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Ci 值进行划分,Ci ≥0. 8 的合理病例38 例(29. 23%), 0. 6≤Ci <0. 8 的基本合理病例60 例(46. 15%),Ci <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。     

2012—2015年1380株肝移植术后感染病原菌的分布及耐药性分析

目的了解江苏省人民医院肝移植术后感染病原菌的分布及耐药性,为临床合理用药提供参考。方法对2012年1月—2015年1月江苏省人民医院肝移植术后感染病原菌的分布及耐药性进行统计分析。结果共分离出病原菌1 380株,主要来源于痰液标本。病原菌分布以革兰阴性菌为主,占69.57%,革兰阳性菌和真菌分别占20.07%、10.36%;其中革兰阴性菌以鲍曼不动杆菌、肺炎克雷伯菌为主,革兰阳性菌以溶血葡萄球菌为主;革兰阴性菌对美罗培南、阿米卡星、亚胺培南较为敏感,耐药率均低于30%,对头孢曲松、氨曲南等的耐药率均较高;革兰阳性菌对万古霉素、利奈唑胺、替考拉宁较为敏感,耐药率均低于20%,对氨苄西林、诺氟沙星等耐药率均较高。结论肝移植术后感染病原菌的构成主要是鲍曼不动杆菌、肺炎克雷伯菌和溶血葡萄球菌,临床选择抗菌药物时建议选用病原菌表现较低耐药性的美罗培南、阿米卡星、万古霉素、利奈唑胺等药物。     

美罗培南治疗药物监测的HPLC方法探索及其临床采样流程建立

目的：建立HPLC法测定人血浆中美罗培南的血药浓度，结合其稳定性研究制定临床采样流程，并应用到治疗药物监测个体化给药方案设计。方法：血浆样品经甲醇沉淀蛋白，取上清加水稀释后进样分析；色谱柱为Venusil HILIC（4.6 mm×250 mm，5.0 μm）；流动相为50 mmol·L^-1磷酸二氢钾含0.05%甲酸-乙腈（30：70，V/V）；流速0.8 mL·min^-1；检测波长为299 nm；柱温40℃；分别考察美罗培南全血、溶血样本在不同温度、不同采血管等条件下的稳定性。结果：美罗培南在0.38~71.30 μg·mL^-1范围内线性关系良好（r=0.999 9），定量下限为0.38 μg·mL^-1，低、中、高浓度的萃取回收率在101.87%~107.89%，日内、日间RSD均小于2.81%；以EDTA-K2为最佳的临床采血管，EDTA-K2管和肝素钠管中的美罗培南能在室温（19~22℃）下稳定4 h；溶血样本在2~6℃冰箱存放7 h稳定，但相对于EDTA-K2管和血浆质控，肝素钠管会使美罗培南检出率偏高；血浆样本在室温（19~22℃）、2~6℃冰箱内6 h、-40℃冻存20 d、-40℃反复冻融3次均稳定。结论：建立的TDM临床采样流程充分考虑了临床采样的实际情况并能确保美罗培南药物的稳定性及分析检测结果的准确性，可满足临床血药浓度监测需求。     

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.     

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.     

美罗培南与亚胺培南／西司他丁钠治疗细菌感染有效性和安全性的Meta分析

目的运用Meta分析的方法综合比较评价美罗培南与亚胺培南／西司他丁钠治疗细菌感染的有效性和安全性。方法制定原始文献的纳入和排除标准及检索策略,检索文献数据库,收集有关美罗培南与亚胺培南／西司他丁钠治疗细菌感染的随机对照试验研究报告,剔除不符合要求的文献后,纳入文献17篇,提取文献数据进行定量综合分析。结果综合分析显示,美罗培南和亚胺培南／西司他丁钠治疗细菌感染痊愈率计算OR值（95％cI）为1．07（0．85～1．34）,有效率OR值（95％CI）为0．90（O．67～1．22）,不良反应发生率OR值（95％CI）为0．84（0．56～1．26）。结论美罗培南与亚胺培南／西司他丁钠在治疗细菌感染时有效性和安全性相当。     

