Conference Schedule

Day1: October 11, 2018

Keynote Forum

Biography

John James Stewart Cadwell received his Degree in Pharmacology from the University of Miami in 1981. He spent additional time studying at the University of Nottingham and the National Institute of Medical Research at Mill Hill, U.K. In 2000, he founded FiberCell Systems Inc., a company specializing in the research and supply of hollow fiber bioreactors. He has over 10 publications in the field and three patents relating to hollow fiber systems and is considered a World Expert in the field.


Abstract

Emerging antibiotic resistance presents a serious global health threat. Two million people in the United States were infected with antibiotic resistant bacteria in 2014 and more than 20,000 died as a direct result of these infections, many more from complications. Antimicrobial resistance has been identifed as one of the three greatest threats to human health. Antibiotic discovery and development require static susceptibility testing to screen compounds, in vitro pharmacodynamics/ pharmacokinetic (PK/PD) studies to model drug dynamics and efficacy, and testing in animal models to provide critical information prior to the clinical evaluation of new antibiotics. The one compartment PK/PD model typically consists of an open central reservoir containing the organism of interest, a source of diluent and a waste reservoir. 1) Open system, not bio safe 2) Bacteria numbers change over time 3)Large volume requires large amount of drug and diluent 4) Rapid changes in drug concentration not possible, cannot model short half-lives. Animal models have many shortcomings though they have served as a primary development tool for many years; few of them are as follows: 1) PK/PD may not match human values; 2) Cannot sample same animal over time; 3) Difficult to study large numbers of bacteria to reveal resistance; 4) Many infections cannot be modeled in a mouse or other animal. To address these shortcomings, the two-compartment in vitro pharmacokinetic model, the hollow fiber infection model (HFIM) utilizing hollow fiber bioreactors was developed. The advantages of the HFIM are as follows: 1) Closed, bio-safe system; 2) Large number of organism can be tested, revealing resistance; 3) Precisely simulates human PK/PD; 4) Repetitive sampling over time, both drug and organism; 5) Total kill can be determined; 6) Single use, disposable, reproducible; 7) Two drug models can be tested; 8) Can model both dosing curve and elimination curve and; 9) Can look at bacteria in different growth phases and in combination with cells. The clinical utility of the HFIM has been demonstrated and is now endorsed by the EMA. An overview of historic pk/pd models is presented and the utility of the system as it relates to antibiotics and other drugs are discussed.

Biography

Jerry T Thornthwaite received his PhD in chemistry and biophysics from Florida State University in 1977. He was Founder and Director of the two largest oncology laboratories in Miami. He founded the Cancer Research Institute and has been the Director for the last 28 years, while serving on the faculty of several universities including Miami and East Tennessee State University. His current work in translational medicine is involved in develop­ing formulations for the treatment of malaria, cancer, Alzheimer’s disease and MRSA. He has published over 60 technical articles and abstracts and has participated in numerous technical presentations and has seven pat­ents. In 1972, he discovered what is now recognized as the Natural Killer Cell, the cornerstone for our surveillance defense mechanism against the survival of cancer cells. He developed the application of NutraNanoSpheres (NNS) to health and wellness, and developed the first truly water-soluble malaria drug. He has spent the last 13 years in medical missions in Haiti, having pioneered a cure for malaria that is clinical trials in Nigeria and other African countries.


Abstract

The natural killer cell (NKC) is the cell-mediated cornerstone of innate immunity. The purpose of this presentation is to give a historical perspective of the author’s discovery of NKC and the application of supplements in the enhancement of NKC in human cancers for the development of human health and well-being. Since the discovery of the NKC, as observed by Nomarski optics, scanning (SEM)/transmission electron microscopy (TEM) with cellular numeration and enrichment using bovine serum albumin (BSA) continuous gradients, there have been significant research and clinical studies to increase the effectiveness of NKC in the destruction of cancer cells. Based on significant research and clinical studies, at least 16 components have been identified that enhance or may enhance NKC activity. These supplements include alpha-lipoic acid, arabinoxylin, curcumin, garlic, genistein, ginseng, lentinan, mistletoe, N-acetylcysteine, resveratrol, selenium, vitamin B, vitamin C, vitamin D3, vitamin E and zinc. Futher research is underway to activate NKC in primary and metastic cancer.

Tracks

  • Discovery of Antibiotics | Antibiotic Therapy | Antibiotic Resistance and Prevention | Antimicrobial Resistance | Alternatives to Antibiotics | Antimicrobial Peptides | Antibiotics for Emerging and Re-Emerging Diseases
Location: Balvenie Glenmorangie

Jerry T Thornthwaite

Cancer Research Institute of West Tennessee, USA

Chair

Lovisa Ringstad

RISE Research Institutes of Sweden, Sweden

Co Chair

Biography

Sunil Palchaudhuri-PhD, DSc- is Professor of Immunology and Microbiology at the WSU School of Medicine, USA for the past 36 years, after his Postdoc­toral training in Canada (NRC Scholarship) and NIH Post Doctoral Fellow­ship at NYU School of Medicine with Professor W K Maas. He was awarded the New York State Irma T Hirschl Career Scientist Award in 1975–1980 and was the Fogarty Senior International Fellow (1984) working on an epidemic in Kolkata caused by an antibiotic resistant strain of Shigella dysenteriae. He was a Fulbright Visiting Professor, in 1993–1994 at the Calcutta School of Tropical Medicine, Kolkata with Mother Teresa to develop an early detection technique for leprosy in children. He is a Reviewer in Journal of Bacteriology Editorial Board. He has published extensively in international journals of re­pute such as Journal of Molecular Biology, Proceedings of the National Acad­emy of Sciences of the United States of America, Journal of Bacteriology, etc. Currently, he is preparing manuscripts on Antibiotic Resistance Crisis, Transposons And Bacterial Diseases.

