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Artificial Organs     Hybrid Journal   (Followers: 1)
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Asia Pacific Journal of Clinical Trials : Nervous System Diseases     Open Access  
Asian Bioethics Review     Full-text available via subscription   (Followers: 2)
Asian Journal of Cell Biology     Open Access   (Followers: 6)
Asian Journal of Health     Open Access   (Followers: 3)
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Asian Journal of Medical Sciences     Open Access   (Followers: 1)
Asian Journal of Scientific Research     Open Access   (Followers: 2)
Asian Journal of Transfusion Science     Open Access   (Followers: 2)
Asian Medicine     Hybrid Journal   (Followers: 4)
ASPIRATOR : Journal of Vector-borne Disease Studies     Open Access  
Astrocyte     Open Access  
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Atención Primaria     Open Access   (Followers: 1)
Audiology - Communication Research     Open Access   (Followers: 8)
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Australian Coeliac     Full-text available via subscription   (Followers: 2)
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Avicenna     Open Access   (Followers: 2)
Avicenna Journal of Medicine     Open Access   (Followers: 1)
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Journal Cover Antibiotics
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  This is an Open Access Journal Open Access journal
   ISSN (Print) 2079-6382
   Published by MDPI Homepage  [156 journals]
  • Antibiotics, Vol. 6, Pages 20: Choline Kinase, A Novel Drug Target for the
           Inhibition of Streptococcus pneumoniae

    • Authors: Tahl Zimmerman, Salam Ibrahim
      First page: 20
      Abstract: Gram-positive pathogens, such as Streptococcus pneumoniae, can have deleterious effects on both human and animal health. Antibiotics and antimicrobials have been developed to treat infections caused by such pathogens and to prevent food contamination. However, these strategies have been increasingly thwarted by the emergence of resistant bacteria strains. Thus, new methods for controlling Gram-positive pathogen growth need to be continuously developed. Choline analogs, such as Hemicholinium-3 (HC-3), have been shown to be useful in blocking cell division in eukaryotic cells through the inhibition of choline kinase, an enzyme which catalyzes the production of phosphocholine from choline and ATP. In some Gram-positive pathogens, choline kinase is an important enzyme in the production of the cell wall element, lipoteichoic acid. However, it is not known if inhibiting this enzyme has any effect on cell division in Gram-positive bacteria. Using the R6 strain as a model, we tested the ability of HC-3 to block the activity of choline kinase in S. pneumoniae and inhibit cell growth. Mass-spectrometry measurements of crude extracts revealed that HC-3 blocked choline kinase activity. Turbidity measurements and population counts showed that HC-3 inhibited cell growth. Competition assays with choline suggested that HC-3 also blocked choline transporters. Western blots showed that lipoteichoic acid production was blocked in the presence of HC-3, and autolytic assays showed that this decrease in lipoteichoic acids caused cells to be more resistant to autolysis. Scanning electron microscopy revealed that HC-3 distorted the cell wall. This study thus establishes choline kinase as a novel drug target for S. pneumoniae.
      Citation: Antibiotics
      PubDate: 2017-09-25
      DOI: 10.3390/antibiotics6040020
      Issue No: Vol. 6, No. 4 (2017)
  • Antibiotics, Vol. 6, Pages 21: Probiotics for the Prevention of
           Antibiotic-Associated Diarrhea in Outpatients—A Systematic Review and

    • Authors: Sara Blaabjerg, Daniel Artzi, Rune Aabenhus
      First page: 21
      Abstract: A common adverse effect of antibiotic use is diarrhea. Probiotics are living microorganisms, which, upon oral ingestion, may prevent antibiotic-associated diarrhea (AAD) by the normalization of an unbalanced gastrointestinal flora. The objective of this systematic review was to assess the benefits and harms of probiotics used for the prevention of AAD in an outpatient setting. A search of the PubMed database was conducted and yielded a total of 17 RCTs with 3631 participants to be included in the review. A meta-analysis was conducted for the primary outcome: the incidence of AAD. The pooled results found that AAD was present in 8.0% of the probiotic group compared to 17.7% in the control group (RR 0.49, 95% CI 0.36 to 0.66; I2 = 58%), and the species-specific results were similar regarding the probiotic strains L. rhamnosus GG and S. boulardii. However, the overall quality of the included studies was moderate. A meta-analysis of the ten trials reporting adverse events demonstrated no statistically significant differences in the incidence of adverse events between the intervention and control group (RD 0.00, 95% CI −0.02 to 0.02, 2.363 participants). The results suggests that probiotic use may be beneficial in the prevention of AAD among outpatients. Furthermore, the use of probiotics appears safe.
      Citation: Antibiotics
      PubDate: 2017-10-12
      DOI: 10.3390/antibiotics6040021
      Issue No: Vol. 6, No. 4 (2017)
  • Antibiotics, Vol. 6, Pages 22: Antibiotic Prescribing for Uncomplicated
           Acute Bronchitis Is Highest in Younger Adults

