亚胺培南/西司他丁钠致老年患者癫痫样发作1例

1例老年男性患者因脑梗死合并肺部感染接受"头孢唑肟"抗感染治疗10 d后未治愈,换用亚胺培南/西司他丁钠(泰能,0.5 g,q8h)治疗d 3出现癫痫样发作,考虑系该药物的不良反应。本例患者出现癫痫样发作可能与患者年龄大且合并有肾功能不全有关,更换美罗培南后避免了患者癫痫样发作等严重不良反应的发生。     

亚胺培南或美罗培南联合利福平降低不动杆菌防耐药突变浓度的体外研究

目的在体外探讨亚胺培南(IMP)和美罗培南(MER)单用及其分别与利福平(RFP)联用对不动杆菌的防耐药突变浓度(MPC)的影响,为防止细菌耐药的产生提供理论依据。方法采用琼脂二倍稀释法,测定IMP或MER与RFP在体外单独以及联合应用的最低抑菌浓度(MIC)、计算部分抑菌浓度(FIC)指数。用肉汤法富集浓度为1010CFU/ml不动杆菌,采用琼脂平板二倍稀释法测定IMP和MER单药以及分别与RFP联用时对16株临床分离不动杆菌的MPC,并计算相应的选择指数(SI)。结果 IMP或MER分别与RFP联合应用后均以无关作用为主,未见拮抗作用,存在一定比例协同作用。IMP和MER单用对上述16株不动杆菌的SI均为16～128;分别与RFP联合使用SI均下降为1～32,联合用药较单独用药SI下降2～32倍。结论 IMP或MER分别与RFP联合使用均可降低其单用对不动杆菌的MPC,缩小MSW,防止耐药突变菌的产生。     

左奥硝唑等4种抗菌药的防耐药突变浓度测定及临床用药剂量合理性的分析

目的：测定左奥硝唑、亚胺培南西司他丁钠、莫西沙星和替硝唑单用或联用时的防耐药突变浓度,为临床上的合理用药提供依据。方法：选用体外脆弱拟杆菌ATCC25285,分别以微量肉汤稀释法测定供试药物的体外最低抑菌浓度;棋盘格法测定分级抑菌浓度指数;平板法测定单独用药及联合用药后的防耐药突变浓度。分析比较各药防耐药突变浓度与体内最大血药浓度之间的关系。结果：左奥硝唑、亚胺培南西司他丁钠、莫西沙星和替硝唑单独使用时对脆弱拟杆菌ATCC25285的防耐药突变浓度分别为10．24、5．12、4．0和20．24mg·L-1;按临床目前使用的常规剂量,各药的体内最大血药浓度与其防耐药突变浓度之比分别为1．82、2．73～4．69、0．75～1．0和0．684～1．02;而左奥硝唑与莫西沙星、亚胺培南西司他丁钠联用后的防耐药突变浓度分别降低为3．2和1．6mg·L-1,联用后的FIC分别为0．75和0．5。表明左奥硝唑与莫西沙星、亚胺培南西司他丁钠联用可明显缩小各自的防耐药突变浓度。结论：左奥硝唑在目前的常规剂量下,不易引起耐药性,但替硝唑的剂量应予适当增加。左奥硝唑与莫西沙星、亚胺培南西司他丁钠联用有助于减少耐药性。     

三维实验法检测耐亚胺培南的铜绿假单胞菌产β-内酰胺酶

[目的]了解耐亚胺培南的铜绿假单胞菌产β-内酰胺酶的分布及分离率。[方法]采用K-B法进行药物敏感试验,筛选耐亚胺培南的铜绿假单胞菌;再进行改良三维实验,对菌株所产β-内酰胺酶进行分析。[结果]临床分离耐亚胺培南的铜绿假单胞菌40株中,单产超广谱β-内酰胺酶（ESBLs）9株（22.5%）,单产高产染色体头孢菌素酶（AmpC）2株（5.0%）,5株为超超广谱β-内酰胺酶（SSBL）（12.5%）,3株产酶量过高或其他原因（7.5%）,21株无酶活性（52.5%）。[结论]产β-内酰胺酶是耐亚胺培南铜绿假单胞菌的主要耐药机制之一。     

