A case series of confusional states and other neurotoxic effects caused by ertapenem

Danés, Imma; Pérez, Elena Cónde; Pigrau, Carles; Gracia, Rosa Maria; Perelló, Manel; Sueiras, M.; Aguilera, Cristina; Agustí, Antònia

doi:10.1111/bcp.14582

Cited by 5 publications

(7 citation statements)

References 14 publications

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“… 11 In patients with hypoalbuminemia and reduced renal clearance, free active ertapenem drug levels may be higher and therefore CNS toxicity may be increased. 29 , 33 , 34 Among patients with available serum albumin level data, 86% had hypoproteinemia. Moreover, most of the patients were elderly and about half of the patients had impaired renal function, suggesting that patients with advanced age or renal insufficiency with hypoproteinemia should be alert to ertapenem-related neurotoxicity.…”

Section: Discussionmentioning

confidence: 99%

Ertapenem-Induced Neurotoxicity: A Literature Review of Clinical Characteristics and Treatment Outcomes

Wang¹,

Zhou²,

Zhou³

et al. 2023

IDR

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Background Neurotoxicity is a rare adverse event for ertapenem. Given the limited evidence, large patient data are needed to aid in the identification and management of this fatal complication. Aim of the review, we summarize the characteristics, risk factors, and treatment of ertapenem-induced neurotoxicity. Methods Pubmed, Web of Science, Embase, Cochrane library, Wanfang, CNKI, China VIP database were searched up from 31 October 2001 to 31 December 2022. All articles concerning neurotoxicity induced by ertapenem were included. The retrieved articles were screened by two experienced clinicians by reading the titles, abstracts, and full texts. Results A total of 66 patients were included, with a median age of 71.5 years (range 40–92), of whom 45 (68.2%) were male. Twelve patients (18.2%) received irrational doses (exceeding the recommended dose), and 30 patients (45.5%) had chronic renal insufficiency. The median time to symptom onset was 5 (range 1–14). Epileptiform seizures (42.4%), visual hallucinations (36.4%), altered mental status (25.8%), and confusion (22.7%) were the most common symptoms of ertapenem-induced neurotoxicity. Of the 29 patients with reported albumin levels, 25 had serum albumin <3.5 g/dl. Ertapenem was discontinued in 95.5% of patients, and 90.9% recovered completely. Median time to symptom recovery was 7 days (range 1–42) after intervention including antiepileptic administration, or hemodialysis. Conclusion Neurotoxicity is a rare adverse event for ertapenem, especially in patients with advanced age, renal insufficiency, pre-existing neurological disease, and hypoalbuminemia. This adverse reaction usually resolves with medication interruption, or antiepileptic administration and hemodialysis.

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Section: Discussionmentioning

confidence: 99%

Ertapenem-Induced Neurotoxicity: A Literature Review of Clinical Characteristics and Treatment Outcomes

Wang¹,

Zhou²,

Zhou³

et al. 2023

IDR

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“…Data from clinical trials and other open‐label studies, which have previously evaluated ertapenem safety as an end point, stated seizures as an uncommon drug‐related adverse event, observed in between 0.1% and 0.5% of treated patients 19 . Furthermore, other cases of neurological adverse events, including altered level of consciousness, hallucinations, confusional state or abnormal movements related to ertapenem administration, have been published elsewhere 3–11 . By contrast, studies assessing frequency or factors contributing to ertapenem toxicity are scarce.…”

Section: Discussionmentioning

confidence: 99%

“…The main clinical outcome was the presence of any suspicious neurological side effect related to ertapenem administration. Based on literature reviews 1,11 and according to the Common Terminology Criteria for Adverse Events 14 we search for confusional status, depressed level of consciousness, hallucinations, myoclonia, delirium, non‐convulsive status epilepticus and seizures. For individuals with presumed neurotoxicity, clinical and pharmacologic data were reviewed by three clinical pharmacists (D.C., A.P.…”

Section: Methodsmentioning

confidence: 99%

“…19 Furthermore, other cases of neurological adverse events, including altered level of consciousness, hallucinations, confusional state or abnormal movements related to ertapenem administration, have been published elsewhere. [3][4][5][6][7][8][9][10][11] By contrast, studies assessing frequency or factors contributing to ertapenem toxicity are scarce. Our research identified 13 cases of ertapenem-related neurotoxicity (13%), including one patient who experienced epileptic seizures (1%).…”