    • Authors: Larissa Grigoryan, Roger Zoorob, Jesal Shah, Haijun Wang, Monisha Arya, Barbara W. Trautner
      First page: 22
      Abstract: Reducing inappropriate antibiotic prescribing is currently a global health priority. Current guidelines recommend against antibiotic treatment for acute uncomplicated bronchitis. We studied antibiotic prescribing patterns for uncomplicated acute bronchitis and identified predictors of inappropriate antibiotic prescribing. We used the Epic Clarity database (electronic medical record system) to identify all adult patients with acute bronchitis in family medicine clinics from 2011 to 2016. We excluded factors that could justify antibiotic use, such as suspected pneumonia, COPD or immunocompromising conditions. Of the 3616 visits for uncomplicated acute bronchitis, 2244 (62.1%) resulted in antibiotic treatment. The rates of antibiotic prescribing were similar across the years, p value for trend = 0.07. Antibiotics were most frequently prescribed in the age group of 18–39 years (66.9%), followed by the age group of 65 years and above (59.0%), and the age group of 40–64 years (58.7%), p value < 0.001. Macrolides were significantly more likely to be prescribed for younger adults, while fluoroquinolones were more likely to be prescribed for patients 65 years or older. Duration of antibiotic use was significantly longer in older adults. Sex and race were not associated with antibiotic prescribing. Our findings highlight the urgent need to reduce inappropriate antibiotic use for uncomplicated acute bronchitis, particularly in younger adults.
      Citation: Antibiotics
      PubDate: 2017-10-27
      DOI: 10.3390/antibiotics6040022
      Issue No: Vol. 6, No. 4 (2017)
  • Antibiotics, Vol. 6, Pages 23: Exploring Patient Awareness and Perceptions
           of the Appropriate Use of Antibiotics: A Mixed-Methods Study

    • Authors: Marion Davis, Tsai-Ling Liu, Yhenneko Taylor, Lisa Davidson, Monica Schmid, Traci Yates, Janice Scotton, Melanie Spencer
      First page: 23
      Abstract: In the outpatient setting, estimates suggest that 30% of the antibiotics prescribed are unnecessary. This study explores patient knowledge and awareness of appropriate use of antibiotics and expectations regarding how antibiotics are used for their treatment in outpatient settings. A survey was administered to a convenience sample of patients, parents, and caregivers (n = 190) at seven primary care clinics and two urgent care locations. Fisher’s exact tests compared results by patient characteristics. Although 89% of patients correctly believed that antibiotics work well for treating infections from bacteria, 53% incorrectly believed that antibiotics work well for treating viral infections. Patients who incorrectly believed that antibiotics work well for treating viral infections were more than twice as likely to expect a provider to give them an antibiotic when they have a cough or common cold. Patients who completed the survey also participated in semi-structured interviews (n = 4), which were analyzed using thematic analysis. Patients reported experiencing confusion about which illnesses may be treated by antibiotics and unclear communication from clinicians about the appropriate use of antibiotics. Development of easy to understand patient educational materials can help address patients’ incorrect perceptions of appropriate antibiotic use and facilitate patient-provider communication.
      Citation: Antibiotics
      PubDate: 2017-10-31
      DOI: 10.3390/antibiotics6040023
      Issue No: Vol. 6, No. 4 (2017)
  • Antibiotics, Vol. 6, Pages 24: Fosfomycin: Pharmacological, Clinical and
           Future Perspectives

