Abstract BACKGROUND: Meropenem is an effective -lactam antibiotic that is frequently used to treat serious infections in both intensive care unit (ICU) and febrile neutropenic hematology/oncology (Hem/Onc) patients. Studies suggest that to be effective, meropenem concentrations must be maintained above the inhibitory concentrations for the majority of a dosing interval. However, the pharmacokinetics (PK) of meropenem seem to differ in critically ill patients compared with healthy or less ill subjects used to select labeled dosing regimens. OBJECTIVES: This study was designed to investigate meropenem PK in critically ill patients and to see how often standard dosing regimens produced adequate plasma concentrations. A secondary objective was to investigate how achieved concentrations were related to outcomes (morbidity and mortality) in these patients. METHODS: Meropenem plasma concentrations over time were measured using a high pressure liquid chromatography assay in febrile Hem/Onc and ICU patients who were treated with standard meropenem dosing schedules. Outcomes such as fever control and survival were assessed in these patients and compared with individual meropenem PK data and with recommended target concentrations. RESULTS: A total of 25 subjects including 10 febrile Hem/Onc and 15 ICU patients with a variety of serious illnesses and baseline renal function were studied. Mean peak concentrations were less variable than were pre-dose concentrations. Post peak and trough concentrations were often below recommended minimum inhibitory concentrations. Both clearance and volumes of distribution were greater than reported in less ill subjects, only in part explained by increased renal clearance. Therefore, serum concentrations often did not exceed recommended concentration targets even for moderately sensitive organisms. Inadequate concentrations were especially common in the mostly ill, febrile neutropenic Hem/Onc subjects and seemed to explain at least some therapeutic failures. Conversely, drug accumulation occurred in ICU subjects with decreased renal function. CONCLUSIONS: Standard meropenem dosing regimens were inadequate in many critically ill febrile, neutropenic Hem/Onc, and septic ICU patients. These data suggest a role for meropenem concentration monitoring in such patients.

目的 评价武汉地区2012-2014年碳青霉烯类抗生素的应用情况和趋势,为临床合理用药提供参考.方法 对武汉地区34家医院2012-2014年碳青霉烯类抗生素的品种、金额进行分类统计,并结合临床应用情况进行分析.结果 3年来美罗培南、亚胺培南/西司他丁、比阿培南的用药频度、消耗金额呈增长趋势,且美罗培南始终居于首位,2014年统计的碳青霉烯类购药金额与用药人次同步性较好.结论 武汉地区碳青霉烯类抗生素的应用基本合理,美罗培南(0.50g)与其他同类药物比较,在安全性和有效性方面均具有一定优势,是临床治疗严重感染优先选用的一线药物.

美罗培南属碳青霉烯类抗生素,抗菌谱广,对需氧和厌氧的革兰阴性菌、阳性菌的多数菌株具有良好的抗菌作用。近年来国内有文献报道其不良反应,现概述如下。

1 病例介绍 例1,男,60岁.2014年2月3日因发热1周入院.入院诊断:发热原因待查.既往有十二指肠球部溃疡病史,无肝病史,无药物过敏史.入院检测肝功能:丙氨酸氨基转移酶(ALT)28 U·L-1,天冬氨酸氨基转移酶(AST)38 U·L-1,碱性磷酸酶(alkaline phosphatase,ALP)54 U·L-1.入院第2天,给予注射用美罗培南(商品名:海正美特,浙江海正药业股份有限公司,规格:每支0.5g,批准文号:国药准字H20030331,批号:130410) 1.0 g加入0.9％氯化钠注射液100 mL静脉滴注,tid,合用注射用阿奇霉素0.5 g,qd,静脉滴注.第4天,因患者胃部不适,加用注射用泮托拉唑钠.第9天,患者发热症状有所好转,医嘱停用注射用阿奇霉素.

目的：研究分析美罗培南治疗急性白血病合并重症肺部感染的临床效果。方法84例急性白血病合并重症肺部感染患者，随机分为对照组和观察组，各42例。对照组采用亚胺培南/西司他丁钠治疗，观察组采用美罗培南治疗。对比两组患者治疗总有效率、细菌清除率和不良反应发生情况。结果观察组治疗总有效率、细菌清除率及不良反应发生情况均优于对照组(P<0.05)。结论美罗培南治疗急性白血病合并重症肺部感染患者效果显著，可明显提高治疗有效率和细菌清除率，减少不良反应，值得推广。

目的初步探讨美罗培南对血液系统肿瘤伴发热及中性粒细胞减少患儿的疗效及安全性。方法收集2012年7月至2013年10月湖南省儿童医院住院的血液系统肿瘤伴中性粒细胞减少及初次发热经美罗培南治疗患儿的病例资料,分析美罗培南的疗效及安全性。并根据不同肿瘤类别、中性粒细胞绝对数减少程度分组比较。结果共55例纳入研究,微生物学检测确诊及临床确诊感染的病例分别为22例（40.0%）、24例（43.6%）、未知感染源者9例（16.4%）。实体瘤患儿的发热性中性粒细胞减少（FN）持续时间及住院时间较白血病患儿短（P〈0.05）,治疗有效率差异无统计学意义;ANC≥0.2×109·L-1组的FN持续时间及住院时间较ANC〈0.2×109·L-1组患儿短（P〈0.05）,治疗有效率高于后者;未出现不良反应、总有效率89.1%（49/55）。结论应用美罗培南治疗血液系统肿瘤伴发热及FN患儿安全有效,可作为临床医师初期经验性抗菌药物选用的药物。

临床抗感染治疗过程中,应用抗生素治疗一段时间后患者的体温突然升高并且伴有中性粒细胞的减少.这时通常 会首先考虑患者中性粒细胞减少的原因与感染相关.某些细菌本身对中性粒细胞具有杀伤作用(如金葡菌产生的杀白细胞素),有些感染则能直接抑制骨髓产粒细胞 的过程,又或是患者长期处于一种中性粒细胞的慢性消耗状态,从而造成中性粒细胞计数下降.另外由于应用化疗药物对中性粒细胞产生抑制作用的现象也比较常 见.然而抗生素造成中性粒细胞减少的可能性也不能忽视.如果此时患者发热伴中性粒细胞减少的原因是抗生素而非感染,那么单纯的加大抗感染力度非但无效,反 而会使患者的病情进一步加重.本文对抗生素导致中性粒细胞减少发生的概率、机制以及临床特点作一介绍.