 


Abstract

In antibiotic resistance crisis and antigenic variation, an alternative preventive therapy needs to be developed against the pathogen S. pneumoniae and therefore its growth curve is highly important. We have shown that S. pneumoniae grows in three different phases—pre-competent, competent and post-competent. Dr. Fred Griffith’s (1928) smooth colony is our growth curve but his rough colony needs interpretation. In our growth curve, smooth colony shows uneven contour after 48 hours of growth and becomes rough colony which is equivalent to our post-competent phase confirming the heterogeneity of their growth phases (pre-competent, competent and post-competent). Pre-competent shows only the growth in size with a distinct morphological change—round to oval. Then they attain the competent phase with a cleavage site to excrete pheromone and receive bio-signalling (an ability to reproduce). The post-competent phase shows the thinning of peptidoglycan layers as the purple becomes pink by Gram staining technique. During this period there is an autolysis of the old, following the depletion of nutrients in the growth media (starvation) and the nutrients released promote the young to grow out radially but all are still in chain (heterogeneity of pre-competent, competent and post-competent). The heterogeneity of their growth phases is confirmed by the presence of pink and purple members in the same population. If the growth medium (rich or minimal) contains xylitol—a five-carbon sugar alcohol, xylitol phosphate is formed and interferes in their bio-signalling essential for reproduction of the competent. Interaction of StkP and PASTA located at the cleavage site of diplococcic shaped bacteria is necessary for reproduction. Xylitol should provide an ideal alternative preventive therapy for children (body immunity is growing) and the elderly (body immunity is decaying).

 

Biography

Dr Cindy Gunawan is a nano-biologist with expertise in the fundamental and translational research of nanoparticle-cell interactions. She received her PhD in Biotechnology from the University of New South Wales (UNSW) and had her post-doctoral training in the School of Chemical Engineering UNSW. Dr Gunawan was then awarded the Chancellor’s Research Fellowship to un­dertake research in the University of Technology Sydney (UTS). She is cur­rently a Senior Lecturer in UTS and an Adjunct Senior Lecturer in UNSW. Dr Gunawan has published 24 papers, mostly in high impact journals.

 


Abstract

As resistance to antibiotics rises rapidly, the ability to rely on other less conventional antimicrobials has assumed greater importance and this has led to the growing momentum in the engineering and applications of nanoparticles.Nanosilver (NAg) with its proven efficacy against broad spectrum of microbes, is currently one of the most commercialized antimicrobial nanoparticles. The nanoparticle has been incorporated in medical devices, such as wound dressings, catheters and implants, to prevent or fight infections. Companies have also been adding NAg in vast arrays of consumer products, from personal care, clothing to household appliances and even, baby products. The widespread use has fuelled an escalating concern for the emergence of resistant bacteria toward these nanoparticles. Our research group has found the natural ability of bacteria to adapt to NAg toxicity. These bacteria, ranging from environmental to clinically-relevant Gram-negatives and Gram-positives, developed unique adaptation responses under prolonged exposure to NAg. Some of these bacteria indeed exhibited resistance traits, capable to proliferate when in the presence of an otherwise toxic NAg dosages. We detected genomic mutations in these bacteria, and in some cases, even with no native prevalence of silver resistance determinants. These bacteria are capable to exhibit the resistance traits even after discontinuation of the nanoparticle exposure. The observations of the emergence of resistant bacteria are relevant to wider microbial communities, presenting consequences of extensive microorganism exposure, including those that dwell in the human body, to biologically active silver derived from NAg products.

 

Biography

George Hanna is a second-year graduate student in the Drug Discovery and Biomedical Sciences department at the Medical University of South Caro­lina. He received his BS in Marine Biology from the College of Charleston. Prior to beginning his graduate-research he worked for South Carolina’s Department of Natural Resources, studying the influence of ecosystem processes on commercially important species of fish and crustaceans as well as the utilization of mariculture for stock enhancement. Now, working in the lab of Dr. Mark Hamann, George’s interests stem from how ecology can be leveraged to inform the isolation and characterization of relevant bioactive natural products. His current work focuses on the use traditional medicinal and edible terrestrial plants and marine algae as a source of novel therapeutics, with a specific interest in the control of drug resistant infection diseases.

 


Abstract

Plants and microbes depend on a dynamic set of interactions to thrive. Probing these biological relationships has led to the discovery of a new class of antibiotics called the platanosides, identified from the American Sycamore. The antibiotics are potent inhibitors of MRSA and VRSA as well as VRE. The potential utility of these molecules in the control of drug resistance will be presented. These represent a new class of antibiotics for the control of drug resistant Gram -/+ infectious diseases. The ecological role of these molecules appears to be the control of key phytopathogenic diseases common in agriculture.

 

Biography

Libor Kvitek completed his PhD in Physical Chemistry at Charles University in Prague (1993). After a short employment in the pharmaceutics industry, he started his academic career at Palacký University in Olomouc (1991), where he works as Associate Professor of Physical Chemistry. His main research interest is Nanotechnology and Coin Metal Nanoparticles. He has published more than 60 papers in reputed journals (H-index 19; more than 3000 citations) and currently he is serving as the Vice Dean of the Faculty of Science, Palacký University in Olomouc.

