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  Subjects -> BIOLOGY (Total: 2982 journals)
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BIOLOGY (1420 journals)                  1 2 3 4 5 6 7 8 | Last

Showing 1 - 200 of 1720 Journals sorted alphabetically
AAPS Journal     Hybrid Journal   (Followers: 18)
Achievements in the Life Sciences     Open Access   (Followers: 4)
ACS Synthetic Biology     Full-text available via subscription   (Followers: 20)
Acta Biologica Colombiana     Open Access   (Followers: 6)
Acta Biologica Hungarica     Full-text available via subscription   (Followers: 4)
Acta Biologica Sibirica     Open Access  
Acta Biomaterialia     Hybrid Journal   (Followers: 25)
Acta Biotheoretica     Hybrid Journal   (Followers: 5)
Acta Chiropterologica     Full-text available via subscription   (Followers: 6)
acta ethologica     Hybrid Journal   (Followers: 4)
Acta Limnologica Brasiliensia     Open Access   (Followers: 3)
Acta Médica Costarricense     Open Access   (Followers: 2)
Acta Musei Silesiae, Scientiae Naturales : The Journal of Silesian Museum in Opava     Open Access  
Acta Parasitologica     Hybrid Journal   (Followers: 9)
Acta Scientiarum. Biological Sciences     Open Access   (Followers: 2)
Acta Scientifica Naturalis     Open Access   (Followers: 2)
Actualidades Biológicas     Open Access   (Followers: 1)
Advanced Health Care Technologies     Open Access   (Followers: 4)
Advances in Antiviral Drug Design     Full-text available via subscription   (Followers: 3)
Advances in Bioinformatics     Open Access   (Followers: 18)
Advances in Biological Regulation     Hybrid Journal   (Followers: 4)
Advances in Biology     Open Access   (Followers: 8)
Advances in Biosensors and Bioelectronics     Open Access   (Followers: 6)
Advances in Cell Biology     Open Access   (Followers: 23)
Advances in Cellular and Molecular Biology of Membranes and Organelles     Full-text available via subscription   (Followers: 12)
Advances in Developmental Biology     Full-text available via subscription   (Followers: 11)
Advances in DNA Sequence-Specific Agents     Full-text available via subscription   (Followers: 5)
Advances in Ecological Research     Full-text available via subscription   (Followers: 39)
Advances in Ecology     Open Access   (Followers: 13)
Advances in Environmental Sciences - International Journal of the Bioflux Society     Open Access   (Followers: 20)
Advances in Enzyme Research     Open Access   (Followers: 10)
Advances in Experimental Biology     Full-text available via subscription   (Followers: 7)
Advances in Genome Biology     Full-text available via subscription   (Followers: 12)
Advances in High Energy Physics     Open Access   (Followers: 20)
Advances in Human Biology     Open Access  
Advances in Life Science and Technology     Open Access   (Followers: 14)
Advances in Life Sciences     Open Access   (Followers: 4)
Advances in Marine Biology     Full-text available via subscription   (Followers: 16)
Advances in Molecular and Cell Biology     Full-text available via subscription   (Followers: 21)
Advances in Planar Lipid Bilayers and Liposomes     Full-text available via subscription   (Followers: 3)
Advances in Regenerative Biology     Open Access   (Followers: 1)
Advances in Structural Biology     Full-text available via subscription   (Followers: 7)
Advances in Virus Research     Full-text available via subscription   (Followers: 5)
African Journal of Range & Forage Science     Hybrid Journal   (Followers: 6)
AFRREV STECH : An International Journal of Science and Technology     Open Access   (Followers: 1)
Ageing Research Reviews     Hybrid Journal   (Followers: 7)
Aging Cell     Open Access   (Followers: 9)
Agrokémia és Talajtan     Full-text available via subscription   (Followers: 2)
Agrokreatif Jurnal Ilmiah Pengabdian kepada Masyarakat     Open Access  
AJP Cell Physiology     Full-text available via subscription   (Followers: 13)
AJP Endocrinology and Metabolism     Full-text available via subscription   (Followers: 22)
AJP Lung Cellular and Molecular Physiology     Full-text available via subscription   (Followers: 3)
Al-Kauniyah : Jurnal Biologi     Open Access  
Alasbimn Journal     Open Access   (Followers: 1)
AMB Express     Open Access   (Followers: 1)
Ambix     Hybrid Journal   (Followers: 3)
American Biology Teacher     Full-text available via subscription   (Followers: 12)
American Fern Journal     Full-text available via subscription   (Followers: 1)
American Journal of Agricultural and Biological Sciences     Open Access   (Followers: 10)
American Journal of Bioethics     Hybrid Journal   (Followers: 10)
American Journal of Biostatistics     Open Access   (Followers: 9)
American Journal of Human Biology     Hybrid Journal   (Followers: 12)
American Journal of Medical and Biological Research     Open Access   (Followers: 5)
American Journal of Plant Sciences     Open Access   (Followers: 19)
American Journal of Primatology     Hybrid Journal   (Followers: 14)
American Malacological Bulletin     Full-text available via subscription   (Followers: 3)
American Naturalist     Full-text available via subscription   (Followers: 63)
Amphibia-Reptilia     Hybrid Journal   (Followers: 6)
Anaerobe     Hybrid Journal   (Followers: 4)
Analytical Methods     Full-text available via subscription   (Followers: 7)
Anatomical Science International     Hybrid Journal   (Followers: 2)
Animal Cells and Systems     Hybrid Journal   (Followers: 4)
Annales de Limnologie - International Journal of Limnology     Hybrid Journal   (Followers: 1)
Annales françaises d'Oto-rhino-laryngologie et de Pathologie Cervico-faciale     Full-text available via subscription   (Followers: 3)
Annales Henri Poincaré     Hybrid Journal   (Followers: 3)
Annales UMCS, Biologia     Open Access   (Followers: 1)
Annals of Applied Biology     Hybrid Journal   (Followers: 8)
Annals of Biomedical Engineering     Hybrid Journal   (Followers: 18)
Annals of Human Biology     Hybrid Journal   (Followers: 4)
Annual Review of Biomedical Engineering     Full-text available via subscription   (Followers: 17)
Annual Review of Biophysics     Full-text available via subscription   (Followers: 25)
Annual Review of Cell and Developmental Biology     Full-text available via subscription   (Followers: 37)
Annual Review of Food Science and Technology     Full-text available via subscription   (Followers: 14)
Annual Review of Genomics and Human Genetics     Full-text available via subscription   (Followers: 18)
Annual Review of Phytopathology     Full-text available via subscription   (Followers: 10)
Anthropological Review     Open Access   (Followers: 23)
Anti-Infective Agents     Hybrid Journal   (Followers: 3)
Antibiotics     Open Access   (Followers: 8)
Antioxidants     Open Access   (Followers: 4)
Antioxidants & Redox Signaling     Hybrid Journal   (Followers: 8)
Antonie van Leeuwenhoek     Hybrid Journal   (Followers: 5)
Anzeiger für Schädlingskunde     Hybrid Journal   (Followers: 1)
Apidologie     Hybrid Journal   (Followers: 4)
Apmis     Hybrid Journal   (Followers: 1)
APOPTOSIS     Hybrid Journal   (Followers: 8)
Applied Bionics and Biomechanics     Open Access   (Followers: 8)
Applied Vegetation Science     Full-text available via subscription   (Followers: 9)
Aquaculture Environment Interactions     Open Access   (Followers: 2)
Aquaculture International     Hybrid Journal   (Followers: 22)
Aquaculture Reports     Open Access   (Followers: 3)
Aquaculture, Aquarium, Conservation & Legislation - International Journal of the Bioflux Society     Open Access   (Followers: 6)
Aquatic Biology     Open Access   (Followers: 4)
Aquatic Ecology     Hybrid Journal   (Followers: 30)
Aquatic Ecosystem Health & Management     Hybrid Journal   (Followers: 13)
Aquatic Science and Technology     Open Access   (Followers: 3)
Aquatic Toxicology     Hybrid Journal   (Followers: 19)
Archaea     Open Access   (Followers: 3)
Archiv für Molluskenkunde: International Journal of Malacology     Full-text available via subscription   (Followers: 3)
Archives of Biomedical Sciences     Open Access   (Followers: 7)
Archives of Microbiology     Hybrid Journal   (Followers: 8)
Archives of Natural History     Hybrid Journal   (Followers: 7)
Archives of Oral Biology     Hybrid Journal   (Followers: 2)
Archives of Virology     Hybrid Journal   (Followers: 5)
Archivum Immunologiae et Therapiae Experimentalis     Hybrid Journal   (Followers: 2)
Arid Ecosystems     Hybrid Journal   (Followers: 3)
Arquivos do Instituto Biológico     Open Access   (Followers: 1)
Arquivos do Museu Dinâmico Interdisciplinar     Open Access  
Arthropod Structure & Development     Hybrid Journal   (Followers: 2)
Arthropods     Open Access   (Followers: 1)
Artificial DNA: PNA & XNA     Hybrid Journal   (Followers: 2)
Artificial Photosynthesis     Open Access   (Followers: 1)
Asian Bioethics Review     Full-text available via subscription   (Followers: 1)
Asian Journal of Biodiversity     Open Access   (Followers: 5)
Asian Journal of Biological Sciences     Open Access   (Followers: 3)
Asian Journal of Cell Biology     Open Access   (Followers: 5)
Asian Journal of Developmental Biology     Open Access   (Followers: 2)
Asian Journal of Medical and Biological Research     Open Access   (Followers: 2)
Asian Journal of Nematology     Open Access   (Followers: 3)
Asian Journal of Poultry Science     Open Access   (Followers: 4)
Australian Life Scientist     Full-text available via subscription   (Followers: 2)
Australian Mammalogy     Hybrid Journal   (Followers: 5)
Autophagy     Hybrid Journal   (Followers: 2)
Avian Biology Research     Full-text available via subscription   (Followers: 3)
Avian Conservation and Ecology     Open Access   (Followers: 7)
Bacteriology Journal     Open Access   (Followers: 2)
Bacteriophage     Full-text available via subscription   (Followers: 3)
Bangladesh Journal of Bioethics     Open Access  
Bangladesh Journal of Plant Taxonomy     Open Access  
Bangladesh Journal of Scientific Research     Open Access   (Followers: 1)
Berita Biologi     Open Access   (Followers: 1)
Between the Species     Open Access   (Followers: 1)
Bio Tribune Magazine     Hybrid Journal  
BIO Web of Conferences     Open Access  
BIO-Complexity     Open Access  
Bio-Grafía. Escritos sobre la Biología y su enseñanza     Open Access  
Bioanalytical Reviews     Hybrid Journal   (Followers: 2)
Biocatalysis and Biotransformation     Hybrid Journal   (Followers: 6)
Biochemistry and Cell Biology     Full-text available via subscription   (Followers: 14)
Biochimie     Hybrid Journal   (Followers: 7)
BioControl     Hybrid Journal   (Followers: 5)
Biocontrol Science and Technology     Hybrid Journal   (Followers: 5)
Biodemography and Social Biology     Hybrid Journal   (Followers: 1)
Biodiversidad Colombia     Open Access  
Biodiversity : Research and Conservation     Open Access   (Followers: 26)
Biodiversity and Natural History     Open Access   (Followers: 5)
Biodiversity Data Journal     Open Access   (Followers: 3)
Biodiversity Informatics     Open Access  
Bioedukasi : Jurnal Pendidikan Biologi FKIP UM Metro     Open Access  
Bioeksperimen : Jurnal Penelitian Biologi     Open Access  
Bioelectrochemistry     Hybrid Journal   (Followers: 2)
Bioelectromagnetics     Hybrid Journal   (Followers: 1)
Bioenergy Research     Hybrid Journal   (Followers: 2)
Bioengineering and Bioscience     Open Access   (Followers: 1)
BioEssays     Hybrid Journal   (Followers: 10)
Bioethics     Hybrid Journal   (Followers: 14)
BioéthiqueOnline     Open Access  
Biofabrication     Hybrid Journal   (Followers: 3)
Biogeosciences (BG)     Open Access   (Followers: 9)
Biogeosciences Discussions (BGD)     Open Access   (Followers: 1)
Bioinformatics     Hybrid Journal   (Followers: 233)
Bioinformatics and Biology Insights     Open Access   (Followers: 14)
Bioinspiration & Biomimetics     Hybrid Journal   (Followers: 6)
Biointerphases     Open Access   (Followers: 1)
Biojournal of Science and Technology     Open Access  
Biologia     Hybrid Journal  
Biologia on-line : Revista de divulgació de la Facultat de Biologia     Open Access  
Biological Bulletin     Partially Free   (Followers: 4)
Biological Control     Hybrid Journal   (Followers: 5)
Biological Invasions     Hybrid Journal   (Followers: 16)
Biological Journal of the Linnean Society     Hybrid Journal   (Followers: 14)
Biological Letters     Open Access   (Followers: 4)
Biological Procedures Online     Open Access  
Biological Psychiatry     Hybrid Journal   (Followers: 41)
Biological Psychology     Hybrid Journal   (Followers: 6)
Biological Research     Open Access  
Biological Rhythm Research     Hybrid Journal   (Followers: 2)
Biological Theory     Hybrid Journal   (Followers: 1)
Biological Trace Element Research     Hybrid Journal  
Biologicals     Full-text available via subscription   (Followers: 9)
Biologics: Targets & Therapy     Open Access   (Followers: 1)
Biologie Aujourd'hui     Full-text available via subscription  
Biologie in Unserer Zeit (Biuz)     Hybrid Journal   (Followers: 44)
Biologija     Open Access  
Biology     Open Access   (Followers: 5)
Biology and Philosophy     Hybrid Journal   (Followers: 16)
Biology Bulletin     Hybrid Journal   (Followers: 1)
Biology Bulletin Reviews     Hybrid Journal  
Biology Direct     Open Access   (Followers: 7)
Biology Letters     Full-text available via subscription   (Followers: 35)
Biology Methods and Protocols     Hybrid Journal  

