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Antibiotics

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https://www.readbyqxmd.com/read/28441360/erythromycin-modification-that-improves-its-acidic-stability-while-optimizing-it-for-local-drug-delivery
#1
Erika L Cyphert, Jaqueline D Wallat, Jonathan K Pokorski, Horst A von Recum
The antibiotic erythromycin has limited efficacy and bioavailability due to its instability and conversion under acidic conditions via an intramolecular dehydration reaction. To improve the stability of erythromycin, several analogs have been developed-such as azithromycin and clarithromycin-which decrease the rate of intramolecular dehydration. We set out to build upon this prior work by developing a conjugate of erythromycin with improved pH stability, bioavailability, and preferential release from a drug delivery system directly at the low pH of an infection site...
April 25, 2017: Antibiotics
https://www.readbyqxmd.com/read/28327498/activity-of-sulfa-drugs-and-their-combinations-against-stationary-phase-b-burgdorferi-in-vitro
#2
Jie Feng, Shuo Zhang, Wanliang Shi, Ying Zhang
Lyme disease is a most common vector-borne disease in the US. Although the majority of Lyme patients can be cured with the standard two- to four-week antibiotic treatment, at least 10%-20% of patients continue to suffer from prolonged post-treatment Lyme disease syndrome (PTLDS). While the cause for this is unclear, one possibility is that persisting organisms are not killed by current Lyme antibiotics. In our previous studies, we screened an FDA drug library and an NCI compound library on B. burgdorferi and found some drug hits including sulfa drugs as having good activity against B...
March 22, 2017: Antibiotics
https://www.readbyqxmd.com/read/28272350/a-risk-assessment-of-antibiotic-pan-drug-resistance-in-the-uk-bayesian-analysis-of-an-expert-elicitation-study
#3
Daniel Carter, André Charlett, Stefano Conti, Julie V Robotham, Alan P Johnson, David M Livermore, Tom Fowler, Mike Sharland, Susan Hopkins, Neil Woodford, Philip Burgess, Stephen Dobra
To inform the UK antimicrobial resistance strategy, a risk assessment was undertaken of the likelihood, over a five-year time-frame, of the emergence and widespread dissemination of pan-drug-resistant (PDR) Gram-negative bacteria that would pose a major public health threat by compromising effective healthcare delivery. Subsequent impact over five- and 20-year time-frames was assessed in terms of morbidity and mortality attributable to PDR Gram-negative bacteraemia. A Bayesian approach, combining available data with expert prior opinion, was used to determine the probability of the emergence, persistence and spread of PDR bacteria...
March 7, 2017: Antibiotics
https://www.readbyqxmd.com/read/28241458/bulgecin%C3%A2-a-%C3%A2-the%C3%A2-key%C3%A2-to%C3%A2-a%C3%A2-broad-spectrum%C3%A2-inhibitor%C3%A2-that%C3%A2-targets%C3%A2-lytic%C3%A2-transglycosylases
#4
Allison H Williams, Richard Wheeler, Constance Thiriau, Ahmed Haouz, Muhamed-Kheir Taha, Ivo G Boneca
Lytic transglycosylases (Lts) are involved in recycling, cell division, and metabolism of the peptidoglycan. They have been understudied for their usefulness as potential antibacterial targets due to their high redundancy in Gram-negative bacteria. Bulgecin A is an O-sulphonated glycopeptide that targets primarily soluble lytic tranglycosylases (Slt). It has been shown that bulgecin A increases the efficacy of β-lactams that target penicillin bindings proteins (PBPs). Here, we present the high-resolution crystal structure of LtgA from Neisseria meningitidis strain MC58, a membrane bound homolog of Escherichia coli Slt, in complex with bulgecin A...
February 22, 2017: Antibiotics
https://www.readbyqxmd.com/read/28208717/final-demonstration-of-the-co-identity-of-lipiarmycin-a3-and-tiacumicin-b-fidaxomicin-through-single-crystal-x-ray-analysis
#5
Stefano Serra, Luciana Malpezzi, Angelo Bedeschi, Claudio Fuganti, Piera Fonte
Lipiarmycin A3 and tiacumicin B possess the same chemical structure and have been considered identical till recently, when some authors have suggested the possibility of a minor difference between the chemical structures of the two antibiotics. In this work we performed a comparative X-ray analysis of lipiarmycin A3 and tiacumicin B. Although the commercial samples of the aforementioned compounds crystallize into two different crystal systems-evidently due to the different crystallization conditions-their chemical structures are identical...
