Design, synthesis and structure-activity relationships of novel macrolones: Hybrids of 2-fluoro 9-oxime ketolides and carbamoyl quinolones with highly improved activity against resistant pathogens.
Abstract
Constitutively erythromycin-resistant apathogens are more difficult to address than inducibly resistant and efflux-resistant strains. Three series of the 4th generation 2-fluoro 9-oxime erythromycin ketolides were synthesized and evaluated. Incorporation of substituted heteroaryl groups (a - m), in contrast to previously reported the unsubstituted heteroaryl groups, proved to the beneficial for enhancement of the activities of the 9-propgargyl ketolide 8 series and the 9-allyl ketolide 14 series. But these aryl groups (a - m) cannot supply the resulting compounds 8 and 14, unlike corresponding the...
Source: European Journal of Medicinal Chemistry - March 2, 2019 Category: Chemistry Authors: Ma CX, Lv W, Li YX, Fan BZ, Han X, Kong FS, Tian JC, Cushman M, Liang JH Tags: Eur J Med Chem Source Type: research
Analyzing the Mechanisms Behind Macrolide Antibiotic-Induced Liver Injury Using Quantitative Systems Toxicology Modeling
ConclusionsThe mechanisms responsible for toxicity can be significantly different within a class of drugs, despite the structural similarity among the drugs. QST modeling can provide valuable insight into the nature of these mechanistic differences. (Source: Pharmaceutical Research)
Source: Pharmaceutical Research - February 7, 2019 Category: Drugs & Pharmacology Source Type: research
Short-course versus long-course therapy of the same antibiotic for community-acquired pneumonia in adolescent and adult outpatients.
CONCLUSIONS: We found no eligible RCTs that studied a short-course of antibiotic compared to a longer-course (with the same antibiotic at the same daily dosage) for CAP in adolescent and adult outpatients. The effects of antibiotic therapy duration for CAP in adolescent and adult outpatients remains unclear.
PMID: 30188565 [PubMed - as supplied by publisher] (Source: Cochrane Database of Systematic Reviews)
Source: Cochrane Database of Systematic Reviews - September 6, 2018 Category: General Medicine Authors: López-Alcalde J, Rodriguez-Barrientos R, Redondo-Sánchez J, Muñoz-Gutiérrez J, Molero García JM, Rodríguez-Fernández C, Heras-Mosteiro J, Marin-Cañada J, Casanova-Colominas J, Azcoaga-Lorenzo A, Hernandez Santiago V, Gómez-García M Tags: Cochrane Database Syst Rev Source Type: research
Synthesis and antibacterial activity of novel ketolides with 11,12-quinoylalkyl side chains.
Abstract
A series of quinoylalkyl side chains was designed and synthesized, followed by introduction into ketolides by coupling with building block 6 or 32. The corresponding targets 7a-n, 33b, and 33e were tested for their in vitro activities against a series of macrolide-sensitive and macrolide-resistant pathogens. Some of them showed a similar antibacterial spectrum and comparable activity to telithromycin. Among them, two C2-F ketolides, compounds 33b and 33e, displayed excellent activities against macrolide-sensitive and macrolide-resistant pathogens.
PMID: 29937059 [PubMed - as supplied by pu...
Source: Bioorganic and Medicinal Chemistry Letters - June 19, 2018 Category: Chemistry Authors: Zhao ZH, Zhang XX, Jin LL, Yang S, Lei PS Tags: Bioorg Med Chem Lett Source Type: research
Use of whole-genome sequencing for Campylobacter surveillance from NARMS retail poultry in the United States in 2015.
In this study, we used the Illuminia MiSeq® to sequence 589 Campylobacter isolates obtained in 2015 from retail poultry meats as part of the National Antimicrobial Resistance Monitoring System (NARMS). WGS data were used to identify the Campylobacter species and to compare the concordance between resistance genotypes and phenotypes. WGS accurately identified 386 C. jejuni and 203 C. coli using gyrA sequence information. Ten resistance genes, including tetO, blaOXA-61, aph(2″)-Ic, aph(2″)-If, aph(2″)-Ig, aph(3')-III, ant(6)-1a, aadE, aph(3")-VIIa, and Inu(C), plus mutations in housekeeping genes (gyrA at position 86...