 


Abstract

Silver is used by people not only as decorative element in jewellery, but also as bioactive element in medicine and food industry for thousands of years. At the turn of the 19th and 20th centuries, colloidal silver was used as the main antibacterial agent in human medicine. However, with the discovery of penicillin in the first half of the 20th century, application of silver and its compounds as antibacterial agent in medicine was diminished. Unfortunately, wide application of antibiotics in medicine practice led to the quick spreading of resistant bacterial strains. Therefore, at the end of 20th century the interest of scientists in silver as an antibacterial agent was renewed. The first article published by Sondi, et al. in 2004 reported excellent antibacterial activity of silver nanoparticles against Gram-negative bacteria. Many studies were published from this time which reported excellent antibacterial activity of silver nanoparticles against both Gram-negative and Gram-positive bacteria including resistant bacteria strains. Rediscovered antibacterial activity of silver was quickly applied in practice, especially in the textile industry. However, toxicity of silver and unknown interactions of its nanoparticles with living matter is the main reason why silver nanoparticles are not used in human medicine to yet. Recently published studies showed that silver nanoparticles can be effectively used in very low concentration with antibiotics due to synergy effect in the antibacterial activity of both agents. Unfortunately, recent researches aimed at the possibility to induce bacterial resistance to silver nanoparticles revealed that bacteria can effectively lower antibacterial activity of silver nanoparticles by the aggregation mechanism induced by the bacterial proteins. This is a new obstacle for possible application of silver nanoparticles in human medicine.

 

Biography

Mihir Yatin Trivedy is a locum doctor in Emergency Medicine, and will enter Core Surgical Training in August of 2018. He is passionate about medical education and is in the first stage of completing a Postgraduate Masters degree in Medical Education, as well as completion of his MRCS.

 


Abstract

Antibiotic prescription is a key part of the role of any doctor. The task of antibiotic prescription often falls to the junior staff, especially in environments such as the emergency department, and on the ward following the ward rounds or consultant instruction. How often do our own prescribing internal guidelines match the local or national guidelines for prescribing? Clinicians are known to prescribe based on memory of a treatment rather than up to date guidelines. A survey was sent to one hundred clinicians (junior doctors – FY1-CT2) with the aim of understanding the thought process when prescribing antibiotics, and whether they consulted the local guidelines for the condition or not, alongside with how regularly they prescribe the drug. This data can be used to shape antibitiotic prescribing in the future and make the way for responsible antibiotic stewardship.

 

Biography

Flavia De Bernardis is the Research Director (2000 to present) and Head of the Mycoses Unit of the Department of Infectious, Diseases, at the Istituto Superiore di Sanità, Rome, Italy. She graduated with an Honours Degree in Biological Sciences in 1977 from the 1st State University, Rome, Italy. She has attended a specialization course (four years) in General Pathology, Catholic University of Rome, 1979–1982. She attended the Medical Mycol­ogy Course, Duke University of Durham, North Carolina, USA in 1985. She was a Guest Researcher for 12 months at the Department of Microbiology, Georgetown, University, Washington DC, USA in 1993. Research activities in­clude molecular diagnosis of mycoses, and virulence factors of C. albicans. She has been the Project Leader of various grant research projects. She has published 102 peer-reviewed papers and 10 book chapters published. She has been invited to 40 national and international congresses as a Guest Speaker. She has been awarded three patents yet.

 


Abstract

The widespread occurrence of vaginal candidiasis and the development of resistance against anti-fungal agents has stimulated interest in understanding the pathogenesis of this disease. The aim of our work was to characterize, in an animal model of vaginal candidiasis, the mechanisms that play a role in the induction of mucosal immunity against C. albicans and the interaction between innate and adaptative immunity. Our studies evidenced the elicitation of cell mediated immunity and antibody mediated immunity with a Th1 protective immunity. An immune response in the vaginal compartment was very encouraging to identify the proper targets for new strategies for vaccination or immunotherapy of vaginal candidiasis. Aspartyl-proteinase (Sap2) which is an important immunodominant antigen and virulence factor of C.albicans acting in mucosal infections, was assembled with virosomes and a vaccine PEV7 was obtained. The results obtained in the mouse model and in the clinical trial conducted by Pevion Biotech on women have evidenced that the vaccine PEV7, intravaginally administered, has an encouraging therapeutic potential for the treatment of recurrent vulvovaginal candidiasis. This opens the way to a modality for anti-Candida protection at mucosal level.

 

Biography

Libera Latino has completed her Ph.D. in Microbiology at the Université Par­is-Saclay (Orsay, France). She is presently working as postdoc at I2BC (Or­say, France) and has published 8 papers in reputed journals.

 


