利奈唑胺谷浓度预测复杂性皮肤软组织感染疗效及血小板减少的回顾性分析

目的 探讨接受利奈唑胺治疗的复杂性皮肤软组织感染患者的目标谷浓度对临床疗效和血小板减少的预测价值。方法 采用回顾性、单中心、观察性对照研究。收集53例根据微生物学检查或临床情况推断为革兰氏阳性菌感染,并接受利奈唑胺治疗的复杂性皮肤软组织感染患者的临床资料。采用SPSS 22.0分析软件进行单因素（t检验,χ²检验）及多因素Logistic回归分析,比较影响临床疗效及血小板减少的相关因素,绘制ROC曲线并寻找最佳临界值以预测临床特征。结果 在有效组和无效组、血小板减少组和正常组之间,利奈唑胺的谷浓度存在显著性差异。多因素Logistic回归分析显示,首次谷浓度是决定利奈唑胺临床疗效和血小板减少的唯一独立变量。临床疗效和血小板减少的ROC曲线下面积分别为0.75和0.76,最佳临界值分别为6.7 μg·mL^-1（灵敏度97%,特定性67%）和7.5 μg·mL^-1（灵敏度77%,特异性68%）。结论 利奈唑胺谷浓度对临床疗效和血小板减少具有较高的预测价值,通过监测血药浓度制定个体化给药方案可提高临床治愈率,减少药物不良反应。     

新型(口恶)唑烷酮类化合物的全合成及抗菌活性研究

目的设计合成(口恶)唑烷酮类化合物,初步评价其体外抗菌活性.方法以间氟苯胺为起始原料,设计合成了10个目标化合物;采用微量液体稀释法,检测目标化合物对金黄色葡萄球菌和表皮葡萄球菌的抑制和杀灭作用.结果与结论所有化合物均未见文献报道,其结构经1H-NMR、MS确认.体外试验表明:化合物Ⅱa的体外抗菌活性与利奈唑酮相当,化合物Ⅱb、Ⅱc和Ⅱd表现出一定的抗菌活性.     

33例利奈唑胺致血小板减少的文献分析

目的：通过对利奈唑胺致血小板减少的文献进行分析,探讨其引起血小板减少的规律,为临床合理应用利奈唑胺提供参考。方法以“利奈唑胺”、“血小板减少”、“不良反应”为关键词对2001～2012年中国知网（CNKI）数据库和维普医学期刊数据库文献进行检索,对其中涉及利奈唑胺致血小板减少的19篇文献中报道的33例病例报告进行统计与分析。结果男性25例,女性8例,60岁以上的老年人23例。高龄、基础血小板值偏低（≤200×10^9·L-1）、疗程长属利奈唑胺致血小板减少的高危因素。经停药、采取相应治疗措施大部分可于7～14d后恢复正常。结论应重视利奈唑胺致血小板减少的不良反应,在应用过程中注意观察,监测血常规,做到及早发现、正确处理。     

Linezolid in the treatment of severe intraabdominal infection: A STROBE-compliant retrospective study

Safety concerns over bone marrow suppression and thrombocytopenia may inhibit the use of linezolid to treat intraabdominal infection (IAI). To evaluate the effectiveness, safety, and prognosis of linezolid in the treatment of severe IAI (SIAI). Patients were divided into a linezolid group and nonlinezolid group according to whether linezolid was prescribed. Subgroup analysis (thrombocytopenia treated with linezolid group (I), and thrombocytopenia treated with nonlinezolid group (II) also was performed. We evaluated the effectiveness of linezolid by analyzing the changes in white blood cells (WBC) and procalcitonin, evaluated safety by analyzing the changes in platelet counts, and evaluated patient outcomes by analyzing the length of hospital stay, the length of ICU stay, and the rates of clinical improvement. Sixty-six adult SIAI patients were treated with anti-gram-positive (G⁺) bacteria drugs for more than 7 days from January 1, 2014, to December 31, 2020. The length of hospital stay, the length of ICU stay, and the rates of clinical improvement were not significantly different between the linezolid group and nonlinezolid group. On the 15th day after anti-G ⁺ bacteria treatment, the WBC of the linezolid group was significantly lower than in the nonlinezolid group (9.00 ± 4.30 vs 13.1 ± 6.19, P < .05). The time for a statistical difference in the decrease of procalcitonin in the linezolid group was earlier than in the nonlinezolid group (day 6 vs day 7, P < .05). There was no statistically significant difference in the changes of platelet counts in the subgroup I (P > .05), but compared with the baseline data (day 0), the time for the statistical difference in the increase of platelets in thrombocytopenia treated with linezolid group was earlier (day 5 vs day 6, P < .05). There was no statistical difference in the changes of platelets in subgroup II (P > .05). In the treatment of severe intraabdominal infection in a single-center, retrospective study, linezolid was not inferior to other antibiotics in patient clinical outcomes or seral WBC and procalcitonin values. Linezolid also induced no evident bone marrow suppression or thrombocytopenia. Linezolid is a good choice for treatment of SIAI.     

