Day :
- Symposia on Clostridium Difficile
Session Introduction
Glenn S Tillotson
TranScrip Partners, USA
Title: Clostridium difficile- an evolving pathogen
Biography:
Glenn Tillotson has 30+ years pharmaceutical experience in early pre-clinical and clinical research, commercialization, medical affairs, scientific communications including publication planning strategic drug development, life cycle management and global launch programs. Dr Tillotson has been instrumental in the development and launch of ciprofloxacin, moxifloxacin, gemifloxacin and other antibacterials. Glenn has held several key committee positions at the American College of Chest Physicians, he is on the Scientific Steering Committee for the GTCBio. Annual Summit on Anti-infective Partnering. Currently Dr Tillotson has published >140 peer-reviewed manuscripts, presented >270 scientific posters and is on several journal Editorial Advisory Boards including the Lancet Infectious Disease, eBioMedicine and F1000.
Abstract:
The remarkable emergence of clostridium difficile in the past decade has led to a plethora of approaches to containing and treating the organism as infection recurrence, changing epidemiology, healthcare costs increase and the recent impact of recurrent infections on the US healthcare payment system has caused concern. Until 2012 there had not been any new advances in the management of this pathogen for 30 years with metronidazole and oral vancomycin being the only therapies available. Fidaxomicin was approved in both US and Europe for the treatment of C diffile infection (CDI). However for various reasons, most financial, this new agent has not been widely adopted even in recurrent cases of CDI. So there is still a need for new methods of ensuring CDI is a less worrying pathogen. Since 2008 there have been several different approaches adopted to manage CDI these include new antibiotics such as surotomycin, cadazolid and SMT 19969, anti-toxin agents, vaccines and biological agents such as non-toxigenic C difficile or faecal transplantation (FMT). In addition some nations have instituted major reviews of the infection control methods and achieved significant reductions in the incidence of CDI in hospitals. However it has been reported that up to 40% of CDI cases now originate in the community setting as opposed to the nosocomial environment. This review will discuss the changing epidemiology, the agents in development and the effect financial controls may have on this disease.
Richard Vickers
Summit Therapeutics, UK
Title: SMT 19969: A selective agent for Clostridium difficile infection
Biography:
Richard completed his PhD from Reading University before undertaking Postdoctoral studies and taking up a stipendiary lectureship at St Catherine’s College, Oxford University. He is currently working as a CSO – Antimicrobials at Summit Therapeutics, a UK based biotech company focused on the development of agents in areas of high unmet medical need
Abstract:
CDI is a leading cause of nosocomial diarrhea and new agents that address both initial infection and reduce rates of recurrent disease are needed. SMT19969 is a selective antimicrobial that is currently undergoing Phase 2 PoC clinical trials for the specific treatment of CDI. The compound has been shown to have highly selective activity against C. difficile but with little or no activity against other organisms including Gram negative and Gram positive anaerobes indigenous to the normal GI microbiota. SMT19969 was superior to vancomycin in the hamster model of CDI with 80-100% survival recorded by day 28 compared to 0-10% survival in the vancomycin arm. In a first in human Phase 1 clinical trial oral administration of SMT19969 was shown to be safe and well tolerated. Plasma levels of SMT19969 were typically at or just above the limit of detection confirming restriction of the drug to the site of infection. Furthermore, faecal samples following multiple oral dosing were analysed for changes in bacterial populations and it was shown that there were no significant changes in gut flora bacteria except for total clostridia which were significantly reduced during the course of dosing. These data demonstrate that SMT 19969 is a potent, bactericidal and selective inhibitor of C. difficile. Phase-1 results show that SMT 19969 is safe and well tolerated with repeat administration resulting in minimal impact on gut flora. These data support continued clinical development of SMT19969 as a potential therapy for CDI that may reduce rates of recurrent disease.
