基于血药浓度监测的美罗培南药物利用评价探索与实践

目的:建立美罗培南药物利用评价方法,评价治疗药物监测(therapeutic drug monitoring,TDM)对临床用药的影响。方法:依据国家卫健委2018版《碳青霉烯类抗菌药物临床应用评价细则》及相关资料,制定美罗培南临床应用评价标准。采用层次分析法(AHP)评估各项评价指标的重要性,并运用逼近理想解排序法(TOPSIS)进行数据处理。对厦门大学附属中山医院2020年6月至10月未开展美罗培南TDM的病例(对照组)和2021年6月至10月开展TDM的病例(监测组)进行对比评价。比较2组临床有效率和细菌学有效率、合理性指标符合率和改善情况以及与最优方案的相对接近度(C_i)。结果:监测组中,ICU患者的血药浓度达标率为70.2%,非ICU患者的血药浓度达标率为42.7%。与对照组相比,监测组临床有效率、细菌学有效率、合理性指标符合率均显著提高(P＜0.05);临床用药不合理(C_i＜0.6)的病例数显著减少(P＜0.05),达到用药基本合理以上水平的病例数增加(C_i≥0.6)。结论:应用TDM有助于提高美罗培南用药的合理性和有效性。     

基于加权TOPSIS法对儿科美罗培南的利用评价

目的:探讨儿科美罗培南使用评价体系,为儿科美罗培南合理应用提供参考。方法:构建儿科美罗培南药物利用评价(DUE)标准,采用加权逼近理想解排序(TOPSIS)法对2020年10月至2021年3月我院儿科使用美罗培南的患儿临床资料进行评价。结果:共纳入130例合格病例,根据其与最佳解的相对接近程度C_i值进行划分,C_i≥0.8的合理病例38例(29.23%),0.6≤C_i<0.8的基本合理病例60例(46.15%),C_i<0.6的不合理病例32例(24.62%)。结论:采用加权TOPSIS法评估儿科美罗培南的合理应用是切实可行的,我院美罗培南的应用仍存在问题,应加强管理,促进美罗培南在儿科患者中的合理应用。     

Clinical features and outcome of patients with cutaneous melioidosis during a nosocomial outbreak in a temperate region of Australia

Six cases of cutaneous melioidosis from southwestern Australia, a non‐endemic region occurred as a result of Burkholderia pseudomallei contamination of normal saline that was used for irrigating superficial wounds. Treatment with parenteral meropenem, given by continuous infusion for 2 weeks, followed by oral antibiotics was successful in all cases.     

高效液相串联质谱法测定小鼠肺组织中美罗培南的含量

目的：采用液相色谱-质谱串联技术（HPLC-MS/MS）,建立测定小鼠肺组织中美罗培南含量的方法,为研究美罗培南在肺内分布的药动学奠定基础。方法：采用Diamonsil C₁₈（150 mm×4.6 mm,5 μm）色谱柱进行分离,流动相为乙腈-0.1%甲酸水,梯度洗脱,流速1.0 mL·min^-1,内标选择厄他培南。电喷雾离子化源（ESI）,正负离子切换,美罗培南为正离子检测模式,内标厄他培南为负离子检测模式。多反应监测（MRM）方式进行定量分析,用于定量分析的离子对分别为美罗培南m/z 384.1→141.2,内标厄他培南m/z 474.4→265.2。结果：小鼠肺组织匀浆中美罗培南在15.625~2 000 ng·mL^-1范围内线性关系良好（r=0.999 7）,平均提取回收率为98.05%~102.54%,日内、日间精密度均小于15%。结论：采用本法测定小鼠肺组织中美罗培南的浓度,灵敏度高,专属性强,可用于肺组织样品中美罗培南快速有效的分析以及美罗培南在肺组织分布的药动学研究。     