    • Authors: Anneke Corinne Dijkmans, Natalia Veneranda Ortiz Zacarías, Jacobus Burggraaf, Johan Willem Mouton, Erik Wilms, Cees van Nieuwkoop, Daniel Johannes Touw, Jasper Stevens, Ingrid Maria Catharina Kamerling
      First page: 24
      Abstract: Fosfomycin is a bactericidal, low-molecular weight, broad-spectrum antibiotic, with putative activity against several bacteria, including multidrug-resistant Gram-negative bacteria, by irreversibly inhibiting an early stage in cell wall synthesis. Evidence suggests that fosfomycin has a synergistic effect when used in combination with other antimicrobial agents that act via a different mechanism of action, thereby allowing for reduced dosages and lower toxicity. Fosfomycin does not bind to plasma proteins and is cleared via the kidneys. Due to its extensive tissue penetration, fosfomycin may be indicated for infections of the CNS, soft tissues, bone, lungs, and abscesses. The oral bioavailability of fosfomycin tromethamine is <50%; therefore, oral administration of fosfomycin tromethamine is approved only as a 3-gram one-time dose for treating urinary tract infections. However, based on published PK parameters, PK/PD simulations have been performed for several multiple-dose regimens, which might lead to the future use of fosfomycin for treating complicated infections with multidrug-resistant bacteria. Because essential pharmacological information and knowledge regarding mechanisms of resistance are currently limited and/or controversial, further studies are urgently needed, and fosfomycin monotherapy should be avoided.
      Citation: Antibiotics
      PubDate: 2017-10-31
      DOI: 10.3390/antibiotics6040024
      Issue No: Vol. 6, No. 4 (2017)
  • Antibiotics, Vol. 6, Pages 25: Identification and Antimicrobial
           Susceptibility Testing of Anaerobic Bacteria: Rubik’s Cube of Clinical

    • Authors: Márió Gajdács, Gabriella Spengler, Edit Urbán
      First page: 25
      Abstract: Anaerobic bacteria have pivotal roles in the microbiota of humans and they are significant infectious agents involved in many pathological processes, both in immunocompetent and immunocompromised individuals. Their isolation, cultivation and correct identification differs significantly from the workup of aerobic species, although the use of new technologies (e.g., matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, whole genome sequencing) changed anaerobic diagnostics dramatically. In the past, antimicrobial susceptibility of these microorganisms showed predictable patterns and empirical therapy could be safely administered but recently a steady and clear increase in the resistance for several important drugs (β-lactams, clindamycin) has been observed worldwide. For this reason, antimicrobial susceptibility testing of anaerobic isolates for surveillance purposes or otherwise is of paramount importance but the availability of these testing methods is usually limited. In this present review, our aim was to give an overview of the methods currently available for the identification (using phenotypic characteristics, biochemical testing, gas-liquid chromatography, MALDI-TOF MS and WGS) and antimicrobial susceptibility testing (agar dilution, broth microdilution, disk diffusion, gradient tests, automated systems, phenotypic and molecular resistance detection techniques) of anaerobes, when should these methods be used and what are the recent developments in resistance patterns of anaerobic bacteria.
      Citation: Antibiotics
      PubDate: 2017-11-07
      DOI: 10.3390/antibiotics6040025
      Issue No: Vol. 6, No. 4 (2017)
  • Antibiotics, Vol. 6, Pages 26: Ubiquitous Nature of Fluoroquinolones: The
           Oscillation between Antibacterial and Anticancer Activities

    • Authors: Temilolu Idowu, Frank Schweizer
      First page: 26
      Abstract: Fluoroquinolones are synthetic antibacterial agents that stabilize the ternary complex of prokaryotic topoisomerase II enzymes (gyrase and Topo IV), leading to extensive DNA fragmentation and bacteria death. Despite the similar structural folds within the critical regions of prokaryotic and eukaryotic topoisomerases, clinically relevant fluoroquinolones display a remarkable selectivity for prokaryotic topoisomerase II, with excellent safety records in humans. Typical agents that target human topoisomerases (such as etoposide, doxorubicin and mitoxantrone) are associated with significant toxicities and secondary malignancies, whereas clinically relevant fluoroquinolones are not known to exhibit such propensities. Although many fluoroquinolones have been shown to display topoisomerase-independent antiproliferative effects against various human cancer cells, those that are significantly active against eukaryotic topoisomerase show the same DNA damaging properties as other topoisomerase poisons. Empirical models also show that fluoroquinolones mediate some unique immunomodulatory activities of suppressing pro-inflammatory cytokines and super-inducing interleukin-2. This article reviews the extended roles of fluoroquinolones and their prospects as lead for the unmet needs of “small and safe” multimodal-targeting drug scaffolds.
      Citation: Antibiotics
      PubDate: 2017-11-07
      DOI: 10.3390/antibiotics6040026
      Issue No: Vol. 6, No. 4 (2017)
  • Antibiotics, Vol. 6, Pages 27: Bacteriophages in the Dairy Environment:
           From Enemies to Allies

    • Authors: Lucía Fernández, Susana Escobedo, Diana Gutiérrez, Silvia Portilla, Beatriz Martínez, Pilar García, Ana Rodríguez
      First page: 27
      Abstract: The history of dairy farming goes back thousands of years, evolving from a traditional small-scale production to the industrialized manufacturing of fermented dairy products. Commercialization of milk and its derived products has been very important not only as a source of nourishment but also as an economic resource. However, the dairy industry has encountered several problems that have to be overcome to ensure the quality and safety of the final products, as well as to avoid economic losses. Within this context, it is interesting to highlight the role played by bacteriophages, or phages, viruses that infect bacteria. Indeed, bacteriophages were originally regarded as a nuisance, being responsible for fermentation failure and economic losses when infecting lactic acid bacteria, but are now considered promising antimicrobials to fight milk-borne pathogens without contributing to the increase in antibiotic resistance.
      Citation: Antibiotics
      PubDate: 2017-11-08
      DOI: 10.3390/antibiotics6040027
      Issue No: Vol. 6, No. 4 (2017)
  • Antibiotics, Vol. 6, Pages 28: Interplay between Colistin Resistance,
           Virulence and Fitness in Acinetobacter baumannii

    • Authors: Gabriela Da Silva, Sara Domingues
      First page: 28
      Abstract: Acinetobacter baumannii is an important opportunistic nosocomial pathogen often resistant to multiple antibiotics classes. Colistin, an “old” antibiotic, is now considered a last-line treatment option for extremely resistant isolates. In the meantime, resistance to colistin has been reported in clinical A. baumannii strains. Colistin is a cationic peptide that disrupts the outer membrane (OM) of Gram-negative bacteria. Colistin resistance is primarily due to post-translational modification or loss of the lipopolysaccharide (LPS) molecules inserted into the outer leaflet of the OM. LPS modification prevents the binding of polymyxin to the bacterial surface and may lead to alterations in bacterial virulence. Antimicrobial pressure drives the evolution of antimicrobial resistance and resistance is often associated with a reduced bacterial fitness. Therefore, the alterations in LPS may induce changes in the fitness of A. baumannii. However, compensatory mutations in clinical A. baumannii may ameliorate the cost of resistance and may play an important role in the dissemination of colistin-resistant A. baumannii isolates. The focus of this review is to summarize the colistin resistance mechanisms, and understand their impact on the fitness and virulence of bacteria and on the dissemination of colistin-resistant A. baumannii strains.
      Citation: Antibiotics
      PubDate: 2017-11-21
      DOI: 10.3390/antibiotics6040028
      Issue No: Vol. 6, No. 4 (2017)
  • Antibiotics, Vol. 6, Pages 29: Activity In Vitro of Clotrimazole against
           Canine Methicillin-Resistant and Susceptible Staphylococcus

    • Authors: Sian-Marie Frosini, Ross Bond
      First page: 29
      Abstract: Emergence of multidrug-resistance in Staphylococcus pseudintermedius (SP) has increased interest in topical therapy as an alternative to systemic antibiotics in canine pyoderma. The antifungal imidazole, clotrimazole, is contained in numerous licensed canine ear preparations. Its in vitro activity against SP has not been evaluated, although previous studies have shown that the related imidazole, miconazole, has significant anti-staphylococcal efficacy. We therefore determined minimum inhibitory concentrations (MICs) of clotrimazole amongst 50 SP isolates (25 methicillin-resistant [MR]SP and susceptible [MS]SP) collected from dogs in Germany during 2010–2011 using an agar dilution method (CLSI VET01-A4). MICs amongst MRSP and MSSP were comparable (MIC50 and MIC90 = 1mg/L for both groups, p = 0.317); overall, 49 isolates had MIC = 1 mg/L and one had MIC = 0.5 mg/L. The relatively low MICs obtained in this study are likely to be exceeded by topical therapy and thus further clinical evaluation of clotrimazole use in canine superficial pyoderma and otitis externa caused by MRSP and MSSP is now warranted.
      Citation: Antibiotics
      PubDate: 2017-11-22
      DOI: 10.3390/antibiotics6040029
      Issue No: Vol. 6, No. 4 (2017)
  • Antibiotics, Vol. 6, Pages 30: Establishing Genotype-to-Phenotype
           Relationships in Bacteria Causing Hospital-Acquired Pneumonia: A Prelude
           to the Application of Clinical Metagenomics

    • Authors: Etienne Ruppé, Abdessalam Cherkaoui, Vladimir Lazarevic, Stéphane Emonet, Jacques Schrenzel
      First page: 30
      Abstract: Clinical metagenomics (CMg), referred to as the application of next-generation sequencing (NGS) to clinical samples, is a promising tool for the diagnosis of hospital-acquired pneumonia (HAP). Indeed, CMg allows identifying pathogens and antibiotic resistance genes (ARGs), thereby providing the information required for the optimization of the antibiotic regimen. Hence, provided that CMg would be faster than conventional culture, the probabilistic regimen used in HAP could be tailored faster, which should lead to an expected decrease of mortality and morbidity. While the inference of the antibiotic susceptibility testing from metagenomic or even genomic data is challenging, a limited number of antibiotics are used in the probabilistic regimen of HAP (namely beta-lactams, aminoglycosides, fluoroquinolones, glycopeptides and oxazolidinones). Accordingly, based on the perspective of applying CMg to the early diagnostic of HAP, we aimed at reviewing the performances of whole genomic sequencing (WGS) of the main HAP-causing bacteria (Enterobacteriaceae, Pseudomonas aeruginosa, Acinetobacter baumannii, Stenotrophomonas maltophilia and Staphylococcus aureus) for the prediction of susceptibility to the antibiotic families advocated in the probabilistic regimen of HAP.
      Citation: Antibiotics
      PubDate: 2017-11-29
      DOI: 10.3390/antibiotics6040030
      Issue No: Vol. 6, No. 4 (2017)
  • Antibiotics, Vol. 6, Pages 31: Antimicrobial Activity of Bee Venom and
           Melittin against Borrelia burgdorferi

    • Authors: Kayla Socarras, Priyanka Theophilus, Jason Torres, Khusali Gupta, Eva Sapi
      First page: 31
      Abstract: Lyme disease is a tick-borne, multi-systemic disease, caused by the bacterium Borrelia burgdorferi. Though antibiotics are used as a primary treatment, relapse often occurs after the discontinuation of antimicrobial agents. The reason for relapse remains unknown, however previous studies suggest the possible presence of antibiotic resistant Borrelia round bodies, persisters and attached biofilm forms. Thus, there is an urgent need to find antimicrobial agents suitable to eliminate all known forms of B. burgdorferi. In this study, natural antimicrobial agents such as Apis mellifera venom and a known component, melittin, were tested using SYBR Green I/PI, direct cell counting, biofilm assays combined with LIVE/DEAD and atomic force microscopy methods. The obtained results were compared to standalone and combinations of antibiotics such as Doxycycline, Cefoperazone, Daptomycin, which were recently found to be effective against Borrelia persisters. Our findings showed that both bee venom and melittin had significant effects on all the tested forms of B. burgdorferi. In contrast, the control antibiotics when used individually or even in combinations had limited effects on the attached biofilm form. These findings strongly suggest that whole bee venom or melittin could be effective antimicrobial agents for B. burgdorferi; however, further research is necessary to evaluate their effectiveness in vivo, as well as their safe and effective delivery method for their therapeutic use.
      Citation: Antibiotics
      PubDate: 2017-11-29
      DOI: 10.3390/antibiotics6040031
      Issue No: Vol. 6, No. 4 (2017)
  • Antibiotics, Vol. 6, Pages 13: Antibacterial Activity and Toxicity of
           Analogs of Scorpion Venom IsCT Peptides

