Recent advances in the development and use of molecular tests to predict antimicrobial resistance in Neisseria gonorrhoeae

Introduction: The number of genetic tests, mostly real-time PCRs, to detect antimicrobial resistance (AMR) determinants and predict AMR in Neisseria gonorrhoeae is increasing. Several of these assays are promising, but there are important shortcomings and few assays have been adequately validated and quality assured.

Areas covered: Recent advances, focusing on publications since 2012, in the development and use of molecular tests to predict gonococcal AMR for surveillance and for clinical use, advantages and disadvantages of these tests and of molecular AMR prediction compared with phenotypic AMR testing, and future perspectives for effective use of molecular AMR tests for different purposes.

Expert commentary: Several challenges for direct testing of clinical, especially extra-genital, specimens remain. The choice of molecular assay needs to consider the assay target, quality controls, sample types, limitations intrinsic to molecular technologies, and specific to the chosen methodology, and the intended use of the test. Improved molecular- and particularly genome-sequencing-based methods will supplement AMR testing for surveillance purposes, and translate into point-of-care tests that will lead to personalized treatments, while sparing the last available empiric treatment option (ceftriaxone). However, genetic AMR prediction will never completely replace phenotypic AMR testing, which detects also AMR due to unknown AMR determinants.     

Recent advances in antimicrobial therapy.

Metronidazole is a relatively nontoxic, oral agent which may prove to be useful in the treatment of infections caused by susceptible anaerobic organisms. Use of metronidazole to treat anaerobic infections presently is investigational.     

Recent trends and advances in polyindole-based nanocomposites as potential antimicrobial agents: a mini review

Infections caused by multi-drug resistant microbes are a big challenge to the medical field and it necessitates the need for new biomedical agents that can act as potential candidates against these pathogens. Several polyindole based nanocomposites were found to exhibit the ability to release reactive oxygen species (ROS) and hence they show excellent antimicrobial properties. The features of polyindole can be fine-tuned to make them potential alternatives to antibiotics and antifungal medicines. This review clearly portrays the antimicrobial properties of polyindole based nanocomposites, reported so far for biomedical applications. This review will give a clear insight into the scope and possibilities for further research on the biomedical applications of polyindole based nanocomposites.

This review clearly portrays the antimicrobial properties of polyindole based nanocomposites, reported so far for antimicrobial applications and it gives clear insight into the scope and possibilities for further research on the biomedical application of polyindole based nanocomposites.     

弯曲菌对抗菌药和生物消杀剂耐药和适应机制的研究进展

弯曲菌,特别是空肠弯曲菌,是世界三大食源性病原菌之一,其对抗菌药和生物消杀剂耐药性的产生和传播是食品安全关注的重点。 与敏感菌株相比,细菌获得耐药性后其生长力、体内外定植力和致病力等方面会出现一系列的生理变化,即产生适应性,以便更好地在特定条件下生存。 适应性的强弱决定了耐药菌在宿主和环境中流行扩散的风险。 本研究综述了弯曲菌对主要抗菌药和生物消杀剂的耐药性和适应性机制,为预防和控制弯曲菌耐药性流行和扩散提供理论支撑。     

淋球菌对六种抗生素耐药性分析

目的探讨淋球菌对青霉素、四环素、喹诺酮、阿奇霉素、头孢曲松、大观霉素六种抗生素的敏感性,为临床用药提供参考。方法通过对212例淋病患者对六种抗生素的药敏试验结果进行统计,分析淋球菌对六种抗生素的耐药性。结果 212株淋球菌菌株药物敏感试验结果显示,对青霉素的耐药性达79.7%,对四环素耐药性达75.4%,对喹诺酮耐药性达70.3%,对阿奇霉素耐药达12.3%,尚未出现对大观霉素、头孢曲松具有耐药性的菌株。结论淋球菌对青霉素、四环素、喹诺酮耐药严重,尚未出现对头孢曲松和大观霉素耐药的菌株。     

抗生素的合理使用与遏制细菌耐药性的发展

由病原微生物引起的感染仍然是人类健康的主要威胁。根据1998年世界卫生组织的统计资料,感染死亡人数占全部死亡人数的第二位。而在全球因感染死亡人数中,发展中国家几乎占到二分之一。 尽管抗生素的发展大大地降低了感染的发病率和病死率,但细菌耐药性的出现和蔓延却严重影响和破     

Role of the membrane potential in bacterial resistance to aminoglycoside antibiotics.