Characterisation of OXA-51, a novel class D carbapenemase found in genetically unrelated clinical strains of Acinetobacter baumannii from Argentina

Acinetobacter baumannii is now one of the most frequently encountered nosocomial pathogens in intensive therapy units, and is renowned for being difficult to treat because of resistance to most antibiotics. Carbapenems are the remaining drugs of choice in many centres, but carbapenem resistance is now emerging in strains worldwide. Two subgroups of carbapenem-hydrolysing beta-lactamases, which differ in their amino-acid homology, have been found in some resistant strains. This report describes the emergence and characterisation of a novel carbapenemase (OXA-51) in genetically distinct carbapenem-resistant A. baumannii strains from Argentina. Enzyme kinetics and inhibitor studies were performed spectrophotometrically with purified beta-lactamase. Amplification of the gene was achieved with a two-step PCR method employing arbitrary partially degenerate and gene-specific primers. Transfer of imipenem resistance was attempted with the use of broth and membrane filter methods. Attempts to produce plasmid-cured variants were made in ethidium bromide curing experiments. OXA-51 was identified in two clones of A. baumannii, and was found to have < 63% amino-acid identity with subgroups 1 and 2. Enzyme kinetic studies confirmed that OXA-51 was a molecular class D enzyme with carbapenemase activity, and that it displayed the highest affinity for imipenem (Km value 11 microM). Sequence analysis of the gene identified distinct differences within conserved class D motifs when compared with subgroups 1 and 2. Attempts to transfer imipenem resistance and to determine a plasmid location for the gene failed. OXA-51 is the first of a new subgroup of carbapenemases to emerge in multiresistant clinical isolates of A. baumannii.     

Alveolar and serum concentrations of imipenem in two lung transplant recipients supported with extracorporeal membrane oxygenation

Venovenous extracorporeal membrane oxygenation (ECMO) is increasingly used in patients with respiratory failure who fail conventional treatment. Postoperative pneumonia is the most common infection after lung transplantation (40%). Imipenem is frequently used for empirical treatment of nosocomial pneumonia in the intensive care unit. Nevertheless, few data are available on the impact of ECMO on pharmacokinetics, and no data on imipenem dosing during ECMO. Currently, no guidelines exist for antibiotic dosing during ECMO support. We report the cases of 2 patients supported with venovenous ECMO for refractory acute respiratory distress syndrome following single lung transplantation for pulmonary fibrosis, treated empirically with 1 g of imipenem intravenously every 6 h. Enterobacter cloacae was isolated from the respiratory sample of Patient 1 and Klebsiella pneumoniae was isolated from the respiratory sample of Patient 2. Minimum inhibitory concentrations of the 2 isolated strains were 0.125 and 0.25 mg/L, respectively. Both patients were still alive on day 28. This is the first report, to our knowledge, of imipenem concentrations in lung transplantation patients supported with ECMO. This study confirms high variability in imipenem trough concentrations in patients on ECMO and with preserved renal function. An elevated dosing regimen (4 g/24 h) is more likely to optimize drug exposure, and therapeutic drug monitoring is recommended, where available. Population pharmacokinetic studies are indicated to develop evidence‐based dosing guidelines for ECMO patients.     