    • Authors: Roberto de la Salud Bea, Adam Petraglia, Michael Ascuitto, Quentin Buck
      First page: 13
      Abstract: Seven analogs of the natural, α-helix peptides IsCT1 and IsCT2—found in the venom of scorpion Opithancatus Madagascariensis—have been synthesized and tested to compare their antibacterial and hemolytic activity against natural peptides. In general, results show that increasing hydrophobicity by substituting positions 5 and 9 of the sequences with alanine, valine, and leucine, enhances antibacterial activity. However, this also increases hemolytic activity. The analog with an increased net positive charge from +1 to +3 produces moderate bacterial growth inhibition but also has high hemolytic activity. On the other hand, the analog with a negative net charge (−1) has low antibacterial properties but also no cytotoxicity under the tested conditions, a similar result was found for five of the seven studied analogs.
      PubDate: 2017-06-28
      DOI: 10.3390/antibiotics6030013
      Issue No: Vol. 6, No. 3 (2017)
  • Antibiotics, Vol. 6, Pages 14: Macromolecular Conjugate and Biological
           Carrier Approaches for the Targeted Delivery of Antibiotics

    • Authors: Nhan Tram, Pui Ee
      First page: 14
      Abstract: For the past few decades, the rapid rise of antibiotic multidrug-resistance has presented a palpable threat to human health worldwide. Meanwhile, the number of novel antibiotics released to the market has been steadily declining. Therefore, it is imperative that we utilize innovative approaches for the development of antimicrobial therapies. This article will explore alternative strategies, namely drug conjugates and biological carriers for the targeted delivery of antibiotics, which are often eclipsed by their nanomedicine-based counterparts. A variety of macromolecules have been investigated as conjugate carriers, but only those most widely studied in the field of infectious diseases (e.g., proteins, peptides, antibodies) will be discussed in detail. For the latter group, blood cells, especially erythrocytes, have been successfully tested as homing carriers of antimicrobial agents. Bacteriophages have also been studied as a candidate for similar functions. Once these alternative strategies receive the amount of research interest and resources that would more accurately reflect their latent applicability, they will inevitably prove valuable in the perennial fight against antibiotic resistance.
      PubDate: 2017-07-04
      DOI: 10.3390/antibiotics6030014
      Issue No: Vol. 6, No. 3 (2017)
  • Antibiotics, Vol. 6, Pages 15: Comparative Study on Antistaphylococcal
           Activity of Lipopeptides in Various Culture Media

    • Authors: Maciej Jaśkiewicz, Damian Neubauer, Wojciech Kamysz
      First page: 15
      Abstract: Staphylococcus aureus bacteria are one of the leading microorganisms responsible for nosocomial infections as well as being the primary causative pathogen of skin and wound infections. Currently, the therapy of staphylococcal diseases faces many difficulties, due to a variety of mechanisms of resistance and virulence factors. Moreover, a number of infections caused by S. aureus are connected with biofilm formation that impairs effectiveness of the therapy. Short cationic lipopeptides that are designed on the basis of the structure of antimicrobial peptides are likely to provide a promising alternative to conventional antibiotics. Many research groups have proved a high antistaphylococcal potential of lipopeptides, however, the use of different protocols for determination of antimicrobial activity may be the reason for inconsistency of the results. The aim of this study was to learn how the use of various bacteriological media as well as solvents may affect activity of lipopeptides and their cyclic analogs. Obtained results showed a great impact of these variables. For example, cyclic analogs were more effective when dissolved in an aqueous solution of acetic acid and bovine serum albumin (BSA). The greater activity against planktonic cultures was found in brain-heart infusion broth (BHI) and tryptic-soy broth (TSB), while the antibiofilm activity was higher in the Mueller-Hinton medium.
      Citation: Antibiotics
      PubDate: 2017-08-02
      DOI: 10.3390/antibiotics6030015
      Issue No: Vol. 6, No. 3 (2017)
  • Antibiotics, Vol. 6, Pages 16: Self-Assessment of Antimicrobial
           Stewardship in Primary Care: Self-Reported Practice Using the TARGET
           Primary Care Self-Assessment Tool

