Scientific Program

Day 1

KEYNOTE SPEAKERS
  • The hollow fiber infection model: principles and practice

    University of Miami
    USA
    Biography

    John J.S. 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, outside of London. He served in various capacities in the biomedical research fields until 2000 when he was founder of 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. 2 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 identified 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; and the disadvantages of it include open system (not bio safe), bacteria numbers change over time, large volume requires large amount of drug and diluent, rapid changes in drug concentration is not possible and cannot model the short half-lives. Animal models have many shortcomings though they have served as a primary development tool for many years because PK/PD may not match human values, cannot sample same animal over time, difficult to study large numbers of bacteria to reveal resistance and many infections cannot be modeled in a mouse or other animal. To address these shortcomings the two-compartment in-vitro pharmacokinetic model utilizing hollow fiber bioreactors was developed, the hollow ber infection model (HFIM). The advantages of the HFIM are as follows: Closed bio-safe system, large number of organism can be tested, revealing resistance, precisely simulates human PK/PD, repetitive sampling over time, both drug and organism, total kill can be determined, single use, disposable, reproducible, two drug models can be tested, can model both dosing curve and elimination curve and 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.

  • Metadichol a novel nano lipid: a solution for the post-antibiotic era

    CEO of nanorx inc.
    USA
    Biography

    CEO of Nanorx INC has a Ph.D. in Organic Chemistry from Oregon State University(1979) and an M.S in Chemistry(1972) from I.I.T Mumbai, India.He has worked on drug discovery for over 25 years at Columbia University, Max-Planck Institute, Germany, Ciba-Geigy (now Novartis) and Boehringer Ingelheim. He has over 15 US and International patents and another 15 pending patent applications

    Abstract

    Metadichol is a nanoemulsion of long-chain alcohols found in many foods such as rice, sugar cane, wheat, peanuts etc. Metadichol acts as inverse/protean agonist on nuclear vitamin D receptors (VDR) that are present in cells throughout the body to stimulate the immune system. Metadichol is a class of unique nanoemulsion molecules that are active against in-vitro viruses, bacteria and parasites. In assays, metadichol showed no cytotoxicity and strongly inhibited cell death caused by each of the pathogens tested. It is a safe and effective inhibitor of various human pathogens. In addition to acting on VDR it shows cross reactivity against other nuclear receptors. And how this leads to mitigation of infections including gene expression analysis and human clinical case studies will be presented. Because it consists of natural components of conventional foods and has no known negative side effects, it has the potential to serve as a novel, broad-spectrum treatment against viruses, bacteria and parasites that confront public health today without eliciting a resistance, that is characteristic of the therapeutics in the market today.

  • Delayed inflammatory response renders diabetic wound vulnerable to infection and microbiome shift toward pathogenic bacteria

    Rush Medical College USA
    USA
    Abstract

    Enhanced bacterial infection and microbiome shift toward pathogenic bacteria are major co-morbidities that contribute to impaired healing in diabetic ulcer. The underlying reasons for the impaired infection control in diabetic wound remain poorly understood. We used the cutaneous full-thickness wound models in STZ-injected type 1 diabetic (T1D) rats and db/db T2D mice, to study the early dynamics of bacterial infection control in normal and diabetic wound tissues. Surprisingly, we have found that unlike chronic diabetic ulcers which suffer from persistent unresolving inflammation, the acute phase of inflammatory response- which is needed to counter invading pathogens early after injury- is significantly delayed in diabetic wounds, rendering these wounds susceptible to bacterial infection and healing impairment. Importantly, treatment with a pro-inflammatory chemokine jumpstarts inflammatory response and promotes healing in diabetic wound, indicating that inadequate inflammatory response early after injury in diabetic wound is just as harmful as the persistent inflammatory state that dominates these wounds as they become chronic. Our data further suggest that normal wound tissues express pathogen-specific antimicrobial peptides (ps-AMPs) that preferentially target pathogenic bacteria amongst commensals by recognizing specific virulence structure(s) that are only found in pathogenic bacteria. In contrast, pathogen-specific antimicrobial defenses are impaired in diabetic wounds, thus setting the stage for the microbiome shift toward pathogenic bacteria. We further show that the inability to control pathogenic bacteria leads to persistent inflammatory state and impaired healing in diabetic wound. We posit that inadequate chemokine expression in diabetic wound early after injury leads to delayed inflammatory response, which in turn results in reduced ps-AMPs, rendering diabetic wound vulnerable to infection with pathogenic bacteria, which exacerbate wound damage and drive diabetic wound toward persistent unresolving inflammatory state. We further propose that pro-inflammatory chemokine therapy may be used to jumpstart inflammatory response and restore antimicrobial defenses and stimulate healing in diabetic wound.

