万古霉素单药与联合β-内酰胺类药物对脓毒症患者急性肾损伤发生和预后的影响#br#

摘要：目的　探讨万古霉素（VAN）单药治疗与VAN联合哌拉西林-他唑巴坦（TZP）或美罗培南（MEM）的抗生素方案对脓毒症患者急性肾损伤（AKI）发生、持续时间、恢复情况及临床预后的影响。方法　研究纳入接受VAN、TZP或MEM治疗并维持至少48 h的脓毒症患者338例,其中78例患者接受VAN单药治疗（VAN组）,175例患者接受VAN+TZP治疗（VAN+TZP组）,余85例患者接受VAN+MEM治疗（VAN+MEM组）。比较3组患者临床资料、AKI发生情况和临床结果。采用Kaplan-Meier分析和Log-rank检验比较3组患者AKI发生概率。采用多因素Logistic回归模型分析AKI发生的独立危险因素。结果　VAN+TZP组与VAN+MEM组患者的急性生理与慢性健康评估Ⅱ（APACHEⅡ）评分、去甲肾上腺素使用比例明显高于VAN组。VAN+TZP组肾上腺素、多巴胺使用比例明显高于VAN组与VAN+MEM组。与VAN组和VAN+TZP组比较,VAN+MEM组患者的两性霉素与氨基糖苷类使用比例最高,而血管紧张素转换酶抑制剂/血管紧张素Ⅱ受体拮抗剂（ACEI/ARB）使用比例最低（P＜0.05）。3组患者VAN剂量及抗生素疗程差异无统计学意义。VAN+TZP组患者AKI发生率明显高于VAN组与VAN+MEM组（50.3% vs. 23.1% vs. 25.9%,P＜0.01）,而后2组患者AKI发生率差异无统计学意义（P＞0.016 7）。VAN+TZP组患者AKI 2级比例明显高于VAN组与VAN+MEM组（21.7% vs. 7.7% vs. 9.4%,P＜0.01）。3组患者30 d内透析需求、AKI恢复率、AKI恢复时血肌酐（SCr）、AKI持续时间、住院天数与30 d病死率差异无统计学意义（P＞0.05）。Kaplan-Meier分析显示,VAN+TZP组患者AKI的累积发生风险明显高于VAN组和VAN+MEM组患者（log-rankχ2=14.491,P=0.001）。多因素Logistic回归模型分析结果显示,APACHEⅡ评分增加（OR=1.041,95%CI：1.008～1.075,P=0.013）、使用去甲肾上腺素（OR=2.200,95%CI：1.254～3.860,P=0.006）和VAN+TZP联合治疗（OR=2.064,95%CI：1.104～3.856,P=0.023）是影响AKI发生的独立危险因素。结论　VAN+TZP联合治疗的脓毒症患者AKI发生率高于VAN单药和VAN+MEM联合治疗,但对最终临床结果没有决定性的影响。     

美罗培南在老年人体中生理药动学模型的建立与应用

目的：建立美罗培南在老年人体中生理药动学模型,为老年人临床用药提供指导。方法：查阅相关文献,获得美罗培南的药物理化性质及吸收、分配、代谢和排泄等特异参数,及健康成人和老年人美罗培南静脉注射PK研究数据。利用PK-Sim^®软件建立成人生理药动学（physiologically based pharmacokinetic,PBPK）模型并外推至老年人群体。采用平均折叠错误（mean fold error,MFE）法比较C_max、T_max、AUC_0-∞预测与实测值之间差异,以评估PBPK模型的准确性,并模拟肾功能不全的老年人群PK研究进行剂量推荐。结果：建立的美罗培南成人PBPK模型,其AUC和C_max的MFE值皆在0.5和2以内。所有老年人PBPK模型符合0.5结论：本研究建立的美罗培南成人PBPK模型可以外推至老年人群体,为老年人临床个性化用药提供参考。     

美罗培南耐药铜绿假单胞菌多药外排泵研究

目的 研究美罗培南耐药铜绿假单胞菌的多药外排泵机制.方法 采用琼脂稀释法测定美罗培南对141株铜绿假单胞菌的最低抑菌浓度(MIC),同时观察加入泵抑制剂MC207110后的美罗培南对141株铜绿假单胞菌MIC变化,检测多药外排泵机制.实时定量PCR检测外排泵mRNA水平的表达.PCR扩增外排泵编码基因及调控基因并测序分...     