亚胺培南/西司他丁和美罗培南治疗机械通气患者痰分离铜绿假单胞菌的耐药风险差异

目的了解亚胺培南/西司他丁、美罗培南治疗机械通气患者多重耐药铜绿假单胞菌感染的耐药情况及药物疗效。 方法选取某院2010年1月-2015年12月痰培养为耐药铜绿假单胞菌的78例机械通气患者,分为亚胺培南/西司他丁治疗组（44例）和美罗培南治疗组（34例）,比较两组患者的基础状况,细菌对所用抗菌药物产生耐药的时间,以及药物疗效差异。 结果两组患者的基础资料具有可比性,应用亚胺培南/西司他丁和美罗培南治疗前,两组患者分离的铜绿假单胞菌对喹诺酮类、头孢他啶、哌拉西林、阿米卡星的耐药情况比较,差异均无统计学意义（均P>0.05）。应用抗菌药物治疗至第6天,亚胺培南治疗组和美罗培南治疗组患者对所使用的抗菌药物耐药率（22.73% vs 8.82%）比较,差异无统计学意义（P>0.05）;治疗至第8、10、12天,亚胺培南治疗组耐药率分别为40.91%、77.27%、97.73%,均高于美罗培南治疗组（分别为17.65%、32.35%、44.12%;均P<0.05）。不同抗菌药物治疗后铜绿假单胞菌产生耐药的平均时间：亚胺培南/西司他丁治疗组为9.0 d,美罗培南治疗组为13.5 d。两组患者疗效（64.71% vs 74.19%）比较,差异无统计学意义（P=0.41）。结论应用亚胺培南/西司他丁治疗机械通气患者多重耐药铜绿假单胞菌感染发生耐药的风险高于美罗培南,治疗第7天两组患者药物疗效无明显差异。     

美罗培南输注时间和剂量对铜绿假单胞菌感染患者疗效的影响

目的探讨美罗培南输注时间对中重症铜绿假单胞菌患者的疗效影响及其安全性。方法方便性抽样选取2009年6月至2010年9月在东阳市人民医院住院、年龄18～60岁的中重度铜绿假单胞菌感染、临床判断需要给予美罗培南连续治疗的51例患者,获得知情同意书后随机分为三组:大剂量30min输注治疗组(A组)、大剂量3h输注治疗组(B组)和小剂量3h输注治疗组(C组),每组各17例患者,观察三组患者的临床疗效及治疗期间的不良反应。首要疗效标准为给药72h后体温及白细胞计数的变化,次要疗效标准包括抗生素临床疗效及细菌学疗效,安全性评估包括不良事件观察及不良反应发生率。结果给药72h后,白细胞计数各组间比较差异无统计学意义(均P>0.05);体温下降幅度B组高于A组和C组(P<0.05),A组和C组间比较差异无统计学意义(P>0.05)。停药当天,B组临床有效率及细菌清除率高于A组和C组(P<0.05),A组和C组间比较差异无统计学意义(P>0.05)。结论采用传统1.0g剂量时,持续输注3h给药方式对体温的控制、临床治疗疗效以及细菌清除方面优于持续输注30min给药方式;而每8h应用美罗培南0.5g持续输注3h与每8h应用美罗培南1.0g持续输注30min相比具有非劣效性。     

Experience with cefepime versus meropenem as empiric monotherapy for neutropenia and fever in pediatric patients with solid tumors

A prospective, open-label, randomized, comparative study in pediatric cancer patients was conducted to evaluate the efficacy and safety of cefepime and meropenem in the empiric therapy of febrile neutropenic patients. Febrile episodes were classified as microbiologically documented infection, clinical documented infection, or fever of unknown origin. Clinical response to therapy was classified as success or failure. In this period 37 children with solid tumors including lymphoma, 25 males, 12 females, had neutropenia on 65 occasions. Microbiologically documented infections occurred in 21 episodes (32.31%). Frequency of positive bacteria isolated was higher than gram-negative bacteria. There was no infection-related death. There were no statistical differences between the cefepime and meropenem groups for duration of fever or neutropenia, response rate, and necessity for modification. Cefepime appears to be as effective and safe as meropenem for empiric treatment of febrile episodes in neutropenic pediatric cancer patients.     

MEROPENEM IN THE TREATMENT OF FEBRILE NEUTROPENIC CHILDREN

The aim of this retrospective study was to evaluate the clinical effectiveness of meropenem in immunocompromised children. Between January 1998 and December 2002 in the hemato-oncological units of our hospital meropenem was used in 87 febrile events diagnosed in 55 patients, and 328 bacterial cultures were evaluated. Microorganisms were detected and identified in 64 of the 328 hemocultures; there was a predominance of gram-positive strains (67%). In 49.4% the infection was documented microbiologically. In 16 additional cases the infection was proven clinically and 32.2% of the episodes were considered to be fever of unknown origin. The success rate of the meropenem therapy—excluding the proven fungal or coagulase-negative Staphylococcus infections—was 72.9% and for the whole cohort 49.4%. The results demonstrate that meropenem is effective and well-tolerated when used for the treatment of neutropenic cancer children.