Background and importance Carbapenems, such as ertapenem, are beta-lactam-type antibiotics used to treat a wide variety of infections. Neurological disorders have been observed in patients during ertapenem treatment, although the factors that contribute to this toxicity are not well defined and ertapenem plasma levels have not been taken into account.
Aim and objectives The aim of the study was to evaluate the relationship between ertapenem plasma concentrations and ertapenem-induced neurological toxicity.
Material and methods Retrospective cohort study conducted at a tertiary care medical centre, from October 2019 to February 2021.
Adult patients treated with ertapenem for a minimum period of 72 hours having at least one determination of ertapenem concentration were included, favouring those with old age and comorbidities. Critical patients were excluded.
The modified Karch–Lasagna algorithm was used to establish and categorise the relationship between ertapenem use and the appearance of any clinical signs or symptoms that might indicate neurotoxicity, considering neurotoxicity when a score ≥6 was obtained.
To analyse ertapenem blood samples we use a high-resolution liquid chromatography system with an UV/visible detector. Non-parametric tests were performed to search for any difference between groups.
Results 102 patients were included, 53% males, with a median age of 72 years.
Ertapenem plasma concentration was analysed at a mean of 6.4 (±4.1) days since starting antibiotic administration. 13/102 patients (12.7%) presented neurological disorders during ertapenem treatment, mainly confusional state and drowsiness. We also noted 3 cases of hallucinations as well as 1 patient who presented epileptic seizure and finally died.
Mean ertapenem blood concentration in patients who experienced neurotoxicity was 32.16 μg/mL (95% CI 8 to 56.3) vs 14.63 μg/mL (95% CI 11.4 to 17.8) for those who did not present. A statistically significant difference was observed in the median ertapenem blood concentration between the two groups (18.66 μg/mL neurotoxicity group vs 9.7 μg/mL control group; p= 0.014).
Conclusion and relevance We can conclude that the group of patients who presented neurological disorders had higher concentrations of ertapenem. Therapeutic drug monitoring can help identify those patients with high risk for neurotoxicity.
However, more studies are needed to define which patients could obtain the greatest benefit from a close control of ertapenem blood concentration in order to prevent this neurotoxicity.
Conflict of interest No conflict of interest
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