Department of Internal Medicine, CHU de Caen, 14000, Caen, France.
Department of Infectious Diseases, CHU de Caen, Université de Caen-Normandie, Avenue de la Côte de Nacre, 14000, Caen, France.
Drug Saf. 2017 Dec;40(12):1171-1198. doi: 10.1007/s40264-017-0578-2.
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.
β-内酰胺类抗生素是常用的抗生素药物。为了描述β-内酰胺类抗生素引起的神经不良反应的临床特征、风险标志物和结局,我们进行了一般文献回顾,以提供关于最常用的β-内酰胺类抗生素的最新临床数据。对于法国可获得的每类(替卡西林、哌拉西林、替莫西林、头孢他啶、头孢吡肟、头孢匹罗、头孢卡品酯、头孢托罗、头孢洛林、头孢妥仑匹酯、头孢唑南和氨曲南)选定药物,我们通过在 PubMed 上进行电子搜索,对截至 2016 年 4 月的系统文献进行了综述。纳入了报告原始数据的文章,这些文章用法语、西班牙语、葡萄牙语或英语写成,并且有关于神经症状(如癫痫发作、警觉性改变、意识模糊状态、肌阵挛、定位体征和/或幻觉)患者的个体数据,这些患者在使用β-内酰胺类抗生素后出现了这些症状。哌拉西林和厄他培南的神经不良反应通常表现为癫痫发作和幻觉(分别超过 50%和 25%的病例)。抗生素治疗通常根据肾功能进行调整(超过 70%),并且四分之一至三分之一的病例存在潜在的脑异常。相比之下,头孢他啶和头孢吡肟的神经不良反应通常包括异常运动,但很少有幻觉和癫痫发作。这些反应与肾功能不全(超过 80%)相关,并且很少根据肾功能调整剂量。否则,似乎单环β-内酰胺类药物没有严重的神经不良反应,并且应该避免使用丙戊酸和碳青霉烯类药物的组合。在服用β-内酰胺类抗生素的患者中出现警觉性改变、肌阵挛和/或癫痫发作,特别是如果与肾功能不全或潜在的脑异常相关时,应导致医生怀疑药物不良反应,并考虑改变抗菌治疗。