Ertapenem-induced encephalopathy in a patient with liver abscess and acute kidney injury

Design

Case presentation

A male patient in his late 70s with baseline normal cognitive function presented with acute kidney injury (AKI; eGFR 32 mL/min/1.73 m²). He was started on clarithromycin and teicoplanin due to a history of penicillin allergy. After 3 days, his clinical status deteriorated to septic shock.

CT scan showed liver abscess, for which his antibiotics were changed to meropenem 1 g TID (lowered to BID because eGFR 38 mL/min/1.73 m²). On day 15, the patient was clinically improving (eGFR 58 mL/min/1.73 m²), and meropenem was switched to ertapenem 1 g daily for outpatient therapy based on microbiologist recommendations.

Two days after beginning ertapenem, the patient exhibited symptoms including night-time delirium, disorientation, insomnia, appetite loss, jerking movements, and hallucinations. Extensive investigations, including lumbar puncture, brain imaging (CT and MRI), electroencephalogram (EEG), and repeat abdominal imaging, revealed no abnormalities.

Following a systematic cessation of suspected medications one by one, the patient’s symptoms resolved rapidly within two days of discontinuing ertapenem, strongly implicating the medication as the causative agent. The patient was eventually discharged with no further signs of insomnia, hallucination, or agitation observed during the patient’s recovery.

Study Author Conclusions

The report attributed the patient's neurotoxicity to several underlying factors, including AKI, hypoalbuminemia, and advanced age, which are known to elevate the risk of carbapenem neurotoxicity due to prolonged drug half-life and altered protein binding. The pharmacokinetics of ertapenem, which is highly protein-bound and predominantly eliminated renally, coupled with impaired renal clearance, likely resulted in elevated free drug concentrations leading to central nervous system (CNS) toxicity.

This case provides a valuable lesson on the importance of considering medication-related adverse effects in the differential diagnosis of acute delirium and the need to balance the risks and benefits of investigations in elderly patients.

Ertapenem-Induced Hallucinations and Delirium in an Elderly Patient

Design

Case presentation

A 71-year-old morbidly obese male with multiple comorbidities, including chronic kidney disease and diabetic foot osteomyelitis, presented with ertapenem-induced hallucinations and delirium. The patient, receiving outpatient intravenous antibiotics (daptomycin 1 g daily and ertapenem 1 g daily) through an antimicrobial stewardship program, was admitted to a tertiary care hospital for acute heart failure exacerbation. Notably, his presentation included profound neuropsychiatric symptoms, including fluctuating orientation, visual hallucinations, and suicidal ideations—a marked departure from his baseline cognitive state.

A comprehensive diagnostic evaluation, which encompassed physical examination, laboratory studies, imaging, and a psychiatric assessment, failed to identify an alternate etiology for the patient’s symptoms. Drug-induced toxicity was therefore suspected, and ertapenem was discontinued on hospital day 4 while daptomycin therapy was maintained. The patient exhibited a dramatic clinical improvement, with resolution of neuropsychiatric manifestations and normalization of mentation within 72 hours. The patient was discharged to a nursing facility after day 12, finishing his 6-week course of daptomycin as previously planned.

Study Author Conclusions

The Naranjo probability scale, applied retrospectively, indicated a probable relationship between ertapenem and the adverse effects based on the timeline and absence of other explanations. 

This case report and literature review demonstrates the potential severity of non-seizure-related neurotoxicity associated with ertapenem. As this toxicity can be life-threatening if unrecognized, it is crucial that clinicians across all practice settings be proactive in detecting and preventing it.