Serotonin syndrome due to concomitant use of linezolid and methadone

Serotonin syndrome is a potentially life‐threatening adverse drug reaction typically caused by a single or combination of two or more medications with serotonergic properties due to increased serotonin release. Our case is a 60‐year‐old drug‐addict man who was admitted to the poisoning department of Loghman hospital with methadone poisoning. On the fifth day of hospitalization and after initiating the linezolid treatment for VAP, the patient began to run a fever with agitation, tremor, spontaneous clonus movement in the hands, and tachycardia. Due to patients'' manifestations and after ruling out other diagnoses, serotonin syndrome was confirmed with the possibility of concomitant use of linezolid and methadone. Linezolid administration was promptly discontinued, and vancomycin therapy was initiated (1000 mg twice a day intravenously). Supportive therapies were performed. Finally, tremor, rigidity, and clonus movement disappeared within 48 h.     

TDM联合Logistic模型对利奈唑胺致血小板减少症危险因素的研究

目的：研究利奈唑胺治疗重症感染患者发生血小板减少的危险因素。方法：采用逻辑回归分析方法，结合TDM技术，针对患者用药治疗前生理特点、治疗期间临床指标特征情况、治疗药物监测结果、感染类型与合并用药情况这五个方面，通过构建Logistic回归模型，并联合ROC曲线对血小板减少症的发生情况进行预测分析。结果：108例患者（男性65例，女性43例），35例患者出现了血小板减少症状。采用逐步回归的Logistic分析法显示，患者年龄、血肌酐浓度、血小板基线值、谷浓度是发生血小板减少症的独立危险因素。综合上述独立危险因素，建立Logistic回归方程：Logit （P）=0.056×X_C-0.094×X_PLT+0.086×X_Scr-0.082×X_Age+1.927，并通过构建联合预测因子的ROC曲线，对Logistic回归方程进行变换得到联合预测因子的计算公式，Y联合=X_C-1.678×X_PLT+1.535×X_Scr-1.464×X_Age。结论：患者应用利奈唑胺治疗时，可将该患者的年龄、血肌酐浓度、血小板基线值、谷浓度代入方程中（Y_联合=X_C-1.678×X_PLT +1.535×X_Scr-1.464×X_Age），若计算出的结果小于520.62（ROC最佳临界值），则该患者在治疗期间出现血小板减少症的风险较高，此时需要加强血常规监测，并根据结果及时调整给药方案。     

17例利奈唑胺所致不良反应文献分析

目的探讨利奈唑胺不良反应发生的规律及特点。方法采用《万方数据知识服务平台》进行检索并查阅原始文献,对2000～2010年国内医药期刊报道的利奈唑胺所致不良反应进行统计、分析。结果利奈唑胺所致不良反应主要表现为对血液系统的影响如血小板减少、乳酸中毒等。利奈唑胺致血小板减少的机制不明,可能与免疫诱导有关;利奈唑胺引起的乳酸性中毒的机制尚未完全阐明,目前认为可能与线粒体蛋白质合成抑制和线粒体基因多态性有关。结论临床医师、药师应重视利奈唑胺所致的不良反应,确保用药合理、安全、有效。     

HPLC法检测人血浆中利奈唑胺浓度

目的建立检测人血浆利奈唑胺的HPLC法。方法以Eclipse XDB-C_（18）为色谱柱;甲醇-水（45：55,V/V）为流动相,流速1.0mL·min~（-1）;血浆样品经70%高氯酸沉淀后,在254nm波长下进行检测。结果利奈唑胺在质量浓度0.25～50mg·L~（-1）内线性关系良好（r=0.999 8）,定量下限为0.25mg·L~（-1）;低、中、高浓度的日间、日内精密度（RSD）均〈10%,相对回收率分别为96.40%、103.24%、100.33%,提取回收率〉75%。结论本方法操作简便,结果准确,适用于血浆中利奈唑胺浓度的检测。     

利奈唑胺致血小板减少及其防治

利奈唑胺为恶唑烷酮类抗生素,主要用于革兰阳性细菌引起的呼吸道和皮肤感染以及耐万古霉素肠球菌引起的感染.利奈唑胺的常见不良反应为腹泻、恶心、呕吐、头痛、皮疹等.利奈唑胺可致血小板减少,其危险因素为长时间治疗、高龄以及肾功能不全.利奈唑胺所致血小板减少的机制可能与骨髓抑制或免疫介导致血小板减少有关.防治血小板减少的措施:避免大剂量和长时间应用利奈唑胺;用药期间严密监测血小板水平;避免将利奈唑胺与抑制骨髓的药物联用;患者出现血小板减少应立即停药,严重患者可考虑输注血小板.