Comparison of in vitro activities of meropenem productions on Klebsiella pneumoniae isolated from hospitalized patients

Purpose: Antimicrobial activities of meropenem products on Klebsiella pneumoniae isolates were determined. Methods: 212 non-duplicated Klebsiella pneumoniae isolates were examined for in vitro meropenem susceptibility test by using the following disks, which were made from Meronem (AstraZeneca, UK), Exipenem (Exir, Iran) and Meroxan (DAANA, Iran) powders. MIC₅₀ and MIC₉₀ for meropenem antibiotics were determined.Results: Meronem had good activities against most isolates of Klebsiella pneumoniae, and only a few strains had a rather high MIC. Exipenem and Meroxan showed a similar activity with Meronem. Conclusion: Regarding the comparison of two internal generic meropenem products with the external Meronem product have shown that they are equivalents in terms of microbiological activity, as measured using the disk diffusion and MIC. In developing countries, we suggested preparing disks with antibiotic powders that can be an equivalent function in microbiological activity with standard disks. In addition, since it demonstrated significant antimicrobial activity against the Klebsiella pneumoniae. For use of Exipenem and Meroxan in vivo, it would be better to perform additional testing (activity against different species, stability etc.).     

美罗培南配合免疫球蛋白治疗新生儿败血症的疗效及其对炎症因子的影响

目的?探讨新生儿败血症患儿实施美罗培南配合免疫球蛋白治疗的疗效及炎症水平变化。方法?选取2016年4月—2018年4月海南医学院第二附属医院收治的新生儿败血症患儿100例,以挂号就诊单病案号单、双数为基准,分为研究组和对照组。治疗组采用美罗培南+免疫球蛋白治疗,对照组采用美罗培南治疗,对比两组临床症状改善时间、临床疗效、炎症水平及临床指标。结果?研究组拒奶改善时间、体温改善时间、神经系统症状改善时间、血培养转阴时间及住院时间低于对照组（P?<0.05）,研究组总有效率高于对照组（P?<0.05）,研究组治疗前后白细胞介素-6、白细胞介素-1、高敏感C反应蛋白及肿瘤坏死因子-α的差值高于对照组（P?<0.05）,研究组治疗前后分化抗原3、分化抗原8、免疫球蛋白G及免疫球蛋白M的差值高于对照组（P?<0.05）。结论?新生儿败血症患儿实施美罗培南配合免疫球蛋白治疗的临床疗效显著,可明显改善机体炎症水平,值得借鉴。     

Effect of sodium mercaptoacetic acid on different antimicrobial disks in the sodium mercaptoacetic acid double disk synergy test for detection of IMP-1 metallo-β-lactamase-producing Pseudomonas aeruginosa isolates in Japan

We determined the optimal antimicrobial in the sodium mercaptoacetic acid double disk synergy test (SMA-DDST) for the detection of IMP-1-producing Pseudomonas aeruginosa isolates in Japan and evaluated the performance of the test.Fifty-four P. aeruginosa clinical isolates were tested, including 39 IMP-1 producers and 15 non-metallo-β-lactamase (MBL)-producing carbapenem- and ceftazidime (CAZ)-resistant isolates. The SMA-DDST was performed with CAZ, cefepime (CFPM), imipenem (IPM), meropenem (MEPM), doripenem (DRPM), or biapenem (BIPM)-containing disks. The sensitivity of the SMA-DDST with CAZ, CFPM, IPM, MEPM, DRPM, and BIPM was 39/39 (100%), 36/39 (92%), 18/39 (46%), 8/39 (21%), 19/39 (49%), and 36/39 (92%), respectively. The specificity was 15/15 (100%) for all SMA-DDSTs. This suggests that the isolates may have a resistance mechanism other than MBL production for IPM, MEPM, or DRPM. Since the CAZ resistance mechanism in P. aeruginosa is the same as that of CFPM, but differs from that of carbapenems, we conclude that combining CAZ with BIPM SMA-DDSTs can prevent any failure in the detection of IMP-1-producing P. aeruginosa.