        1 2 3 4 5 6 7 8 | Last

Journal Cover Antibiotics
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  This is an Open Access Journal Open Access journal
   ISSN (Print) 2079-6382
   Published by MDPI Homepage  [148 journals]
  • Antibiotics, Vol. 6, Pages 11: Erythromycin Modification That Improves Its
           Acidic Stability while Optimizing It for Local Drug Delivery

    • Authors: Erika Cyphert, Jaqueline Wallat, Jonathan Pokorski, Horst von Recum
      First page: 11
      Abstract: 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. To develop this new drug conjugate, adamantane-1-carbohydrazide was covalently attached to erythromycin via a pH-degradable hydrazone bond. Since Staphylococcus aureus infection sites are slightly acidic, the hydrazone bond will undergo hydrolysis liberating erythromycin directly at the infection site. The adamantane group provides interaction with the drug delivery system. This local delivery strategy has the potential of reducing off-target and systemic side-effects. This work demonstrates the synthesis of a pH-cleavable, erythromycin conjugate that retains the inherent antimicrobial activity of erythromycin, has an increased hydrophobicity, and improved stability in acidic conditions; thereby enhancing erythromycin’s bioavailability while simultaneously reducing its toxicity.
      PubDate: 2017-04-25
      DOI: 10.3390/antibiotics6020011
      Issue No: Vol. 6, No. 2 (2017)
       
  • Antibiotics, Vol. 6, Pages 1: Acknowledgement to Reviewers of Antibiotics
           in 2016

    • Authors: Antibiotics Office
      First page: 1
      Abstract: The editors of Antibiotics would like to express their sincere gratitude to the following reviewers  for assessing manuscripts in 2016.[...]
      PubDate: 2017-01-10
      DOI: 10.3390/antibiotics6010001
      Issue No: Vol. 6, No. 1 (2017)
       
  • Antibiotics, Vol. 6, Pages 2: Fused-Ring Oxazolopyrrolopyridopyrimidine
           Systems with Gram-Negative Activity

    • Authors: Yiyuan Chen, Jonathan Moloney, Kirsten Christensen, Mark Moloney
      First page: 2
      Abstract: 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.
      PubDate: 2017-01-13
      DOI: 10.3390/antibiotics6010002
      Issue No: Vol. 6, No. 1 (2017)
       
  • Antibiotics, Vol. 6, Pages 3: 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

    • Authors: Leonard Amaral, Miguel Viveiros
      First page: 3
      Abstract: 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. The mechanisms of action by which TZ brings about successful therapeutic outcomes are presented in detail.
      PubDate: 2017-01-14
      DOI: 10.3390/antibiotics6010003
      Issue No: Vol. 6, No. 1 (2017)
       
  • Antibiotics, Vol. 6, Pages 4: Docking into Mycobacterium tuberculosis
           Thioredoxin Reductase Protein Yields Pyrazolone Lead Molecules for
           Methicillin-Resistant Staphylococcus aureus

    • Authors: Noreena Sweeney, Lauren Lipker, Alicia Hanson, Chris Bohl, Katie Engel, Kelsey Kalous, Mary Stemper, Daniel Sem, William Schwan
      First page: 4
      Abstract: 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. aureus strains, including drug-resistant clinical isolates. The findings support continued development of the pyrazolone compounds as potential anti-S. aureus antibiotics.
      PubDate: 2017-01-28
      DOI: 10.3390/antibiotics6010004
      Issue No: Vol. 6, No. 1 (2017)
       
  • Antibiotics, Vol. 6, Pages 5: Moxifloxacin Increases Heart Rate in Humans

    • Authors: Jay Mason, Thomas Moon
      First page: 5
      Abstract: (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). The maximum mean heart rate (HR) increase for the seven studies combined was 2.4 bpm (95% CI 1.6, 3.3) at hour 2. The range of mean maximum increases among the seven studies was 2.1 to 4.3 bpm. For the seven studies combined, the increase was statistically significant at all but the 24 h time point. The maximum observed individual increase in HR was 36 bpm and the mean maximum increase was 30 ± 4.1 bpm by time point and 8 ± 6.9 bpm by subject. Many antibiotics increase HR, some several-fold more than moxifloxacin. However, clinicians and clinical investigators give little attention to this potential adverse effect in the medical literature; (4) Conclusions: The observed moxifloxacin-induced increase in HR is large enough to be clinically relevant, and it is a potentially important confounder in thorough QT studies using moxifloxacin as an active control. More attention to heart rate effects of antibiotics is warranted.
      PubDate: 2017-02-05
      DOI: 10.3390/antibiotics6010005
      Issue No: Vol. 6, No. 1 (2017)
       
