Reversible Choreoathetosis in a Patient with End-stage Renal Disease from Administration of Ceftriaxone

Abstract

A wide spectrum of neurological manifestations may be induced in patients with impaired renal function when receiving beta-lactam antibiotics due to the altered pharmacokinetics. Beta-lactam antibiotics is commonly chosen for treatment in patients with end-stage renal disease due to its good penetration into the cerebrospinal fluid and long half-life.Here, we present a case of a 73-year-old Malay lady with end-stage renal disease who was admitted for treatment of gastroenteritis. She presented with acute onset of diarrhoea and vomiting for two days. She was febrile during admission and was prescribed intravenous ceftriaxone 2 grams daily for coverage of bacterial gastroenteritis. Among the investigations done, white cell count were raised together with the C-reactive protein. Stool and blood cultures were also sent for further investigations. Over a three-day period, her general condition improved and she was discharged home. The onset of clinical manifestation of choreoathetosis was noticed by her caregiver on the same day of discharge. She was brought back to the emergency department and was readmitted for further workup of the new presenting complain of abnormal movement and disorientation. Haemodialysis was arranged and immediately commenced during her admission. The renal nurses reported that her neurological symptoms were noticeably improved after completion of the initial dialysis without any treatment.Ceftriaxone including other beta lactam antibiotics penetrates the blood-brain barrier and induces glutamate in excess in the striatum and cerebral cortex, resulting in neurological hyper excitability disorders despite appropriate renal adjusted dosage for end-stage renal disease patients on haemodialysis.

Ceftriaxone-induced encephalopathy in a patient with a normal renal function

“…We did a literature review on PubMed in April 2023 without a time limit and identified 15 case reports,4 6–9 11–13 15–18 20 21 26 7 small case series2 3 5 10 14 19 27 and 2 pharmacovigilance database analysis22 28 discussing serious neurological effects of ceftriaxone in humans.…”

“…Ceftriaxone-related adverse neurological effects are uncommon to very rare and mostly mild (dizziness, headache, ataxia, paresthesia) 1. However, multiple case reports2–21 and a case series from a French pharmacovigilance database22 have been published on more severe reactions, notably encephalopathy, trouble of consciousness and choreoathetosis. With ceftriaxone being one of the most commonly used parenteral antibiotics worldwide23, there is a possibility that many more cases of these severe adverse reactions are not readily recognised or may be confused with common delirium.…”

Physiologically-based pharmacokinetic modeling for single and multiple dosing regimens of ceftriaxone in healthy and chronic kidney disease populations: a tool for model-informed precision dosing

“…Other studies have demonstrated the influence of the kidney functional state on toxicity and how ceftriaxone led to side effects ( Kim et al, 2012 ; Safadi et al, 2014 ; Tan and Tun, 2019 ; Yamada et al, 2020 ; Oyama et al, 2021 ). For instance, a case series reported that ceftriaxone treatment for a long period at high dosages was associated with the development of pseudolithiasis in patients with severe renal impairment who received dialysis ( Oyama et al, 2021 ).…”

Ceftriaxone-induced encephalopathy in a patient with multicentric glioma

“…[2,9] An alternate hypothesis is that ceftriaxone causes the release of inflammatory cytokines like tumor necrosis factor-alpha which triggers neurotoxicity. [14] Renal impairment [1,3,5,7,9,10,11,13,15] and old age [1,3,5,7,9,10,13,15] are the main predisposing factors observed in most patients diagnosed with CIE in the literature. Hepatic dysfunction, [5] impaired biliary excretion, [3] administration of high-dose ceftriaxone, [8] and preexisting neurological conditions [1,12] are the other risk factors associated with CIE. Cerebrovascular disease, [10,14] meningitis, [8] and cerebral contusion [15] are the neurological conditions that have been reported to predispose to CIE. e risk factors in the case we present are old age and the presence of a multicentric glioma.…”

“…[ 2 , 9 ] An alternate hypothesis is that ceftriaxone causes the release of inflammatory cytokines like tumor necrosis factor-alpha which triggers neurotoxicity. [ 14 ]…”