Issue: 2019 > September > editorial

Therapeutic drug monitoring of flucloxacillin

P.L.A. van Daele
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I favour therapeutic drug monitoring. It potentially decreases the risk of toxicity while increasing therapeutic effects of medication. Yet, therapeutic drug monitoring is not necessary for every prescribed drug. It is especially useful in drugs with a small therapeutic window, for example, lithium or antiepileptics, or when there is a strong relation between drug concentration and effect.
In the current issue of the journal, Dijkmans et al. elaborate on therapeutic drug monitoring in patients treated with flucloxacillin who are scheduled to switch from intravenous to oral administration. They state that orally administered flucloxacillin has variable absorption and by performing an oral absorption test (OAT), it is possible to identify patients with inadequate or decreased flucloxacillin absorption. In their paper, they describe two tests, one with and one without interruption of the intravenous administration. Both tests perform equally well, however the test in which the intravenous administration is not interrupted is much easier to conduct. In the study, just over 13% of patients showed, in the authors’ opinion, an inadequate increase in serum level.1
There have been previous reports on therapeutic drug monitoring of beta-lactam antibiotics but most have focused on critically ill patients in an intensive care unit, demonstrating that in such situations drug monitoring can be useful to optimise antibiotic exposure and maximise effectiveness, thereby potentially improving outcome.2-5 It is unclear whether this conclusion also holds true for the current study as the patient population is different and apparently less ill, knowing that they can switch route of administration. It would have been informative if we would have known the outcome of those who failed the test. Did they switch therapy? Was there an increase in flucloxacillin dose? Was their outcome worse? And what to do with patients with mild infection, who never need intravenous therapy? Need they be tested?
The authors plea that other institutions adopt their above-mentioned approach of OAT in the management of patients with severe S. aureus infections. It would be been more convincing if they had demonstrated that their approach also improves outcome.



  1. Dijkmans AC, Kweekel DM, Balmforth C, et al. The simplified oral flucloxacillin absorption test: an accurate method to identify patients with inadequate oral flucloxacillin absorption. Neth J Med. 2019;77:255-60.
  2. Muller AE, Huttner B, Huttner A. Therapeutic Drug Monitoring of Beta-Lactams and Other Antibiotics in the Intensive Care Unit: Which Agents, Which Patients and Which Infections? Drugs [Internet]. 2018 Mar 23 [cited 2019 Sep 8];78(4):439–51. Available from: http://link.springer. com/10.1007/s40265-018-0880-z
  3. Patel BM, Paratz J, See NC, et al. Therapeutic Drug Monitoring of Beta-Lactam Antibiotics in Burns Patients—A One-Year Prospective Study. Ther Drug Monit [Internet]. 2012 Apr [cited 2019 Sep 8];34(2):160–4. Available from: openurl?sid=WKPTLP:landingpage&an=00007691-201204000-00008.
  4. Huttner A, Harbarth S, Hope WW, Lipman J, Roberts JA. Therapeutic drug monitoring of the ß-lactam antibiotics: what is the evidence and which patients should we be using it for?: Figure 1. J Antimicrob Chemother [Internet]. 2015 Jul 17 [cited 2019 Sep 8];70(12):dkv201. Available from:
  5. Roberts JA, Abdul-Aziz MH, Lipman J, et al. Individualised antibiotic dosing for patients who are critically ill: challenges and potential solutions. Lancet Infect Dis [Internet]. 2014 Jun [cited 2019 Sep 8];14(6):498–509. Available from: