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https://www.readbyqxmd.com/read/28223393/novel-bacterial-topoisomerase-inhibitors-with-potent-broad-spectrum-activity-against-drug-resistant-bacteria
#1
Cédric Charrier, Anne-Marie Salisbury, Victoria J Savage, Thomas Duffy, Emmanuel Moyo, Nathan Chaffer-Malam, Nicola Ooi, Rebecca Newman, Jonathan Cheung, Richard Metzger, David McGarry, Mark Pichowicz, Ralph Sigerson, Ian R Cooper, Gary Nelson, Hayley S Butler, Mark Craighead, Andrew J Ratcliffe, Stuart A Best, Neil R Stokes
The Novel Bacterial Topoisomerase Inhibitor class is an investigational type of antibacterial inhibitor of DNA gyrase and topoisomerase IV that do not have cross-resistance with the quinolones. Here, we report the evaluation of the in vitro properties of a new series of this type of small molecules. Exemplar compounds selectively and potently inhibited the catalytic activities of Escherichia coli DNA gyrase and topoisomerase IV but did not block the DNA breakage-reunion step. Compounds showed broad-spectrum inhibitory activity against a wide range of Gram-positive and Gram-negative pathogens, including biodefence microorganisms, and Mycobacterium tuberculosis No cross-resistance with quinolone-resistant Staphylococcus aureus and E...
February 21, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28223390/expression-of-the-aac-6-ib-cr-gene-in-class-1-integrons
#2
Sophie Raherison, Thomas Jove, Margaux Gaschet, Emilie Pinault, Aurore Tabesse, Carmen Torres, Marie-Cécile Ploy
The aac(6')-Ib-cr is a plasmid-mediated quinolone resistance (PMQR) gene embedded within a gene cassette, most often within an integron. It confers resistance to both quinolones and aminoglycosides. We investigated the role of a 101-bp fragment frequently present upstream of the aac(6')-Ib-cr gene cassette and found it contributes to the expression of aac(6')-Ib-cr and provides an alternative START codon confirming the length of the AAC(6')-Ib-cr protein to 199-aa.
February 21, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28223380/vitamin-k3-induces-the-expression-of-the-stenotrophomonas-maltophilia-smevwx-multidrug-efflux-pump
#3
P Blanco, F Corona, M B Sánchez, J L Martínez
Stenotrophomonas maltophilia is an opportunistic pathogen, with increasing prevalence, able to cause infections in immunocompromised patients or in those with a previous pathology. The treatment of the infections caused by this bacterium is often complicated due to the several intrinsic antibiotic resistance mechanisms that it presents. Multidrug efflux pumps are among the best studied mechanisms of S. maltophilia antibiotic resistance. Some of these efflux pumps have a basal expression level but, in general, their expression is often low and only reaches high levels when the local regulator is mutated or bacteria are in the presence of an effector...
February 21, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28221698/monoprotected-l-amino-acid-l-mpaa-accelerated-bromination-chlorination-and-iodination-of-c-sp2-h-bonds-by-iridium-iii-catalysis
#4
Subban Kathiravan, Ian A Nicholls
Halogenated arenes are important structural motifs commonly found in biologically active molecules and used for a variety of transformations in organic synthesis. Herein, we report the mono-protected L-amino acid (L-MPAA) accelerated iridium(III) catalyzed halogenation of (hetero)anilides at room temperature. This reaction constitutes the first example of an iridium(III)/L-MPAA catalyzed general halogenation of (hetero)arenes through C(sp2)-H activation. Furthermore, we demonstrate the potential utility of our method through its use in the synthesis a quinolone derivative...
February 21, 2017: Chemistry: a European Journal
https://www.readbyqxmd.com/read/28216048/chloroquine-blocks-the-kir4-1-channels-by-an-open-pore-blocking-mechanism
#5
Leticia G Marmolejo-Murillo, Iván A Aréchiga-Figueroa, Eloy G Moreno-Galindo, Ricardo A Navarro-Polanco, Aldo A Rodríguez-Menchaca, Meng Cui, José A Sánchez-Chapula, Tania Ferrer
Kir4.1 channels have been implicated in various physiological processes, mainly in the K(+) homeostasis of the central nervous system and in the control of glial function and neuronal excitability. Even though, pharmacological research of these channels is very limited. Chloroquine (CQ) is an amino quinolone derivative known to inhibit Kir2.1 and Kir6.2 channels with different action mechanism and binding site. Here, we employed patch-clamp methods, mutagenesis analysis, and molecular modeling to characterize the molecular pharmacology of Kir4...