- The Vast Area of Antibiotics & Antibiotic Prophylaxis
Antibiotic Resistance: Opportunities and Challenges
Microorganisms in Recent Drug Discovery
Responsible Use of Antibiotics
Optimization of therapy-General principles
Chair
Glenn S Tillotson
TranScrip Partners, USA
Session Introduction
Jon B Bruss
Theravance Biopharma, USA
Title: Glycopeptides revisited
Time : 12:45-13:10
Biography:
Dr. Bruss completed his MD at the University of New Mexico School of Medicine. He completed a pediatric residency at the Children’s Hospital of New Mexico and a fellowship in infectious diseases at Boston Children’s Hospital and Harvard University. Other degrees include a Master of Science in Public Health from Tulane University School of Public Health and a Master of Business Administration from Northwestern University Kellogg School of Business. He held academic positions at Harvard University and University of Washignton. He has experience in clinical drug development, including work with seven classes of antibiotics, multiple anti-virals, anti-fungals, vaccines and biologics.
Abstract:
Vancomycin was isolated from soil from the jungles of Borneo in 1953 by scientists at Eli Lily & Co. It is a naturally occurring antibiotic produced by the soil bacterium Amycolatopsis orientalis (formerly Nocardia orientalis). It was approved in 1958 by the US FDA to treat penicillin resistant staphylococci. Vancomycin has subsequently become a primary treatment for infections due to MRSA, however it is steadily losing potency due to increasing minimum inhibitory concentrations for many strains of MRSA. Since the discovery of vancomycin, several other glycopeptide, lipodepsipeptide, and lipoglycopeptide antibiotics, all members of this class, have been discovered or synthesized including bleomycin (1966), teicoplanin (1975), ramoplanin (1984), dalbavancin (1996), oritavancin (1996), and telavancin (2000). Some of the newer semisynthetic members of this class have multiple mechanisms of action and greater potency against a wider spectrum of Gram-positive pathogens, including those with reduced susceptibility to vancomycin. This presentation will describe the various members of this class and compare their attributes and clinical use. Emphasis will be placed on the declining utility of vancomycin and the advantages of the newer lipoglycopeptides.
Tadashi Shimamoto
Hiroshima University, Japan
Title: Characterization of integrons and antimicrobial resistance genes in Gram-negative bacteria isolated from seafood in Japan: Identification of a novel β-lactamase-encoding gene, blaCMY-39
Time : 13:10-13:35
Biography:
Tadashi Shimamoto has completed his PhD at the age of 28 years from Okayama University, Japan and postdoctoral studies from University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School. He is a professor and a vice dean of Graduate School of Biosphere Science, Hiroshima University. He has published more than 60 papers in reputed journals and has been serving as an editorial board member of Microbiology and Immunology
Abstract:
The emergence and dissemination of antimicrobial resistance amongst bacteria is a growing problem for public health worldwide. Large quantities of seafood are consumed in Japan each year; however, little is currently known about the prevalence of integron and antibiotic resistance genes in seafood-associated bacteria in Japan. Therefore, PCR and DNA sequencing were used in the current study to screen and characterize integrons and resistance determinants in 215 Gram-negative bacteria isolated from retail seafood products from Hiroshima Prefecture, Japan. Class 1 integrons were identified in six bacterial isolates (three Aeromonas hydrophila, one Citrobacter freundii, one Enterobacter cloacae, and one Klebsiella oxytoca), and contained gene cassettes encoding resistance to trimethoprim (dfrA12 and dfrA17), aminoglycosides (aadA2), and β-lactams (blaPSE-1). All isolates were negative for class 2 integrons. β-lactamase-encoding genes were identified in seven isolates (four C. freundii and three E. cloacae), including the narrow-spectrum β-lactamase-encoding gene blaTEM-1, and AmpC β-lactamase-encoding genes blaCMY-2, blaCMY-13, and blaCMY-39. blaCMY-39 is a novel gene isolated from a C. freundii strain and encodes resistance to cephamycins and third generation cephalosporins. blaCMY-39 was cloned and expressed in Escherichia coli TG1. Plasmid-mediated quinolone resistance genes, including qnrB2, qnrB6, and qnrS1, were also identified in 10 isolates (six C. freundii, two E. cloacae, one Citrobacter koseri, and one Pantoea spp.). This study highlights the presence of integrons and antimicrobial resistance genes in seafood-associated bacteria in Japan, and indicates that seafood could be a route of transmission of antibiotic-resistant bacteria to humans.
