Impact of transporter-mediated drug absorption, distribution, elimination and drug interactions in antimicrobial chemotherapy

A comprehensive list of drug transporters has recently become available as a result of extensive genome analysis. Membrane transporters play important roles in determining the pharmacokinetic aspects of intestinal absorption, tissue distribution, and the urinary and biliary excretions of a wide variety of therapeutic drugs. The identification and characterization of transporters responsible for the transfer of nutrients and xenobiotics, including drugs, is expected to provide a scientific basis for understanding drug disposition, as well as the molecular mechanisms of drug–drug/drug–food/drug–protein interactions and inter-individual/inter-species differences. This review focuses on the influence of transporters on the pharmacokinetics of β-lactam antibiotics, new quinolones, and other antimicrobial agents, as well as focusing on the drug–drug interactions associated with transporter-mediated uptake from the small intestine and transporter-mediated elimination from the kidney and liver.     

1685株鲍曼不动杆菌的临床分布及耐药性研究

目的探讨川北医学院附属医院鲍曼不动杆菌感染的临床分布和耐药特点,为该菌的感染治疗与预防提供依据。方法该院2011~2014年住院患者送检标本中分离的1 685株鲍曼不动杆菌的分布及耐药性检测。结果鲍曼不动杆菌主要分离自痰液标本,占73.1%;以重症监护病房和神经外科病房检出率最高;该菌仅对头孢哌酮/舒巴坦和米诺环素耐药率低,分别为27.9%和26.9%;对亚胺培南、美罗培南的耐药率分别为77.4%、73.9%;对其余多种抗菌药物耐药率在62.0%以上。结论鲍曼不动杆菌的耐药率较高并具有多重耐药性,临床治疗应及时进行细菌耐药性监测并根据药敏试验结果选择合适的抗菌药物。     

鲍曼不动杆菌的耐药性检测及多重耐药菌株质粒图谱分析

目的 对我院分离的鲍曼不动杆菌多重耐药菌株进行质粒图谱分析,以了解耐药菌的流行情况,指导临床合理用药。方法 收集用K-B法对临床分离的鲍曼不动杆菌进行药敏试验,对多重耐药菌株进行质粒图谱分析。结果 143株鲍曼不动杆菌对临床常用抗生素均有不同程度的耐药,对第三代头孢菌素的耐药率最高,达44．1％-100％,其次为美洛培南和亚胺培南,分别为21．7％和23.3％,对头孢哌酮／舒巴坦的耐药率最低,为9．5％。质粒图谱显示被测15株高度多重耐药菌株中有7株质粒图谱相同,结合临床资料,定为流行株。结论 我院鲍曼不动杆菌呈现严重多重高度耐药现象,外科重症监护(ICU)病房存在鲍曼不动杆菌的流行株。     

牙周基础治疗联合抗生素对中重度慢性牙周炎患者IL-33、IL-6的影响研究

目的探讨牙周基础治疗联合抗生素对中重度慢性牙周炎患者IL-33、IL-6的影响。方法选取上海市闵行区浦江镇社区卫生服务中心2016年12月—2018年12月接诊的78例中重度慢性牙周炎患者进行研究。根据治疗方法的不同,将其均分为对照组和观察组各39例。对照组采取牙周基础治疗,观察组在对照组的基础上联合抗生素治疗。比较分析两组患者治疗后的有效率,治疗前和治疗后3个月的白细胞介素-33(IL-33)、白细胞介素-6(IL-6)、C-反应蛋白(CRP)、肿瘤坏死因子(TNF-α)水平、牙周指标(牙龈指数、龈沟出血指数、探诊后出血指数以及牙周袋深度)以及不良反应情况。结果观察组患者治疗总有效率(94.87%)明显高于对照组(79.48%),差异有统计学意义(P0.05)。治疗前,两组患者的IL-33、IL-6、CRP、TNF-α、GI、SBI、BOP和PD水平差异无统计学意义(P0.05)。治疗3个月后,观察组IL-33、IL-6、CRP、TNF-α、GI、SBI、BOP和PD水平均明显低于对照组,差异有统计学意义(P0.05)。观察组不良反应发生率明显低于对照组,差异有统计学意义(P0.05)。结论牙周基础治疗联合抗生素能够改善中重度慢性牙周炎患者的血清炎性因子水平和牙周指标,且预后良好,值得临床上推广应用。     