February 16, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28208218/antibiotic-resistance-in-escherichia-coli-in-husbandry-animals-the-african-perspective
#6
REVIEW
Carla Andrea Alonso, Myriam Zarazaga, Rym Ben Sallem, Ahlem Jouini, Karim Ben Slama, Carmen Torres
In the last years different surveillances have been published in Africa, especially in Northern countries, regarding antimicrobial resistance among husbandry animals. Information is still scarce, but the available data shows a worrying picture. Although the highest resistance rates have been described against tetracycline, penicillins and sulphonamides, prevalence of plasmid mediated quinolone resistance genes and extended-spectrum β-lactamase (ESBL) are being increasingly reported. Among ESBLs, the CTX-M-1 group was dominant in most African surveys, being CTX-M-15 the main variant both in animals and humans, except in Tunisia where CTX-M-1 was more frequently detected among E...
February 16, 2017: Letters in Applied Microbiology
https://www.readbyqxmd.com/read/28207768/prevalence-of-mdr-pathogens-of-bacterial-meningitis-in-egypt-and-new-synergistic-antibiotic-combinations
#7
Mona M Abdelkader, Khaled M Aboshanab, Marwa A El-Ashry, Mohammad M Aboulwafa
The aim of this study was identifying bacterial pathogens involved in meningitis, studying their antibiotic resistance profiles, investigating the antibiotic resistance genes as well as evaluating the use of various antibiotic combinations. Antibiotic susceptibility tests were evaluated according to CLSI guidelines. Antibiotic combinations were evaluated by calculating the Fractional Inhibitory Concentration (FIC) index. A total of 71 bacterial isolates were recovered from 68 culture positive CSF specimens...
2017: PloS One
https://www.readbyqxmd.com/read/28197902/neuropsychiatric-effects-of-antimicrobial-agents
#8
REVIEW
Nicholas Zareifopoulos, George Panayiotakopoulos
Antimicrobial drugs used in clinical practice are selected on the basis of their selective toxicity against bacterial cells. However, all exhibit multiple offsite interactions with eukaryotic cell structures, resulting in adverse reactions during antimicrobial pharmacotherapy. A multitude of these side effects involve the nervous system as antimicrobials at clinically relevant concentrations seem to interact with many of the same molecules usually implicated in the action of psychotropic drugs. The importance of such events cannot be overstated, as the misdiagnosis of an adverse drug reaction as a symptom of a primary psychiatric or neurological disorder entails great suffering for the patient affected as well as significant costs for the healthcare system...
February 14, 2017: Clinical Drug Investigation
https://www.readbyqxmd.com/read/28197140/molecular-characteristics-of-carbapenem-resistant-enterobacter-cloacae-in-ningxia-province-china
#9
Zhiyun Shi, Huizheng Zhao, Gang Li, Wei Jia
The emergence of carbapenem-resistant Enterobacteriaceae (CRE) has become a major public health concern worldwide and a new challenge in the treatment of infectious diseases. The molecular characteristics of Enterobacter cloacae in Ningxia China are unknown. In this study, we reported 10 carbapenem-resistant E. cloacae isolates from the General Hospital of Ningxia Medical University, the largest university hospital in Ningxia between January 2012 and December 2013. Bacteria isolates were identified by Vitek2 compact and the identity of non-duplicate E...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28195128/a-ligand-directed-divergent-catalytic-approach-to-establish-structural-and-functional-scaffold-diversity
#10
Yen-Chun Lee, Sumersing Patil, Christopher Golz, Carsten Strohmann, Slava Ziegler, Kamal Kumar, Herbert Waldmann
The selective transformation of different starting materials by different metal catalysts under individually optimized reaction conditions to structurally different intermediates and products is a powerful approach to generate diverse molecular scaffolds. In a more unified albeit synthetically challenging strategy, common starting materials would be exposed to a common metal catalysis, leading to a common intermediate and giving rise to different scaffolds by tuning the reactivity of the metal catalyst through different ligands...
