Centre Hospitalier de Valenciennes, Valenciennes, France.
Centre Hospitalier Régional et Universitaire de Lille, Lille, France.
BMC Infect Dis. 2023 Oct 13;23(1):685. doi: 10.1186/s12879-023-08652-8.
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.
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.
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.
磷霉素是一种杀菌抗生素，用于治疗多药耐药细菌感染，其静脉制剂的应用较少。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的病例，这是一种罕见的不良反应，可能是致命的。
一名 45 岁女性因脑膜瘤切除术后的手术后脑膜炎被收入重症监护病房。首先引入了美罗培南和万古霉素。怀疑与美罗培南有关的 DRESS 综合征。在静脉注射磷霉素三天后诊断为中性粒细胞减少症，四天后出现粒细胞缺乏症。还观察到嗜酸性粒细胞增多症。进行了骨髓抽吸，显示中性粒细胞系消失，显著嗜酸性粒细胞增多。停止使用美罗培南。继续使用磷霉素，并添加了非格司亭。由于非格司亭没有效果，怀疑与磷霉素有关，因此停用。观察到中性粒细胞计数增加。由于病情复杂、病情不利以及急需再次手术，再次使用磷霉素进行了挑战，随后中性粒细胞计数下降。
这是第三篇报道磷霉素引起的粒细胞缺乏症的论文，也是第一份详细描述病例的论文。根据时间和症状学标准以及文献数据，该事件被 Naranjo 药物不良反应概率量表评为可能。文献数据稀缺。产品特性总结提到，仅报道了少数几例短暂性中性粒细胞减少症和粒细胞缺乏症病例。对 FDA 不良事件报告系统数据库的分析突出显示，使用磷霉素治疗的患者中粒细胞缺乏症的频率高于预期。静脉注射磷霉素通常用于接受其他药物治疗的患者，因此很少是唯一的怀疑对象。在我们的病例中，骨髓抽吸的结果、中性粒细胞计数突然下降伴嗜酸性粒细胞增多，尽管剂量减少但没有改善，提示免疫过敏机制。然而，怀疑由美罗培南引起的 DRESS 与粒细胞缺乏症之间的重叠并不能确定因果关系。应提高对这种副作用的认识。