Antibiotics and Bone Cements: Experimental and Clinical Long-Term Observations

Comparing several antibiotics and different bone cements, the mixture of Palacos® R (polymethylmethacrylate, PMMA) with gentamicin proved to be the most suitable one as far as a high and sustained release of the antibiotic from the artificial resin is concerned. A continuous leaching of gentamicin was observed for more than 5 years. Gentamicin proved to be stable in Palacos R for the whole period of time.

The release of 12 antibiotics from Palaes R was evaluated in vitro. Four other bone cements were included in this ttudy as well, in order to evaluate the leaching of gentamicin from these materials. the combination Gentamicin-Palacos R (GP) showed a 2–3 fold higher and much more prolonged release than did the other mixtures. From this investigation, which also included studies of commercially available antibiotic bone cement mixtures, it is quite obvious that there exist distinct differences in the various bone cements as well as in the various antibiotics as regards their qualification for use in alloarthroplasty.

Pharmacokinetic studies in patients after implantation of GP showed low gentamicin concentrations in serum (on average 1.8μg/ml) and urine. However, in wound exudate, derived directly from the vicinity of the implanted cement, gentamicin concentrations up to 150μg/ml were observed. Also in tissue samples from the vicinity of the implant, high concentrations were measurable for a long period of time (up to 5 1/2 years).     

4238份血培养标本的病原菌分布情况及耐药性研究

目的对该院2012年6月至2016年6月血培养标本中病原菌分布情况及耐药性的研究。方法选用BD Bactec FX-200血培养分析仪对2012年6月至2016年6月共4 238份标本进行检测并对鉴定结果进行回顾性分析。结果 4 238份血培养标本中检测出阳性标本455株,阳性率为10.74%,革兰阳性菌占38.02%,革兰阴性菌占60.00%,真菌占1.98%;主要分布在新生儿和中老年患者中,分别为6.78%和76.17%。其中肠杆菌科占54.10%,以大肠埃希菌和肺炎克雷伯菌为主,非发酵菌占2.90%。革兰阳性球菌以葡萄球菌属为主,占25.87%。肠杆菌科对美罗培南、亚胺培南等较为敏感,非发酵菌对哌拉西林/他唑巴坦较为敏感,葡萄球菌和链球菌对万古霉素较为敏感。结论结合患者病原菌分布及耐药情况,临床医生应合理用药增强菌血症和真菌血症的治愈率。     

Using antimicrobial host defense peptides as anti-infective and immunomodulatory agents

Virtually all life forms express short antimicrobial cationic peptides as an important component of their innate immune defenses. They serve as endogenous antibiotics that are able to rapidly kill an unusually broad range of bacteria, fungi and viruses. Consequently, considerable efforts have been expended to exploit the therapeutic potential of these antimicrobial peptides. Within the last couple of years, it has become increasingly clear that many of these peptides, in addition to their direct antimicrobial activity, also have a wide range of functions in modulating both innate and adaptive immunity. For one class of antimicrobial peptides, such as the human defensins, their primary role may even be as immunomodulators. These properties potentially provide entirely new therapeutic approaches to anti-infective therapy.     

Clinical relevance of the ESKAPE pathogens

In recent years, the Infectious Diseases Society of America has highlighted a faction of antibiotic-resistant bacteria (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacter spp.) – acronymically dubbed ‘the ESKAPE pathogens’ – capable of ‘escaping’ the biocidal action of antibiotics and mutually representing new paradigms in pathogenesis, transmission and resistance. This review aims to consolidate clinically relevant background information on the ESKAPE pathogens and provide a contemporary summary of bacterial resistance, alongside pertinent microbiological considerations necessary to face the mounting threat of antimicrobial resistance.