新抗真菌剂三氮唑含硫化合物的合成

作者合成了１２个三氮唑类化合物，其中１０个为三氮唑含硫化合物，后者未见文献报道。作者还对这些化合物进行了体外抗真菌活性的测定。     

An Update on the Status of Potent Inhibitors of Metallo-β-Lactamases

The production of metallo-β-lactamases is the most important strategy by which pathogenic bacteria become resistant to currently known β-lactam antibiotics. The emergence of these enzymes is particularly concerning for the future treatment of bacterial infections. There are no clinically available drugs capable of inhibiting any of the metallo-β-lactamases, so there is an urgent need to find such inhibitors. In this review, an up-to-date status of the inhibitors investigated for the inhibition of metallo-β-lactamases has been given so that this rich source of structural information of presently known metallo-β-lactamases could be helpful in generating a broad-spectrum potent inhibitor of metallo-β-lactamases.     

Epidemiological study of Candida infections in blood: susceptibilities of Candida spp. to antifungal agents, and clinical features associated with the candidemia

The purpose of this study was to evaluate the susceptibility to antifungal agents of Candida spp. isolated from blood samples from patients in our hospital, located in Osaka, Japan. We also examined the clinical background of these patients. We analyzed fungi isolated from clinical blood samples obtained in our hospital over a period of 10 years (1993 to 2002). Antifungal susceptibility testing was carried out for six agents, using the National Committee of Clinical Laboratory Standards (NCCLS) M-27-A2 method. The clinical backgrounds were reviewed using the medical records of 125 patients who were diagnosed as having candidemia. The major fungi isolated were Candida parapsilosis (39.2%) and C. albicans (30.1%), and both were sensitive to fluconazole. One strain of C. glabrata and six strains of C. krusei were resistant to fluconazole, and they constituted 4.4% of all Candida spp. isolated. With the exception of C. parapsilosis, most fungi were susceptible to micafungin, although there is no universally agreed breakpoint for this drug. Analysis of the patients' clinical backgrounds revealed that the major underlying disease was cancer (46.4% excluding hematological malignancies). C. krusei was detected almost exclusively in patients with hematological malignancies. Indwelling venous catheters had been responsible for infection in 93.6% of the infected patients. The clinical outcomes of the 125 patients were favorable in 52% and poor in 48%, and subsequent removal of the indwelling catheters was effective in about half of the patients in whom this was done, with good prognosis. To prevent mycosis and its complications, indwelling catheters should be avoided as much as possible. Attention must be paid to the possibility that resistant isolates of Candida spp. can be selected as a result of the use of antifungal agents.     

Posaconazole for the treatment of mucormycosis

Posaconazole (PCZ) is an orally administered, extended-spectrum triazole antifungal agent with activity against the Mucorales. This article describes the clinical and laboratory data supporting its use against this rare group of pathogens. To date, PCZ has been mostly used for salvage therapy and at present there is no strong published clinical evidence to support its role as a single agent in the treatment of mucormycosis. Further studies are required to explore its role as a single agent and in combination therapy for the management of these infections.     

老年患者感染假丝酵母菌的耐药性分析

目的了解老年患者感染假丝酵母菌的菌群分布、耐药性及交叉耐药情况。方法对从老年住院患者分离出的136株假丝酵母菌进行药敏及交叉耐药分析。结果感染率居前三位的假丝酵母菌分别为白假丝酵母菌(50.74%)、光滑假丝酵母菌(19.85%)、热带假丝酵母菌(18.38%)。假丝酵母菌最常见感染部位为呼吸道,占86.76%。分离率较高的白假丝酵母菌、光滑假丝酵母菌、热带假丝酵母菌对两性霉素B、5-氟胞嘧啶的敏感率均在90%以上;三唑类药物中伏立康唑的敏感性最高,伊曲康唑的敏感率最低;氟康唑与伊曲康唑之间的交叉耐药率最高,为100%,氟康唑与伏立康唑之间的交叉耐药率为38.89%。结论假丝酵母菌属对三唑类药物的敏感性存在较大差异,三唑类药物之间存在严重的交叉耐药现象,临床治疗应依据药敏结果合理选择药物。     

A 13-week feeding study of butylated hydroxyanisole: the subsequent regression of the induced lesions in male Fischer 344 rat forestomach epithelium

Feeding butylated hydroxyanisole (BHA) to male Fischer 344 rats at concentrations of 2, 0.5, 0.25, 0.1 and 0% for 13 weeks led to proliferative lesions developing in the forestomach epithelium of the 2%-treated rats but not in other groups. The [methyl-3H]thymidine labelling index was raised in the 2%- and 0.5%-treated groups and showed an apparent no observable effect level at 0.25%. Within 1 week after withdrawal of BHA the labelling indexes in all treated groups returned to near the values in the controls. The induced mucosal lesions, however, reverted more slowly and even after 9 weeks on the basal diet, the stratified squamous epithelium along the lesser curvature, was still slightly thicker than the control. There were multilayered basal cell processes in the lamina propria with connections to the basal cell layer. The possible significance of these results to the ultimate development of cancer is discussed.     

Antifungal agents for the treatment of systemic fungal infections in children

Traditionally, the mainstay of systemic antifungal therapy has been amphotericin B deoxycholate (conventional amphotericin B). Newer agents have been developed to fulfill special niches and to compete with conventional amphotericin B by virtue of having more favourable toxicity profiles. Some agents have displaced conventional amphotericin B for the treatment of specific fungal diseases. For example, voriconazole has emerged as the preferred treatment for invasive pulmonary aspergillosis. This notwithstanding, conventional amphotericin B remains a useful agent for the treatment of paediatric fungal infections. Knowledge of the characteristics of the newer agents is important, given the increasing numbers of patients who are being treated with these drugs. Efforts need to be directed at research aimed at generating paediatric data where these are lacking. The antifungal agents herein described are most often used as monotherapy regimens because there is no uniform consensus on the value of combination therapy, except for specific scenarios.     

Synthesis and Biological Evaluation of Novel 1,2,3‐Triazolonucleotides

A general procedure for the preparation of 1,2,3‐triazole analogs of nucleosides from diethyl 2‐azidoethoxymethyl‐ and 2‐azidoethoxyethylphosphonates was elaborated. The application of microwave irradiation shortened the reaction time to 10 min in comparison to ca. 48 h when 1,3‐dipolar cycloadditions were performed under standard conditions. All compounds were evaluated in vitro for inhibitory activity against a broad variety of DNA and RNA viruses. None of the compounds were antivirally active at subtoxic concentrations. Compound 17k exhibited moderate inhibitory effects on the proliferation of human T‐lymphocyte cells (IC₅₀ = 64 µM for CEM).     

N-乙腈基-5-氯苯并三氮唑的合成及异构体组成分布和产率探讨

目的 探讨5-氯苯并三氮唑N-上引入乙腈基所得产物异构体组成分布和产率的影响.方法 以5-氯苯并三氮唑和苯并三氮唑分别与氯乙腈反应,在无水碳酸钾/乙酸乙酯的反应体系中、100 ℃ 温度条件下合成了目标化合物,并采用红外吸收光谱,核磁共振图谱进行结构表征.结果 苯并三氮唑及衍生物与氯乙腈在无水碳酸钾作用下反应,反应物不同...