  • SYN-004 (ribaxamase), an orally administered ?-lactamase for prevention of Clostridium difficile infection; colonization by antimicrobial resistant pathogens and preservation of the diversity of the gut microbiome

    Synthetic Biologics, Inc.
    USA
    Biography

    John F. Kokai-Kun, PhD is Vice President of Non-clinical Affairs for Synthetic Biologics, Inc. (Rockville, MD). He received his BS in Biochemistry from Juniata College in Huntingdon, PA and his PhD in Microbiology from the University of Pittsburgh, School of Medicine. He served as a post-doctoral researcher at the Uniformed Services University of the Health Sciences in Bethesda, MD. Dr. Kokai-Kun has 20 years of experience in the drug development industry and has held positions with several biotechnology and pharmaceutical companies where his research and development efforts have focused primarily on anti-bacterial drugs and vaccines. He is also an Adjunct Assistant Professor of Microbiology and Immunology at the Uniformed Services University.

    Abstract

    SYN-004 (ribaxamase) is an orally administered ?-lactamase designed to be given with IV ?-lactam antibiotics. Ribaxamase remains localized in the intestine where it is available to degrade excreted ?-lactam antibiotics which protects the gut microbiome from disruption by these still functional antibiotics. This protection of the gut microbiome is expected to prevent the deleterious effects of the antibiotics including, Clostridium difficile infection (CDI), colonization by opportunistic pathogens and emergence of antibiotic resistance in the gut. Ribaxamase was well tolerated in Phase 1 clinical studies and efficiently degraded ceftriaxone excreted into the human intestine in Phase 2a clinical studies, where it also did not alter the plasma pharmacokinetics of the ceftriaxone. A global Phase 2b, double-blind, placebo-controlled study was conducted to determine whether ribaxamase could prevent C. difficile infection with additional endpoints for antibiotic-associated diarrhea, colonization by opportunistic pathogens, changes in the gut microbiome and emergence of antibiotic resistant organisms in the gut. Four hundred and twelve patients, a modified intent to treat population, enriched for higher risk for CDI, were admitted to the hospital for at least 5 days of IV ceftriaxone for treatment of a lower respiratory tract infection. Patients were randomized 1:1 to receive ribaxamase or placebo during treatment for 72 hours. Later fecal samples were collected at pre-specified points for determination of colonization by opportunistic pathogens and to examine changes to the fecal microbiome. Patients were monitored for 6 weeks after antibiotic treatment for CDI (as defined as diarrhea plus the presence of C. difficile toxin as determined by the local clinical laboratory). The study was powered at 80% for the reduction in CDI with a 1-sided alpha = 0.05. The study met its primary endpoint with a 71.4% relative risk reduction in CDI (1-sided p=0.0454), a statistically significant 43.9% relative risk reduction in new colonization by vancomycin resistant enterococci (1-sided p=0.0002) and demonstration of significant protection of the gut microbiome in the ribaxamase group as compared with the placebo group. These data support that ribaxamase maintains the balance of the gut microbiome, thereby preventing opportunistic infections like CDI and preventing colonization by opportunistic antibiotic-resistant pathogens.

  • Key role of cutaneous neuropeptides in skin-bacterial communication and virulence

    Normandie Universite, France
    France
    Biography

    Marc G J Feuilloley has started his carrier in Cell Biology and Endocrinology an INSERM unit before tuning to Microbiology in 1996. When he joined his present research laboratory (LMSM) of which he is Director since 2008 and where he has developed Microbial Endocrinology. He is an Invited Professor at the Max Plank Institute, expert for national and international agencies. He is managing a parallel technology transfer society for cosmetic and pharmaceutical industry and is involved in the 1st world pole in cosmetic industry (Cosmetic-Valley). He is the author of 138 articles in international journals and more than 340 oral and poster communications in national and international conferences.

    Abstract

    Skin is the principal neuroendocrine organ of the human body but it is also hosting its second microbial population. In skin, neuropeptides released by nerve terminals and cells diffuse in upper epidermal layers and sweat and it was recently shown that some of these peptides control skin bacteria virulence. Substance P, CGRP and Atrial Natriuretic Peptides (ANP, CNP) can be detected by bacteria between micro- and pico-molar concentrations through moonlighting (i.e. multifunctional) proteins, such as the Thermo Unstable Ribosomal Elongation Factor (EfTu), the chaperone DnaK or the amidase AmiC which are translocated to the bacterial surface through specific systems, including MscL mechanosensitive channels, and acquire environmental sensor functions. Substance P, CGRP, ANP and CNP are without effect on bacterial growth at physiological concentrations but modulate the cytotoxicity, virulence and biofilm formation activity of very different skin bacterial species, such as Staphylococcus aureus, Staphylococcus epidermidis, Bacillus cereus, Pseudomonas fluorescens or Propionibacterium acnes. The effect of neuropeptides on bacteria is generally rapid (<5 min) but can last for days in the case of biofilm formation and leads to dramatic increases of virulence (>400%). Some of these neuropeptides, such as substance P and CGRP, have antagonistic effects. Others are only acting on one specific species, such as CGRP on S. epidermidis or have opposite actions, such as CNP on biofilm formation by S. aureus and P. acnes. The microbiote is integrating these host signals which determine its aggressivity and skin reaction. New dermo cosmetic products are now designed on this basis.

