质粒介导的tet(A)突变体对肺炎克雷伯氏菌替加环素耐药的影响

替加环素是治疗多重耐药肺炎克雷伯氏菌感染的为数不多的抗菌药物之一,但替加环素耐药肺炎克雷伯氏菌的出现给临床治疗带来了严重威胁。本实验从临床分离到1株替加环素耐药肺炎克雷伯氏菌,电转化实验获得了一个对替加环素耐药的质粒,功能性分析发现该质粒中的tet(A)基因发生了双移码突变,且药敏实验证实这些突变可单独使替加环素的MIC值增加8倍,米诺环素和四环素的MIC值增加128倍。研究证实,质粒介导的tet(A)突变体可导致肺炎克雷伯氏菌对替加环素耐药,扩宽了对肺炎克雷伯氏菌替加环素耐药机制的认识,并为该类型耐药基因在革兰氏阴性菌中的扩散控制提供了依据。     

替加环素耐药机制研究进展

替加环素作为新型四环素类抗生素，是治疗产碳青霉烯酶多重耐药肠杆菌感染的最后一道防线之一。近年来，替加环素耐药菌株的出现严重限制了替加环素的临床使用。最初认为替加环素的耐药机制是由染色体编码的外排泵介导，不能通过水平转移导致菌株耐药。随着研究的深入，发现质粒上的某些外排泵突变或高表达也可导致菌株替加环素敏感性降低。最近报道质粒介导的tet（X）变异体能够使菌株对替加环素产生高水平耐药，并通过可接合性质粒在不同种属细菌间传播。文章通过介绍细菌染色体介导替加环素耐药机制以及质粒介导的替加环素耐药机制，阐述了高水平替加环素耐药基因tet（X）变异体的流行情况和传播机制，并对动物源菌株出现高水平替加环素耐药基因tet（X）变异体提出合理性解释，旨在为相关科研人员和临床工作者提供参考。     

Antibiotic treatment of zebrafish mycobacteriosis: tolerance and efficacy of treatments with tigecycline and clarithromycin

Zebrafish (Danio rerio) are a popular model organism used in a growing number of research fields. Maintaining healthy, disease‐free laboratory fish is important for the integrity of many of these studies. Mycobacteriosis is a chronic bacterial infection caused by several Mycobacterium spp. and is the second most common disease found in laboratory zebrafish. Current mycobacteriosis control measures recommend the removal of infected fish and in severe outbreaks, depopulation. These measures can be effective, but less disruptive measures should be assessed for controlling mycobacteriosis, particularly when valuable and rare lines of fish are affected. Here, the in vivo efficacy of two drug candidates, tigecycline (1 μg g^?1) and clarithromycin (4 μg g^?1), was tested in adult zebrafish experimentally infected with Mycobacterium chelonae. We assessed both short (14 day)‐ and long‐term (30 day) treatments and evaluated fecundity and pathological endpoints. Fecundity and histology results show that zebrafish tolerated antibiotics. Antibiotic treatments did not significantly impact the prevalence of acid‐fast granulomas; however, the severity of infections (acid‐fast granuloma intensity) was significantly decreased following treatments.     

Advance on the Tigecycline Resistance Mechanism

Tigecycline,as a new tetracycline antibiotic,is one of the last lines of defense against carbapenems-producing enterobacter multidrug-resistant infections.In recent years,the emergence of tigecycline-resistant strains has severely restricted the clinical use of tigecycline.It was originally believed that the resistance mechanism of tigecycline was mediated by the efflux pump encoded by the chromosome,which could not lead to drug resistance by horizontal transfer.With the deepening of research,it was found that some efflux pump mutations or high expression on the plasmid could also cause the strain's tigecycline sensitivity to decrease.Recently,it has been reported that the plasmid-mediated tet(X) variant can make the strain highly resistant to tigecycline,and can be spread among different species of bacteria through adaptable plasmids.This article described the prevalence and transmission mechanism of high-level tigecycline resistance gene tet(X) variants by introducing bacterial chromosome-mediated tigecycline resistance mechanisms and plasmid-mediated tigecycline resistance mechanisms,and provided a reasonable explanation for the high-level variant of the tigecycline resistance gene tet(X) in animal-derived strains,aiming to provide reference for relevant scientific researchers and clinical workers.     

Pharmacokinetics of tigecycline in turkeys following different routes of administration

The aim of this research had been to determine the pharmacokinetics of tigecycline (TIG) in turkey after intravenous (i.v.), intramuscular (i.m.), subcutaneous (s.c.), and oral (p.o.) administration at a dose of 10 mg/kg. TIG concentrations in plasma were determined using high‐performance liquid chromatography with tandem mass spectrometry. Mean concentrations of TIG in turkey plasma in the i.v. group were significantly higher than concentrations of this drug obtained after using the other administration routes. No significant differences were demonstrated in respect to the concentrations achieved after i.m. and s.c. administration. The bioavailability of TIG after i.m., s.c., and p.o. administration was 32.59 ± 5.99%, 34.91 ± 9.62%, and 0.97 ± 0.57%, respectively. Values of half‐life in the elimination phase were 23.49 ± 6.51 hr, 25.42 ± 4.42 hr, and 26.62 ± 5.19 hr in i.v., i.m., and s.c. groups, respectively, values of mean residence time were 7.92 ± 1.41 hr, 19.62 ± 2.82 hr, and 17.55 ± 2.59 hr in i.v., i.m., and s.c. groups, respectively, whereas the volume of distribution was 14.85 ± 5.71 L/kg, 14.68 ± 2.56 L/kg, and 15.37 ± 3.00 L/kg in i.v., i.m., and s.c. groups, respectively. Because TIG is not absorbed from the gastrointestinal tract in turkeys to a clinically significant degree, this drug given p.o. could find application in commercial turkey farms only to treat gastrointestinal tract infections.