  • Antibiotics, Vol. 6, Pages 6: Diminished Antimicrobial Peptide and
           Antifungal Antibiotic Activities against Candida albicans in Denture
           Adhesive

    • Authors: Amber Bates, Jorge Garaicoa, Carol Fischer, Kim Brogden
      First page: 6
      Abstract: 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 1.0% adhesive, HNP-1, HBD2, HBD3, IP-10, LL37 (only one strain), histatin 5 (only one strain), lactoferricin B, and SMAP28 showed diminished activity against C. albicans. In gels with 1.0% adhesive, amphotericin B and chlorhexidine dihydrochloride were active against both strains of C. albicans. These results suggest that denture adhesive may inactivate innate immune mediators in the oral cavity increasing the risk of C. albicans infections, but inclusion of antifungal antibiotics to denture adhesive may aid in prevention or treatment of Candida infections and denture stomatitis.
      PubDate: 2017-02-06
      DOI: 10.3390/antibiotics6010006
      Issue No: Vol. 6, No. 1 (2017)
       
  • Antibiotics, Vol. 6, Pages 7: Final Demonstration of the Co-Identity of
           Lipiarmycin A3 and Tiacumicin B (Fidaxomicin) through Single Crystal X-ray
           Analysis

    • Authors: Stefano Serra, Luciana Malpezzi, Angelo Bedeschi, Claudio Fuganti, Piera Fonte
      First page: 7
      Abstract: 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. These results confirmed the previous assigned chemical structure of lipiarmycin A3 and its absolute configuration as well as its co-identity with the chemical structure of tiacumicin B, providing the definitive proof that these pharmaceutical compounds are identical in all respects.
      PubDate: 2017-02-08
      DOI: 10.3390/antibiotics6010007
      Issue No: Vol. 6, No. 1 (2017)
       
  • Antibiotics, Vol. 6, Pages 8:
           Bulgecin A: The Key to a Broad‐Spectrum Inhibitor 
           That Targets Lytic Transglycosylases

    • Authors: Allison Williams, Richard Wheeler, Constance Thiriau, Ahmed Haouz, Muhamed‐Kheir Taha, Ivo Boneca
      First page: 8
      Abstract: 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. The LtgA‐bulgecin A complex reveals the mechanism of inhibition by bulgecin A at near atomic resolution. We further demonstrate that bulgecin A is not only a potent inhibitor of LtgA, but most importantly, it restores the efficacy of β‐lactam antibiotics in strains of N. meningitidis and Neisseria gonorrhoeae that have reduced susceptibility to β‐lactams. This is particularly relevant for N. gonorrhoeae where no vaccines are available. This work illustrates how best to target dangerous pathogens using a multiple drug target approach, a new and alternative approach to fighting antibiotic resistance.
      PubDate: 2017-02-22
      DOI: 10.3390/antibiotics6010008
      Issue No: Vol. 6, No. 1 (2017)
       
  • Antibiotics, Vol. 6, Pages 9: A Risk Assessment of Antibiotic
           Pan-Drug-Resistance in the UK: Bayesian Analysis of an Expert Elicitation
           Study

    • Authors: Daniel Carter, André Charlett, Stefano Conti, Julie Robotham, Alan Johnson, David Livermore, Tom Fowler, Mike Sharland, Susan Hopkins, Neil Woodford, Philip Burgess, Stephen Dobra
      First page: 9
      Abstract: 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. Overall probability was modelled using Monte Carlo simulation. Estimates of impact were also obtained using Bayesian methods. The estimated probability of widespread occurrence of PDR pathogens within five years was 0.2 (95% credibility interval (CrI): 0.07–0.37). Estimated annual numbers of PDR Gram-negative bacteraemias at five and 20 years were 6800 (95% CrI: 400–58,600) and 22,800 (95% CrI: 1500–160,000), respectively; corresponding estimates of excess deaths were 1900 (95% CrI: 0–23,000) and 6400 (95% CrI: 0–64,000). Over 20 years, cumulative estimates indicate 284,000 (95% CrI: 17,000–1,990,000) cases of PDR Gram-negative bacteraemia, leading to an estimated 79,000 (95% CrI: 0–821,000) deaths. This risk assessment reinforces the need for urgent national and international action to tackle antibiotic resistance.
      PubDate: 2017-03-07
      DOI: 10.3390/antibiotics6010009
      Issue No: Vol. 6, No. 1 (2017)
       
  • Antibiotics, Vol. 6, Pages 10: Activity of Sulfa Drugs and Their
           Combinations against Stationary Phase B. burgdorferi In Vitro

    • Authors: Jie Feng, Shuo Zhang, Wanliang Shi, Ying Zhang
      First page: 10
      Abstract: 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. burgdorferi stationary phase cells. In this study, we evaluated the relative activity of three commonly used sulfa drugs, sulfamethoxazole (Smx), dapsone (Dps), sulfachlorpyridazine (Scp), and also trimethoprim (Tmp), and assessed their combinations with the commonly prescribed Lyme antibiotics for activities against B. burgdorferi stationary phase cells. Using the same molarity concentration, dapsone, sulfachlorpyridazine and trimethoprim showed very similar activity against stationary phase B. burgdorferi enriched in persisters; however, sulfamethoxazole was the least active drug among the three sulfa drugs tested. Interestingly, contrary to other bacterial systems, Tmp did not show synergy in drug combinations with the three sulfa drugs at their clinically relevant serum concentrations against B. burgdorferi. We found that sulfa drugs combined with other antibiotics were more active than their respective single drugs and that four-drug combinations were more active than three-drug combinations. Four-drug combinations dapsone + minocycline + cefuroxime + azithromycin and dapsone + minocycline + cefuroxime + rifampin showed the best activity against stationary phase B. burgdorferi in these sulfa drug combinations. However, these four-sulfa-drug–containing combinations still had considerably less activity against B. burgdorferi stationary phase cells than the Daptomycin + cefuroxime + doxycycline used as a positive control which completely eradicated B. burgdorferi stationary phase cells. Future studies are needed to evaluate and optimize the sulfa drug combinations in vitro and also in animal models.
      PubDate: 2017-03-22
      DOI: 10.3390/antibiotics6010010
      Issue No: Vol. 6, No. 1 (2017)
       
  • Antibiotics, Vol. 5, Pages 32: The Novel Aminomethylcycline Omadacycline
           Has High Specificity for the Primary Tetracycline-Binding Site on the
           Bacterial Ribosome

    • Authors: Corina Heidrich, Sanya Mitova, Andreas Schedlbauer, Sean Connell, Paola Fucini, Judith Steenbergen, Christian Berens
      First page: 32
      Abstract: 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. All three antibiotics are inhibited by mutations in the 16S rRNA that mediate resistance to tetracycline in Brachyspira hyodysenteriae, Helicobacter pylori, Mycoplasma hominis, and Propionibacterium acnes. Chemical probing with dimethyl sulfate and Fenton cleavage with iron(II)-complexes of the tetracycline derivatives revealed that each antibiotic interacts in an idiosyncratic manner with the ribosome. X-ray crystallography had previously revealed one primary binding site for tetracycline on the ribosome and up to five secondary sites. All tetracyclines analyzed here interact with the primary site and tetracycline also with two secondary sites. In addition, each derivative displays a unique set of non-specific interactions with the 16S rRNA.
      PubDate: 2016-09-22
      DOI: 10.3390/antibiotics5040032
      Issue No: Vol. 5, No. 4 (2016)
       
  • Antibiotics, Vol. 5, Pages 33: The Peptidoglycan Pattern of Staphylococcus
           carnosus TM300—Detailed Analysis and Variations Due to Genetic and
           Metabolic Influences

    • Authors: Julia Deibert, Daniel Kühner, Mark Stahl, Elif Koeksoy, Ute Bertsche
      First page: 33
      Abstract: 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. carnosus TM300 PGN revealed substantial differences in its composition compared to the known pattern of S. aureus. While in S. aureus the uncross-linked stem peptide consists of a pentapeptide, in S. carnosus, this part of the PGN is shortened to tripeptides. Furthermore, we found the PGN composition to vary when cells were incubated under certain conditions. The collective overproduction of HlyD, FtsE and FtsX—a putative protein complex interacting with penicillin-binding protein 2 (PBP2)—caused the reappearance of classical penta stem peptides. In addition, under high sugar conditions, tetra stem peptides occur due to overflow metabolism. This indicates that S. carnosus TM300 cells adapt to various conditions by modification of their PGN.
      PubDate: 2016-09-23
      DOI: 10.3390/antibiotics5040033
      Issue No: Vol. 5, No. 4 (2016)
       
  • Antibiotics, Vol. 5, Pages 34: Discrepancy in Vancomycin AUC/MIC Ratio
           Targeted Attainment Based upon the Susceptibility Testing in
           Staphylococcus aureus

    • Authors: Seenae Eum, Robert Bergsbaken, Craig Harvey, J. Warren, John Rotschafer
      First page: 34
      Abstract: 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 < 0.0001). An AUC of 450 mg∙h/L or greater was required to achieve 100% target attainment using either Vitek 2 or E-test MIC results.
      PubDate: 2016-09-27
      DOI: 10.3390/antibiotics5040034
      Issue No: Vol. 5, No. 4 (2016)
       