  • Rapid diagnosis of drug-resistant tuberculosis

    The University of Hong Kong, Hong Kong
    Hong Kong
    Biography

    WC Yam is currently an Associate Professor in the Department of Microbiology, Faculty of Medicine from the University of Hong Kong. As a Clinical Scientist and Fellow Member of Royal College of Pathologists, he aims at rapid diagnosis of emerging infectious diseases including tuberculosis, drug resistant HIV-1, and SARS Corona virus which he had achieved major advancement for clinical application. More recently, he has been using molecular method to study drug resistant Mycobacterium tuberculosis and HIV. The studies on multi-drug resistant Mycobacterium tuberculosis and HIV-1 have included the development of Next Generation Sequencing.

    Abstract

    Tuberculosis (TB) has reemerged as a global public health concern with an annual mortality of 3 millions. Coincident with the resurgence of tuberculosis, there is also an alarming increase of infections, due to multiple drug resistant tuberculosis (MDR-TB) organisms which are resistant to two or more of the first line anti-tuberculosis drugs including isoniazid and rifampicin. Recent threat has included extensively drug resistant tuberculosis (XDR-TB) defined as MDR-TB resistant to any fluoroquinolone and at least one second-line injectable drug. For rapid diagnosis of Mycobacterium tuberculosis (M. tb), Nucleic Acid Amplification assays such as PCR facilitates the adequate and timely management of antituberculosis therapy. Conventional antimycobacterial susceptibility testing remains the standard protocol to monitor drug resistant strains. More than 90% of rifampicin resistant M. tb has been shown to be caused by mutations inside the 81-bp rifampicin resistance determining region (RRDR) located in the center of the rpoB (encodes for ?–subunit of the RNA polymerase) gene. In Hong Kong, PCR-sequencing of rpoB gene of M. tb isolates revealed mutations in codons D516V, H526D and S531L inside RRDR accounted for most rifampicin-resistant M. tb. PCR-sequencing also identified hotspot mutations at positions 90, 91 and 94 of gyrase A (gyrA) gene accounted for over 85% of Ofloxacin-resistant M. tb in Hong Kong. For isoniazid resistance, multiple allele-specific PCRs (MAS-PCRs) assays targeting the mutations in codon 315 of katG gene and the 15th nucleotide preceding the mabA-inhA operon successfully identified 60-75% isoniazid-resistant M. tb in clinical specimens. Using PCR-sequencing, novel mutations associated with rifampicin and Ofloxacin resistance were also identified among treatment experienced patients. Current study on massive parallel targeted sequencing (MPTS) for simultaneous prediction of drug susceptibility in Mycobacterium tuberculosis from respiratory specimens shows promising results. The cost-effectiveness of development, introduction and availability of these methods for rapid diagnostics improves public health control and early initiation of anti-tuberculosis therapy.

oral sessions
Speaker
  • Rapid detection of bacterial resistance to ?-lactam antibiotics using liquid chromatography – tandem mass spectrometry
    Speaker
    Michael Thompson
    Thompson Group Bioanalytical Chemistry
    Canada
    Biography

    Professor Michael Thompson obtained his undergraduate degree from the University of Wales, UK and his PhD in analytical chemistry from McMaster University. Following a period as Science Research Council PDF at Swansea University he was appointed Lecturer in Instrumental Analysis at Loughborough University. He then moved to the University of Toronto where he is now Professor of Bioanalytical Chemistry. He has held a number of distinguished research posts including the Leverhulme Fellowship at the University of Durham and the Science Foundation Ireland E.T.S Walton Research Fellowship at the Tyndall National Institute, Cork City. He is recognized internationally for his pioneering work over many years in the area of research into new biosensor technologies and the surface chemistry of biochemical and biological entities. He has made major contributions to the label-free detection of immunochemical and nucleic acid interactions and surface behavior of cells using ultra high frequency acoustic wave physics. Thompson has served on the Editorial Boards of a number of major international journals including Analytical Chemistry and The Analyst and is currently Editor-in-Chief of the monograph series “Detection Science” for the Royal Society of Chemistry, UK. He has been awarded many prestigious international prizes for his research including The Robert Boyle Gold Medal of the Royal Society of Chemistry and the E.W.R. Steacie Award of the Chemical Society of Canada. He was made a Fellow of the Royal Society of Canada in 1999.

