Therapeutic drug monitoring — formative SAQs

SAQ 1 — Vancomycin monitoring in a child with serious MRSA infection (10 marks, 15 minutes)

Stem: A six-year-old, 20 kg child is receiving intravenous vancomycin for a complicated methicillin-resistant Staphylococcus aureus bacteraemia. The team asks you to design the therapeutic drug monitoring plan, state the target, and interpret an unexpectedly low trough. [1]

Model answer

Target (2 marks). The therapeutic target for serious MRSA infection is the 24-hour area under the concentration–time curve over the minimum inhibitory concentration — an AUC₂₄/MIC of 400 or more — per the 2020 consensus guideline from ASHP, IDSA, PIDS and SIDP. State that AUC-guided monitoring is preferred over a trough-only strategy because it achieves target exposure while reducing nephrotoxicity. [1]

Sampling (3 marks). Wait for steady state — about four to five half-lives, which in this child is around the fourth dose — before interpreting a maintenance trough. Draw the true trough within 30 to 60 minutes before the next dose, from a clean line, not during the infusion. AUC can be calculated from two timed levels (for example a peak after the infusion ends and a trough before the next dose) or estimated by Bayesian forecasting from a single level. Always document the dose, the dosing interval, the time of the last dose, and the time the sample was drawn. [1]

Interpreting an unexpectedly low trough (3 marks). Before changing the dose, exclude a sampling error (drawn at the wrong time or from the infusing line) and confirm the dose and interval were given as written. If the sample is valid, a low trough in a critically ill child often reflects augmented renal clearance — a state of high glomerular filtration driven by inflammation, fever and vasopressors — which clears vancomycin faster than standard dosing assumes. The response is not to assume underdosing but to raise the dose, shorten the interval, or move to Bayesian AUC dosing, then recheck. [1]

Daily review and safety (2 marks). Each day ask whether the drug is still needed, plan de-escalation once the organism and sensitivities return, and avoid co-administered nephrotoxins. Treat the child as well as the number: a low level in an improving child still needs correction of exposure, while a high level with a rising creatinine means withhold the next dose and recheck. [1]

SAQ 2 — A child with a toxic phenytoin level and hypoalbuminaemia (10 marks, 15 minutes)

Stem: A nine-year-old on long-term phenytoin for epilepsy presents with new horizontal nystagmus and an unsteady gait. The total phenytoin level is 28 mg/L (reference 10 to 20 mg/L). The albumin is 22 g/L. Outline the mechanism, the immediate management, and the dose-adjustment principle. [8] [9]

Model answer

Mechanism (3 marks). The level and the signs fit early phenytoin toxicity. Phenytoin follows saturable Michaelis-Menten kinetics: the enzyme that clears it approaches its maximum capacity (Vmax) within the therapeutic range, governed by the Michaelis-Menten constant (Km). Near the top of the range, clearance saturates, so a small dose increase produces a disproportionately large rise in level. Nystagmus typically appears around 20 to 30 mg/L, ataxia around 30 mg/L, and drowsiness and confusion at higher levels. [8]

The protein-binding trap (3 marks). Phenytoin is about 90 per cent bound to albumin, so only the free 10 per cent acts on the brain. With an albumin of 22 g/L, the free fraction rises, so the total level understates the active concentration — a child can be toxic on a total level that looks only mildly above range. Request a free phenytoin level (target free 1 to 2 mg/L) or apply an albumin-based correction to the total. [9]

Immediate management (2 marks). Withhold the next dose, provide supportive care, and protect the airway if the child is drowsy. There is no specific reversal agent; recheck the level as it falls. Review the recent history for an interacting drug (an enzyme inhibitor that has raised the level) or an inadvertent dose increase. [8]

Dose-adjustment principle (2 marks). When restarting, lower the maintenance dose in a small step and recheck, because near the top of the range a small dose change moves the level a lot. Never make a large maintenance increment. Document the new target, the free-level result, and the review date, and arrange follow-up monitoring at steady state. [8] [9]