  • Antibiotics, Vol. 5, Pages 35: Resistance to β-Lactams in Neisseria ssp
           Due to Chromosomally Encoded Penicillin-Binding Proteins

    • Authors: André Zapun, Cécile Morlot, Muhamed-Kheir Taha
      First page: 35
      Abstract: 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.
      PubDate: 2016-09-28
      DOI: 10.3390/antibiotics5040035
      Issue No: Vol. 5, No. 4 (2016)
       
  • Antibiotics, Vol. 5, Pages 36: Pectocin M1 (PcaM1) Inhibits Escherichia
           coli Cell Growth and Peptidoglycan Biosynthesis through Periplasmic
           Expression

    • Authors: Dimitri Chérier, Sean Giacomucci, Delphine Patin, Ahmed Bouhss, Thierry Touzé, Didier Blanot, Dominique Mengin-Lecreulx, Hélène Barreteau
      First page: 36
      Abstract: 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. Indeed, when appropriately addressed to the periplasm of E. coli, this pectocin could exert its deleterious effects, i.e., the enzymatic degradation of the peptidoglycan lipid II precursor, which resulted in the arrest of the biosynthesis of this essential cell wall polymer, dramatic morphological changes and, ultimately, cell lysis. This result leads to the conclusion that colicin M and its various orthologues constitute powerful antibacterial molecules able to kill any kind of bacterium, once they can reach their lipid II target. They thus have to be seriously considered as promising alternatives to antibiotics.
      PubDate: 2016-10-08
      DOI: 10.3390/antibiotics5040036
      Issue No: Vol. 5, No. 4 (2016)
       
  • Antibiotics, Vol. 5, Pages 37: Antimicrobial Usage and Antimicrobial
           Resistance in Animal Production in Southeast Asia: A Review

    • Authors: Nguyen Nhung, Nguyen Cuong, Guy Thwaites, Juan Carrique-Mas
      First page: 37
      Abstract: 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. Most of the published work relates to non-typhoidal Salmonella (NTS), Escherichia coli (E. coli), and Campylobacter spp. (mainly from Vietnam and Thailand), Enterococcus spp. (Malaysia), and methicillin-resistant Staphylococcus aureus (MRSA) (Thailand). However, most studies used the disk diffusion method for antimicrobial susceptibility testing; breakpoints were interpreted using Clinical Standard Laboratory Institute (CSLI) guidelines. Statistical models integrating data from publications on AMR in NTS and E. coli studies show a higher overall prevalence of AMR in pig isolates, and an increase in levels of AMR over the years. AMU studies (mostly from Vietnam) indicate very high usage levels of most types of antimicrobials, including beta-lactams, aminoglycosides, macrolides, and quinolones. This review summarizes information about genetic determinants of resistance, most of which are transferrable (mostly plasmids and integrons). The data in this review provide a benchmark to help focus research and policies on AMU and AMR in the region.
      PubDate: 2016-11-02
      DOI: 10.3390/antibiotics5040037
      Issue No: Vol. 5, No. 4 (2016)
       
  • Antibiotics, Vol. 5, Pages 38: Conformational Response of 30S-bound IF3 to
           A-Site Binders Streptomycin and Kanamycin

    • Authors: Roberto Chulluncuy, Carlos Espiche, Jose Nakamoto, Attilio Fabbretti, Pohl Milón
      First page: 38
      Abstract: 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. Steady and pre-steady state binding experiments show that both aminoglycosides bring IF3 domains apart, promoting an elongated state of the factor. Binding of Initiation Factor IF1 triggers closure of IF3 bound to the 30S complex, while both aminoglycosides revert the IF1-dependent conformation. Our results uncover dynamic perturbations across the 30S subunit, from the A-site to the platform, and suggest that both aminoglycosides could interfere with prokaryotic translation initiation by modulating the interaction between IF3 domains with the 30S platform.
      PubDate: 2016-12-13
      DOI: 10.3390/antibiotics5040038
      Issue No: Vol. 5, No. 4 (2016)
       
  • Antibiotics, Vol. 5, Pages 39: Quorum Sensing and the Use of Quorum
           Quenchers as Natural Biocides to Inhibit Sulfate-Reducing Bacteria

    • Authors: Giantommaso Scarascia, Tiannyu Wang, Pei-Ying Hong
      First page: 39
      Abstract: 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. Genome databases of SRBs are mined to look for putative QS systems and homologous protein sequences representative of autoinducer receptors or synthases. Subsequently, this review puts forward the potential use of quorum quenchers as natural biocides against SRBs and outlines the potential strategies for the implementation of this approach.
      PubDate: 2016-12-15
      DOI: 10.3390/antibiotics5040039
      Issue No: Vol. 5, No. 4 (2016)
       
  • Antibiotics, Vol. 5, Pages 22: Techniques for Screening Translation
           Inhibitors

    • Authors: Ilya Osterman, Alexey Bogdanov, Olga Dontsova, Petr Sergiev
      First page: 22
      Abstract: The machinery of translation is one of the most common targets of antibiotics. The development and screening of new antibiotics usually proceeds by testing antimicrobial activity followed by laborious studies of the mechanism of action. High-throughput methods for new antibiotic screening based on antimicrobial activity have become routine; however, identification of molecular targets is usually a challenge. Therefore, it is highly beneficial to combine primary screening with the identification of the mechanism of action. In this review, we describe a collection of methods for screening translation inhibitors, with a special emphasis on methods which can be performed in a high-throughput manner.
      PubDate: 2016-06-24
      DOI: 10.3390/antibiotics5030022
      Issue No: Vol. 5, No. 3 (2016)
       
  • Antibiotics, Vol. 5, Pages 24: Ribosomal Antibiotics: Contemporary
           Challenges

    • Authors: Tamar Auerbach-Nevo, David Baram, Anat Bashan, Matthew Belousoff, Elinor Breiner, Chen Davidovich, Giuseppe Cimicata, Zohar Eyal, Yehuda Halfon, Miri Krupkin, Donna Matzov, Markus Metz, Mruwat Rufayda, Moshe Peretz, Ophir Pick, Erez Pyetan, Haim Rozenberg, Moran Shalev-Benami, Itai Wekselman, Raz Zarivach, Ella Zimmerman, Nofar Assis, Joel Bloch, Hadar Israeli, Rinat Kalaora, Lisha Lim, Ofir Sade-Falk, Tal Shapira, Leena Taha-Salaime, Hua Tang, Ada Yonath
      First page: 24
      Abstract: Most ribosomal antibiotics obstruct distinct ribosomal functions. In selected cases, in addition to paralyzing vital ribosomal tasks, some ribosomal antibiotics are involved in cellular regulation. Owing to the global rapid increase in the appearance of multi-drug resistance in pathogenic bacterial strains, and to the extremely slow progress in developing new antibiotics worldwide, it seems that, in addition to the traditional attempts at improving current antibiotics and the intensive screening for additional natural compounds, this field should undergo substantial conceptual revision. Here, we highlight several contemporary issues, including challenging the common preference of broad-range antibiotics; the marginal attention to alterations in the microbiome population resulting from antibiotics usage, and the insufficient awareness of ecological and environmental aspects of antibiotics usage. We also highlight recent advances in the identification of species-specific structural motifs that may be exploited for the design and the creation of novel, environmental friendly, degradable, antibiotic types, with a better distinction between pathogens and useful bacterial species in the microbiome. Thus, these studies are leading towards the design of “pathogen-specific antibiotics,” in contrast to the current preference of broad range antibiotics, partially because it requires significant efforts in speeding up the discovery of the unique species motifs as well as the clinical pathogen identification.
      PubDate: 2016-06-29
      DOI: 10.3390/antibiotics5030024
      Issue No: Vol. 5, No. 3 (2016)
       
  • Antibiotics, Vol. 5, Pages 25: Non-Response to Antibiotic Treatment in
           Adolescents for Four Common Infections in UK Primary Care 1991–2012: A
           Retrospective, Longitudinal Study

    • Authors: Ellen Berni, Laura Scott, Sara Jenkins-Jones, Hanka De Voogd, Monica Rocha, Chris Butler, Christopher Morgan, Craig Currie
      First page: 25
      Abstract: We studied non-response rates to antibiotics in the under-reported subgroup of adolescents aged 12 to 17 years old, using standardised criteria representing antibiotic treatment failure. Routine, primary care data from the UK Clinical Practice Research Datalink (CPRD) were used. Annual, non-response rates by antibiotics and by indication were determined. We identified 824,651 monotherapies in 415,468 adolescents: 368,900 (45%) episodes for upper respiratory tract infections (URTIs), 89,558 (11%) for lower respiratory tract infections (LRTIs), 286,969 (35%) for skin/soft tissue infections (SSTIs) and 79,224 (10%) for acute otitis media (AOM). The most frequently prescribed antibiotics were amoxicillin (27%), penicillin-V (24%), erythromycin (11%), flucloxacillin (11%) and oxytetracycline (6%). In 1991, the overall non-response rate was 9.3%: 11.9% for LRTIs, 9.5% for URTIs, 7.1% for SSTIs, 9.7% for AOM. In 2012, the overall non-response rate was 9.2%. Highest non-response rates were for AOM in 1991–1999 and for LRTIs in 2000–2012. Physicians generally prescribed antibiotics to adolescents according to recommendations. Evidence of antibiotic non-response was less common among adolescents during this 22-year study period compared with an all-age population, where the overall non-response rate was 12%.
      PubDate: 2016-07-04
      DOI: 10.3390/antibiotics5030025
      Issue No: Vol. 5, No. 3 (2016)
       
