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Antibiotics, Volume 6, Issue 3 (September 2017) – 7 articles

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344 KiB  
Article
Point Prevalence Surveys of Antimicrobial Use among Hospitalized Children in Six Hospitals in India in 2016
by Sumanth Gandra, Sanjeev K. Singh, Dasaratha R. Jinka, Ravishankar Kanithi, Ashok K. Chikkappa, Anita Sharma, Dhanya Dharmapalan, Anil Kumar Vasudevan, Onkaraiah Tunga, Akhila Akula, Garima Garg, Yingfen Hsia, Srinivas Murki, Gerardo Alvarez-Uria, Mike Sharland and Ramanan Laxminarayan
Antibiotics 2017, 6(3), 19; https://doi.org/10.3390/antibiotics6030019 - 13 Sep 2017
Cited by 40 | Viewed by 5782
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 [...] Read more.
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. Full article
(This article belongs to the Special Issue Surveillance of Antimicrobial Use and Resistance in Children)
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1560 KiB  
Article
Synthesis and Immunological Evaluation of Virus-Like Particle-Milbemycin A3/A4 Conjugates
by Andris Zeltins, Māris Turks, Dace Skrastina, Jevgeņija Lugiņina, Ieva Kalnciema, Ina Balke, Ērika Bizdēna and Vitalijs Skrivelis
Antibiotics 2017, 6(3), 18; https://doi.org/10.3390/antibiotics6030018 - 11 Sep 2017
Cited by 4 | Viewed by 3333
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 [...] Read more.
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. Full article
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1067 KiB  
Article
Identification of Staphylococcus aureus Cellular Pathways Affected by the Stilbenoid Lead Drug SK-03-92 Using a Microarray
by William R. Schwan, Rebecca Polanowski, Paul M. Dunman, Sara Medina-Bielski, Michelle Lane, Marc Rott, Lauren Lipker, Amy Wescott, Aaron Monte, James M. Cook, Douglas D. Baumann, V.V.N. Phani Babu Tiruveedhula, Christopher M. Witzigmann, Cassandra Mikel and Md Toufiqur Rahman
Antibiotics 2017, 6(3), 17; https://doi.org/10.3390/antibiotics6030017 - 11 Sep 2017
Cited by 4 | Viewed by 5327
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 [...] Read more.
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. Full article
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816 KiB  
Article
Self-Assessment of Antimicrobial Stewardship in Primary Care: Self-Reported Practice Using the TARGET Primary Care Self-Assessment Tool
by Rebecca Owens, Leah Ffion Jones, Michael Moore, Dirk Pilat and Cliodna McNulty
Antibiotics 2017, 6(3), 16; https://doi.org/10.3390/antibiotics6030016 - 16 Aug 2017
Cited by 8 | Viewed by 6236
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 [...] Read more.
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. Full article
(This article belongs to the Special Issue Top 35 of Antibiotics Travel Awards 2017)
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1728 KiB  
Article
Comparative Study on Antistaphylococcal Activity of Lipopeptides in Various Culture Media
by Maciej Jaśkiewicz, Damian Neubauer and Wojciech Kamysz
Antibiotics 2017, 6(3), 15; https://doi.org/10.3390/antibiotics6030015 - 02 Aug 2017
Cited by 11 | Viewed by 5779
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 [...] Read more.
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. Full article
(This article belongs to the Special Issue Antibiotic Synthesis)
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2124 KiB  
Review
Macromolecular Conjugate and Biological Carrier Approaches for the Targeted Delivery of Antibiotics
by Nhan Dai Thien Tram and Pui Lai Rachel Ee
Antibiotics 2017, 6(3), 14; https://doi.org/10.3390/antibiotics6030014 - 04 Jul 2017
Cited by 9 | Viewed by 6313
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 [...] Read more.
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. Full article
(This article belongs to the Special Issue Antibiotic Synthesis)
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694 KiB  
Article
Antibacterial Activity and Toxicity of Analogs of Scorpion Venom IsCT Peptides
by Roberto De la Salud Bea, Adam F. Petraglia, Michael R. Ascuitto and Quentin M. Buck
Antibiotics 2017, 6(3), 13; https://doi.org/10.3390/antibiotics6030013 - 28 Jun 2017
Cited by 13 | Viewed by 4447
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 [...] Read more.
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. Full article
(This article belongs to the Special Issue Antibiotic Synthesis)
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