February 8, 2017: Antibiotics
https://www.readbyqxmd.com/read/28178179/diminished-antimicrobial-peptide-and-antifungal-antibiotic-activities-against-candida-albicans-in-denture-adhesive
#6
Amber M Bates, Jorge L Garaicoa, Carol L Fischer, Kim A Brogden
The underlying causes of denture stomatitis may be related to the long-term use of adhesives, which may predispose individuals to oral candidiasis. In this study, we hypothesize that antimicrobial peptides and antifungal antibiotics have diminished anti-Candida activities in denture adhesive. To show this, nine antimicrobial peptides and five antifungal antibiotics with and without 1.0% denture adhesive were incubated with Candida albicans strains ATCC 64124 and HMV4C in radial diffusion assays. In gels with 1...
February 6, 2017: Antibiotics
https://www.readbyqxmd.com/read/28165431/moxifloxacin-increases-heart-rate-in-humans
#7
Jay W Mason, Thomas E Moon
(1) Background: We assessed the effect of moxifloxacin on heart rate, and reviewed the heart rate effects of other antibiotics; (2) Methods: A total of 335 normal volunteers had 12-lead electrocardiograms recorded at multiple time points before and during treatment with moxifloxacin and with placebo in seven consecutive, thorough QT studies of crossover design; (3) Results: The average baseline heart rate across the seven studies was 61.5 bpm. The heart rate after moxifloxacin dosing was analyzed at five time points shared by all seven studies (hours 1, 2, 3, 12 and 24)...
February 5, 2017: Antibiotics
https://www.readbyqxmd.com/read/28134858/docking-into-mycobacterium-tuberculosis-thioredoxin-reductase-protein-yields-pyrazolone-lead-molecules-for-methicillin-resistant-staphylococcus-aureus
#8
Noreena L Sweeney, Lauren Lipker, Alicia M Hanson, Chris J Bohl, Katie E Engel, Kelsey S Kalous, Mary E Stemper, Daniel S Sem, William R Schwan
The thioredoxin/thioredoxin reductase system (Trx/TrxR) is an attractive drug target because of its involvement in a number of important physiological processes, from DNA synthesis to regulating signal transduction. This study describes the finding of pyrazolone compounds that are active against Staphylococcus aureus. Initially, the project was focused on discovering small molecules that may have antibacterial properties targeting the Mycobacterium tuberculosis thioredoxin reductase. This led to the discovery of a pyrazolone scaffold-containing compound series that showed bactericidal capability against S...
January 28, 2017: Antibiotics
https://www.readbyqxmd.com/read/28098814/thioridazine-a-non-antibiotic-drug-highly-effective-in-combination-with-first-line-anti-tuberculosis-drugs-against-any-form-of-antibiotic-resistance-of-mycobacterium-tuberculosis-due-to-its-multi-mechanisms-of-action
#9
REVIEW
Leonard Amaral, Miguel Viveiros
This review presents the evidence that supports the use of thioridazine (TZ) for the therapy of a pulmonary tuberculosis infection regardless of its antibiotic resistance status. The evidence consists of in vitro and ex vivo assays that demonstrate the activity of TZ against all encountered Mycobacterium tuberculosis (Mtb) regardless of its antibiotic resistance phenotype, as well as in vivo as a therapy for mice infected with multi-drug resistant strains of Mtb, or for human subjects infected with extensively drug resistant (XDR) Mtb...
January 14, 2017: Antibiotics
https://www.readbyqxmd.com/read/28098784/fused-ring-oxazolopyrrolopyridopyrimidine-systems-with-gram-negative-activity
#10
Yiyuan Chen, Jonathan G Moloney, Kirsten E Christensen, Mark G Moloney
Fused polyheterocyclic derivatives are available by annulation of a tetramate scaffold, and been shown to have antibacterial activity against a Gram-negative, but not a Gram-positive, bacterial strain. While the activity is not potent, these systems are structurally novel showing, in particular, a high level of polarity, and offer potential for the optimization of antibacterial activity.
January 13, 2017: Antibiotics
https://www.readbyqxmd.com/read/27983678/quorum-sensing-and-the-use-of-quorum-quenchers-as-natural-biocides-to-inhibit-sulfate-reducing-bacteria
#11
Giantommaso Scarascia, Tiannyu Wang, Pei-Ying Hong
Sulfate-reducing bacteria (SRB) are one of the main protagonist groups of biocorrosion in the seawater environment. Given their principal role in biocorrosion, it remains a crucial task to develop strategies to reduce the abundance of SRBs. Conventional approaches include the use of biocides and antibiotics, which can impose health, safety, and environmental concerns. This review examines an alternative approach to this problem. This is achieved by reviewing the role of quorum sensing (QS) in SRB populations and its impact on the biofilm formation process...