    Abstract

    Antibiotic susceptibility testing (AST) can involve automated platforms that produce results in 10 hours following bacterial colony growth. However, AST may require 10-72 hours before definitive, individualized treatment can begin. An assay was developed for the detection of bacterial resistance due to enzymatic degradation of ?-lactam antibiotics with the goal of designing a liquid chromatography – tandem mass spectrometry acquisition method capable of performing AST at an accelerated rate in comparison to the current standards. The assay consisted of a one-hour bacterial incubation with a multiplexed panel of ampicillin, cefazolin, cefotaxime, and imipenem at 0.5 ?g/mL, and a concurrent incubation of cefoxitin at 2 ?g/mL. The assay used the extent of antibiotic hydrolysis as a means of measuring resistance quantitatively. Hydrolysis percentages were obtained by chromatographic peak area integration. The assay could differentiate between three types of ?-lactamase enzymes: carbapenemases, Class A ?-lactamases and Class C Amp C ?-lactamases. An antibiotic resistance profile for a single clinical isolate could be obtained in 2 hours and 35 minutes following bacterial colony growth.

  • Clinical and cost-effectiveness evidence of S53P4 bioactive glass in the eradication of osteomyelitis
    Speaker
    Jacobus Johannes Christiaan Arts
    Maastricht University
    Netherlands
    Abstract

    Introduction: S53P4 bioactive glass is a novel biodegradable antibacterial bone graft substitute that enables a one-stage surgery in local chronic osteomyelitis treatment. This study assessed eradication of infection and bone healing capacities of S53P4 bioactive glass in a cohort of 25 osteomyelitis patients. Secondly, we performed an cost-effectiveness analysis of two-stage surgery with PMAA antbiotic beads versus one-stage with S53P4 bioactive glass in a cohort of 37 patients. Methods: All patients with clinically, haematologically and radiologically evident chronic osteomyelitis were included and treated with extensive debridement surgery, S53P4 bioactive glass implantation and systemic antibiotic administration. Primary endpoint was eradication of infection based on clinical, blood samples and radiological outcomes. Secondly, we conducted a retrospective cohort study and all patients with chronic osteomyelitis in long bones, who received one of two treatment algorithms, from 2006 until 2015 were included. All hospital-related costs from diagnosis until one year postop were clarified and compared. Patient outcomes were eradication of infection based on blood analysis, X-ray imaging and clinical outcomes. Results: Between 2011-2016, 25 patients were included with a mean follow-up of 23 months (4–57). Hospital stay was short with a mean of 18 days (4–40) and patients required an average of 1.4 surgeries (1–4). The inflammatory parameter C-reactive protein (CRP) showed normalization after a mean duration of 46 days. At the end of follow-up haematological and clinical outcomes showed eradication of infection in 24 (96%) of all patients. Radiological assessment showed that none of all patients exhibited persisting signs of infection and bone healing was observed in 22 (88%) patients based on changes on conventional radiology. A total of 37 patients are included in the costeffectiveness study, based on treatment 16 patients were allocated to the S53P4 group and 21 to the control group. These groups were not significantly different at baseline. We observed a decrease in hospitalization days of 14 days (p<0.001) and the number of surgeries decreased from 2.33 to 1.25 (p<0.001). Despite the higher material costs versus €2.132,50 to €362,97 (P=0.004), we observed total costs of €18.586,49 in the treatment group versus €27.134,96 in the control group. Eradication of infection is seen in 100% of patients in the treatment group compared to 76% in the control group (p=0.066). The combination of the total costs and the success rates of these two treatments result in an incremental cost-effectiveness ratio (ICER) of €-35.618,63/successfully treated patient.

  • Development of bacteriophage therapy for novel treatment of antibiotic-resistant bacterial infections
    Speaker
    Terry Ann Else
    Touro University Nevada
    USA
    Biography

    Terry Ann Else obtained her PhD at the University of Nevada, Las Vegas in 2002. She is an Associate Professor at Touro University Nevada teaching medical microbiology/immunology to medical and graduate level students since 2004. She is board certified as a Clinical Laboratory Scientist. Her research interests include bacteriophage therapy research studying the pathogens, Streptococcus pneumoniae and Neisseria gonorrhoeae, in collaboration with Associate Professor Karen Duus, PhD also at Touro University Nevada. Terry Ann Else has been active in the American Society for Microbiology and served as regional planning coordinator for local ASM branches in the southwestern US and Hawaii.