The electrical potential difference (delta psi) across the membrane of Escherichia coli was measured by the distribution of lipid-soluble cations and correlated with resistance to dihydrostreptomycin, where resistance is presumed due to reduced uptake of the drug. A good correlation between the two measured parameters was found under all conditions tested, which included effects of several mutations, inhibitors, changes in pH, and osmolarity. The most dramatic changes were seen when pH was varied; in wild-type strains resistance increased more than 100-fold, and delta psi fell by 70 mV when pH was reduced from 8.5 to 5.5. These results were interpreted as support for a model in which the uptake of the polycationic aminoglycosides is electrogenic and therefore driven by delta psi. The factor common to mutations and conditions which increase resistance was a reduction in delta psi. A simple model was developed which relates the minimal inhibitory concentration to the rate of aminoglycoside uptake and the rate of growth.     

质粒介导的替加环素耐药机制的研究进展

1概述替加环素(tigecycline)是四环素类衍生的新型甘氨酰环素类抗菌药物,其在米诺环素的中心构架上增加了9-叔丁基-甘氨酰胺基侧链修饰结构[1]。替加环素进入细菌后可逆地结合于核糖体30S亚单位中的16S r RNA,阻断t RNA进入A位点从而抑制蛋白质转录翻译过程。通过结构研究发现,替加环素与核糖体30S亚基结合的同时,也与核糖体亚基H34残基相互作用,所以两者的结合比其他四环素类药物更牢固,抑制细菌蛋白合成的能力是四环素的20倍[2]。     

铜绿假单胞菌对喹诺酮类抗菌药物耐药机制的研究进展

铜绿假单胞菌是医院感染中常见的机会致病菌。在下呼吸道感染和重症肺炎中该菌作为病原菌是提示预后差的一项重要指标。而它对抗菌药物耐药是导致治疗失败的主要原因。其耐药机制较为复杂，尤其是多耐药菌株的出现使治疗更为棘手。目前，在世界范围内没有一种单药治疗铜绿假单胞菌感染的有效率达到90％以上。多耐药铜绿假单     

The PhoQ-activating potential of antimicrobial peptides contributes to antimicrobial efficacy and is predictive of the induction of bacterial resistance

Antimicrobial peptides (AMPs) are among the leading candidates to replace antibiotics which have been rendered ineffective by the evolution of resistant bacterial strains. Concerns do exist, however, that the therapeutic administration of AMPs may also select for resistant strains but with much more dire consequences, as these peptides represent an endogenous and essential component of host immune defense. The recent demonstration that AMPs function as ligands for the bacterial sensory kinase PhoQ for the initiation of virulence and adaptive responses lends credence to these concerns. While the ability to serve as PhoQ ligands suggests that the therapeutic administration of AMPs could (i) exacerbate infections by promoting bacterial virulence and (ii) select resistant mutants by encouraging adaptive behaviors, it also provides a rational basis for AMP selection and optimization. Here, we demonstrate that derivatives of a representative AMP have differential abilities to serve as PhoQ ligands and that this correlates with the ability to induce bacterial adaptive responses. We propose that PhoQ-activating potential is a logical parameter for AMP optimization and introduce a novel strategy for the treatment of minimal bactericidal concentration data that permits the discrimination and quantification of the contributions of PhoQ-activating potential and direct antimicrobial activity to net antimicrobial efficiency.     

Recent advances in the synthesis of the carbocyclic nucleosides as potential antiviral agents

Compared with 4'-oxonucleosides, there have been far fewer systematic structure-activity relationship studies on carbocyclic nucleosides as antiviral and antitumour agents. This is mainly because of the synthetic problems in preparing the carbasugars. However, the recent discovery of the ring-closing metathesis (RCM) (a powerful tool for the preparation of 5-membered carbasugar via C-C bond formation) has made it possible to synthesize the key carbasugars to a preparative scale. This review summarizes the asymmetric syntheses of carbasugars and carbocyclic nucleosides, using an RCM reaction as a key step. Furthermore, the review includes valuable information for designing and synthesizing novel carbocyclic nucleosides.     

耐亚胺培南铜绿假单胞菌耐药特征及β-内酰胺类耐药基因研究

目的分析该院2005年1～12月临床分离的34株耐亚胺培南铜绿假单胞菌对常用抗生素的耐药特征以及B～内酰胺类耐药相关基因存在状况。方法应用BDPhoenix100全自动微生物分析仪进行细菌鉴定和药物敏感试验,头孢哌酮／舒巴坦敏感性检测采用K—B法。应用PCR方法检测12种β-内酰胺类耐药相关基因,分别为TEM、SHV、CARB、OXA-10、PER、VEB、GES、DHA、IMP、VIM、GIM、SPM。结果亚胺培南耐药铜绿假单胞菌除对阿米卡星100．00％敏感外,对哌拉西林、哌拉西林／他唑巴坦敏感率为48．00％～55．00％,对第3、4代头孢菌素、氨曲南、喹诺酮类等抗生素抗菌活性差,敏感率为3．22％～29．03％。对美洛配能29．03％敏感,对氨苄西林／舒巴坦、氯霉素、四环素、复方新诺明全部耐药。β-内酰胺类耐药相关基因TEM、CARB、DHA、IMP阳性率分别为5．9％、32．4％、14．7％、17．6％,而SHV、0XA-10、PER、VEB、GES、VIM、GIM、SPM均为阴性。结论耐亚胺培南的铜绿假单胞菌除对阿米卡星敏感外,对其他常用抗生素耐药严重。携带TEM、CARB、DHA、IMP基因是本组试验菌株对β-内酰胺类抗生素和亚胺培南耐药的重要机制。     

