Table 2. Naranjo Adverse Drug Reaction Probability
Scale* (Total score 5-8 : A probable drug reaction, with a
reasonable temporal sequence to support the reaction)
The pathophysiology of beta-lactam induced neurotoxicity is not yet
fully known. However, several mechanisms have been linked to beta-lactam
induced CNS toxicity as following:
- By decreasing gamma-aminobutyric acid (GABA) neuroinhibitory tone
through a concentration dependent inhibition GABAA receptor complex
subunits either in a competitive (cephalosporins) or non-competitive
(penicillins) way.1 Therefore, benzodiazepines and
barbiturates which act as positive modulators of GABAA receptors, are
more effective than phenytoin and other anti-convulsive agents to treat
seizures induced by beta-lactams.1,18
- The direct GABAA receptor complex antagonistic action as beta-lactam
antibiotics can bind directly to it due to the GABAA receptor similarity
with the beta-lactam ring.1
- In addition, cephalosporins can induce endotoxin and cytokine release
leading to neurotoxic effects.1
Our case highlights the importance of keeping in mind the pros and cons
when using antibiotics including beta-lactams in “at risk patients”
such as those with renal impairment, advanced age, or underlying CNS
abnormalities, and to appropriately choose the dose and duration of
therapy. When a patients is receiving a beta-lactam and develops an
altered mental status, hallucinations with or without seizures, it is
essential to think about adverse drug reactions after ruling other
causes. Having a low threshold of suspicion, therapeutic drug
monitoring, and a continuous electroencephalogram (EEG) monitoring could
improve the early detection of beta-lactam induced neurotoxicity and
therefore, improve patients’ outcome by discontinuation of the offending
agent.