Abstract

Colicins are plasmid-encoded bacteriocins produced by some Escherichia coli strains in order to kill competitors belonging to the same or related species. All known colicins share a same structural organization in three domains, each of them being devoted to a specific function: translocation through the outer membrane, binding to a specific outer membrane receptor and toxicity, from N to C termini, respectively (Cascalès et al., 2007). Among colicins, colicin M (ColM) is the smallest colicin known to date and the only one known to interfere with peptidoglycan biosynthesis. It targets and cleaves the peptidoglycan lipid II intermediate at the periplasmic face of the inner membrane by exhibiting a phosphodiesterase activity leading to the formation of undecaprenol and 1-pyrophospho- MurNAc-(pentapeptide)-GlcNAc (El Ghachi et al., 2006). These two products cannot be used or recycled for peptidoglycan biosynthesis, leading to cell lysis. During last years, several homologues of ColM produced by various bacteria such as Pseudomonas (Barreteau et al., 2009), Burkholderia (Ghequire and De Mot, 2015) and Pectobacterium (Grinter et al., 2012, 2014) were identified and characterized. These ColM-like proteins exhibit the same mode of action as ColM and displayed cytotoxic activity towards a limited number of bacterial species. Accordingly, no crossed cytotoxic activity has been demonstrated (Barreteau et al., 2009; Chérier et al., 2016), presumably due to the high specificity of reception and translocation machineries. Thus, reaching the lipid II target is clearly the crucial and limiting step to be considered in a perspective of exploitation of these colicin family members as tomorrow’s antibiotics. We recently showed that the pectocin M1 (PcaM1, produced by P. carotovorum) and some of its variants were able to kill E. coli cells once addressed to the periplasm of this species using appropriate pASK vectors (Chérier et al., 2016). In these conditions, PcaM1 and its isolated catalytic domain were effectively able to catalyze the degradation of lipid II, leading to the arrest of peptidoglycan biosynthesis and cell lysis. To the best of our knowledge, this was the first example of a ColM-like protein capable of killing another bacterial species, without any treatment affecting cell wall integrity. This result and the fact that lipid II is an essential and specific component through the whole bacterial world make of ColM and its orthologues very interesting agents to be exploited as new antibacterial agents. We thus propose the creation of a range of chimera colicins by an engineering approach, in order to get potent antibacterial molecules able to fight, either specifically or not, against various pathogenic bacterial species. Our first goal consists in getting chimera proteins with a narrow-spectrum antimicrobial activity. Our presentation will deal with our preliminary and encouraging results.

 

Biography

Urszula Godlewska received her BSc and MSc Degree in Biology (special­izing in Microbiology) in 2012 from the University of Wroclaw. Her Master’s thesis under the guidance of Dr. Bozena Futoma-Koloch focused on the strategies of multiple host complement system evasion by Salmonella. In 2014, she joined Professor Joanna Cichy’s research group at Jagiellonian University as a PhD student. She is currently working on a project which ex­amines the role of antimicrobial peptides derived from chemerin in immune host defense.

 


Abstract

The epithelium secretes a variety of antimicrobial factors that play a role in eliminating pathogenic microorganisms. We have recently characterized antimicrobial activity of skin-localized protein chemerin that was primarily known for its properties to support immune cell infiltration to inflammatory sites and to regulate differentiation of fat cells. An internal 20-amino acid peptide V66-P85 (p4) exhibits most of the antimicrobial activity of active chemerin in vitro and inhibits growth of a broad range of microorganisms, including skin, lung or oral cavity associated bacteria as well as fungal pathogen C. albicans. Here we demonstrate that p4 exhibits toxic activity against MRSA strains and limits the growth of S. aureus in experimental model of topical skin infection. Using chemically synthesized p4 sister peptides we demonstrate critical role of cysteine and positively charged amino acids for antimicrobial activity of p4. Dimerization of p4 through C-mediated crosslinking was found to be crucial for either binding to bacteria or bacteria killing, suggesting that p4 acts as antimicrobial agent under oxidized conditions. Fluorescence microscopy, TEM and immunogold labeling revealed that mechanisms of p4 action involve membrane and intracellular off-membrane targets and that p4 triggers rapid bacteria death by compromising membranes integrity. Our data gives important clues as to how the p4 exerts lethality on bacteria. Since p4 displays rapid lytic activity against skin pathogens but not human erythrocytes, p4 holds the promise to improve treatment of skin infections.

 

Biography

Nuvee Prapasarakul received his Graduate Degree from the Faculty of Veter­inary Science, Chulalongkorn University and his PhD from Tokyo University of Agriculture and Technology. He was granted the Fellowship from Crow­ford Foundation, Murdoch University, Western Australia. He has been work­ing as an Associate Professor at his graduated school, and has been serving as the Director of General Education Center, and Director of Diagnosis and Monitoring of Animal Pathogens Research Unit, in his graduated university. His research on microbiological theories, especially diagnosis, pathogenesis and antimicrobial resistance for bacteria and fungi, is recognized with his reputed publications, continuously.

 


Abstract

Numerous studies have provided antimicrobial resistance data in pigs on farms, or in pork in retail outlets, but temporal relationships in individual pigs have not been fully evaluated. The aims of this study were: i) to evaluate whether or not routine in-feed antimicrobial use in pigs resulted in differences in antimicrobial resistance (AMR) amongst commensal E. coli at different stages of the production cycle, and ii) to determine whether resistant strains were present in pig meat post-slaughter. A total of 300 E. coli isolates were examined for antibiograms, antimicrobial resistance genes, plasmid replicons and molecular types. The isolates were from fecal samples from two cohorts, each of 10 pigs, from two farms either using or not using in-feed antimicrobials (farms A and NA, respectively), sampled four times during the production cycle. E. coli isolates from thigh meat were obtained post-slaughter. Nearly all isolates were resistant to β-lactam group antimicrobials and tetracycline. E. coli resistant to gentamicin and tobramycin containing aadA1, aadA2 and aadB and extended-spectrum beta-lactamase producing (ESBLP) E. coli contained bla¬CTX-M-1 were significantly increased in the nursery and growing periods in farm A compared to farm NA. Plasmid replicons IncFrep and IncFIB were commonly found, whereas IncI1-Iγ and IncHI2 were most common in the nursery period. Sequence type 10 (ST10) was the most common type found in live pigs, but it was not found in pig meat. ST604, ST877, ST1209 and ST2798 containing ESBLP were found only in live pigs; whereas, ESBLP strains were found in pig meat. In conclusion, a high incidence of multidrug resistant E. coli was found at all collection times, but in farm A there was increased resistance to some antimicrobials in the nursery and grower period. Isolates recovered from pig meat largely differed from those detected in the feces of the same live pigs sampled during the production period.