Source: Food Microbiology - March 13, 2018 Category: Food Science Authors: Whitehouse CA, Young S, Li C, Hsu CH, Martin G, Zhao S Tags: Food Microbiol Source Type: research
Ribonucleotide reductase as a drug target against drug resistance Mycobacterium leprae: A molecular docking study.
Abstract
Leprosy is a chronic infection of skin and nerve caused by Mycobacterium leprae. The treatment is based on standard multi drug therapy consisting of dapsone, rifampicin and clofazamine. The use of rifampicin alone or with dapsone led to the emergence of rifampicin-resistant Mycobacterium leprae strains. The emergence of drug-resistant leprosy put a hurdle in the leprosy eradication programme. The present study aims to predict the molecular model of ribonucleotide reductase (RNR), the enzyme responsible for biosynthesis of nucleotides, to screen new drugs for treatment of drug-resistant leprosy. Th...
Source: Infection, Genetics and Evolution - February 15, 2018 Category: Genetics & Stem Cells Authors: Mohanty PS, Bansal AK, Naaz F, Gupta UD, Dwivedi VD, Yadava U Tags: Infect Genet Evol Source Type: research
Antibiotic susceptibility of Francisella tularensis subsp. holarctica strains isolated from tularaemia patients in France between 2006 and 2016
ConclusionsF. tularensis strains isolated in France remain susceptible to antibiotic classes recommended for tularaemia treatment. Because fluoroquinolones display the lowest MIC90, have bactericidal activity and have lower therapeutic failure rates compared with doxycycline, they may be advocated as first-line treatment of mild cases of tularaemia, predominant in Europe. MIC data also indicate that azithromycin or telithromycin may be possible therapeutic options against biovar I strains from Western Europe in case of contraindication to first-line antibiotics. (Source: Journal of Antimicrobial Chemotherapy)
Source: Journal of Antimicrobial Chemotherapy - December 14, 2017 Category: Microbiology Source Type: research
In Vitro Activity of the Novel Lactone Ketolide Nafithromycin (WCK 4873) When Tested against Contemporary Clinical Bacteria from a Global Surveillance Program.
Abstract
Nafithromycin (WCK 4873), a novel antimicrobial agent of the lactone ketolide class, is currently in Phase 2 development for treatment of community-acquired bacterial pneumonia (CABP): A total of 4,739 non-duplicate isolates were selected from a 2014 global surveillance program from medical institutions located in 43 countries within the United States, Europe, Latin America, and Asia-Pacific. Nafithromycin and comparator agents were susceptibility tested by reference broth microdilution methods. Nafithromycin was active against Staphylococcus aureus (MIC50/90, 0.06/>2 μg/mL), including erythro...
Source: Antimicrobial Agents and Chemotherapy - October 2, 2017 Category: Microbiology Authors: Flamm RK, Rhomberg PR, Sader HS Tags: Antimicrob Agents Chemother Source Type: research
The Macrolide Antibiotic Renaissance
Abstract
Macrolides represent a large family of protein synthesis inhibitors with high clinical interest due to their applicability for human medicine. Macrolides are composed of a macrocyclic lactone of different ring sizes, to which one or more deoxy‐sugar or amino‐sugar residues are attached. Macrolides act as antibiotics by binding to bacterial 50S ribosomal subunit and interfering with protein synthesis. The high affinity of macrolides for bacterial ribosomes, together with the highly conserved structure of ribosomes across virtually all of the bacterial species, is consistent with their broad‐spectrum activity....
Source: British Journal of Pharmacology - June 30, 2017 Category: Drugs & Pharmacology Authors: Dinos P George Tags: REVIEW ARTICLE Source Type: research
Potentiation of Antibiotic Activity by a Novel Cationic Peptide: Potency and Spectrum of Activity of SPR741.