    Abstract

    Since their discovery, antibiotics have become a widely used antidote to bacterial infections. However, the prevalent use of antibiotics and the adaptability of bacteria give rise to antibiotic-resistant bacterial strains. Bacteriophages were discovered at about the same time as antibiotics, but with a few exceptions, their use against infectious bacterial pathogens is not common. The objective of this research effort is to isolate and characterize novel lytic bacteriophages against specific bacterial pathogens that can be used in lieu of or in combination with antibiotics. We chose two pathogenic bacterial species (Streptococcus pneumoniae and Neisseria gonorrhoeae) for which antibacterial resistance is becoming widespread and is of great public health concern. According to the CDC in the US, Streptococcus pneumoniae is responsible for approximately 22,000 deaths annually and the number of Neisseria gonorrhoeae infections currently averages approximately 350,000 cases per year. Our sources of bacteriophage populations were water pools located in Boulder Beach (Nevada), Amargosa Valley (Nevada) and wastewater collected from local treatment facilities in Las Vegas, Nevada. Our approach was to amplify bacteria species-specific bacteriophages from these samples by enriching for those phages able to be amplified through lytic infections of the specific bacteria. DNA sequencing and phage community analyses results suggest that the water samples used in our studies contain numerous bacterial-specific lytic phages.

  • Disulfide bond formation in gastric pathogen Helicobacter pylori: An Achillae’s heel for secretion of pro-inflammatory virulence proteins
    Speaker
    Carole Creuzenet
    The University of Western Ontario
    Canada
    Biography

    Carole Creuzenet has completed her PhD in Biochemistry at the University of Nantes and The National Institute for Agronomical Research (France). She has completed her Post-doctoral studies at the Massachusetts Institute of Technology (USA) and the University of Guelph (Canada). She is Associate Professor at the University of Western Ontario (London, Canada) where her lab focuses on virulence factors from bacterial gastrointestinal pathogens such as Campylobacter jejuni, Helicobacter pylori and Yersinia pseudotuberculosis. Her focus is on glycolipids and glycoproteins as well as on novel secreted proteins and their folding partners. She has published 38 papers in reputed journals.

    Abstract

    H. pylori causes gastritis, gastric ulcers and cancers but the mechanisms of virulence are not fully understood. It produces secreted proteins which may play a role in eliciting gastric inflammation, including the helicobacter cysteine rich protein HcpE (HP0235) whose biological function is unknown. Our goal was to investigate if HcpE is secreted by H. pylori and is involved in host/pathogen interactions, and identify components essential for its production. Using a combination of anti-HcpE ELISA and western blots, knockout mutagenesis, phenotypic analyses and biochemical assays, we demonstrate that HcpE is secreted by many strains as a soluble protein and in association with outer membrane vesicles. We show that infected patients produce anti-HcpE antibodies, indicating in situ HcpE production. We show that HcpE comprises many disulfide bonds and identify DsbK (HP0231) as a folding factor necessary for HcpE production, and show that recombinant DsbK can refold unprocessed, reduced HcpE in vitro. This highlights the first biologically relevant substrate for DsbK. Furthermore, we show that DsbK has disulfide bond (Dsb) forming activity on reduced lysozyme and has DsbA-like activity upon expression in E. coli, despite its similarity with DsbG. Also, we show a role of DsbK in redox homeostasis in H. pylori. Finally, we show an important role for DsbK and HcpE in host-pathogen interactions, including murine gastric colonization and pro-inflammatory cytokine production in human gastric explants and in murine splenocytes. Both proteins will be investigated as therapeutic targets to treat H. pylori infections and prevent gastric ulcers and cancers.

Antimicrobials Resistance
Microbial Pathogenesis
Antimicrobial Stewardship
Antibiotics

Day 2

KEYNOTE SPEAKERS
  • Antivirulents vs. Antibiotics

    Case Western Reserve University
    USA
    Abstract

    Antimicrobial resistance poses one of the most severe global challenges to public health. Increased resistance of pathogens to antibiotics coupled with the paucity of development of new antibiotics threatens to propel us back into the pre-antibiotic era when infectious diseases were the most frequent cause of death. The inherent problem with antibiotics is that sooner or later resistance emerges and the antibiotic becomes ineffective. Antivirulence agents represent an attractive alternative to antibiotics. These agents disarm the pathogen of its disease-causing toxins and virulence factors without killing the organism, thereby eliminating the selective pressure that frequently results in resistance. Indeed, emergence of resistance to an antivirulence agent has not been reported, to the best of my knowledge. Moreover, since antivirulence compounds do not kill the bacteria, this would also prevent the collateral damage caused by antibiotics to the beneficial commensals that colonize humans. Antivirulence treatment leaves the host immune system intact to carry out its task of clearing an infection. However, for immunocompromised patients combination therapy with an antibiotic would be in order. Some antivirulence agents potentiate the efficacy of antibiotics, such that even obsolete antibiotics could be brought back into the clinic. Moreover, antivirulence agents have been shown to inhibit biofilm formation and promote would heal. Thus, antivirulence agents may provide a solution to the global threat of antimicrobial resistance.