Coping with antibiotic resistance: combining nanoparticles with antibiotics and other antimicrobial agents

The worldwide escalation of bacterial resistance to conventional medical antibiotics is a serious concern for modern medicine. High prevalence of multidrug-resistant bacteria among bacteria-based infections decreases effectiveness of current treatments and causes thousands of deaths. New improvements in present methods and novel strategies are urgently needed to cope with this problem. Owing to their antibacterial activities, metallic nanoparticles represent an effective solution for overcoming bacterial resistance. However, metallic nanoparticles are toxic, which causes restrictions in their use. Recent studies have shown that combining nanoparticles with antibiotics not only reduces the toxicity of both agents towards human cells by decreasing the requirement for high dosages but also enhances their bactericidal properties. Combining antibiotics with nanoparticles also restores their ability to destroy bacteria that have acquired resistance to them. Furthermore, nanoparticles tagged with antibiotics have been shown to increase the concentration of antibiotics at the site of bacterium–antibiotic interaction, and to facilitate binding of antibiotics to bacteria. Likewise, combining nanoparticles with antimicrobial peptides and essential oils generates genuine synergy against bacterial resistance. In this article, we aim to summarize recent studies on interactions between nanoparticles and antibiotics, as well as other antibacterial agents to formulate new prospects for future studies. Based on the promising data that demonstrated the synergistic effects of antimicrobial agents with nanoparticles, we believe that this combination is a potential candidate for more research into treatments for antibiotic-resistant bacteria.     

Coping with antibiotic resistance: combining nanoparticles with antibiotics and other antimicrobial agents

The worldwide escalation of bacterial resistance to conventional medical antibiotics is a serious concern for modern medicine. High prevalence of multidrug-resistant bacteria among bacteria-based infections decreases effectiveness of current treatments and causes thousands of deaths. New improvements in present methods and novel strategies are urgently needed to cope with this problem. Owing to their antibacterial activities, metallic nanoparticles represent an effective solution for overcoming bacterial resistance. However, metallic nanoparticles are toxic, which causes restrictions in their use. Recent studies have shown that combining nanoparticles with antibiotics not only reduces the toxicity of both agents towards human cells by decreasing the requirement for high dosages but also enhances their bactericidal properties. Combining antibiotics with nanoparticles also restores their ability to destroy bacteria that have acquired resistance to them. Furthermore, nanoparticles tagged with antibiotics have been shown to increase the concentration of antibiotics at the site of bacterium-antibiotic interaction, and to facilitate binding of antibiotics to bacteria. Likewise, combining nanoparticles with antimicrobial peptides and essential oils generates genuine synergy against bacterial resistance. In this article, we aim to summarize recent studies on interactions between nanoparticles and antibiotics, as well as other antibacterial agents to formulate new prospects for future studies. Based on the promising data that demonstrated the synergistic effects of antimicrobial agents with nanoparticles, we believe that this combination is a potential candidate for more research into treatments for antibiotic-resistant bacteria.     

Emergence of resistance to biocides during differentiation of Acanthamoeba castellanii

A synchronous encystment method was used to study the order of development of resistance of Acanthamoeba castellanii to a range of biocides. The emerging resistance during encystation to short-term exposure to the minimum amoebicidal concentrations of each biocide tested was recorded during the first 36 h of the differentiation process. Hydrochloric acid and moist heat were tested as possible resistance markers. Development of the acid-insoluble, proteincontaining, ectocyst wall and the cellulose endocyst wall was followed by quantification of the acid- and alkali-insoluble residues of cell samples removed from synchronous encystment cultures up to 36 h. Resistance to chemical agents (polyhexamethylene biguanide, benzalkonium chloride, propamidine isethionate, pentamidine isethionate, dibromopropamidine isethionate, hydrogen peroxide) and to moist heat was seen to develop between 14 and 24 h after trophozoites were inoculated into the encystment media. Resistance to hydrochloric acid developed between 0 and 2 h and to chlorhexidine diacetate between 24 and 36 h. Levels of acid-insoluble residues began to increase after 8 h and alkali-insoluble residues (cellulose) were detected after 16 h and coincided with the emergence of resistance to all the agents tested except hydrochloric acid. The results suggest that resistance to the biocides tested probably results largely from the physical barrier of the cyst walls rather than as a consequence of a metabolically dormant cyst.