  • Antibiotics, Vol. 5, Pages 26: Biotin Protein Ligase Is a Target for New
           Antibacterials

    • Authors: Jiage Feng, Ashleigh Paparella, Grant Booker, Steven Polyak, Andrew Abell
      First page: 26
      Abstract: There is a desperate need for novel antibiotic classes to combat the rise of drug resistant pathogenic bacteria, such as Staphylococcus aureus. Inhibitors of the essential metabolic enzyme biotin protein ligase (BPL) represent a promising drug target for new antibacterials. Structural and biochemical studies on the BPL from S. aureus have paved the way for the design and development of new antibacterial chemotherapeutics. BPL employs an ordered ligand binding mechanism for the synthesis of the reaction intermediate biotinyl-5′-AMP from substrates biotin and ATP. Here we review the structure and catalytic mechanism of the target enzyme, along with an overview of chemical analogues of biotin and biotinyl-5′-AMP as BPL inhibitors reported to date. Of particular promise are studies to replace the labile phosphoroanhydride linker present in biotinyl-5′-AMP with alternative bioisosteres. A novel in situ click approach using a mutant of S. aureus BPL as a template for the synthesis of triazole-based inhibitors is also presented. These approaches can be widely applied to BPLs from other bacteria, as well as other closely related metabolic enzymes and antibacterial drug targets.
      PubDate: 2016-07-25
      DOI: 10.3390/antibiotics5030026
      Issue No: Vol. 5, No. 3 (2016)
       
  • Antibiotics, Vol. 5, Pages 27: Exploring Experiences of Delayed
           Prescribing and Symptomatic Treatment for Urinary Tract Infections among
           General Practitioners and Patients in Ambulatory Care: A Qualitative Study
           

    • Authors: Sinead Duane, Paula Beatty, Andrew Murphy, Akke Vellinga
      First page: 27
      Abstract: “Delayed or back up” antibiotic prescriptions and “symptomatic” treatment may help to reduce inappropriate antibiotic prescribing for Urinary Tract Infections (UTI) in the future. However, more research needs to be conducted in this area before these strategies can be readily promoted in practice. This study explores General Practitioner (GP) and patient attitudes and experiences regarding the use of delayed or back-up antibiotic and symptomatic treatment for UTI. Qualitative face to face interviews with General Practitioners (n = 7) from one urban and one rural practice and telephone interviews with UTI patients (n = 14) from a rural practice were undertaken. Interviews were analysed using framework analysis. GPs believe that antibiotics are necessary when treating UTI. There was little consensus amongst GPs regarding the role of delayed prescribing or symptomatic treatment for UTI. Delayed prescribing may be considered for patients with low grade symptoms and a negative dipstick test. Patients had limited experience of delayed prescribing for UTI. Half indicated they would be satisfied with a delayed prescription the other half would question it. A fear of missing a serious illness was a significant barrier to symptomatic treatment for both GP and patient. The findings of this research provide insight into antibiotic prescribing practices in general practice. It also highlights the need for further empirical research into the effectiveness of alternative treatment strategies such as symptomatic treatment of UTI before such strategies can be readily adopted in practice.
      PubDate: 2016-08-15
      DOI: 10.3390/antibiotics5030027
      Issue No: Vol. 5, No. 3 (2016)
       
  • Antibiotics, Vol. 5, Pages 28: The Membrane Steps of Bacterial Cell Wall
           Synthesis as Antibiotic Targets

    • Authors: Yao Liu, Eefjan Breukink
      First page: 28
      Abstract: Peptidoglycan is the major component of the cell envelope of virtually all bacteria. It has structural roles and acts as a selective sieve for molecules from the outer environment. Peptidoglycan synthesis is therefore one of the most important biogenesis pathways in bacteria and has been studied extensively over the last twenty years. The pathway starts in the cytoplasm, continues in the cytoplasmic membrane and finishes in the periplasmic space, where the precursor is polymerized into the peptidoglycan layer. A number of proteins involved in this pathway, such as the Mur enzymes and the penicillin binding proteins (PBPs), have been studied and regarded as good targets for antibiotics. The present review focuses on the membrane steps of peptidoglycan synthesis that involve two enzymes, MraY and MurG, the inhibitors of these enzymes and the inhibition mechanisms. We also discuss the challenges of targeting these two cytoplasmic membrane (associated) proteins in bacterial cells and the perspectives on how to overcome the issues.
      PubDate: 2016-08-26
      DOI: 10.3390/antibiotics5030028
      Issue No: Vol. 5, No. 3 (2016)
       
  • Antibiotics, Vol. 5, Pages 29: From Erythromycin to Azithromycin and New
           Potential Ribosome-Binding Antimicrobials

    • Authors: Dubravko Jelić, Roberto Antolović
      First page: 29
      Abstract: Macrolides, as a class of natural or semisynthetic products, express their antibacterial activity primarily by reversible binding to the bacterial 50S ribosomal subunits and by blocking nascent proteins’ progression through their exit tunnel in bacterial protein biosynthesis. Generally considered to be bacteriostatic, they may also be bactericidal at higher doses. The discovery of azithromycin from the class of macrolides, as one of the most important new drugs of the 20th century, is presented as an example of a rational medicinal chemistry approach to drug design, applying classical structure-activity relationship that will illustrate an impressive drug discovery success story. However, the microorganisms have developed several mechanisms to acquire resistance to antibiotics, including macrolide antibiotics. The primary mechanism for acquiring bacterial resistance to macrolides is a mutation of one or more nucleotides from the binding site. Although azithromycin is reported to show different, two-step process of the inhibition of ribosome function of some species, more detailed elaboration of that specific mode of action is needed. New macrocyclic derivatives, which could be more potent and less prone to escape bacterial resistance mechanisms, are also continuously evaluated. A novel class of antibiotic compounds—macrolones, which are derived from macrolides and comprise macrocyclic moiety, linker, and either free or esterified quinolone 3-carboxylic group, show excellent antibacterial potency towards key erythromycin-resistant Gram-positive and Gram-negative bacterial strains, with possibly decreased potential of bacterial resistance to macrolides.
      PubDate: 2016-09-01
      DOI: 10.3390/antibiotics5030029
      Issue No: Vol. 5, No. 3 (2016)
       
  • Antibiotics, Vol. 5, Pages 30: The Search for Herbal Antibiotics: An
           In-Silico Investigation of Antibacterial Phytochemicals

    • Authors: Mary Snow Setzer, Javad Sharifi-Rad, William Setzer
      First page: 30
      Abstract: 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). In addition, 35 known inhibitors were docked with their respective targets for comparison purposes. Prenylated polyphenolics showed the best docking profiles, while terpenoids had the poorest. The most susceptible protein targets were peptide deformylases and NAD+-dependent DNA ligases.
      PubDate: 2016-09-12
      DOI: 10.3390/antibiotics5030030
      Issue No: Vol. 5, No. 3 (2016)
       
  • Antibiotics, Vol. 5, Pages 31: Reconsultation and Antimicrobial Treatment
           of Urinary Tract Infection in Male and Female Patients in General Practice
           

    • Authors: Meera Tandan, Sinead Duane, Martin Cormican, Andrew Murphy, Akke Vellinga
      First page: 31
      Abstract: 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. An antimicrobial was prescribed significantly more often to females (77%) than males (63%). Nitrofurantoin was prescribed more often for females and less often for males (58% vs. 41%), while fluoroquinolones were more often prescribed for males (11% vs. 3%). Overall, reconsultation was 1.4 times higher in females, and if the antimicrobial prescribed was not the recommended first-line (nitrofurantoin), reconsultation after empirical prescribing was significantly higher. However, the reconsultation was similar for males and females if the antimicrobial prescribed was first-line. When a urine culture was obtained, a positive culture was the most important predictor of reconsultation (Odds ratio 1.8 (95% CI 1.3–2.5)). This suggests, when prescribing empirically, that male and female UTI patients should initially be treated with first-line antimicrobials (nitrofurantoin) with different durations (50–100 mg four times daily for three days in females and seven days for males). However, the consideration of a culture test before prescribing antimicrobials may improve outcomes.
      PubDate: 2016-09-15
      DOI: 10.3390/antibiotics5030031
      Issue No: Vol. 5, No. 3 (2016)
       
  • Antibiotics, Vol. 5, Pages 14: Structural Insights into Protein-Protein
           Interactions Involved in Bacterial Cell Wall Biogenesis