February 14, 2017: Nature Communications
https://www.readbyqxmd.com/read/28194411/antibiotic-resistance-of-campylobacter-recovered-from-faeces-and-carcasses-of-healthy-livestock
#11
Akosua B Karikari, Kwasi Obiri-Danso, Enoch H Frimpong, Karen A Krogfelt
Campylobacter is of major significance in food safety and human and veterinary medicine. This study highlighted resistance situation in the area of veterinary public health in Ghana. Using selective mCCDA agar, isolates were confirmed phenotypically on API CAMPY and genotypically by multiplex PCR of IpxA gene. The susceptibility profile of species to common and relevant antibiotics was determined by the Kirby-Bauer disk diffusion method. Cattle, sheep, goat, and pig faecal samples analysed, respectively, yielded 13...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28193670/subinhibitory-concentrations-of-ciprofloxacin-enhance-antimicrobial-resistance-and-pathogenicity-of-enterococcus-faecium
#12
Clara Sinel, Margherita Cacaci, Pierrick Meignen, François Guérin, Bryan W Davies, Maurizio Sanguinetti, Jean-Christophe Giard, Vincent Cattoir
Enterococcus faecium has emerged as a major opportunistic pathogen for two decades, with the spread of hospital-adapted multidrug-resistant clones. Members of the intestinal microbiota, they are subjected to numerous bacterial stresses, including antibiotics at subinhibitory concentrations (SICs). Since fluoroquinolones are extensively prescribed, SICs are very likely to occur in vivo with potential effects on bacterial metabolism with subsequent modulation of opportunistic traits. The aim of the study was to evaluate globally the impact of subinhibitory concentrations (SICs) of ciprofloxacin on antimicrobial resistance and pathogenicity of E...
February 13, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28193666/qnre1-a-member-of-a-new-family-of-plasmid-located-quinolone-resistance-genes-originated-from-the-chromosome-of-enterobacter-spp
#13
Ezequiel Albornoz, Nathalie Tijet, Denise De Belder, Sonia Gomez, Florencia Martino, Alejandra Corso, Roberto G Melano, Alejandro Petroni
qnrE1, found in a clinical Klebsiella pneumoniae, resulted undetectable by PCR assays used for the six qnr families. qnrE1 was located on a conjugative plasmid (ca. 185 kb) and differed from qnrB alleles by 25%. Phylogenetic reconstructions of qnr genes and proteins, and analysis of the qnrE1 surroundings showed that this gene belongs to a new qnr family and was likely mobilized by ISEcp1 from the chromosome of Enterobacter spp. to plasmids of K. pneumoniae.
February 13, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28193648/pharmacodynamics-of-finafloxacin-ciprofloxacin-and-levofloxacin-in-serum-and-urine-against-tem-and-shv-type-extended-spectrum-beta-lactamase-producing-enterobacteriaceae-isolated-from-patients-with-urinary-tract-infections
#14
A Dalhoff, S Schubert, A Vente
Background: Pharmacodynamics of finafloxacin, ciprofloxacin and levofloxacin against ESBL-producing Enterobacteriaceae were compared. As quinolones loose activity in acidic media and in particular in urine, their activities were tested in parallel under conventional conditions and in acidic artificial urine.Methods: TEM- and SHV-type ESBL-producing E. coli and K. pneumoniae and their wild-type counterparts were exposed in a modified Grasso model to serum- and urine-concentrations following oral doses of finafloxacin 800mg qd, immediate- release ciprofloxacin 500mg bid, extended release ciprofloxacin-XR 1000mg qd, levofloxacin 500mg qd, or levofloxacin 750mg qd...
February 13, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28193274/evaluation-of-medicines-dispensing-pattern-of-private-pharmacies-in-rajshahi-bangladesh
#15
Shuvashis Saha, Md Tawhid Hossain
BACKGROUND: In developing country like BANGLADESH, people depend more on pharmacies due to expediency, shorter waiting time, cost reduction, availability of credit and flexible opening hours. The aim of this study was to investigate medicines dispensing patterns of the pharmacies in RAJSHAHI, BANGLADESH and to identify and analyze contribution of drugsellers and quacks in irrational drug use. METHODS: This cross-sectional study was conducted during January 2016 - April, 2016 in 75 randomly selected private pharmacies including both licensed and unlicensed pharmacies of covering LAKSHMIPUR area...
