Case Presentation: A 63-year-old male presented with altered mental status of one day duration. The patient’s history was significant for CAD, CKD Stage 3, and a recent whipple procedure for cholangiocarcinoma complicated by abdominal abscess requiring percutaneous drainage and prolonged course of ertapenem (renally dosed). He was admitted to the hospital with encephalopathy after having received 18 days of ertapenem, only oriented to self when at baseline he was fully alert and oriented to self, place, time, and situation. His vital signs were within normal limits. Initial neurological exam was non-focal, and initial metabolic profile, complete blood count and CT head were without any acute abnormality. Extensive work-up was conducted to delineate the etiology of the patient’s acute encephalopathy. Infectious work-up, including blood and urine cultures, diagnostic paracentesis, and a respiratory viral panel were unremarkable. CT Abdomen and Pelvis showed the previously known abdominal fluid collection with an interval decrease in size. CT Chest was significant for a moderate loculated left pleural effusion and bilateral pulmonary nodules suggestive of metastatic progression of disease. MR Brain was suggestive of a small right frontal subacute infarct and bilateral small subdural hematomas, but no evidence of enhancing mass or metastases. The hospital course was complicated by new onset myoclonic jerks, ptosis, diplopia, dysarthria, and upper extremity weakness. EEG showed no epileptiform activity. Neuromuscular disease testing revealed a negative acetylcholine receptor antibody and a positive paraneoplastic panel significant for the P/Q-type calcium channel antibody (0.06 nmol/L, normal ≤ 0.02 nmol/L). Due to the negative work-up and high suspicion that ertapenem could be the possible culprit for the acute neurological changes, ertapenem was discontinued. Two days after discontinuation the patient was oriented to self and place, and after six days the encephalopathy and acute neurological deficits had completely resolved.
Discussion: Multiple cases of ertapenem-induced encephalopathy and myoclonic seizures have been reported in recent years, particularly in patients with renal dysfunction. Although onset of encephalopathy typically occurs within the first week of antibiotic use, there are reports of symptoms occurring up to three weeks after starting treatment, as was evident in our case. Unlike Lambert-Eaton myasthenic syndrome and small cell lung cancer, no well-known correlations have been reported between neuromuscular junction disorders and cholangiocarcinoma. Although the positive albeit low titer for the P/Q-type calcium channel antibody supports the presence of a paraneoplastic syndrome, the timing of symptom onset and resolution better supports an ertapenem-associated neuromuscular junction disorder and encephalopathy. Early recognition of ertapenem-induced encephalopathy and neurological deficits, and discontinuation of the antibiotic is essential to reverse and restore neurological function.
Conclusions: Ertapenem is a commonly used antibiotic with both early and delayed onset of rare central nervous system adverse effects that may mimic a paraneoplastic process. In addition to the known effects of encephalopathy and myoclonic seizures, it is important to consider symptoms of neuromuscular junction dysfunction as part of the spectrum, as early recognition of these symptoms can lead to prompt drug discontinuation and reversal of neurological deficits.