Xing Haiyan, Cheng Caiyi, Zhang Yihua, Cai Yongqing, Wang Xianfeng, Deng Dongmei, Xu Lunshan, Xu Minhui, Chen Jianhong
Department of Pharmacy, Daping Hospital, Army Medical University, Chongqing, China.
Department of Neurosurgery, Daping Hospital, Army Medical University, Chongqing, China.
Front Pediatr. 2021 Jul 27;9:564991. doi: 10.3389/fped.2021.564991. eCollection 2021.
Nosocomial meningitis with multidrug-resistant (MDR) or extensively drug-resistant (XDR) is a life-threatening complication in neurosurgery. Treatment of these infections is challenging because of poor penetration of the available antibiotics into the cerebrospinal fluid (CSF). Intrathecal (ITH) or intraventricular (IVT) administration of antibiotics is increasingly used as the last treatment option against MDR/XDR Gram-negative bacteria meningitis not responding to intravenous (IV) regimens. However, pertinent data in pediatric patients is scarce. A 14-year-old male patient developed meningitis from an MDR strain of following endoscopic endonasal resection of craniopharyngioma. Despite a combination therapy involving IV tigecycline, we observed clinical and bacteriologic failure. The patient was then successfully treated with an ITH and IV polymyxin B-based combination. Quantification of tigecycline and polymyxin B in CSF was performed with two-dimensional high-performance liquid chromatography (2D-HPLC) and HDLC coupled with tandem mass spectrometry (HPLC-MS/MS), respectively. Adverse drug reactions (neurotoxicity and skin hyperpigmentation), probably induced by polymyxin B, were acceptable and reversible. The case illustrates ITH and IV Polymyxin B-based combination is an optimal therapeutic option against MDR meningitis in this pediatric patient. In the future, real-time PK/PD data obtained from patients during ITH/IVT polymyxin B therapy should be required to optimize polymyxin use with maximal efficacy and minimal adverse effects.
耐多药（MDR）或广泛耐药（XDR）的医院获得性脑膜炎是神经外科中危及生命的并发症。由于现有抗生素难以穿透脑脊液（CSF），这些感染的治疗具有挑战性。鞘内（ITH）或脑室内（IVT）给予抗生素越来越多地被用作针对对静脉（IV）治疗方案无反应的MDR/XDR革兰氏阴性菌脑膜炎的最后治疗选择。然而，儿科患者的相关数据很少。一名14岁男性患者在经鼻内镜下切除颅咽管瘤后，因MDR菌株感染而发生脑膜炎。尽管采用了静脉注射替加环素的联合治疗，但我们观察到临床和细菌学治疗失败。该患者随后通过ITH和基于多粘菌素B的静脉联合治疗成功治愈。分别采用二维高效液相色谱（2D-HPLC）和HDLC与串联质谱联用（HPLC-MS/MS）对脑脊液中的替加环素和多粘菌素B进行定量分析。可能由多粘菌素B引起的药物不良反应（神经毒性和皮肤色素沉着）是可接受的且可逆的。该病例表明，ITH和基于多粘菌素B的静脉联合治疗是该儿科患者MDR脑膜炎的最佳治疗选择。未来，需要在ITH/IVT多粘菌素B治疗期间从患者获得实时药代动力学/药效学（PK/PD）数据，以优化多粘菌素的使用，使其疗效最大化且不良反应最小化。