Section: Mcg ML à1mentioning

confidence: 99%

“…2 Despite the fact that some of the ertapenem neurotoxic effects could be attributable to end stage or severe renal disease, 3,4 in some cases they also have been observed in patients with moderate to normal renal function. [5][6][7][8][9][10][11] Besides renal dysfunction, other factors have been suggested to increase risk for neurotoxicity in patients taking ertapenem, including previous neurologic damage or haemoglobin level. 12 Nevertheless, as far as we know, only case reports or studies limited to analyse risk factors for seizures in patients receiving ertapenem have been previously published.…”

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confidence: 99%

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Ertapenem blood concentration: A retrospective cohort study to analyse risk of neurotoxicity

Campany‐Herrero,

Pau‐Parra,

González‐Moreno

et al. 2023

Brit J Clinical Pharma

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AimsSeveral cases of ertapenem‐related neurotoxicity have been published in the current literature. However, studies evaluating the ertapenem blood concentration (EBC) as a risk of these adverse events are scarce. We aimed to evaluate the relationship between the trough EBC and the risk of neurological toxicity.MethodsThis was a retrospective study, including patients who underwent ertapenem treatment between October 2019 and February 2021. We excluded patients in the critical care unit and those whose blood samples were not properly taken in order to analyse ertapenem trough concentration. We also excluded patients whose clinical follow‐up was not properly realized for the entire period of ertapenem treatment. The main outcome was the presence of any suspicious neurological side effect owing to ertapenem administration and its relationship with the plasma concentration. Secondary outcomes were to identify clinical and analytical data contributing to a higher risk of neurotoxicity.ResultsThe initial cohort comprised 158 individuals. For the final analysis we evaluated 102 patients, reporting a neurological alteration in 13/102 (12.7%). Mean trough EBC was significantly higher in patients showing neurotoxicity in comparison with those who did not (37.8 mcg mL−1, standard deviation [SD] ± 35.7 vs. 14.6 mcg mL−1, SD ± 15.2; P = .002). In multivariable logistic regression analysis, EBC (odds ratio [OR] = 1.07; P = .006), a moderate renal insufficiency (OR = 9.2; P = .02) and a history of previous neurologic disease (OR = 9.9; P = .02) were identified as risk factors of neurological alteration during ertapenem treatment.ConclusionsIn patients at risk, determining the ertapenem plasma concentration may help to minimize the risk of neurotoxicity.

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Probable ertapenem-induced encephalopathy; case report and suggested alternatives for chronic prostatitis

2022

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Ertapenem is a carbapenem antibiotic usually reserved for complicated infections. Drug-induced neurotoxicity is a rare adverse reaction associated with ertapenem, and may be directly related to its chemical structure. We report a case of a 64-year-old male with a hematological history and chronic prostatitis that was admitted to hospital for gait instability, clumsiness, dysarthria and tremors. He started ertapenem intravenous 1 g once daily a week prior to admission. Creatinine clearance calculation by the Cockcroft-Gault method was 52 mL/min and total protein levels were low. Ertapenem's administration was discontinued and the patient's neurological symptoms improved dramatically just one day after. The result of the Naranjo Scale was six, suggesting a probable adverse drug reaction. We discussed if he could receive meropenem in case of severe infection such as septic shock. Considering the patient's medical history, the chemical structure of meropenem and the fact that there are almost no reported cases of neurotoxicity from this drug, we assume that meropenem could be used in case of severe infection in patients with history of neurotoxicity caused by ertapenem if no added risk factors are present, such as renal failure.

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A case series of confusional states and other neurotoxic effects caused by ertapenem

Cited by 5 publications

References 14 publications

Ertapenem-Induced Neurotoxicity: A Literature Review of Clinical Characteristics and Treatment Outcomes

Ertapenem-Induced Neurotoxicity: A Literature Review of Clinical Characteristics and Treatment Outcomes

Ertapenem blood concentration: A retrospective cohort study to analyse risk of neurotoxicity

Probable ertapenem-induced encephalopathy; case report and suggested alternatives for chronic prostatitis

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