors and Nephrotoxicity with cyclosporin (immunosuppressant)
(d) Increases nephrotoxicity with aminoglycosides and loop diuretics
(e) Serotonin syndrome
(f) Ototoxicity with furosemide

Question 12

Give adverse reactions of the following antibiotics:

(a) Penicillins
(b) Co-amoxicalv
(c) Quinolones e.g. ciprofloxacin
(d) Macrolides e.g. clarithromycin
(e) Trimethroprim
(f) Glycopeptides
(g) Linezoid
(h) Aminoglycosides

Answer 12

(a) Allergy
(b) Cholestatic jaundice
(c) Tendonitis and prolonged QT intervals
(d) Prokinetic (diarrhoea)
(e) Erythema multiforme
(f) Otoxicity and nephrotoxicity
(g) Optic neuropathy and blood disorders
(h) Otoxcity and nephrotoxicity

Question 13

What antibiotics should we be aware of in pregnancy?

Answer 13

Quinolones, Trimepthroprim (folate antagonist), Aminoglycosides and Nitrofurantoin.

Question 14

What type of antibiotics are patients with penicillin allergy also able to cross-react with?

Answer 14

Cephalosporines such as cefuroxime

Question 15

What are the limitations of antibiotics?

Answer 15

• Antibiotics will not treat non-infectious diseases e.g. inflammatory conditions such as pancreatitis or diverticulitis
  
  • Antibiotics will not treat contaminated samples
  • Antibiotics may only be the supporting actor in some infections that require surgical intervention
  • All antibiotics “damage” your microbiome