February 13, 2017: BMC Health Services Research
https://www.readbyqxmd.com/read/28188647/formation-of-heterocyclic-amines-in-chinese-marinated-meat-effects-of-animal-species-and-ingredients-rock-candy-soy-sauce-and-rice-wine
#16
Pan Wang, Yanting Hong, Weixin Ke, Xiaosong Hu, Fang Chen
BACKGROUND: Heterocyclic aromatic amines (HAAs) are one type of neo-formed contaminants in protein-rich foods during heat processing. Recently, accumulative studies have focused on the formation of HAs in Western foods. However, there is little knowledge about the occurrence of HAAs in traditional Chinese foods. The objective of this study was to determinate the contents of main HAs in traditional marinated meat products by UPLC-MS/MS, and to investigate the effects of animal species and the ingredients (soy sauce, rock candy, and rice wine) on the formation of HAAs in marinated meats...
February 11, 2017: Journal of the Science of Food and Agriculture
https://www.readbyqxmd.com/read/28177131/dispersive-liquid-liquid-microextraction-of-quinolones-in-porcine-blood-validation-of-a-ce-method-using-univariate-calibration-or-multivariate-curve-resolution-alternating-least-squares-for-overlapped-peaks
#17
Carla M Teglia, María S Cámara, Luciana Vera-Candioti
In the previously published part of this study, we detailed a novel strategy based on dispersive liquid-liquid microextraction to extract and preconcentrate nine fluoroquinolones in porcine blood. Moreover, we presented the optimized experimental conditions to obtain complete CE separation between target analytes. Consequently, this second part reports the validation of the developed method to determine flumenique, difloxacin, enrofloxacin, marbofloxacin, ofloxacin, ciprofloxacin, through univariate calibration, and enoxacin, danofloxacin, and gatifloxacin through multivariate curve resolution analysis...
February 8, 2017: Electrophoresis
https://www.readbyqxmd.com/read/28163699/a-systematic-review-of-in-vitro-and-in-vivo-activities-of-anti-toxoplasma-drugs-and-compounds-2006-2016
#18
REVIEW
Mahbobeh Montazeri, Mehdi Sharif, Shahabeddin Sarvi, Saeed Mehrzadi, Ehsan Ahmadpour, Ahmad Daryani
The currently available anti-Toxoplasma agents have serious limitations. This systematic review was performed to evaluate drugs and new compounds used for the treatment of toxoplasmosis. Data was systematically collected from published papers on the efficacy of drugs/compounds used against Toxoplasma gondii (T. gondii) globally during 2006-2016. The searched databases were PubMed, Google Scholar, Science Direct, ISI Web of Science, EBSCO, and Scopus. One hundred and eighteen papers were eligible for inclusion in this systematic review, which were both in vitro and in vivo studies...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28159338/emergence-of-quinolone-resistant-strains-in-streptococcus-pneumoniae-isolated-from-paediatric-patients-since-the-approval-of-oral-fluoroquinolones-in-japan
#19
Noriko Takeuchi, Misako Ohkusu, Tadashi Hoshino, Sachiko Naito, Akiko Takaya, Tomoko Yamamoto, Naruhiko Ishiwada
Tosufloxacin (TFLX) is a fluoroquinolone antimicrobial agent. TFLX granules for children were initially released in Japan in 2010 to treat otitis media and pneumonia caused by drug-resistant bacteria, e.g. penicillin-resistant Streptococcus pneumoniae and beta-lactamase-negative, ampicillin-resistant Haemophilus influenzae. The evolution of bacterial resistance since TFLX approval is not known. To clarify the influence of quinolones administered to children since their approval, we examined the resistance mechanism of TFLX-resistant S...
January 31, 2017: Journal of Infection and Chemotherapy: Official Journal of the Japan Society of Chemotherapy
https://www.readbyqxmd.com/read/28159174/antimicrobial-therapy-for-legionnaire-s-disease-antibiotic-stewardship-implications
#20
REVIEW
Cheston B Cunha, Burke A Cunha
Legionnaire's disease is a common cause of community-acquired pneumonia (CAP). Although no single clinical feature is diagnostic, if characteristic extrapulmonary findings are present a presumptive clinical syndromic diagnosis is possible. Depending on geographic location, season, and physician awareness, Legionnaire's disease may be included in the differential diagnosis of CAP. Some antibiotics effective against Legionella sp are also effective in treating the typical bacterial causes of CAP. From an antimicrobial stewardship program (ASP) perspective, monotherapy is preferred to double-drug therapy...
March 2017: Infectious Disease Clinics of North America
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