    • Authors: Federica Laddomada, Mayara Miyachiro, Andréa Dessen
      First page: 14
      Abstract: The bacterial cell wall is essential for survival, and proteins that participate in its biosynthesis have been the targets of antibiotic development efforts for decades. The biosynthesis of its main component, the peptidoglycan, involves the coordinated action of proteins that are involved in multi-member complexes which are essential for cell division (the “divisome”) and/or cell wall elongation (the “elongasome”), in the case of rod-shaped cells. Our knowledge regarding these interactions has greatly benefitted from the visualization of different aspects of the bacterial cell wall and its cytoskeleton by cryoelectron microscopy and tomography, as well as genetic and biochemical screens that have complemented information from high resolution crystal structures of protein complexes involved in divisome or elongasome formation. This review summarizes structural and functional aspects of protein complexes involved in the cytoplasmic and membrane-related steps of peptidoglycan biosynthesis, with a particular focus on protein-protein interactions whereby disruption could lead to the development of novel antibacterial strategies.
      PubDate: 2016-04-28
      DOI: 10.3390/antibiotics5020014
      Issue No: Vol. 5, No. 2 (2016)
       
  • Antibiotics, Vol. 5, Pages 15: Antibiotics and RNase P

    • Authors: Denis Drainas
      First page: 15
      Abstract: RNase P is an essential endonuclease in tRNA biogenesis, which generates the mature 5′-termini of tRNAs. Most forms of RNase P are ribonucleoproteins, i.e., they consist of an essential RNA and protein subunits. The catalytic function of ribonucleoprotein RNase P enzymes resides entirely in the RNA subunit. Its high structural and functional diversity among representatives of a vast variety of phylogenetic domains indicates that RNase P could serve as a molecular target and a useful screening system for the development of new drugs in the battle against bacterial drug resistance.
      PubDate: 2016-05-06
      DOI: 10.3390/antibiotics5020015
      Issue No: Vol. 5, No. 2 (2016)
       
  • Antibiotics, Vol. 5, Pages 16: Small Molecule Docking Supports Broad and
           Narrow Spectrum Potential for the Inhibition of the Novel Antibiotic
           Target Bacterial Pth1

    • Authors: Paul Ferguson, W. Holloway, William Setzer, Hana McFeeters, Robert McFeeters
      First page: 16
      Abstract: Peptidyl-tRNA hydrolases (Pths) play ancillary yet essential roles in protein biosynthesis by recycling peptidyl-tRNA. In E. coli, inhibition of bacterial Pth1 leads to accumulation of peptidyl-tRNA, depletion of aminoacyl-tRNA, and cell death. Eukaryotes have multiple Pths and Pth1 knock out was shown to have no effect on viability in yeast. Thereby, bacterial Pth1 is a promising target for novel antibiotic development. With the abundance of Pth1 structural data, molecular docking was used for virtual screening of existing, commercially available antibiotics to map potential interactions with Pth enzymes. Overall, 83 compounds were docked to eight different bacterial Pth1 and three different Pth2 structures. A variety of compounds demonstrated favorable docking with Pths. Whereas, some compounds interacted favorably with all Pths (potential broad spectrum inhibition), more selective interactions were observed for Pth1 or Pth2 and even specificity for individual Pth1s. While the correlation between computational docking and experimentation still remains unknown, these findings support broad spectrum inhibition, but also point to the possibility of narrow spectrum Pth1 inhibition. Also suggested is that Pth1 can be distinguished from Pth2 by small molecule inhibitors. The findings support continued development of Pth1 as an antibiotic target.
      PubDate: 2016-05-10
      DOI: 10.3390/antibiotics5020016
      Issue No: Vol. 5, No. 2 (2016)
       
  • Antibiotics, Vol. 5, Pages 17: The Oligopeptide Permease Opp Mediates
           Illicit Transport of the Bacterial P-site Decoding Inhibitor GE81112

    • Authors: Alessandro Maio, Letizia Brandi, Stefano Donadio, Claudio Gualerzi
      First page: 17
      Abstract: GE81112 is a tetrapeptide antibiotic that binds to the 30S ribosomal subunit and specifically inhibits P-site decoding of the mRNA initiation codon by the fMet-tRNA anticodon. GE81112 displays excellent microbiological activity against some Gram-positive and Gram-negative bacteria in both minimal and complete, chemically defined, broth, but is essentially inactive in complete complex media. This is due to the presence of peptides that compete with the antibiotic for the oligopeptide permease system (Opp) responsible for its illicit transport into the bacterial cells as demonstrated in the cases of Escherichia coli and Bacillus subtilis. Mutations that inactivate the Opp system and confer GE81112 resistance arise spontaneously with a frequency of ca. 1 × 10−6, similar to that of the mutants resistant to tri-l-ornithine, a known Opp substrate. On the contrary, cells expressing extrachromosomal copies of the opp genes are extremely sensitive to GE81112 in rich medium and GE81112-resistant mutations affecting the molecular target of the antibiotic were not detected upon examining >109 cells of this type. However, some mutations introduced in the 16S rRNA to confer kasugamycin resistance were found to reduce the sensitivity of the cells to GE81112.
      PubDate: 2016-05-24
      DOI: 10.3390/antibiotics5020017
      Issue No: Vol. 5, No. 2 (2016)
       
  • Antibiotics, Vol. 5, Pages 18: Ribosome Assembly as Antimicrobial Target

    • Authors: Rainer Nikolay, Sabine Schmidt, Renate Schlömer, Elke Deuerling, Knud Nierhaus
      First page: 18
      Abstract: Many antibiotics target the ribosome and interfere with its translation cycle. Since translation is the source of all cellular proteins including ribosomal proteins, protein synthesis and ribosome assembly are interdependent. As a consequence, the activity of translation inhibitors might indirectly cause defective ribosome assembly. Due to the difficulty in distinguishing between direct and indirect effects, and because assembly is probably a target in its own right, concepts are needed to identify small molecules that directly inhibit ribosome assembly. Here, we summarize the basic facts of ribosome targeting antibiotics. Furthermore, we present an in vivo screening strategy that focuses on ribosome assembly by a direct fluorescence based read-out that aims to identify and characterize small molecules acting as primary assembly inhibitors.
      PubDate: 2016-05-27
      DOI: 10.3390/antibiotics5020018
      Issue No: Vol. 5, No. 2 (2016)
       
  • Antibiotics, Vol. 5, Pages 19: Insights into the Stress Response Triggered
           by Kasugamycin in Escherichia coli

    • Authors: Christian Müller, Lena Sokol, Oliver Vesper, Martina Sauert, Isabella Moll
      First page: 19
      Abstract: The bacteriostatic aminoglycoside antibiotic kasugamycin inhibits protein synthesis at an initial step without affecting translation elongation. It binds to the mRNA track of the ribosome and prevents formation of the translation initiation complex on canonical mRNAs. In contrast, translation of leaderless mRNAs continues in the presence of the drug in vivo. Previously, we have shown that kasugamycin treatment in E. coli stimulates the formation of protein-depleted ribosomes that are selective for leaderless mRNAs. Here, we provide evidence that prolonged kasugamycin treatment leads to selective synthesis of specific proteins. Our studies indicate that leaderless and short-leadered mRNAs are generated by different molecular mechanisms including alternative transcription and RNA processing. Moreover, we provide evidence for ribosome heterogeneity in response to kasugamycin treatment by alteration of the modification status of the stalk proteins bL7/L12.
      PubDate: 2016-06-01
      DOI: 10.3390/antibiotics5020019
      Issue No: Vol. 5, No. 2 (2016)
       
  • Antibiotics, Vol. 5, Pages 20: Chloramphenicol Derivatives as
           Antibacterial and Anticancer Agents: Historic Problems and Current
           Solutions

    • Authors: George Dinos, Constantinos Athanassopoulos, Dionissia Missiri, Panagiota Giannopoulou, Ioannis Vlachogiannis, Georgios Papadopoulos, Dionissios Papaioannou, Dimitrios Kalpaxis
      First page: 20
      Abstract: Chloramphenicol (CAM) is the D-threo isomer of a small molecule, consisting of a p-nitrobenzene ring connected to a dichloroacetyl tail through a 2-amino-1,3-propanediol moiety. CAM displays a broad-spectrum bacteriostatic activity by specifically inhibiting the bacterial protein synthesis. In certain but important cases, it also exhibits bactericidal activity, namely against the three most common causes of meningitis, Haemophilus influenzae, Streptococcus pneumoniae and Neisseria meningitidis. Resistance to CAM has been frequently reported and ascribed to a variety of mechanisms. However, the most important concerns that limit its clinical utility relate to side effects such as neurotoxicity and hematologic disorders. In this review, we present previous and current efforts to synthesize CAM derivatives with improved pharmacological properties. In addition, we highlight potentially broader roles of these derivatives in investigating the plasticity of the ribosomal catalytic center, the main target of CAM.
      PubDate: 2016-06-03
      DOI: 10.3390/antibiotics5020020
      Issue No: Vol. 5, No. 2 (2016)
       
  • Antibiotics, Vol. 5, Pages 21: Choline Binding Proteins from Streptococcus
           pneumoniae: A Dual Role as Enzybiotics and Targets for the Design of New
           Antimicrobials