December 15, 2016: Antibiotics
https://www.readbyqxmd.com/read/27983590/conformational-response-of-30s-bound-if3-to-a-site-binders-streptomycin-and-kanamycin
#12
Roberto Chulluncuy, Carlos Espiche, Jose Alberto Nakamoto, Attilio Fabbretti, Pohl Milón
Aminoglycoside antibiotics are widely used to treat infectious diseases. Among them, streptomycin and kanamycin (and derivatives) are of importance to battle multidrug-resistant (MDR) Mycobacterium tuberculosis. Both drugs bind the small ribosomal subunit (30S) and inhibit protein synthesis. Genetic, structural, and biochemical studies indicate that local and long-range conformational rearrangements of the 30S subunit account for this inhibition. Here, we use intramolecular FRET between the C- and N-terminus domains of the flexible IF3 to monitor real-time perturbations of their binding sites on the 30S platform...
December 13, 2016: Antibiotics
https://www.readbyqxmd.com/read/27827853/antimicrobial-usage-and-antimicrobial-resistance-in-animal-production-in-southeast-asia-a-review
#13
REVIEW
Nguyen T Nhung, Nguyen V Cuong, Guy Thwaites, Juan Carrique-Mas
Southeast Asia is an area of great economic dynamism. In recent years, it has experienced a rapid rise in the levels of animal product production and consumption. The region is considered to be a hotspot for infectious diseases and antimicrobial resistance (AMR). We reviewed English-language peer-reviewed publications related to antimicrobial usage (AMU) and AMR in animal production, as well as antimicrobial residues in meat and fish from 2000 to 2016, in the region. There is a paucity of data from most countries and for most bacterial pathogens...
November 2, 2016: Antibiotics
https://www.readbyqxmd.com/read/27740593/pectocin-m1-pcam1-inhibits-escherichia-coli-cell-growth-and-peptidoglycan-biosynthesis-through-periplasmic-expression
#14
Dimitri Chérier, Sean Giacomucci, Delphine Patin, Ahmed Bouhss, Thierry Touzé, Didier Blanot, Dominique Mengin-Lecreulx, Hélène Barreteau
Colicins are bacterial toxins produced by some Escherichia coli strains. They exhibit either enzymatic or pore-forming activity towards a very limited number of bacterial species, due to the high specificity of their reception and translocation systems. Yet, we succeeded in making the colicin M homologue from Pectobacterium carotovorum, pectocin M1 (PcaM1), capable of inhibiting E. coli cell growth by bypassing these reception and translocation steps. This goal was achieved through periplasmic expression of this pectocin...
October 8, 2016: Antibiotics
https://www.readbyqxmd.com/read/27690121/resistance-to-%C3%AE-lactams-in-neisseria-ssp-due-to-chromosomally-encoded-penicillin-binding-proteins
#15
REVIEW
André Zapun, Cécile Morlot, Muhamed-Kheir Taha
Neisseria meningitidis and Neisseria gonorrhoeae are human pathogens that cause a variety of life-threatening systemic and local infections, such as meningitis or gonorrhoea. The treatment of such infection is becoming more difficult due to antibiotic resistance. The focus of this review is on the mechanism of reduced susceptibility to penicillin and other β-lactams due to the modification of chromosomally encoded penicillin-binding proteins (PBP), in particular PBP2 encoded by the penA gene. The variety of penA alleles and resulting variant PBP2 enzymes is described and the important amino acid substitutions are presented and discussed in a structural context...
September 28, 2016: Antibiotics
https://www.readbyqxmd.com/read/27690120/discrepancy-in-vancomycin-auc-mic-ratio-targeted-attainment-based-upon-the-susceptibility-testing-in-staphylococcus-aureus
#16
Seenae Eum, Robert L Bergsbaken, Craig L Harvey, J Bryan Warren, John C Rotschafer
This study demonstrated a statistically significant difference in vancomycin minimum inhibitory concentration (MIC) for Staphylococcus aureus between a common automated system (Vitek 2) and the E-test method in patients with S. aureus bloodstream infections. At an area under the serum concentration time curve (AUC) threshold of 400 mg∙h/L, we would have reached the current Infectious Diseases Society of America (IDSA)/American Society of Health System Pharmacists (ASHP)/Society of Infectious Diseases Pharmacists (SIDP) guideline suggested AUC/MIC target in almost 100% of patients while using the Vitek 2 MIC data; however, we could only generate 40% target attainment while using E-test MIC data (p < 0...
