Meropenem‐Induced Facial Myoclonus

Carbapenems are beta‐lactam antibiotics with the potential to cause neurotoxicity. Carbapenem‐induced myoclonus is rare, with less than 10 cases described in the literature. It may occur from hours to days after initiating treatment and completely resolves after discontinuing or reducing its dose. We present a 15‐year‐old boy who developed facial myoclonus while receiving meropenem.

Case Report

A 15‐year‐old boy with hereditary sensory and autonomic neuropathy type‐III (HSAN‐III), also known as familial dysautonomia, was admitted due to an esophageal tear caused by violent retching during a hyperadrenergic autonomic crisis ¹ triggered by COVID‐19 pneumonia. He required tracheostomy, placement of a nasogastric tube as an esophageal stent, and total parenteral nutrition. Due to psychomotor agitation increasing the risk of further esophageal damage, and severe hypertension the patient was prescribed midazolam, risperidone, and a transdermal clonidine patch. He had a protracted course, complicated by multiple intercurrent events, including a retroperitoneal abscess, treated with meropenem. At day 8 after meropenem initiation, he developed involuntary, spontaneous, irregular, arrhythmic, facial movements, of varying amplitude seemingly involving the right zygomaticus muscle. No other body areas were visibly affected. On the second day, the movements progressed to seemingly involve the left zygomaticus as well, asynchronous from the right side (Video 1). Otherwise, the patient had no changes in his baseline neurological examination, characterized by a decreased sensation of pain and temperature, mild limb ataxia, and absent deep tendon and corneal reflexes. He was afebrile. His blood pressure ranged from 93/36 mmHg to 166/120 mmHg, consistent with afferent baroreflex failure associated with his genetic condition. ¹

Video 1.

Segment 1: involuntary, spontaneous, irregular, arrhythmic, facial movements, of varying amplitude seemingly involving the right zygomaticus muscle. Segment 2: On the second day, the movements progressed to involve the left zygomaticus muscle, asynchronous from the right side.

His medications included meropenem 20 mg/Kg every 8 h for retroperitoneal abscess, risperidone 0.75 mg every 12 h, midazolam 0.06 mg/Kg/h, clonidine 0.2 mg/24 h transdermal patch, famotidine 20 mg for gastric ulcer prophylaxis, and total parenteral nutrition.

Brain MRI (DWI, SWI, FLAIR, T1, T2) and magnetic resonance angiography revealed a 3 mm ophthalmic artery infundibulum, with no other intracranial abnormalities. A 24 h video EEG showed mild generalized background slowing, and excess diffuse beta activity, but no ictal correlates with the facial movements. His serum Na, K, calcium, magnesium, phosphorus, and creatinine were normal. Blood urea nitrogen was initially increased (56 mg/dL, upper normal limit, 26 mg/dL) but subsequently normalized. Hemoglobin was low (consistent with moderate anemia), with normal platelets, he had leukocytosis with a normal differential, and elevated C reactive protein.

Carbapenem‐induced myoclonus was suspected. Due to the benefits outweighing the risks of discontinuing treatment, the patient continued the full course of meropenem for 13 more days. As the movements caused no distress to the patient, no symptomatic treatment was trialed. Facial myoclonus persisted throughout the rest of the antibiotic course. On the first day after meropenem was discontinued, the facial movements improved. On the second day, the movements disappeared. No other significant changes to treatment were made before the movements were resolved.

Discussion

While seizures and encephalopathy induced by carbapenems are commonly reported, very few patients with carbapenem‐induced myoclonus have been described 3–10 (Table S1). In patients receiving doses higher than recommended for their weight or renal function, or those with an underlying central nervous system disorder, the incidence of carbapenem‐induced neurotoxicity can increase from 1% to up to 11%. ² Most patients with carbapenem‐induced myoclonus ² , ³ , ⁴ , ⁵ , ⁶ , ⁷ , ⁸ , ⁹ , ¹⁰ had decreased renal function or were inadvertently administered higher doses than indicated for their body weight. The onset of myoclonus after initiation of treatment seems to be variable and ranges from immediate to a few days. In all cases, the movement disappeared promptly after either reducing the dose or discontinuing the medication. Although in our patient myoclonus appeared 8 days after starting meropenem, no other metabolic abnormalities were associated neither with the onset nor with the resolution of these movements, which resolved promptly after the antibiotic was discontinued. Although we did not perform surface EMG and EEG back‐averaging to better characterize the pathophysiology, we hypothesize that the origin of myoclonus in our patient was segmental due to its localized nature, affecting initially one side of the face, and progressing bilaterally. Moreover, brainstem dysfunction in FD may have contributed to the onset of facial myoclonus. ¹¹ , ¹² Another factor that may have predisposed our patient to develop this side effect is that his body weight may have been overestimated due to his prolonged admission and need for parenteral nutrition, resulting in the administration of a higher dose of meropenem. Recognition of this side effect can help avoid unnecessary treatments and provide reassurance about prognosis once other causes have been ruled out.

Author Roles

(1) Research project: A. Conception, B. Organization, C. Execution; (2) Statistical Analysis: A. Design, B. Execution, C. Review and Critique; (3) Manuscript Preparation: A. Writing of the first draft, B. Review and Critique.

P.M.V.: 1A, 1B, 1C, 3A

K.D.: 1A, 1B, 1C, 3B

Z.K.: 1A, 1B, 1C, 3B

A.G.D.: 1A, 1B, 3B

S.F.: 1A, 1B, 3B

H.K.: 1A, 1B, 3B

Disclosures

Ethical Compliance Statement: The authors confirm that the approval of an institutional review board was not required for this work. Consent was obtained from the patient and his parents, as well as written authorization for the use and disclosure of the video for academic purposes. We confirm that we have read the Journal's position on issues involved in ethical publication and affirm that this work is consistent with those guidelines.

Funding Sources and Conflicts of Interest: The authors declare that there are no conflicts of interest relevant to this work.

Financial Disclosures for the Previous 12 Months: Dr. Patricio Millar Vernetti has received research funding from Theravance Biopharma Inc. Dr. Kaia Dalamo has no disclosures to report. Zenith Khan has no disclosures to report. Dr. Alejandra Gonzalez‐Duarte has received funding and honoraria from Alnylam Pharmaceuticals and Pfizer as a speaker and consultant for ATTR amyloidosis. Dr. Steven Frucht has no disclosures to report. Dr. Horacio Kaufmann received research funding from the NIH, The Michael J. Fox Foundation, MSA Coalition, Familial Dysautonomia Foundation, FDA, and Biogen; is an advisory board member for Lundbeck, Biogen, Biohaven, Theravance, PTC Therapeutics, ONO, Takeda, Vaxxinity, and Lilly; and is Editor‐in‐Chief of Clinical Autonomic Research.

Supporting information

Table S1. Characteristics of patients with carbapenem‐induced myoclonus