 

Biography

Vineeta Singh works as a full time Scientist at the National Institute of Ma­laria Research, Delhi, India. She has a PhD in Biotechnology from BITS, Pi­lani. Her job profile is diverse ranging from research in the field of Parasite Biology to mentoring PhD students. She has more than 30 research articles, review papers and chapters in international journals to her credit. She is also a Principal Investigator in various research projects. Studies related to the biology and pathogenicity of Plasmodium falciparum and P. vivax are the major research areas of her laboratory. Her long term aim is to achieve more insight about the malaria pathogenesis which seems to be changing rapidly.

 


Abstract

The malaria infection is the interplay of several complex factors, among which drug resistance and gametocyte biology are the crucial ones. The purpose of this study was to assess the current drug sensitivity profile in the field isolates and type the Pfg377 genes. In vitro drug sensitivity assay was used to assess the susceptibility of P. falciparum field isolates collected from Mewat (Haryana), located in Northern region of India to four anti-malarial drugs. The inhibitory concentrations (IC50) for the four drugs, viz. chloroquine (CQ), artesunate (AS), sulfadoxine (SD) and pyrimethamine (PYR) were in the range of 10.11–113.2 nM, 2.26–4.08 nM, 13.31–43.91 nM and 0.76– 4.91 nM, respectively in the evaluated 25 field isolates. The Pfg377 allele typing in the 26 field isolates revealed different types of haplotypes (A, B, C and D) in them. The types varied among themselves by the size and number of repeats and deletions. We also compared the allelic types of the Pfg377 gene in the cryopreserved and adapted isolates of P. falciparum to determine the parasite lines in them. The allele types or presence of different clones in the same sample could not be correlated significantly with resistance to any of the four drugs tested in the study. Our study revealed different drug sensitivity profiles of field isolates from Mewat region and by allele typing of Pfg377 gene, it was found that different haplotypes of field isolates were circulating in parasite population. The Pfg377 allele typing is suitable for detecting carriers of low number of gametocytes which play a critical role in malaria transmission. Active surveillance and continued monitoring of the artemisinin-based combination therapy (ACT) is required for identification of emerging artesunate resistance in the country for malaria control programmes.

 

Biography

Farzana Rashid has completed her PhD from Beijing University of Chemi­cal Technology, China. She has published more than 30 papers in reputed National and International journals and has been serving as an Associate Professor at Lahore College for Women University, Lahore.

 


Abstract

Microbial drug resistance caused by different pathogenic bacteria has been a major threat to mankind. Therefore, the development of more efficient materials with enhanced antimicrobial activity is of great significance. Nanoparticles (NPs) are thus ideal antimicrobials: ZnO nanoparticles are well known and are regarded as bio-safe materials. The present study is designed to study antimicrobial behavior of undoped and doped (Mn and Co) ZnO nanoparticles and their combined effect with β-lactam antibiotics against differentclinical isolates. The antimicrobial activity of doped-ZnO NPs was determined at different percent doping including 5 mol%, 10 mol%, 15 mol% and 20 mol% and pure ZnO NPs were studied at different concentrations by Kirby’s disc diffusion assay. The cytotoxicity and antioxidant activity of undoped and doped- ZnO NPs was investigated by Brine shrimp lethality Assay and α-α-diphenyl-β-picrylhydrazyl (DPPH) scavenging activity respectively. The results showed that antimicrobial activity was increased by the doping of ZnO nanoparticles, as the zone of inhibition against Escherichia coli increased from 8 to 14mm with doping. The obtained results thus suggested that antimicrobial activity and antioxidant potential was enhanced by doping of ZnO NPs while the cytotoxicity analysis showed no toxic effect of doped-ZnO NPs at lower concentration on Artemiasalina. The present study can be used to form different drugs in combination with nanoparticles for their utilization in production of medicines to cope with the emerging drug resistance among pathogenic bacteria.

 

Day2: October 12, 2018

Keynote Forum

Biography

Alan W Decho is the Professor and Director of the Microbial Interactions Lab­oratory at the University of South Carolina, Arnold School of Public Health. He completed his PhD from LSU, then conducted his Fulbright Post-Doctoral Fellow at CSIRO Laboratories in Australia. His research centers on attached forms of bacteria, called ‘biofilms’, and the use of nanotechnology for com­batting biofilms. His lab is examining bacterial cell-cell communication (quo­rum sensing-QS) and the use of nanoparticles to control QS; searching natural environments for novel antibiotics to thwart biofilms; and determining how nanoparticles can be used as antibiotic-delivery vehicles. He has published more than 110 papers in journals such as Nature, Nature Nanotechnology, ACS Infectious Diseases and Chemical Reviews. He also serves as Associate Dean for Research in the Arnold School of Public Health at USC.

 


Abstract

The challenge of antibiotic-resistant infections (ARI) extends to global scales. New antibiotics having novel mechanisms of action and more-efficient delivery approaches to infections are needed to slow the climb in this emerging crisis. Engineered nanoparticles (NP) have been successfully used in eukaryotic systems, including humans for drug delivery purposes. Their applications to the microbial realm for delivery of antibiotics and other antimicrobials has remained steps behind due to methodological limitations, and the physiological properties and defenses of bacteria. The present talk will overview some recent advances toward attacking and manipulating bacterial cells to illustrate (hopefully) how engineered NPs can be used to obviate the seemingly strong defenses used by bacteria in pathogen infections. Specifically addressed topics will be: enhancing current antibiotic efficacy with molecular enhancers; attaching multiple antibiotics to NPs; and NP-antibiotic entry into bacterial cells. Major obstacles exist in nano-based approaches and negate the ‘one solution fits all’ approach using NPs. A first broad obstacle is how to specifically target the pathogens of interest, while not significantly impacting the 1–2 kg of ‘good’ bacteria that humans typically possess and require to varying extents. A further complication is in the adaptability of bacterial surface signatures, and their capability to ‘hide’ within protective biofilms. A third obstacle addresses the selection of resistant variants to any antimicrobial attack. These and other issues for consideration will be addressed at teh conference.

