国产美罗培南治疗急性细菌性感染的临床试验

目的:研究国产美罗培南用于抗感染治疗的临床疗效和安全性.方法:将30例中、重度急性细菌性感染患者按随机对照平行法分成2组,治疗组14例,给予美罗培南0.5g,q8h,静脉滴注;对照组16例,给予泰能(亚胺培南/西司他丁)1.0g,q8h,静脉滴注.两药疗程均为7～10d.结果:两组的临床痊愈率均为50%;临床有效率治疗组和对照组分别为85.7%和87.5%;细菌清除率分别为84.6%和85.7%;不良反应发生率分别为14.3%和18.8%.以上指标两组差异均无显著性(P>0.05).结论:国产新药美罗培南用于抗感染治疗安全有效.     

美罗培南与亚胺培南/西司他丁随机对照治疗急性细菌性感染

目的:研究国产美罗培南治疗急性细菌性感染的临床疗效和安全性.方法:选择中、重度急性细菌性感染患者.治疗组30例,给予美罗培南0.5 g,tid,静脉滴注;对照组26例,给予亚胺培南/西司他丁(泰能)1.0 g,tid,静脉滴注.两药疗程均为7～10 d.结果:美罗培南组和泰能组的临床痊愈率分别为63.3%和65.4%;临床有效率分别为93.3%和96.2%;细菌清除率分别为88.0%和85.7%;不良反应发生率分别为10.0%和7.7%.以上指标差异均无显著性(P>0.05).结论:国产美罗培南治疗急性细菌性感染是有效和安全的,与泰能相比差异无显著性.     

单次静脉美罗培南在健康人体的药代动力学

目的 研究单剂量美罗培南静脉制剂药代动力学,为临床提供合理给药方案。方法 中国健康受试者10名随机分组交叉给药,30 min内静脉点滴美罗培南500,1 000mg,分别在给药前,给药后0.25,0.5,0.75,1,1.5,2,3,4,5,6,8 h取血,并于0~2,2-6,6～12,12—24 h留取尿样本,用高效液相色谱法测定美罗培南血药浓度及尿药浓度。结果 血药浓度数据经3P97程序分析血药浓度-时间曲线为二室模型,静脉点滴500,1 000 mg主要药代动力学参数Cmax分别为23.08±4.00,48.19±9.78 mg·L-1,AUC分别为27.47±3.80,55.56±6.72 mg·h·L-1,,tl/2B分别为1.08±0.19,1.15±0.15 h,CL分别为18.91±2.48,18.68±2.32L·h-1,Vd分别为13.48±2.94,13.93±2.40L。12 h原形药物在尿中累积排泄百分率分别为(60.11±5.20)％与(61.23±9.81)％。结论 美罗培南单次给药在中国健康人体耐受良好,药物主要经肾脏排泄。     

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.     

Meta-analysis: combination of meropenem vs ceftazidime and amikacin for empirical treatment of cancer patients with febrile neutropenia

Background:Meropenem monotherapy vs ceftazidime plus amikacin have been approved for use against febrile neutropenia. To assess the effectiveness and safety of them for empirical treatment of cancer patients with febrile neutropenia, we conducted a meta-analysis of randomized controlled trial.Methods:Randomized controlled trials on ceftazidime plus amikacin, or/and monotherapy with meropenem for the treatment of cancer patients with febrile neutropenia were identified by searching Cochrane Library, PubMed, Science Direct, Wiley Online, Science Citation Index, Google (scholar), National Center for Biotechnology Information, and China National Knowledge Infrastructure. Data on interventions, participants’ characteristics and the outcomes of therapy, were extracted for statistical analysis. Seven trials fulfilled the inclusion criteria.Result:The treatment with ceftazidime plus amikacin was more effective than meropenem (OR = 1.17; 95% CI 0.93–1.46; 1270 participants). However, the treatment effects of the 2 therapy methods were almost parallel in adults (OR = 1.15; 95% CI 0.91–1.46; 1130 participants older than 16). Drug-related adverse effects afflicted more patients treated with ceftazidime plus amikacin (OR = 0.78; 95% CI 0.52–1.15; 1445 participants). The common responses were nausea, diarrhea, rash, and increased in serum glutamic oxaloacetic transaminase, serum glutamic pyruvic transaminase and bilirubin.Conclusion:Ceftazidime plus amikacin should be the first choice for empirical treatment of cancer patients with febrile neutropenia, and meropenem may be chosen as a last defense against pathogenic bacteria.     

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。     

Meropenem and Vaborbactam: Stepping up the Battle against Carbapenem‐resistant Enterobacteriaceae

Vaborbactam (VAB; formerly RPX7009) is a novel beta‐lactamase inhibitor based on a cyclic boronic acid pharmacophore with potent inhibitory activity against Ambler class A and C beta‐lactamases. It has been co‐formulated with meropenem to restore its activity against Klebsiella pneumoniae carbapenemases (KPC). VAB does not inhibit class B or D carbapenemases, nor does it improve the activity of meropenem against multidrug‐resistant nonfermenting gram‐negative bacilli, notably Acinetobacter spp. and Pseudomonas aeruginosa. The purpose of this article is to review existing data pertaining to the biochemistry, mechanism of action, pharmacokinetics/pharmacodynamics, in vitro activity, and current progress in clinical trials of meropenem and VAB (MV). Phase 1 studies have demonstrated single and multiple doses of VAB up to 2000 mg, alone or in combination with meropenem 2000 mg administered as a prolonged infusion over 3 hours, are well tolerated with an adverse effect profile similar to that of meropenem monotherapy. The available data suggest preexisting resistance among KPC‐producing isolates is rare. Strains with elevated MICs have been characterized by multiple resistance determinants including porin defects, increased drug efflux, and increased blaKPC expression. It remains uncertain whether multifactorial resistance will emerge during MV treatment and with more widespread use. Early data are positive for complicated urinary tract infections and MV compared with best available therapy in patients with serious carbapenem‐resistant Enterobacteriaciae (CRE) infections. As clinicians contemplate how to incorporate MV into CRE treatment strategies, it will be important to track and understand resistance, discern the role, if any, of combination therapy in enhancing efficacy and/or preserving activity, and define the specific therapeutic niche of MV among the expanding anti‐CRE armamentarium.     

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.).