Ertapenem neurotoxicity in liver transplantation

Design

Case presentation

A 72-year-old female liver transplant recipient presented with ertapenem-induced neurotoxicity. The patient, with a history of hypertension, type II diabetes, and HCV-induced cirrhosis, developed neuropsychiatric symptoms, including visual and auditory hallucinations and sleep-wake dysregulation, following a seven-day course of ertapenem for a urinary tract infection caused by Klebsiella BLEE. Initial evaluations, including CT, MRI, and electroencephalogram, excluded structural brain abnormalities. Similarly, tacrolimus levels remained stable, ruling out immunosuppressive toxicity. Based on a Naranjo score of six and the temporal connection to ertapenem administration, a pharmacologic etiology was deemed probable. Discontinuation of ertapenem and symptomatic treatment with haloperidol led to symptom resolution.

Study Author Conclusions

Neurotoxicity due to the use of ertapenem is infrequent. Hence we should consider hepatic encephalopathy and neurotoxicity due to immunosuppressive drugs in patients with liver transplant for the differential diagnosis. Treatment consists of discontinuation of the drug and symptomatic management with neuroleptics.

Ertapenem-induced encephalopathy

Design

Case presentation

A 59-year-old Caucasian male with stage 3 chronic kidney disease (CKD) developed non-seizure-related neurotoxicity after ertapenem exposure. The patient, admitted for dyspnea and empyema, was treated with vancomycin and ertapenem 500 mg IV q24h (due to admission eGFR of 22 mL/min/1.73m²), later increased to 1000 mg with improving renal function.

By day 7 of therapy, the patient exhibited symptoms of delirium, disorientation, and agitation, which progressed to visual hallucinations and severe agitation, requiring intubation for airway protection. Despite discontinuation of other potential causative medications and non-pharmacologic interventions, no improvement was observed until ertapenem was stopped. Within 24 hours of ertapenem cessation, the patient was successfully extubated, with mental status returning to baseline.

The patient was discharged the following day in stable condition, underscoring a probable causative link between ertapenem and neurotoxicity, as supported by a Naranjo Scale score of 6. 

Study Author Conclusions

This report highlighted the susceptibility of patients with moderate CKD to ertapenem-induced neurotoxicity, despite current dosing recommendations primarily targeting those with end-stage renal disease. The patient’s rapid resolution after discontinuation of ertapenem, absence of significant systemic or metabolic derangements, and lack of evidence for infectious or structural CNS pathology further solidify ertapenem as the likely cause.

Ertapenem’s known antagonism of gamma-aminobutyric acid (GABA) type A receptors in the central nervous system was implicated in the adverse effects, exacerbated by its lipophilicity and altered clearance in renal impairment. The case emphasizes the importance of considering carbapenem-induced neurotoxicity in patients with acute cognitive changes, particularly those with renal dysfunction, and advocates for more cautious dosing strategies in this population.

Ertapenem-Induced Encephalopathy in a Patient With Normal Renal Function

Design

Case presentation

A 67-year-old male with normal renal function presented with ertapenem-induced encephalopathy. The patient, with a history of lumbar spine osteomyelitis and other co-morbidities, presented with acute hallucinations and altered mental status five days after initiating ertapenem therapy at 1 g daily for treatment of post-surgical infections. Clinical examinations revealed lethargy, incoherent speech, mild asterixis, and tremor, while laboratory assessments showed stable renal function, normal electrolytes, and no significant abnormalities in infectious or metabolic markers. Imaging studies, including computed tomography of the head and chest, were unremarkable, and an electroencephalogram showed no seizure activity. The Naranjo Adverse Drug Reaction Probability Scale assigned a score of 7, indicating a probable adverse drug reaction to ertapenem; ertapenem was then stopped in favor of ceftazidine 2 g q8h, after which hallucinations and neurological symptoms improved. The patient returned to his baseline mental status within 2 days of stopping ertapenem therapy.

Study Author Conclusions

We are sharing our experience of a patient with normal renal function who developed neurotoxicity following standard dosing of ertapenem. The goal of this case report is to draw attention to the neurologic and encephalopathic potential of ertapenem. Identifying ertapenem as a potential causative agent of these conditions can spare unnecessary investigations and health care expenditures. In our patient, supportive care following discontinuation of ertapenem resulted in complete resolution of his hallucinations and altered mental status.