  • Progress in replacing antibiotics in farm animal production

    University of Maryland
    USA
    Biography

    Dr. Debabrata Biswas is an Assistant Professor of Food Safety in the Department of Animal and Avian Sciences, and Center for Food safety and Security Systems at the University of Maryland-College Park, MD. Dr. Biswas is a bacteriologist and has committed to develop crosscutting research programs in foodborne bacterial infection control and food safety area. His research focuses on developing alternatives to sub-therapeutic (growth promoting) and therapeutic (animal disease control) and mitigate the emerging issue of antibiotic resistance bacterial pathogens in farm animal production system. His research also target to define the colonization mechanism of foodborne zoonotic bacterial pathogens their in animal reservoirs and the mechanism by which pathogens become resistance against antimicrobial components. He also investigates the role of natural products in control of foodborne bacterial colonization in animals and mechanism of antimicrobial activity of these components.

    Abstract

    The current trend in the development of antibiotic resistance by multiple bacterial pathogens has resulted in a troubling loss of effective antibiotic options for human. The emergence of multi-drug-resistant pathogens has necessitated higher dosages and combinations of multiple antibiotics, further exacerbating the problem of antibiotic resistance. Zoonotic bacterial pathogens, such as Salmonella, Campylobacter, Shiga toxin-producing Escherichia coli (such as enterohemorrhagic E. coli or EHEC) and Listeria are the most common and predominant foodborne enteric infectious agents. It was observed that these pathogens gained/developed their ability to survive in the presence of antibiotics either in farm animal gut or farm environment and researchers believe that therapeutic and sub-therapeutic antibiotic use in farm animal production might play an important role in it. The mechanism of action of antimicrobial components used in farm animal production in genomic interplay in the gut and farm environment, has not been fully characterized. Even the risk of promoting the exchange of mobile genetic elements between microbes specifically pathogens needs to be evaluated in depth, to ensure sustainable farm animal production, safety of our food and mitigate/limit the enteric infection with multiple antibiotic resistant bacterial pathogens. Due to the consumer’s demand and considering the current emerging situation, many countries are in process to withdraw antibiotic use in farm animal production. Before withdraw the sub-therapeutic antibiotic or restrict the use of therapeutic antibiotics in farm animal production, it is essential to find alternative natural antimicrobials for promoting growth of farm animal and/or treating animal diseases. Further, it is also necessary to consider whether that compound has the potential to trigger the acquisition or loss of genetic materials in zoonotic and any other bacterial pathogens. Development of alternative therapeutic and sub-therapeutic antimicrobials for farm animal production and food processing and preservation and their effective implementation for sustainable strategies for farm animal production as well as the possible risk for horizontal gene transfer in major enteric pathogens will be focus in the presentation.

oral sessions
Speaker
  • Implementation of antimicrobial stewardship in inpatient and outpatient settings
    Speaker
    Karisma Patel
    Children’s Mercy Kansas City
    USA
    Abstract

    Antibiotic resistance is currently one of the greatest global public health concerns. Antimicrobial stewardship (ASP) has been gaining regulatory interests in an effort to slow the spread of antibiotic resistance and improve antibiotic-related patient safety outcomes. Effective January 1, 2017, The Joint Commission implemented a Medication Management standard of practice for ASP. Additionally, the Centers for Medicare & Medicaid Services has a pending Condition of Participation on ASP and the White House’s Action Plan includes the establishment of ASP programs in all acute care hospitals and improved ASP across all healthcare settings by 2020. In 2016, IDSA and SHEA released new guidelines that focus on the implementation of an effective antimicrobial stewardship program. Strategies such as preauthorization or prospective audit and feedback, development of clinical practice guidelines for common infectious diseases syndromes and incorporation of rapid diagnostic testing have been shown to be highly effective. Other recommendations include the use of antibiotic time-outs and utilization of clinical decision support tools. Hospitals and nursing homes have been the primary focus of ASP implementation guidelines; however, a majority of antibiotic prescribing occurs in the outpatient setting, where an estimated 50% of written prescriptions are inappropriate or unnecessary. In November 2016, the Centers for Disease Control and Prevention published the core elements of outpatient ASP to provide guidance for ASP in outpatient clinicians and facilities. The four elements include commitment, action for policy and practice, tracking and reporting and education and expertise. Establishing effective antibiotic stewardship interventions can protect patients and improve clinical outcomes in both inpatient and outpatient health care settings.

