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Neurological Adverse Effects Attributable to β-Lactam Antibiotics: A Literature Review

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Abstract

β-lactam antibiotics are commonly prescribed antibiotic drugs. To describe the clinical characteristics, risk markers and outcomes of β-lactam antibiotic-induced neurological adverse effects, we performed a general literature review to provide updated clinical data about the most used β-lactam antibiotics. For selected drugs in each class available in France (ticarcillin, piperacillin, temocillin, ceftazidime, cefepime, cefpirome, ceftaroline, ceftobiprole, ceftolozane, ertapenem and aztreonam), a systematic literature review was performed up to April 2016 via an electronic search on PubMed. Articles that reported original data, written in French, Spanish, Portuguese or English, with available individual data for patients with neurological symptoms (such as seizure, disturbed vigilance, confusional state, myoclonia, localising signs, and/or hallucinations) after the introduction of a β-lactam antibiotic were included. The neurological adverse effects of piperacillin and ertapenem are often described as seizures and hallucinations (>50 and 25% of cases, respectively). Antibiotic treatment is often adapted to renal function (>70%), and underlying brain abnormalities are seen in one in four to one in three cases. By contrast, the neurological adverse drug reactions of ceftazidime and cefepime often include abnormal movements but few hallucinations and seizures. These reactions are associated with renal insufficiency (>80%) and doses are rarely adapted to renal function. Otherwise, it appears that monobactams do not have serious neurological adverse drug reactions and that valproic acid and carbapenem combinations should be avoided. The onset of disturbed vigilance, myoclonus, and/or seizure in a patient taking β-lactam antibiotics, especially if associated with renal insufficiency or underlying brain abnormalities, should lead physicians to suspect adverse drug reactions and to consider changes in antibacterial therapy.

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Acknowledgements

The authors gratefully thank Prof. Montastruc for his thorough reading of this article.

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Authors and Affiliations

  1. Department of Internal Medicine, CHU de Caen, 14000, Caen, France

    Samuel Deshayes

  2. Department of Pharmacology, CHU de Caen, Regional Pharmacovigilance Center, 14000, Caen, France

    Antoine Coquerel

  3. University of Caen-Normandy, INSERM Unit 1075, 14000, Caen, France

    Antoine Coquerel

  4. Groupe de Recherche sur l’Adaptation Microbienne (GRAM 2.0), Normandie Université, UNICAEN, UNIROUEN, GRAM, 14000, Caen, France

    Renaud Verdon

  5. Department of Infectious Diseases, CHU de Caen, Université de Caen-Normandie, Avenue de la Côte de Nacre, 14000, Caen, France

    Samuel Deshayes & Renaud Verdon

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Deshayes, S., Coquerel, A. & Verdon, R. Neurological Adverse Effects Attributable to β-Lactam Antibiotics: A Literature Review. Drug Saf 40, 1171–1198 (2017). https://doi.org/10.1007/s40264-017-0578-2

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