    • Authors: Beatriz Maestro, Jesús Sanz
      First page: 21
      Abstract: Streptococcus pneumoniae (pneumococcus) is an important pathogen responsible for acute invasive and non-invasive infections such as meningitis, sepsis and otitis media, being the major cause of community-acquired pneumonia. The fight against pneumococcus is currently hampered both by insufficient vaccine coverage and by rising antimicrobial resistances to traditional antibiotics, making necessary the research on novel targets. Choline binding proteins (CBPs) are a family of polypeptides found in pneumococcus and related species, as well as in some of their associated bacteriophages. They are characterized by a structural organization in two modules: a functional module (FM), and a choline-binding module (CBM) that anchors the protein to the choline residues present in the cell wall through non-covalent interactions. Pneumococcal CBPs include cell wall hydrolases, adhesins and other virulence factors, all playing relevant physiological roles for bacterial viability and virulence. Moreover, many pneumococcal phages also make use of hydrolytic CBPs to fulfill their infectivity cycle. Consequently, CBPs may play a dual role for the development of novel antipneumococcal drugs, both as targets for inhibitors of their binding to the cell wall and as active cell lytic agents (enzybiotics). In this article, we review the current state of knowledge about host- and phage-encoded pneumococcal CBPs, with a special focus on structural issues, together with their perspectives for effective anti-infectious treatments.
      PubDate: 2016-06-14
      DOI: 10.3390/antibiotics5020021
      Issue No: Vol. 5, No. 2 (2016)
       
  • Antibiotics, Vol. 5, Pages 23: Sub-Optimal Treatment of Bacterial Biofilms

    • Authors: Tianyan Song, Marylise Duperthuy, Sun Wai
      First page: 23
      Abstract: Bacterial biofilm is an emerging clinical problem recognized in the treatment of infectious diseases within the last two decades. The appearance of microbial biofilm in clinical settings is steadily increasing due to several reasons including the increased use of quality of life-improving artificial devices. In contrast to infections caused by planktonic bacteria that respond relatively well to standard antibiotic therapy, biofilm-forming bacteria tend to cause chronic infections whereby infections persist despite seemingly adequate antibiotic therapy. This review briefly describes the responses of biofilm matrix components and biofilm-associated bacteria towards sub-lethal concentrations of antimicrobial agents, which may include the generation of genetic and phenotypic variabilities. Clinical implications of bacterial biofilms in relation to antibiotic treatments are also discussed.
      PubDate: 2016-06-22
      DOI: 10.3390/antibiotics5020023
      Issue No: Vol. 5, No. 2 (2016)
       
  • Antibiotics, Vol. 5, Pages 3: Going beyond the Control of Quorum-Sensing
           to Combat Biofilm Infections

    • Authors: Wolf-Rainer Abraham
      First page: 3
      Abstract: Most bacteria attach to surfaces where they form a biofilm, cells embedded in a complex matrix of polymers. Cells in biofilms are much better protected against noxious agents than free-living cells. As a consequence it is very difficult to control pathogens with antibiotics in biofilm infections and novel targets are urgently needed. One approach aims at the communication between cells to form and to maintain a biofilm, a process called quorum-sensing. Water soluble small-sized molecules mediate this process and a number of antagonists of these compounds have been found. In this review natural compounds and synthetic drugs which do not interfere with the classical quorum-sensing compounds are discussed. For some of these compounds the targets are still not known, but others interfere with the formation of exopolysaccharides, virulence factors, or cell wall synthesis or they start an internal program of biofilm dispersal. Some of their targets are more conserved among pathogens than the receptors for quorum sensing autoinducers mediating quorum-sensing, enabling a broader application of the drug. The broad spectrum of mechanisms, the diversity of bioactive compounds, their activity against several targets, and the conservation of some targets among bacterial pathogens are promising aspects for several clinical applications of this type of biofilm-controlling compound in the future.
      PubDate: 2016-01-09
      DOI: 10.3390/antibiotics5010003
      Issue No: Vol. 5, No. 1 (2016)
       
  • Antibiotics, Vol. 5, Pages 4: Microarray Evaluation of Antimicrobial
           Resistance and Virulence of Escherichia coli Isolates from Portuguese
           Poultry

    • Authors: Nuno Mendonça, Rui Figueiredo, Catarina Mendes, Roderick Card, Muna Anjum, Gabriela da Silva
      First page: 4
      Abstract: The presence of antimicrobial resistance and virulence factors of 174 Escherichia coli strains isolated from healthy Portuguese Gallus gallus was evaluated. Resistance profiles were determined against 33 antimicrobials by microbroth dilution. Resistance was prevalent for tetracycline (70%) and ampicillin (63%). Extended-spectrum beta-lactamase (ESBL) phenotype was observed in 18% of the isolates. Multidrug resistance was found in 56% of isolates. A subset of 74 isolates were screened by DNA microarrays for the carriage of 88 antibiotic resistance genes and 62 virulence genes. Overall, 37 different resistance genes were detected. The most common were tet(A) (72%), blaTEM (68%), and sul1 (47%), while 21% isolates harbored an ESBL gene (blaCTX-M group 1, group 2, or group 9). Of these, 96% carried the increased serum survival (iss) virulence gene, while 89% presented the enterobactin siderophore receptor protein (iroN), 70% the temperature-sensitive hemagglutinin (tsh), and 68% the long polar fimbriae (lpfA) virulence genes associated with extraintestinal pathogenic E. coli. In conclusion, prevalence of antibiotic resistant E. coli from the microbiota of Portuguese chickens was high, including to extended spectrum cephalosporins. The majority of isolates seems to have the potential to trigger extraintestinal human infection due to the presence of some virulence genes. However, the absence of genes specific for enteropathogenic E. coli reduces the risk for human intestinal infection.
      PubDate: 2016-01-13
      DOI: 10.3390/antibiotics5010004
      Issue No: Vol. 5, No. 1 (2016)
       
  • Antibiotics, Vol. 5, Pages 5: A Review of Quality Measures for Assessing
           the Impact of Antimicrobial Stewardship Programs in Hospitals

    • Authors: Mary Akpan, Raheelah Ahmad, Nada Shebl, Diane Ashiru-Oredope
      First page: 5
      Abstract: The growing problem of antimicrobial resistance (AMR) has led to calls for antimicrobial stewardship programs (ASP) to control antibiotic use in healthcare settings. Key strategies include prospective audit with feedback and intervention, and formulary restriction and preauthorization. Education, guidelines, clinical pathways, de-escalation, and intravenous to oral conversion are also part of some programs. Impact and quality of ASP can be assessed using process or outcome measures. Outcome measures are categorized as microbiological, patient or financial outcomes. The objective of this review was to provide an overview of quality measures for assessing ASP and the reported impact of ASP in peer-reviewed studies, focusing particularly on patient outcomes. A literature search of papers published in English between 1990 and June 2015 was conducted in five databases using a combination of search terms. Primary studies of any design were included. A total of 63 studies were included in this review. Four studies defined quality metrics for evaluating ASP. Twenty-one studies assessed the impact of ASP on antimicrobial utilization and cost, 25 studies evaluated impact on resistance patterns and/or rate of Clostridium difficile infection (CDI). Thirteen studies assessed impact on patient outcomes including mortality, length of stay (LOS) and readmission rates. Six of these 13 studies reported non-significant difference in mortality between pre- and post-ASP intervention, and five reported reductions in mortality rate. On LOS, six studies reported shorter LOS post intervention; a significant reduction was reported in one of these studies. Of note, this latter study reported significantly (p < 0.001) higher unplanned readmissions related to infections post-ASP. Patient outcomes need to be a key component of ASP evaluation. The choice of metrics is influenced by data and resource availability. Controlling for confounders must be considered in the design of evaluation studies to adequately capture the impact of ASP and it is important for unintended consequences to be considered. This review provides a starting point toward compiling standard outcome metrics for assessing ASP.
      PubDate: 2016-01-13
      DOI: 10.3390/antibiotics5010005
      Issue No: Vol. 5, No. 1 (2016)
       
  • Antibiotics, Vol. 5, Pages 6: Controversies in Antimicrobial Stewardship:
           Focus on New Rapid Diagnostic Technologies and Antimicrobials

    • Authors: Eric Wenzler, Jordan Wong, Debra Goff, Christopher Jankowski, Karri Bauer
      First page: 6
      Abstract: Antimicrobial stewardship programs (ASPs) are challenged with ensuring appropriate antimicrobial use while minimizing expenditures. ASPs have consistently demonstrated improved patient outcomes and significant cost reductions but are continually required to justify the costs of their existence and interventions due to the silo mentality often adopted by hospital administrators. As new technologies and antimicrobials emerge, ASPs are in a constant tug-of-war between providing optimal clinical outcomes and ensuring cost containment. Additionally, robust data on cost-effectiveness of new rapid diagnostic technologies and antimicrobials with subsequent ASP interventions to provide justification are lacking. As the implementation of an ASP will soon be mandatory for acute care hospitals in the United States, ASPs must find ways to justify novel interventions to align themselves with healthcare administrators. This review provides a framework for the justification of implementing a rapid diagnostic test or adding a new antimicrobial to formulary with ASP intervention, reviews approaches to demonstrating cost-effectiveness, and proposes methods for which ASPs may reduce healthcare expenditures via alternative tactics.
      PubDate: 2016-01-14
      DOI: 10.3390/antibiotics5010006
      Issue No: Vol. 5, No. 1 (2016)
       
  • Antibiotics, Vol. 5, Pages 7: Evaluation of a Computerized Decision
           Support Intervention to Decrease Use of Anti-Pseudomonal Carbapenems in
           Penicillin Allergic Patients