September 27, 2016: Antibiotics
https://www.readbyqxmd.com/read/27669322/the-peptidoglycan-pattern-of-staphylococcus-carnosus-tm300-detailed-analysis-and-variations-due-to-genetic-and-metabolic-influences
#17
Julia Deibert, Daniel Kühner, Mark Stahl, Elif Koeksoy, Ute Bertsche
The Gram-positive bacterium Staphylococcus carnosus (S. carnosus) TM300 is an apathogenic staphylococcal species commonly used in meat starter cultures. As with all Gram-positive bacteria, its cytoplasmic membrane is surrounded by a thick peptidoglycan (PGN) or murein sacculus consisting of several layers of glycan strands cross-linked by peptides. In contrast to pathogenic staphylococci, mainly Staphylococcus aureus (S. aureus), the chemical composition of S. carnosus PGN is not well studied so far. UPLC/MS analysis of enzymatically digested S...
September 23, 2016: Antibiotics
https://www.readbyqxmd.com/read/27669321/the-novel-aminomethylcycline-omadacycline-has-high-specificity-for-the-primary-tetracycline-binding-site-on-the-bacterial-ribosome
#18
Corina G Heidrich, Sanya Mitova, Andreas Schedlbauer, Sean R Connell, Paola Fucini, Judith N Steenbergen, Christian Berens
Omadacycline is an aminomethylcycline antibiotic with potent activity against many Gram-positive and Gram-negative pathogens, including strains carrying the major efflux and ribosome protection resistance determinants. This makes it a promising candidate for therapy of severe infectious diseases. Omadacycline inhibits bacterial protein biosynthesis and competes with tetracycline for binding to the ribosome. Its interactions with the 70S ribosome were, therefore, analyzed in great detail and compared with tigecycline and tetracycline...
September 22, 2016: Antibiotics
https://www.readbyqxmd.com/read/27649253/reconsultation-and-antimicrobial-treatment-of-urinary-tract-infection-in-male-and-female-patients-in-general-practice
#19
Meera Tandan, Sinead Duane, Martin Cormican, Andrew W Murphy, Akke Vellinga
Current antimicrobial prescribing guidelines indicate that male and female patients with urinary tract infections (UTIs) should be treated with same antimicrobials but for different durations. The aim of this study was to explore the differences in reconsultations and antimicrobial prescribing for UTI for both males and females. A total of 2557 adult suspected UTI patients participating in the Supporting the Improvement and Management of Prescribing for urinary tract infection (SIMPle) study from 30 general practices were analyzed...
September 15, 2016: Antibiotics
https://www.readbyqxmd.com/read/27626453/the-search-for-herbal-antibiotics-an-in-silico-investigation-of-antibacterial-phytochemicals
#20
Mary Snow Setzer, Javad Sharifi-Rad, William N Setzer
Recently, the emergence and spread of pathogenic bacterial resistance to many antibiotics (multidrug-resistant strains) have been increasing throughout the world. This phenomenon is of great concern and there is a need to find alternative chemotherapeutic agents to combat these antibiotic-resistant microorganisms. Higher plants may serve as a resource for new antimicrobials to replace or augment current therapeutic options. In this work, we have carried out a molecular docking study of a total of 561 antibacterial phytochemicals listed in the Dictionary of Natural Products, including 77 alkaloids (17 indole alkaloids, 27 isoquinoline alkaloids, 4 steroidal alkaloids, and 28 miscellaneous alkaloids), 99 terpenoids (5 monoterpenoids, 31 sesquiterpenoids, 52 diterpenoids, and 11 triterpenoids), 309 polyphenolics (87 flavonoids, 25 chalcones, 41 isoflavonoids, 5 neoflavonoids, 12 pterocarpans, 10 chromones, 7 condensed tannins, 11 coumarins, 30 stilbenoids, 2 lignans, 5 phenylpropanoids, 13 xanthones, 5 hydrolyzable tannins, and 56 miscellaneous phenolics), 30 quinones, and 46 miscellaneous phytochemicals, with six bacterial protein targets (peptide deformylase, DNA gyrase/topoisomerase IV, UDP-galactose mutase, protein tyrosine phosphatase, cytochrome P450 CYP121, and NAD⁺-dependent DNA ligase)...
September 12, 2016: Antibiotics
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