Abstract
Novel approaches to the treatment of multi-drug resistant Gram-negative bacterial infections are urgently required. One approach is to potentiate the efficacy of existing antibiotics whose spectrum of activity is limited by the permeability barrier presented by the Gram-negative outer membrane. Cationic peptides derived from polymyxin B have been used to permeabilize the outer membrane, granting antibiotics that would otherwise be excluded access to their targets. We assessed the in vitro efficacy of combinations of SPR741 with conventional antibiotics against Escherichia coli, Klebsiella pneumoni...
Source: Antimicrobial Agents and Chemotherapy - May 22, 2017 Category: Microbiology Authors: Corbett D, Wise A, Langley T, Skinner K, Trimby E, Birchall S, Dorali A, Sandiford S, Williams J, Warn P, Vaara M, Lister T Tags: Antimicrob Agents Chemother Source Type: research
Epidemiology of antimicrobial resistant Campylobacter spp. isolated from retail meats in Canada.
The objectives of this study were to determine the prevalence of Campylobacter spp. in retail meat (poultry, turkey, pork and beef) purchased in Alberta, Canada and to assess antimicrobial resistance and genetic relatedness of recovered Campylobacter strains with previously isolated strains from clinical and environmental sources. A Comparative Genomic Fingerprinting (CGF) method was used for assessing genetic relatedness of isolates. A total of 606 samples comprising 204, 110, 145 and 147 samples of retail chicken, turkey, ground beef and pork, respectively, were obtained. Campylobacter was isolated from 23.5% (48/204) of...
Source: International Journal of Food Microbiology - April 29, 2017 Category: Food Science Authors: Narvaez-Bravo C, Taboada EN, Mutschall SK, Aslam M Tags: Int J Food Microbiol Source Type: research
Comparison of Pathogen Eradication Rate and Safety of Anti ‐bacterial Agents for Bronchitis: A Network Meta‐analysis
ConclusionsGemifloxacin and levofloxacin are more preferable than others for lowering respiratory tract inflammation and infections considering their balanced performance between pathogen eradication and adverse effects. This article is protected by copyright. All rights reserved (Source: Journal of Cellular Biochemistry)
Source: Journal of Cellular Biochemistry - February 23, 2017 Category: Biochemistry Authors: Jinghua Wang, Haiyang Xu, Dunwei Wang, Mingxian Li Tags: Article Source Type: research
Solithromycin: A Novel Fluoroketolide for the Treatment of Community-Acquired Bacterial Pneumonia
AbstractSolithromycin is a novel fluoroketolide developed in both oral and intravenous formulations to address increasing macrolide resistance in pathogens causing community-acquired bacterial pneumonia (CABP). When compared with its macrolide and ketolide predecessors, solithromycin has several structural modifications which increase its ribosomal binding and reduce its propensity to known macrolide resistance mechanisms. Solithromycin, like telithromycin, affects 50S ribosomal subunit formation and function, as well as causing frame-shift errors during translation. However, unlike telithromycin, which binds to two sites ...
Source: Drugs - November 30, 2016 Category: Drugs & Pharmacology Source Type: research
Assessment of a Severity-Based Algorithm to Detect Signals of Severe Drug-Induced Liver Injury Using Spontaneous Reporting Database
ConclusionsThe results indicate that the severity-based algorithm is sensitive in the early detection of severe hepatotoxicity and can add value to routine pharmacovigilance. Further studies are needed to demonstrate the effectiveness of this method. (Source: Pharmaceutical Medicine)
Source: Pharmaceutical Medicine - November 29, 2016 Category: Drugs & Pharmacology Source Type: research
What Can PROTEKT Tell Us at a Local Level?
Authors: Inoue M
Abstract
Because of increasing antimicrobial resistance in bacterial pathogens causing community-acquired respiratory tract infections (CARTIs), surveillance at local, regional, national and international levels is necessary to provide information to guide empiric antimicrobial therapy. PROTEKT (Prospective Resistant Organism Tracking and Epidemiology for the Ketolide Telithromycin) is a longitudinal, global, multicenter surveillance study designed to monitor the worldwide development of antimicrobial resistance, and disseminate up-to-date information via the internet to assist in the choi...
Source: Journal of Chemotherapy - November 2, 2016 Category: Cancer & Oncology Tags: J Chemother Source Type: research