  • Molecular patterns of multidrug resistance of Mycobacterium leprae in India
    Speaker
    Mallika Lavania
    The Leprosy Mission Trust, India
    India
    Biography

    Mallika Lavania has completed her PhD from Agra University. She is the Senior Research Scientist of Stanley Browne Laboratory, The Leprosy Mission Trust, India, a premier organization which works with individuals and communities disadvantaged by leprosy, irrespective of caste, creed and religion, by addressing their physical, mental, social and spiritual needs to uphold human dignity and eradicate leprosy. She has published more than 30 papers in reputed journals and has been serving as an Editorial Board Member of BMC Infectious Diseases.

    Abstract

    Leprosy caused by multidrug-resistant Mycobacterium leprae is an emerging public health concern worldwide. Global efforts to control leprosy by intensive chemotherapy have led to a significant decrease in the number of registered patients. Current recommended control measures for treating leprosy with MDT are designed to prevent the spread of drug-resistant M. leprae. However, drug resistance has been reported since 1964 for dapsone, 1976 for rifampicin and 1996 for ofloxacin. We report here the identification of a multidrug-resistant strain of M. leprae from relapsed leprosy patients from an endemic region in India. The drug resistant profiles of the isolated strains were confirmed by the identification of mutations in genes previously shown to be associated with resistance to each drug (Rifampicin, Dapsone and Ofloxacin). Two hundred and fifty slit- skin smears samples were collected from relapse leprosy cases from different hospitals of The Leprosy Mission across India between 2009 and 2016. DNAs were extracted from these samples and analyzed for PCR targeting genes associated with drugs (Rifampicin, Dapsone and Ofloxacin) in M. leprae. Thai-53 (Wild-type) and Zensko 4 (MDR) strains were used as reference strains. Twelve strains showed representative mutations in more than two genes and two strain showed mutation in all three genes responsible for rifampicin, dapsone and ofloxacin. Among these eleven strains 9 strains were showed mutation in rifampicin and dapsone and 3 showed in dapsone and ofloxacin. The study showed occurrence of MDR strains of M.leprae in MDT treated leprosy patients from endemic regions of India.

  • Incidence and characterization of multi-drug resistance of Acinetobacter baumannii
    Speaker
    Mohammad Al-Tamimi
    Hashemite University, Jordan
    Jordan
    Biography

    Mohammad Al-Tamimi is working as an Assistant Professor of Medicine at The Hashemite University, Jordan.

    Abstract

    Objectives: A. baumannii is a common cause of infections associated with high mortality and morbidity. It is an important multi-drug resistant microorganism worldwide. The aim of this study is to investigate the incidence and characterization of A. baumannii in tertiary Hospital in Jordan. Methods: A retrospective study was done using data available on Vitek 2 Compact system and using patient files from 2010 to 2016 in Specialty Hospital, Amman. Demographic, clinical, isolates information and antibiotics sensitivity patterns were collected and analyzed using appropriate statistical tests. Results: 622 A. baumannii isolates were reported during the study period with about 99% having high confidence rate. Most isolates were from male, aged 18-60 years, Jordanian, and from infected wounds in surgery and critical care departments. 76.8% of A. baumannii isolates were MDR. Adults over 60, male, non Jordanians, critical ill patients and infected wounds represented significant risk factors for MDR incidence (P<0.0001), while no statistical significant risk associated with years (P>0.0). Resistance pattern indicated high resistance for most Cephalosporins, Carbapenems Fluoroquinolones, and Ampicillin, moderate resistance for Trimethoprim/Sulfamethoxazole and Ampicillin/Sulbactam low resistance for Aminoglycosides and Tetracyclines, and the lowest resistance rates were for Colistin and Tigecycline. Most strains had Aminoglycosides resistant phenotype GEN NET AMI TOB, GEN TOB AMI and TOB GEN NET. Conclusion: Jordan has high rate of A. baumannii MDR, adults, critically ill males with infected wounds have significant high rate of A. baumannii MDR. Continuous surveillance and monitoring of this critical microorganism is required.

  • Introduction of cases of Orf disease in burn wound in Motahari hospital
    Speaker
    Mahnoush Momeni
    Tehran Medical University, Iran
    Iran
    Biography

    Mahnoush Momeni specialized in General Surgery from Tehran Medical University in 2003 and has been working in the Burn and Trauma Center with the plastic surgery team ever since. She is involved in research about burns, wounds and plastic surgery. She is also a member of Burn Research Center at Iran Medical University

    Abstract

    A double -stranded DNA virus of family of Para Pox causes Orf disease. Human infection mostly is because of occupational hazard and infected animals handling. Our patient was an 18 year old woman who was burned in 2015. One week after admission in the hospital she has been undergone skin graft of upper extremity however vegetative granulomatous ulceration was appeared on wound hence grafted area was failed. With careful History investigation we noticed that the water which had been used to turn out the flame was drinking bottle for sheeps. With the suspecting of Orf disease we disinfected all the wounds and dressing tools with Dakin’s solution. We waited about 12 days to do skin graft and most of skin grafted area was taken afterwards .PCR test for Para pox viruses was positive. Conclusion: In burn patient with a history of probable contamination, the Orf disease should be considered. Manipulation of the disease in early stages in burn wound could potentially spread it and change the degree of the wound. For prevention of nosocomial outbreak of orf, wound care and wound disinfection should be done perfectly .Isolation and disinfection of all the dressing tool should be considered. The education of wound care providers in burn hospital and perfect wound disinfection would protect the patient from cross contamination and following this phase all the graft would be taken.