    • Authors: Christina Caplinger, Garret Smith, Richard Remington, Karl Madaras-Kelly
      First page: 7
      Abstract: Allergies to β-lactam antibiotics are commonly documented in hospitalized patients; however, true allergy is uncommon. Cross-reactivity rates for advanced generation cephalosporins and carbapenems are low; particularly for patients without a history of symptoms consistent with type 1 hypersensitivity. We observed that providers preferentially prescribed antipseudomonal carbapenems (APC) over advanced generation cephalosporins for patients with β-lactam allergy history, including those with low risk for antimicrobial-resistant infections. Information was inserted into the computerized decision support system (CDSS) to aid clinicians in assessing β-lactam cross-reactivity risk and selecting appropriate therapy. A retrospective evaluation was conducted in a small hospital to assess the impact of the CDSS changes in APC prescribing. Inpatients (n = 68) who received at least one APC dose during hospitalization over a 13 month pre-intervention period were compared to inpatients who received an APC during the 15 month post-intervention period (n = 59) for documented APC indications and β-lactam allergy history. APC initiations were measured and corrected per 1000 patient-days; interrupted time-series analysis was performed to assess changes in use before and after implementation. Aggregate monthly APC initiations decreased from 7.01 to 6.14 per 1000 patient-days after the implementation (p = 0.03). Post-intervention APC initiations for patients with low-risk β-lactam histories decreased from 92% to 83% (p = 0.17). No adverse events were observed in patients with low-risk β-lactam histories. The intervention was associated with a reduction in APC initiations.
      PubDate: 2016-01-15
      DOI: 10.3390/antibiotics5010007
      Issue No: Vol. 5, No. 1 (2016)
       
  • Antibiotics, Vol. 5, Pages 8: Antimicrobial Stewardship for a Geriatric
           Behavioral Health Population

    • Authors: Kristen Ellis, Georgina Rubal-Peace, Victoria Chang, Eva Liang, Nicolas Wong, Stephanie Campbell
      First page: 8
      Abstract: Antimicrobial resistance is a growing public health concern. Antimicrobial stewardship and multi-disciplinary intervention can prevent inappropriate antimicrobial use and improve patient care. Special populations, especially older adults and patients with mental health disorders, can be particularly in need of such intervention. The purpose of this project was to assess the impact of pharmacist intervention on appropriateness of antimicrobial prescribing on a geriatric psychiatric unit (GPU). Patients ≥18 years old prescribed oral antibiotics during GPU admission were included. Antimicrobial appropriateness was assessed pre- and post-pharmacist intervention. During the six-month pre- and post-intervention phase, 63 and 70 patients prescribed antibiotics were identified, respectively. Subjects in the post-intervention group had significantly less inappropriate doses for indication compared to the pre-intervention group (10.6% vs. 23.9%, p = 0.02), and significantly less antibiotics prescribed for an inappropriate duration (15.8% vs. 32.4%, p < 0.01). There were no significant differences for use of appropriate drug for indication or appropriate dose for renal function between groups. Significantly more patients in the post intervention group had medications prescribed with appropriate dose, duration, and indication (51% vs. 66%, p = 0.04). Pharmacist intervention was associated with decreased rates of inappropriate antimicrobial prescribing on a geriatric psychiatric unit.
      PubDate: 2016-01-19
      DOI: 10.3390/antibiotics5010008
      Issue No: Vol. 5, No. 1 (2016)
       
  • Antibiotics, Vol. 5, Pages 9: Acknowledgement to Reviewers of Antibiotics
           in 2015

    • Authors: Antibiotics Editorial Office
      First page: 9
      Abstract: The editors of Antibiotics would like to express their sincere gratitude to the following reviewers for assessing manuscripts in 2015. [...]
      PubDate: 2016-01-27
      DOI: 10.3390/antibiotics5010009
      Issue No: Vol. 5, No. 1 (2016)
       
  • Antibiotics, Vol. 5, Pages 10: Identification of a Fragment-Based Scaffold
           that Inhibits the Glycosyltransferase WaaG from Escherichia coli

    • Authors: Claudio Muheim, Amin Bakali, Olof Engström, Åke Wieslander, Daniel Daley, Göran Widmalm
      First page: 10
      Abstract: WaaG is a glycosyltransferase that is involved in the biosynthesis of lipopolysaccharide in Gram-negative bacteria. Inhibitors of WaaG are highly sought after as they could be used to inhibit the biosynthesis of the core region of lipopolysaccharide, which would improve the uptake of antibiotics. Herein, we establish an activity assay for WaaG using 14C-labeled UDP-glucose and LPS purified from a ∆waaG strain of Escherichia coli. We noted that addition of the lipids phosphatidylglycerol (PG) and cardiolipin (CL), as well as the detergent 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate (CHAPS) increased activity. We then use the assay to determine if three molecular scaffolds, which bind to WaaG, could inhibit its activity in vitro. We show that 4-(2-amino-1,3-thiazol-4-yl)phenol inhibits WaaG (IC50 1.0 mM), but that the other scaffolds do not. This study represents an important step towards an inhibitor of WaaG by fragment-based lead discovery.
      PubDate: 2016-01-28
      DOI: 10.3390/antibiotics5010010
      Issue No: Vol. 5, No. 1 (2016)
       
  • Antibiotics, Vol. 5, Pages 11: Treatment Modalities and Antimicrobial
           Stewardship Initiatives in the Management of Intra-Abdominal Infections

    • Authors: Charles Hoffmann, Matthew Zak, Lisa Avery, Jack Brown
      First page: 11
      Abstract: Antimicrobial stewardship programs (ASPs) focus on improving the utilization of broad spectrum antibiotics to decrease the incidence of multidrug-resistant Gram positive and Gram negative pathogens. Hospital admission for both medical and surgical intra-abdominal infections (IAIs) commonly results in the empiric use of broad spectrum antibiotics such as fluoroquinolones, beta-lactam beta-lactamase inhibitors, and carbapenems that can select for resistant organisms. This review will discuss the management of uncomplicated and complicated IAIs as well as highlight stewardship initiatives focusing on the proper use of broad spectrum antibiotics.
      PubDate: 2016-02-15
      DOI: 10.3390/antibiotics5010011
      Issue No: Vol. 5, No. 1 (2016)
       
  • Antibiotics, Vol. 5, Pages 12: Glycosyltransferases and
           Transpeptidases/Penicillin-Binding Proteins: Valuable Targets for New
           Antibacterials

    • Authors: Eric Sauvage, Mohammed Terrak
      First page: 12
      Abstract: Peptidoglycan (PG) is an essential macromolecular sacculus surrounding most bacteria. It is assembled by the glycosyltransferase (GT) and transpeptidase (TP) activities of multimodular penicillin-binding proteins (PBPs) within multiprotein complex machineries. Both activities are essential for the synthesis of a functional stress-bearing PG shell. Although good progress has been made in terms of the functional and structural understanding of GT, finding a clinically useful antibiotic against them has been challenging until now. In contrast, the TP/PBP module has been successfully targeted by β-lactam derivatives, but the extensive use of these antibiotics has selected resistant bacterial strains that employ a wide variety of mechanisms to escape the lethal action of these antibiotics. In addition to traditional β-lactams, other classes of molecules (non-β-lactams) that inhibit PBPs are now emerging, opening new perspectives for tackling the resistance problem while taking advantage of these valuable targets, for which a wealth of structural and functional knowledge has been accumulated. The overall evidence shows that PBPs are part of multiprotein machineries whose activities are modulated by cofactors. Perturbation of these systems could lead to lethal effects. Developing screening strategies to take advantage of these mechanisms could lead to new inhibitors of PG assembly. In this paper, we present a general background on the GTs and TPs/PBPs, a survey of recent issues of bacterial resistance and a review of recent works describing new inhibitors of these enzymes.
      PubDate: 2016-02-17
      DOI: 10.3390/antibiotics5010012
      Issue No: Vol. 5, No. 1 (2016)
       
  • Antibiotics, Vol. 5, Pages 13: A Multi-Faceted Approach of One Teaching
           Hospital NHS Trust during the Clostridium difficile Epidemic—Antibiotic
           Management and Beyond

    • Authors: Helena White, Martin Wiselka, David Bell
      First page: 13
      Abstract: The incidence of Clostridium difficile infection (CDI) in the UK rose dramatically during the early years of this century, in part associated with the emergence of the hyper-virulent ribotype 027 strain. The University Hospitals of Leicester (UHL), a 2000-bed acute UK NHS Trust, implemented a number of interventions, which led to an 80% reduction in new cases over a twelve month period. Changes were introduced as a result of collaboration between the Infection Prevention team, the departments of Microbiology and Infectious Diseases, and with the support of the Trust Executive. These strategies are described in detail and included; implementation of antimicrobial stewardship, specific hygiene and cleaning measures, the introduction of a care pathway form for all infected patients, the opening of an isolation ward for patients with CDI, strengthened organisation and clinical management, and rigorous attention to education within the Trust. The implementations described are of continued relevance in the face of new infection challenges, such as the increasing incidence of multi-drug resistant organisms.
      PubDate: 2016-02-26
      DOI: 10.3390/antibiotics5010013
      Issue No: Vol. 5, No. 1 (2016)
       
 
 
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