Discussion and Conclusion
Our report describes a case of beta-lactam induced encephalopathy leading to an altered mental status and somnolence. She received several courses of beta lactam antibiotics including ceftriaxone, pipercillin-tazobactam (Tazocin) and meropenem. The patient symptoms dramatically improved and resolved within 24 hours after beta-lactam discontinuation, consistent with previous case reports describing the neurotoxicity of these antibiotics.1-8 There was no other medical cause identified or other medication regimen changes done to explain her alteration in cognitive status & its resolution. The diagnosis of drug induced neurotoxicity can be challenging, and so far, the discontinuation of the offending agent is the best approach to retrospectively diagnose beta-lactam induced neurotoxicity after ruling out other causes.1
Antibiotic-associated encephalopathy (AAE) can be classified into three unique clinical phenotypes: encephalopathy which usually associated with seizures or myoclonus occurring within days after antibiotic initiation (caused by penicillins and cephalosporins); encephalopathy characterized by psychosis (caused by procaine penicillin, macrolides and quinolones); and encephalopathy with cerebellar signs and MRI abnormalities seen within weeks after initiation of antibiotics (caused by metronidazole).9
The main risk factor associated with beta-lactam neurotoxicity is renal failure, especially if doses were not appropriately adjusted which may lead to significant and rapid accumulation of drug level.4,10,11 Other risk factors include advanced age, low body weight, previous CNS disease, concurrent use of other neurotoxic medications, and critical illness with ICU admission.2 Beta-lactam neurotoxicity have been reported in 10-15% of ICU patients with clinical manifestation ranging from confusion, hallucinations to myoclonus, convulsions and non-convulsive status epilepticus.1 Our patient is unique as she had a normal renal function and body weight, no previous known CNS disease, not critically ill with the only known risk factor was her advanced age.
Not all beta-lactams carry equal risk for neurotoxicity. With regards to pro-convulsing activity of beta-lactams, the highest risk was seen with cefazolin, followed by cefepime, penicillin G, and imipenem, while lower seizure risk was observed with ceftriaxone, piperacillin, cefotaxime, and cefoxitine respectively.1
There are studies reporting neurotoxicity and pro-convulsive effects of imipenem especially in patients suffering from a brain injury.12, 13 In addition, there have been increasingly more studies and reports of neurotoxicity associated with cefepime which can manifest with or without seizures.14-17 In one report, it was found that 7-15% of critically ill patients on cefepime developed neurotoxicity.8 Our patient did not receive the previous commonly reported beta-lactams to be associated with neurotoxicity, as she received ceftriaxone and tazocin before developing the encephalopathy.
Since the clinical picture was highly suggestive of beta-lactam induced neurotoxicity, we used the Naranjo Adverse Drug Reaction Probability Scale and our patient received a score of 6, suggesting a probable adverse drug reaction (Table 2).