背景:磷霉素的静脉注射形式,用于治疗多重耐药细菌感染的杀菌剂抗生素很少开处方。最常见的不良反应是低钾血症和高钠血症。我们描述了一例粒细胞缺乏症,罕见的副作用,可能是致命的。
方法:一名45岁妇女因脑膜瘤切除术后手术后脑膜炎而被送往重症监护病房。首先引入了美罗培南和万古霉素。怀疑有美罗培南的DRESS-Syndrom。在引入肠胃外磷霉素和粒细胞缺乏症四天后,诊断出中性粒细胞减少症。还观察到嗜酸性粒细胞增多。进行骨髓抽吸,显示中性粒细胞线消失,嗜酸性粒细胞明显增多。美罗培南已停产。保持磷霉素并添加非格司亭。因为filgrastim没有效果,怀疑与磷霉素的关系,所以它被保留了。观察到嗜中性粒细胞计数增加。由于案件的复杂性,疾病的不利过程和迫切需要进行翻修手术,我们进行了磷霉素再激发,随后中性粒细胞计数减少.
结论:这是第三篇报告磷霉素诱导的粒细胞缺乏症的论文,和第一个案例的详细描述。根据时间和符号学标准以及书目数据,根据Naranjo不良药物概率量表,该事件被认为是可能的.文献数据很少。产品特征摘要提到,仅报道了少数短暂性中性粒细胞减少症和粒细胞缺乏症。对FDA不良事件报告系统数据库的分析强调了使用磷霉素治疗的患者中粒细胞缺乏的频率高于预期。肠外磷霉素通常用于接受其他药物治疗的患者,所以它很少是唯一的嫌疑人。在我们的案例中,骨髓穿刺的结果,中性粒细胞计数突然下降,伴随嗜酸性粒细胞增多,尽管剂量减少,但没有改善,指向免疫过敏机制。然而,疑似美罗培南诱导的DRESS与粒细胞缺乏症之间的重叠不能确定因果关系.应该提高对这种副作用的认识。
BACKGROUND: The intravenous form of fosfomycin, a bactericide antibiotic used to treat multiresistant bacterial infections is little prescribed. The most common reported adverse effects are hypokaliemia and hypernatremia. We describe a
case of agranulocytosis, a rarely described side effect that may be fatal.
METHODS: A 45 year-old woman was admitted to the intensive care unit for post-surgical meningitis following meningioma resection. Meropenem and vancomycin were first introduced. A DRESS-syndrom with meropenem was suspected. Neutropenia was diagnosed three days after the introduction of parenteral fosfomycin and agranulocytosis four days later. Eosinophilia was also observed. A bone marrow aspiration was performed showing a disappearance of the neutrophil granulocyte line and a significant eosinophilia. Meropenem was discontinued. Fosfomycin was maintained and
filgrastim was added. As
filgrastim had no effect, the relationship with fosfomycin was suspected, so it was then withheld. An increase of the neutrophil count was observed. Because of the complexity of the
case, the unfavorable course of the illness and the urgent need for revision surgery, a rechallenge with fosfomycin was done followed by a decrease of the neutrophil count.
CONCLUSIONS: This is the third paper reporting agranulocytosis induced by fosfomycin, and the first detailed description of a case. Based on chronological and semiological criteria and bibliographic data, the event was qualified as probable with the Naranjo adverse drug probability scale. Literature data is scarce. The summary of product characteristics mentions that only a few cases of transient neutropenia and agranulocytosis have been reported. An analysis of the FDA Adverse Event Reporting System Database highlighted a higher than expected frequency of agranulocytosis in patients treated with fosfomycin. Parenteral fosfomycin is often used in patients receiving other medications, so that it is rarely the only suspect. In our
case, the results of the bone marrow aspiration, the sudden drop of the neutrophil count with concomitant eosinophilia and the absence of improvement despite the dose decrease, point towards an immuno-allergic mechanism. However, the overlap between the suspected DRESS induced by meropenem and the agranulocytosis do not allow to conclude with certainty on the causality. Awareness should be raised about this side effect.