 

Biography

Lovisa Ringstad currently holds the position of Deputy Head for the Formula­tion Development Section at RISE Research Institutes of Sweden. She has a PhD in Pharmaceutical Physical Chemistry from Uppsala University, Sweden (2009). At RISE, she has lead several public and privately funded projects re­lated to formulation development, with specific focus on pharmaceuticals and she is the Coordinator of the FORMAMP project (FP7 collaborative project, www.formampproject.com). Her main research interests are directed towards formulation development, skin delivery and biophysical understanding on the interaction between formulation components as well as with surrounding tis­sue/cells/bacteria. She has published more than 20 papers in peer-reviewed journals.

 


Abstract

Resistance to traditional antibiotics is a rapidly increasing problem, which in the future could make infections impossible to treat and bring the state of medical care back to the pre-antibiotic era from the beginning of the last century. Antimicrobial peptides (AMPs) have a huge potential as new, sustainable therapeutics against infectious diseases, as they are less prone to induce high-level resistance due to their fast and nonspecific mechanism of action. A large variety of AMPs have been identified, analyzed and modified in order to increase their function and efficiency for drug delivery applications. However, the number of products based on AMPs introduced in the market is few. One of the main reasons is the challenge related to the stability of peptides during storage, as well as after administration, which dramatically reduces their efficiency. These challenges can be overcome with novel formulation strategies. In the EU-funded project FORMAMP, the possibility to use different nanoparticles as carriers for AMPs has been explored. Lipid-based, polymer-based and mesoporous silica-based nanoparticles have been used for different AMPs and applications. The peptide-loaded nanocarriers have been further formulated in functional dosage forms for local administration at the infected site (skin and lung). Gels, creams and ointments have been developed for recurrent skin infections, whereas, aerosols and powders for inhalation are being formulated for tuberculosis and cystic fibrosis. The project was recently finalized and in this presentation I will summarize the main findings both in terms of nanoformulation strategies and the successful development for treatment of tuberculosis and skin and soft tissue infections.

 

Tracks

  • Antibiotics of Veterinary Importance | Antibiotics Overuse and Resistance | Antimicrobial Resistance | The Next Generation Approach of Antibiotics | Antimicrobial Peptides | Mechanisms of Antibacterial Resistance | Alternatives to Antibiotics
Location: Balvenie Glenmorangie

Alan W Decho

University of South Carolina, USA

Chair

Libor Kvitek

Palacky University, Czech Republic

Co Chair

Biography

Silke Salavati has graduated as a veterinarian from the Justus-Liebig Uni­versity in Giessen, Germany. She has done a doctoral thesis on the topic of gastric emptying assessment in dogs, followed by a Residency in Small Animal Internal Medicine (Diploma at ECVIM-CA). She also completed her PhD at the Royal Veterinary College (London, UK) on the effect of probiot­ics in canine inflammatory bowel disease. She has worked as a Junior Lec­turer in Giessen, and is Senior lecturer in Small Animal Internal Medicine at the University of Edinburgh since 2016. She has around 50% clinical duties and otherwise performs clinical and non-clinical research related to Canine Gastroenterology. She has published around 25 papers on topics related to Canine Gastroenterology and authored or co-authored several chapters in Small Animal Internal Medicine/Gastroenterology books.

 


Abstract

Chronic enteropathy (CE) or inflammatory bowel disease (IBD) is a common spontaneously occurring idiopathic inflammatory diseases of the gastrointestinal tract in pet dogs. The routine treatment involves dietary modification, antimicrobials (usually tylosin or metronidazole) and immunosuppressive dosages of glucocorticoids. However, there is increasing concern about the long-term use of antimicrobials in this context, and alternative treatment options have been sought. In addition, a number of dogs will not respond well to the traditional treatments mentioned above. Alternative ways to modify the microbiota, which are heavily implicated as one of the drivers of intestinal inflammation (usually in a genetically predisposed host, even though not a lot about genetic risk is known in dogs), that can be considered for these cases include the administration of probiotics or faecal microbiota transplantation (FMT). The most commonly used probiotic in small animals is Enterococcus faecium; however, so far there is not much evidence to suggest it as beneficial in canine CE or IBD cases, as it has a rather pro-inflammatory profile in ex-vivo studies and whole blood assays and did not lead to a significant clinical improvement compared to placebo in dogs with food-responsive CE in a clinical trial. Other commercially available products like mixtures of several probiotic strains (e.g. VSL#3®) are more promising, as there is some evidence that they can be clinically effective as a combination of metronidazole and prednisolone, and functionally can lead to an increase of regulatory T cells within the intestinal mucosa in dogs with IBD. Even though there is an increasing understanding of the canine intestinal and faecal microbiota composition, characteristics and function, there is only anecdotal evidence to support FMT in CE or IBD. Some preliminary data on its clinical success will be presented.

 

Biography

Lakhbir Kaur—MBBS, PGCert (Medical Leadership), AFHEA (Associate fel­low of Higher Education Academy)—obtained her Medical Degree at Queen Mary University of London. She then went on to complete her foundation training at Blackpool Teaching Hospitals and is currently working as a Medi­cal Demonstrator at the University of Central Lancashire. She is undertaking a MRES looking at the use of probiotics in ulcerative colitis.