    • Authors: Rebecca Owens, Leah Jones, Michael Moore, Dirk Pilat, Cliodna McNulty
      First page: 16
      Abstract: Multifaceted antimicrobial stewardship (AMS) interventions including: antibiotic guidance, reviews of antibiotic use using audits, education, patient facing materials, and self-assessment, are successful in improving antimicrobial use. We aimed to measure the self-reported AMS activity of staff completing a self-assessment tool (SAT). The Royal College of General Practitioners (RCGP)/Public Health England (PHE) SAT enables participants considering an AMS eLearning course to answer 12 short questions about their AMS activities. Questions cover guidance, audit, and reflection about antibiotic use, patient facing materials, and education. Responses are recorded digitally. Data were collated, anonymised, and exported into Microsoft Excel. Between November 2014 and June 2016, 1415 users completed the SAT. Ninety eight percent reported that they used antibiotic guidance for treating common infections and 63% knew this was available to all prescribers. Ninety four percent of GP respondents reported having used delayed prescribing when appropriate, 25% were not using Read codes, and 62% reported undertaking a practice-wide antibiotic audit in the last two years, of which, 77% developed an audit action plan. Twenty nine percent had undertaken other antibiotic-related clinical courses. Fifty six percent reported sharing patient leaflets covering infection. Many prescribers reported undertaking a range of AMS activities. GP practice managers should ensure that all clinicians have access to prescribing guidance. Antibiotic audits should be encouraged to enable GP staff to understand their prescribing behaviour and address gaps in good practice. Prescribers are not making full use of antibiotic prescribing-related training opportunities. Read coding facilitates more accurate auditing and its use by all clinicians should be encouraged.
      Citation: Antibiotics
      PubDate: 2017-08-16
      DOI: 10.3390/antibiotics6030016
      Issue No: Vol. 6, No. 3 (2017)
  • Antibiotics, Vol. 6, Pages 17: Identification of Staphylococcus aureus
           Cellular Pathways Affected by the Stilbenoid Lead Drug SK-03-92 Using a

    • Authors: William Schwan, Rebecca Polanowski, Paul Dunman, Sara Medina-Bielski, Michelle Lane, Marc Rott, Lauren Lipker, Amy Wescott, Aaron Monte, James Cook, Douglas Baumann, V.V.N. Tiruveedhula, Christopher Witzigmann, Cassandra Mikel, Md Rahman
      First page: 17
      Abstract: The mechanism of action for a new lead stilbene compound coded SK-03-92 with bactericidal activity against methicillin-resistant Staphylococcus aureus (MRSA) is unknown. To gain insight into the killing process, transcriptional profiling was performed on SK-03-92 treated vs. untreated S. aureus. Fourteen genes were upregulated and 38 genes downregulated by SK-03-92 treatment. Genes involved in sortase A production, protein metabolism, and transcriptional regulation were upregulated, whereas genes encoding transporters, purine synthesis proteins, and a putative two-component system (SACOL2360 (MW2284) and SACOL2361 (MW2285)) were downregulated by SK-03-92 treatment. Quantitative real-time polymerase chain reaction analyses validated upregulation of srtA and tdk as well as downregulation of the MW2284/MW2285 and purine biosynthesis genes in the drug-treated population. A quantitative real-time polymerase chain reaction analysis of MW2284 and MW2285 mutants compared to wild-type cells demonstrated that the srtA gene was upregulated by both putative two-component regulatory gene mutants compared to the wild-type strain. Using a transcription profiling technique, we have identified several cellular pathways regulated by SK-03-92 treatment, including a putative two-component system that may regulate srtA and other genes that could be tied to the SK-03-92 mechanism of action, biofilm formation, and drug persisters.
      Citation: Antibiotics
      PubDate: 2017-09-11
      DOI: 10.3390/antibiotics6030017
      Issue No: Vol. 6, No. 3 (2017)
  • Antibiotics, Vol. 6, Pages 18: Synthesis and Immunological Evaluation of
           Virus-Like Particle-Milbemycin A3/A4 Conjugates