Mucosal pharmacokinetics and pilot study of short course of parenteral imipenem in the eradication of Helicobacter pylori

Abstract Eradication of Helicobacter pylori infection is known to reduce the incidence of duodenal ulcer recurrence. The most commonly used regimen for H. pylori infection is triple antimicrobial therapy for 1-2 weeks. This treatment is associated with frequent side effects and hence unsatisfactory compliance. As in vitro data showed that H. pylori is sensitive to imipenem, the pharmacokinetics of this drug in the gastric milieu, and the clinical efficacy of imipenem with omeprazole in eradicating H. pylori infection were studied. Imipenem/cilastatin levels in serum, gastric secretion and gastric mucosa were assayed in four patients after intravenous injection of a bolus dose of 500 mg. The serum and gastric secretion levels of imipenem achieved were more than 10 times the minimum inhibitory concentration of the drug for H. pylori. Gastric mucosal levels of imipenem vary considerably with time, which probably indicates rapid elimination of the drug into the gastric lumen. In the second part of this study, imipenem/cilastatin was given intravenously for the first 2 days after diagnosis of H. pylori infection in patients with endoscopically confirmed duodenal ulcers. The patients were also treated with 4 weeks of omeprazole. Clearance of H. pylori was initially achieved at the end of 2 days in 20 out of 22 (91%) patients. However, when the biopsies were repeated at 8 weeks, recurrence of H. pylori infection was evident in 19 cases (86.3%) indicating a failure of eradication. It was concluded that imipenem/cilastatin in combination with omeprazole failed to eradicate H. pylori infection.     

亚胺培南与帕尼培南用于重症肺炎初始治疗的疗效观察

目的：评价亚胺培南和帕尼培南用于重症肺炎初始治疗的有效性。方法将96例直入ICU的重症肺炎患者随机分为亚胺培南组（51例）和帕尼培南组（45例）进行治疗,观察临床疗效及细菌清除率。结果亚胺培南和帕尼培南用于初始治疗重症肺炎的总有效率分别为84．3％和66．7％,细菌清除率分别为69．2％和59．3％。结论亚胺培南和帕尼培南用于重症肺炎初始治疗疗效确切,且亚胺培南略优于帕尼培南。     

Combination therapy for carbapenem-resistant Gram-negative bacteria

The emergence of resistant to carbapenems Gram-negative bacteria (CR GNB) has severely challenged antimicrobial therapy. Many CR GNB isolates are only susceptible to polymyxins; however, therapy with polymyxins and other potentially active antibiotics presents some drawbacks, which have discouraged their use in monotherapy. In this context, along with strong pre-clinical evidence of benefit in combining antimicrobials against CR GNB, the clinical use of combination therapy has been raised as an interesting strategy to overcome these potential limitations of a single agent. Polymyxins, tigecycline and even carbapenems are usually the cornerstone agents in combination schemes. Optimization of the probability to attain the pharmacokinetic/pharmacodynamic targets by both cornerstone drug and adjuvant drug is of paramount importance to achieve better clinical and microbiological outcomes. Clinical evidence of the major drugs utilized in combination schemes and how they should be prescribed considering pharmacokinetic/pharmacodynamic characteristics against CR GNB will be reviewed in this article.     

氨曲南和亚胺培南对β－内酰胺酶稳定性和抑酶效应的研究

用紫外分光光度法．以其它青霉素类、头孢菌素类抗生素为对照．研究氨曲南（Ａｚｔｒｅｏｎａｍ．ＡＺ）和亚胺培南（Ｉｍｉｐｅｎｅｍ．ＩＭＰ）对１１种标准β－内酰胺酶的稳定性及抑酶作用。结果表明．ＡＺ．ＩＭＰ与第三代头孢菌素头孢噻甲羧肟．头孢氨噻类似，对１１种标准β－内酰胺酶均高度稳定。除酶Ｋ１对头孢氨噻相对水解率达２５％外．其余均不超过１５％．其余的青霉素类及第一、二代头孢菌素类，除头孢西丁酶稳定性较好外．均对β－内酰胺酶不稳定．大多数相对水解率１００％以上。抑酶结果表明．ＡＺ或ＩＭＰ对β－内酰胺酶抑制，除与β－内酰胺酶类型有关外．还与ＡＺ或ＩＭＰ本身浓度密切关联。