Meropenem Plus Amikacin Versus Piperacillin-Tazobactam Plus Netilmicin as Empiric Therapy for High-Risk Febrile Neutropenia in Children

The aim of this study was to evaluate the efficacy and safety of meropenem plus amikacin compared with piperacillin-tazobactam plus netilmicin for initial empirical antibiotic treatment of high-risk febrile neutropenia in children with cancer. Patients with hematologic malignancy (leukemia or stage III/IV non-Hodgkin lymphoma) who presented with fever and neutropenia (ANC < 500/mm³) and patients with solid tumors who presented with fever and severe neutropenia (ANC < 100/mm³) were considered to be at high risk and eligible for this study. In this prospective study, 33 patients with 50 febrile neutropenic episodes received iv meropenem (20 mg/kg every 8 h) plus amikacin (15 mg/kg/d in 2 divided doses) (in 31 episodes) or piperacillin/tazobactam (100 mg/4 mg/kg every 8 h) plus netilmicin (7 mg/kg every 24 h) (in 19 episodes). Clinical response was determined at 72 h and at completion of the therapy. The groups were comparable in terms of age, sex, initial ANC, use of growth factors, and classification of the infections. An infection was documented microbiologically in 12 episodes (39%) in the meropenem plus amikacin group and in 8 episodes (42%) in the piperacillin/tazobactam plus netilmicin group. Of the 22 microbiological isolates, 37% were gram-positives, 45% were gram-negatives, and 18% were fungi. Most of the clinically documented infections were of lower respiratory tract, gastrointestinal mucosa, or urinary tract origin. The mean duration of neutropenia was 9 days in both groups. Fever persisted for 1–30 days (mean 3 vs. 5 days). The success rate with initial empiric therapy was 52% in the meropenem plus amikacin and 42% in the piperacillin/tazobactam plus netilmicin group, respectively (p= .5). Total success rate (with or without modification) was 97% vs. 90% in the episodes. Three patients died due to infection (1 vs. 2 patients). No major adverse effects were observed in each group. Empirical therapy with meropenem plus amikacin or piperacillin/tazobactam plus netilmicin for high-risk febrile neutropenia is equally effective and safe in pediatric cancer patients.     

国产比阿培南治疗支气管扩张症合并细菌感染的疗效观察

目的评价国产比阿培南治疗支气管扩张症合并细菌感染的疗效和安全性。方法将支气管扩张症合并细菌感染患者98例随机分为两组,比阿培南组(n=48)静脉滴注比阿培南,300～600 mg/次,2次/d;对照组(n=50)静脉滴注美罗培南,500～1 000 mg/次,3次/d,疗程均为7～10 d。结果比阿培南组与对照组治疗支气管扩张症合并细菌感染的临床有效率分别为89.58%(43/48)8、4.00%(42/50);细菌清除率分别为92.86%(26/28)、88.24%(30/34),不良反应发生率分别为6.25%(3/48)、10.00%(5/50),两组比较,差异均无统计学意义(P>0.05)。结论国产比阿培南可安全、有效地治疗支气管扩张症合并细菌感染。     

临床药师参与重症化脓性脑膜炎治疗的实践

目的:探讨临床药师参与病人药物治疗方案设计的意义.方法:通过药学监护重症化脓性脑膜炎病人,了解临床药师参与实践的过程,配合医师为病人提供个体化药物治疗方案.结果:根据病人临床表现,多次更改治疗方案,最终找到合适的抗菌药物,使病人治愈出院.结论:临床药师参与病人药物治疗方案设计,可以协助医师进一步提高药物治疗的安全性和有效性.     

Doripenem vs meropenem against Pseudomonas and Acinetobacter

Recently, doripenem has been approved for the treatment of nosocomial pneumonia (NP), including ventilator-associated pneumonia (VAP). The E-test was performed to determine the MICs of doripenem and meropenem in 203 endotracheal aspirate isolates that consisted of 140 Acinetobacter calcoaceticus-Acinetobacter baumannii complexes and 63 Pseudomonas aeruginosa. Doripenem showed minimum concentration necessary for inhibition of 50% (MIC 50 ) of P. aeruginosa isolates at 0.38 mg/L which is several times (84.2 times) lower than the corresponding MIC 50 value of >32 mg/L for meropenem. The MIC 50 and MIC 90 were similar for both the drugs against A. baumannii. Thus, P. aeruginosa was consistently more susceptible than the A. baumannii.     

RmtC and RmtF 16S rRNA Methyltransferase in NDM-1–Producing Pseudomonas aeruginosa

We investigated 16S rRNA methyltransferases in 38 bla_NDM-1–positive Pseudomonas aeruginosa isolates and found RmtC in 3 isolates, 1 of which also harbored RmtF. The isolates were clonally unrelated; rmtC and rmtF genes were located on a chromosome with the bla_NDM-1 gene. Strategies are needed to limit the spread of such isolates.