    • Authors: Andris Zeltins, Māris Turks, Dace Skrastina, Jevgeņija Lugiņina, Ieva Kalnciema, Ina Balke, Ērika Bizdēna, Vitalijs Skrivelis
      First page: 18
      Abstract: Milbemycins are macrolide antibiotics with a broad spectrum of nematocidal, insecticidal, and acaricidal activity. To obtain milbemycin A3/A4 derivatives suitable for chemical conjugation to protein carriers (milbemycin haptens), succinate linker and a novel 17-atom-long linker containing a terminal carboxylic acid group were attached to the milbemycin core in a protecting group-free synthesis. The obtained milbemycin A3/A4 derivatives were coupled to Potato virus Y-like nanoparticles by the activated ester method. The reaction products were characterized and used in mice immunization experiments. It was found that the mice developed weak specific immune responses toward all tested milbemycin haptens.
      Citation: Antibiotics
      PubDate: 2017-09-11
      DOI: 10.3390/antibiotics6030018
      Issue No: Vol. 6, No. 3 (2017)
  • Antibiotics, Vol. 6, Pages 19: Point Prevalence Surveys of Antimicrobial
           Use among Hospitalized Children in Six Hospitals in India in 2016

    • Authors: Sumanth Gandra, Sanjeev Singh, Dasaratha Jinka, Ravishankar Kanithi, Ashok Chikkappa, Anita Sharma, Dhanya Dharmapalan, Anil Vasudevan, Onkaraiah Tunga, Akhila Akula, Garima Garg, Yingfen Hsia, Srinivas Murki, Gerardo Alvarez-Uria, Mike Sharland, Ramanan Laxminarayan
      First page: 19
      Abstract: The prevalence of antimicrobial resistance in India is among the highest in the world. Antimicrobial use in inpatient settings is an important driver of resistance, but is poorly characterized, particularly in hospitalized children. In this study, conducted as part of the Global Antimicrobial Resistance, Prescribing, and Efficacy in Neonates and Children (GARPEC) project, we examined the prevalence of and indications of antimicrobial use, as well as antimicrobial agents used among hospitalized children by conducting four point prevalence surveys in six hospitals between February 2016 and February 2017. A total of 681 children were hospitalized in six hospitals across all survey days, and 419 (61.5%) were prescribed one or more antimicrobials (antibacterials, antivirals, antifungals). Antibacterial agents accounted for 90.8% (547/602) of the total antimicrobial prescriptions, of which third-generation cephalosporins (3GCs) accounted for 38.9% (213/547) and penicillin plus enzyme inhibitor combinations accounted for 14.4% (79/547). Lower respiratory tract infection (LRTI) was the most common indication for prescribing antimicrobials (149 prescriptions; 24.8%). Although national guidelines recommend the use of penicillin and combinations as first-line agents for LRTI, 3GCs were the most commonly prescribed antibacterial agents (55/149 LRTI prescriptions; 36.9%). In conclusion, 61.5% of hospitalized children were on at least one antimicrobial agent, with excessive use of 3GCs. Hence there is an opportunity to limit their inappropriate use.
      Citation: Antibiotics
      PubDate: 2017-09-13
      DOI: 10.3390/antibiotics6030019
      Issue No: Vol. 6, No. 3 (2017)
  • 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 12: Bacteria from Animals as a Pool of
           Antimicrobial Resistance Genes

    • Authors: Maria Argudín, Ariane Deplano, Alaeddine Meghraoui, Magali Dodémont, Amelie Heinrichs, Olivier Denis, Claire Nonhoff, Sandrine Roisin
      First page: 12
      Abstract: Antimicrobial agents are used in both veterinary and human medicine. The intensive use of antimicrobials in animals may promote the fixation of antimicrobial resistance genes in bacteria, which may be zoonotic or capable to transfer these genes to human-adapted pathogens or to human gut microbiota via direct contact, food or the environment. This review summarizes the current knowledge of the use of antimicrobial agents in animal health and explores the role of bacteria from animals as a pool of antimicrobial resistance genes for human bacteria. This review focused in relevant examples within the ESC(K)APE (Enterococcus faecium, Staphylococcus aureus, Clostridium difficile (Klebsiella pneumoniae), Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacteriaceae) group of bacterial pathogens that are the leading cause of nosocomial infections throughout the world.
      PubDate: 2017-06-06
      DOI: 10.3390/antibiotics6020012
      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

    • 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

    • 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

    • 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)
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