  • Analysis of bovine tuberculin antigens of different potencies by western blot
    Speaker
    Luciene Airy Nagashima
    Federal University of Technology, Brazil
    Brazil
    Biography

    Luciene Airy Nagashima has completed her MD and PhD in Microbiology at the State University of Londrina, Brazil. Her research is focused on immune response to fungal infection, especially with experimental infection with Arthrographis kalrae and its hemolytic factors. She is currently working as an Industrial Biotechnology Analyst in the Institute of Technology of Parana (Brazil), with the production of antigens for the diagnosis of bovine brucellosis, tuberculosis and enzootic bovine leukosis

    Abstract

    Bovine tuberculosis is a chronic disease caused primarily by Mycobacterium bovis. This zoonotic disease constitutes a public health issue and causes damage to the agricultural industry. In Brazil, the National Program for the Control and Eradication of Brucellosis and Tuberculosis establishes mandatory measures such as the diagnosis tests in animals. The standard method for detection of bovine tuberculosis is the tuberculin test, which uses the purified protein derivate (PPD) as antigen. The bovine tuberculin PPD is a complex mixture of proteins derived from the cultivation of M. bovis. Its composition and mechanisms involved in the immune response of the tuberculin test are not entirely clear. In the present work, bovine tuberculins which had low reactivity in the skin test in sensitized guinea pigs compared to a reference preparation, and tuberculins with positive results in potency test were analyzed by immune enzymatic assay (ELISA) and by western blot. The results showed differences in reactivity of the antibodies to the different samples of tuberculin, in both tests. The tuberculins with lower potencies revealed low intensity bands, especially below 30 kDa, which indicates that the proteins in these bands may be essential to the immunogenicity of the product. The identification of these proteins could help to elucidate which proteins are effective in intradermal reaction, enabling the development of more specific tests

  • Appropriate use of antimicrobials: the peculiarity of septic patients
    Speaker
    Francesco Scaglione
    University of Milan
    Italy
    Biography

    Francesco Scaglione is a Professor of Pharmacology at School of Medicine and Director of the Post-graduate School of Clinical Pharmacology at University of Milan. He is the Member of the Executive Committee of the International Society of Chemotherapy and Infections, President of the Federation of the European Societies of Chemotherapy and Chairman of ISC-WG and Anti-Infective Pharmacology and BSI. He is a Consultant for Pharmacotherapy in intensive care of two teaching hospitals in Milan. He speaks regularly at international meetings, is currently supervising six PhD students and holds several University appointments. He is author and co-author of more than 200 original articles, published in international journals.

    Abstract

    The treatment of bloodstream infections remains a significant challenge, with persisting high mortality and morbidity. Appropriate antimicrobial therapy has been shown to reduce mortality among patients with severe infections. In serious infections, the rapidity of antimicrobial therapy following presentation is a critical determinant of outcome for specific conditions including community-acquired pneumonia, ventilator-associated pneumonia, meningitis, bacteremia and septic shock. Moreover, if the therapy is adjusted after the determination of susceptibility, mortality is higher than that of obtained if the treatment is appropriate at the starting of the treatment. However, even if therapy is appropriate and early, mortality remains high in critically ill patients, ranging from 20 to 50%. Rather than appropriate, it is important to define what the term inappropriate means. Usually it is defined as either the use of an antimicrobial agent not covering the infecting microorganisms, or the administration of drugs to which the microorganism responsible for the infection is resistant. An inappropriate dosing regimen is equally significant. Of note, despite appropriate dosage regimens, antimicrobial therapy may fail because of impairment of immunological function, or because of the inability of the antimicrobial agent to achieve adequate concentrations at the infection site because of alterations in its pharmacokinetics resulting from the underlying pathophysiological condition. To optimize antimicrobial therapy, the clinician must possess knowledge of the pharmacokinetic and pharmacodynamic properties of commonly used antimicrobials, and how these parameters may be affected by the constellation of pathophysiological changes occurring during severe infections. Appropriate antimicrobial therapy must be administered as early as possible to reduce mortality significantly.

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