Question 14

a)    Outline the dosing adjustments in a patient with septic shock and moderate to severe renal dysfunction (without dialysis) for the following drug groups:
i.    Aminoglycosides
ii.    Beta lactams
iii.    Carbapenems
iv.    Glycopeptides

(6 marks)

b)    Outline the factors that influence antimicrobial drug dosing for the critically ill patient on renal replacement therapy  (4 marks) 


 

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College comments

Syllabus topic/section: 2.1.21: Applied Pharmacology in Intensive Care; Immunology: Antimicrobials 

Discussion: 

As stated in the syllabus: “Detailed mechanism of action, pharmacokinetic and pharmacodynamic information is not required. This is covered in the Part I syllabus and examination”. This question is a good example of applied pharmacology of commonly used antibiotics in the ICU. The question explored how we alter the use of such medications in clinical practice in patients with renal dysfunction.

Candidates are reminded to be familiar with the glossary terms. Both parts a) and b) were “outline” questions which is defined as: “Provide a summary of the important points”.

For part a), answers that only stated “Reduce dose or interval” received less marks than those that provided more detail including details about the kill characteristics of the drugs, what doses would be given and, if important, what levels would be targeted.

For part b), a broad approach was required, rather than a focus upon one aspect, neglecting others. Good answers considered patient factors, drug factors, kill characteristics including MIC, RRT factors (type and settings) and factors related to the disease and organism.

The rubric is provided to aid in the candidate's future study.
Rubric

Below standard

At standard

Above standard

a)

Outline the dosing adjustments in a patient with septic shock and moderate to severe renal dysfunction (without dialysis) for the following drug

groups

If content for each drug category is partly correct, half marks can be awarded.

  1. Aminoglycosides
  2. Beta Lactams
  3. Carbapenems
  4. Glycopeptides

(6 marks)

Up to 1.5 marks per drug category

b)

Outline the factors that influence antimicrobial drug dosing for the critically ill patient on renal replacement therapy

Content lacking or incorrect

Does not mention drug related considerations or information for drug- related considerations

Gives reasonable content in the drug- related considerations such as

kill characteristics of antibiotics

changes in critically ill

- protein-binding

-volume of distribution ability for therapeutic monitoring

At standard PLUS

Most aspects of patient, drug and RRT related considerations

Content less detailed for RRT-related and/or patient-related considerations

Must describe drug- related considerations to be At Standard

(4 marks)

0-1.5 marks

2-3 marks

3.5 – 4 marks

Interpretation

This question is an alloy of several historically influential questions from the past papers, which makes the maximum mark of 6.0 and the pass rate of 30% difficult to comprehend. The impression one is left with is that the past papers have become deprioritised in the eyes of the preparing candidates, perhaps because it is felt that there will never be any repeated questions. This is of course a self-perpetuating curse, as one can never know whether the questions are repeated unless one is familiar with past questions, and so if all candidates eschew the historical papers, all candidates will be forever surprised by repeated questions, believing them to be completely novel. 
 

a) is a rephrasing of Question 13.3 from the first paper of 2010, which asked the candidates to "briefly outline the dosing adjustment and the monitoring necessary in patients with septic shock for each of the following  drug groups  in patients  with moderate  to severe renal dysfunction (without dialysis)", except this time they left the fluoroquinolones out of it.

In brief:

  • Aminoglycosides keep the same dose, and are interval-adjusted (with monitoring of drug levels)
  • Beta-lactams can be either dose-adjusted or interval-adjusted; monitoring is unnecessary
  • Carbapenems can be either dose-adjusted or interval-adjusted; monitoring is unnecessary
  • Glycopeptides get a loading dose,  and are interval-adjusted (with monitoring of trough drug levels)

b) is reminiscent of Question 4 from the second paper of 2018, which asked for the "principles involved in determining the loading dose and dosing frequency of antimicrobials in patients undergoing continuous veno-venous haemodiafiltration (CVVHDF)". However, this time it was "the factors that influence",  which probably would need to have some structure for four marks. One may wish to introduce a classification here:

  • Pharmacokinetic factors:
    • Volume of distribution
    • Protein binding
    • Hepatic/biliary clearance
    • Ability to monitor levels
  • Pharmacodynamic factors:
    • Antibiotics with time-dependent killing may be dosed more frequently if they are well cleared by CRRT
    • Antibiotics with concentration-dependent killing may be dosed normally
  • CRRT technology
    • Continuous vs. intermittent
    • Dialysis vs. haemofiltration
    • Filter properties, eg. porosity
  • Patient factors
    • Residual renal function
    • Increased susceptibility to toxicity
    • Altered volume of distribution

 For 4 marks, one could not have been too liberal with the details here.

References

McKenzie, Cathrine. "Antibiotic dosing in critical illness." Journal of antimicrobial chemotherapy 66.suppl 2 (2011): ii25-ii31.

Ulldemolins, Marta, et al. "Antibiotic dosing in multiple organ dysfunction syndrome." CHEST Journal 139.5 (2011): 1210-1220.

Chertow, Glenn M., et al. "Guided medication dosing for inpatients with renal insufficiency." Jama 286.22 (2001): 2839-2844.

Linton, A. L., and D. H. Lawson. "Antibiotic therapy in renal failure."Proceedings of the European Dialysis and Transplant Association. Vol. 1. 1970.

Trotman, Robin L., et al. "Antibiotic dosing in critically ill adult patients receiving continuous renal replacement therapy." Clinical infectious diseases 41.8 (2005): 1159-1166.