 


Abstract

Background: Antibiotic resistance is a global concern, threatening the medical field and proving to be a challenge to overcome. The World Health Organisation has identified E. coli as one of the most deadly bacteria with as many as half of the patients around the world not being able to receive treatment due to antibiotic resistance.

Aim: The aim was identify how frontline staff can best tackle antibiotic resistance through looking at prescriptions.

Method: NICE guidelines have stated that nitrofurantoin is first line for urinary tract infections, while previously it was trimethoprim. Therefore, we looked at a general practice (GP), where patients first encounter antibiotics to see whether they received the correct antibiotics. In a three month period, we identified patients who were prescribed trimethoprim and analyzed the results using the following format: correct dose; correct duration; indication documented; why was nitrofurantoin not used: (1. intolerance, 2. allergy, 3. eGFR<30, 4. drug interaction, 5. C&S, 6. other) and; MSU sent appropriately?

Results: 154 patients were identified as having trimethoprim prescribed. 124 patients did not have a reason documented as to why trimethoprim was used over nitrofurantoin. 10 patients did not have the correct duration of antibiotics. 75 MSU’s were sent, of which only 53 were inappropriate.

Conclusion: 124 (80%) of the patients in a three month period potentially did not receive the correct antibiotic. This leaves scope for antibiotic resistance. We realised that the change in the guidance was not communicated through to many of the prescribing staff who are not GP’s themselves and are therefore not in a routine of updating themselves on current guidelines. The WHO organization is striving for changes to tackle the issue of antimicrobial resistance. If these issues are not communicated to front line staff it will be very difficult for to overcome this challenge. The current GP practise has emailed all staff of the change and a second audit is being undertaken.

 

Biography

Collins Njie Ateba has completed his PhD from the North-West University, South Africa. He also received professional training in the Centre of Medical Genetics and Primary Health Care, Yerevan State University, Yerevan, Arme­nia in 2006; Department of Microbiology, Tartu University, Tartu, Estonia in 2007 and the Lethbridge Research Centre, Lethbridge Alberta, Canada in 2014. He is currently an Associate Professor in the Department of Micro­biology, Faculty of Natural and Agricultural Sciences, North-West University, Mafikeng Campus and is the Head of the Department of Microbiology as well as the Water, Food Safety and Phage Therapy/Biocontrol Research Lab­oratory. He is actively involved in research training and lecturing at both un­dergraduate and postgraduate levels. He has been serving as a Host Mentor for the DST/NRF internship program from 2011 till date. He has published more than 30 papers in reputed journals and has been serving as an Editorial Board Member of repute. He has presented research papers in a number of conferences locally and internationally. He is currently classified as an Established Researcher in the “C3” category by the National Research Foun­dation of South Africa.

 


Abstract

 

E. coli O157:H7 is an important causative agent of a variety of food-borne infections including hemorrhagic colitis (HC) and hemolytic uremic syndrome (HUS) in humans. The main source of infection is contaminated food of animal origin and a number of animal species, especially cattle have been associated with this pathogen. Contamination usually occurs when faeces of animals get into contact with carcass during slaughtering. The aim of the present study was to determine the virulence profiles and genetic relationships of E. coli O157:H7 strains isolated from cattle of some commercial farms in the North West Province, South Africa. A motivation is that results may enhance our knowledge of on-farm ecology of E. coli O157:H7 strains as well as their potential to cause diseases in humans. A total of 260 faecal samples were collected from eight farms over a six-month period and assessed for the presence of E. coli O157:H7 through PCR analysis. STEC virulence genes stx1, stx2, eaeA and the hlyA were detected using PCR. The genetic relatedness of the isolates was determined using random amplified polymorphic DNA (RAPD) and pulsed-field gel electrophoresis (PFGE) bacteria 16S rRNA gene fragments were amplified as an internal control, while the rfbO157 and flicH7 gene PCR were used to confirm identities of isolates. A total of 69 (26.5%) E. coli O157:H7 isolates were detected in samples obtained from all the eight farms. The large proportions of the E. coli isolates possessed the stx1 (66.7%) and stx2 (97.1%) genes, respectively. In addition, other accessory virulence genes such as eaeA and hlyA were detected in 30 (43.5%) and 43 (62.3%) of the E. coli isolates, respectively. Pulsed-field gel electrophoresis (PFGE) analysis grouped these isolates into six clusters of closely related types, and the predominant cluster comprising of 17 isolates originating from different farms under study. These results provide valid evidence that cattle harbor virulent and genetically similar E. coli strains particularly those belonging to the serotype O157 and therefore these animals may serve as possible source for zoonotic transfer of these pathogens to humans. The implication is that these isolates may have severe public health consequences on consumers.

 

Biography

Samuel Oppong Bekoe completed his PhD in Pharmaceutical Sciences from the University of Copenhagen, Denmark. He has worked as a Senior Lecturer of Pharmaceutical Chemistry at the Department of Pharmaceuti­cal Chemistry since August 2016 and as a Lecturer since August 2005 at the Faculty of Pharmacy and Pharmaceutical Sciences, KNUST. He has 13 publications in reputed journals and a book chapter.

