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).