 


Abstract

The use of substandard or poor quality antibacterial agents contributes to treatment failures and emergence of antibacterial resistance. Unfortunately, unregulated sale and dispensing of antibacterial agents, especially, in the informal sector through street vending, play a major role in these phenomena. Thus, poor quality antibacterial agents are in circulation with consequent treatment failures and development of resistant strains of pathogens. This study, therefore sought to establish the chemical quality of antibacterial agents in the formal and informal supply chain of selected sites in Ghana, understand why consumers use supplies from informal outlets, and design strategies for improved drug supply management for effective control of antibacterial resistance. Interviews and field observations were carried out to collect data on behaviour and attitudes associated with the use and misuse of antibacterial agents obtained from informal sources and dispensed for use in Ghana. High-throughput LC-MS/MS technique was used to determine the presence and levels of 14 most popular antibacterial active ingredients in 348 pharmaceutical dosage forms acquired from 25 formal (hospitals/health centres, pharmacies, licensed chemical shops) and 10 informal (street vendors) suppliers in Ghana. The first port of call for antibiotic consumers was ‘self-treatment’ with drugs acquired from informal suppliers due to convenience and affordability. The levels of active pharmaceutical ingredients determined were substandard in majority of samples from both formal and informal supply outlets. Higher proportion of products from informal supplies were substandard, with 91% of street vendor samples containing <90% API, out of which 58% contained <50% API. Hence, it can be concluded that substandard antibacterial agents in health delivery systems in Ghana is a reality. An improved and coordinated regulatory action through continuous monitoring and enforcement should fortify other efforts to control antibacterial resistance in Ghana.

 

Biography

Paul J M Sessink studied Chemistry (Organic Chemistry and Toxicology) at the University of Nijmegen (Radboud University) in The Netherlands. In November 1996, he attained a PhD in Medical Sciences at the University of Nijmegen by defending his thesis entitled, “Monitoring of occupational exposure to antineoplastic agents”. In 1995, he founded Exposure Control, a consulting firm that has developed a broad spectrum of methods for envi­ronmental and biological monitoring of hazardous drugs which are of great concern to the (occupational) population world-wide due to potential ad­verse health-effects. He is the Co-Author of approximately 40 scientific pub­lications regarding environmental and biological monitoring of occupational exposure to cytotoxic drugs. An overview of his publications is available on the website www.exposurecontrol.net.

 


Abstract

 

Antibiotics are used in the treatment and prevention of bacterial infections and in the treatment of autoimmune diseases. Preparation and administration of antibiotics is widespread over many departments in hospitals and many healthcare workers are involved in handling these drugs daily. Most common side effects in patients include rash, diarrhea, nausea and vomiting. Allergies or hypersensitivity reactions, and especially anaphylactic reactions are the most severe side effects. Adverse health effects of occupational exposure to antibiotics in healthcare workers are scarcely published. Weak and moderate effects include hypersensitivity, allergic skin reactions and respiratory symptoms. More severe effects include drug resistance and even anaphylactic shock. Healthcare workers handling antibiotics, frequently report that they smell the drugs, have a bitter taste in their mouth, and observe splashes and leakages during the preparation. Piperacillin and ceftriaxone are reported to have additional handling issues that perpetuate the problem. Syringe withdraws from these vials result in leakage along the needle’s shafts. Considering all these aspects, there is a concern that healthcare workers continuously exposed to levels of antibiotics may suffer from adverse health effects, raising a need to reduce potential exposure as much as possible. A few studies were performed, monitoring antibiotics at different departments in hospitals in Europe. The aim was to measure contamination on surfaces during preparation and administration of antibiotics using the most common needle/syringe or needle/spike/syringe combination. Surface contamination was measured by taking wipe samples from potentially contaminated surfaces. The most frequent antibiotics were monitored: vancomycin, meropenem, augmentin, ceftriaxone, cefotaxime, cloxacillin, piperacillin and benzylpenicillin. Extracts of wipe samples were analyzed using LC-MS/MS (detection limit: 1 ng/ml extract or 100 ng per sample) and contamination levels were calculated in ng/cm2. The results of the studies show widespread contamination with antibiotics at nursing departments resulting in potential exposure of the healthcare workers.

 

Biography

Reza Nassiri is a former Associate Dean of Global Health and Director of Institute of International Health at Michigan State University. He is current­ly Professor of Clinical Pharmacology and Family Medicine/Community Health. He is an Expert on Global Health issues, Tropical Diseases and Infec­tious Diseases including HIV/AIDS and Tuberculosis. His current research is focused on antibiotic resistance, public health aspects of tropical disease and infectious diseases, and gaps in HIV/AIDS care delivery systems.

 


Abstract

Antibiotic resistance is one of the largest threats to global health, food security, and development today. The incredible rapid emergence of antibiotic resistance which is taking place worldwide is not only a serious threat to the practice of modern medicine, but equally important, a threat to global public health. The CDC and WHO surveillance data shows that the resistance in E. coli is generally and consistently the highest for antibacterial agents in both human and veterinary medicine. The five riskiest superbugs are recognized as: 1. MRSA; 2. the hospital lurkers: C. diff and Acinetobacter; 3. the food borne pathogens: E. coli and Salmonella; 4. the sexually-transmitted infections: gonorrhea and chlamydia and; 5. tuberculosis. India is a typical example of encountering the deadly bacterial resistance. The discovery of the New Delhi metallo-beta-lactamase-1 (NDM-1) which disables almost all antibiotics directed against it was a turning point in the rapid emergence of blaNDM-1 gene which was first identified in 2008 in people who had traveled in India or sought medical care in South Asia. Tourists can pick up antibiotic-resistant genes in just 2–3 days. The discovery of mrc-1 gene in China which is being transferred between Klebsiella pneumoniae and E. coli further compounded the global burden of antibiotic resistance, and which has already spread to the neighboring countries. In conclusion, antibiotic resistance can affect anyone, of any age, in any country primarily due to misuse of antibiotics in humans and animals is accelerating the process. A growing number of infections–such as pneumonia, tuberculosis, gonorrhea, and salmonellosis – are becoming harder to treat as the antibiotics used to treat them become less effective which may leads to longer hospital stays, higher medical costs and increased mortality.