Biography:
Herbert B. Allen, MD is a graduate of Johns Hopkins Medical School in 1970. Internship was at Johns Hopkins, residency was at Naval Regional Medical Center Philadelphia. He served on the faculty at the University of Pennsylvania for 22 years and at Hahnemann, now Drexel, for 38 years. Currently, he is Professor and Chair of Dermatology at Drexel University College of Medicine. He is certified in dermatology and dermatopathology and has authored more than 40 publications and 2 books.
Abstract:
Penicillin (PCN) has been shown to treat psoriasis effectively and be curative in many cases. Streptococcus is the organism responsible for beginning the process and has previously escaped detection by moving intracellularly or by forming biofilms. The treatment is low dose for many months and thus is similar to rheumatic fever. Arthritis has been shown to be caused by biofilm-forming dental and Lyme treponemes, and these organisms, like the streptococcus in psoriasis, have escaped detection. Penicillin, plus a biofilm-dispersing agent is effective in treating arthritis in which tissue destruction has not already occurred. Alzheimer’s disease has been shown to be caused by those same treponemes involved in arthritis, and, is in every way, similar to the dementia of neurosyphilis caused by Treponema pallidum. These organisms make biofilms that induce B amyloid and a Toll-like receptor 2 response leading to tissue destruction. Penicillin given prior to the organisms arrival in the brain (or before they create biofilms) would effectively prevent dementia in Alzheimer’s as it does in syphilis. We have shown that biofilm-forming staphylococci are integral to the etiology of atopic dermatitis. Along with standard corticosteroid therapy, antibacterial treatment, as opposed to antibiotics, appears to be a better treatment in AD because all the organisms are multi-drug resistant and 60% are MRSA or MSRE. Treatment with PCN in psoriasis, arthritis, and syphilis, has thus far not led to resistance and may actually prevent resistance by killing organisms before they make biofilms and share resistance genes.
Suresh G. Joshi
Drexel University College of Medicine, USA
Title: Nonthermal Plasma-Treated solutions as Antimicrobial Agents in Control of Multi-Drug Resistant Pathogens
Time : 14:45-15:10
Biography:
Suresh G Joshi has completed his MD, MSc and PhD in medical microbiology from University of Pune (UoP), one of the premier universities of India. From 1987 to 2000 he was a faculty at UoP affiliated medical college hopsitals, and contributory at the Interdisciplinary School of Basic Medical Sciences, UoP. From 2000 to 2003 he was a visitng faculty fellow at University of Rochester Medical Center, NY, and from 2003 to 2007, a research scientist and adjunct faculty at Thomas Jefferson University Medical College, Philadelphia, PA. In 2008, he joined Drexel University College of Medicine, Philadelphia, PA, and currrently a director of center for surgical infection and biofilm at Drexel University. He has published over 110 articles and research studies in reputed journals, and internatioal and national proceedings, and has been serving as an Editorial Board Member of repute
Abstract:
Multi-drug resistance in bacterial pathogens (MDRO) is a significant challenge that healthcare facilities faces globally. Surface-associated biofilms often act as reservior of MDRO and a source of dissemination of resistance. MDRO in biofilm form requires much higher doses of antimicrobial biocides than their planktonic counterpart. Such doses are often cytotoxic, and can not be repeatedly used. Additionally, an increase in resistant phenotypes due to spontaneous mutations challenges traditional antibiotics and other antimicrobial agents. Nonthermal plasma treatments are increasingly used in disinfection and sterilization, in different forms of applications, such as direct plasma application over the surface or first treating the liquid of interest, and then applying it over surface (animate or inanimate). Aqueous solutions treated by plasma at atmosphere air contains a complex cocktail of reactive species such as hydrogen peroxide, superoxide, nitric oxide, nitrogen dioxide, nitrite and nitrate, and typically have a low pH (which helps in stabilizing some of these species). All these species are physiologically reactive and known to kill bacteria in suspension by exerting a synergistic antimicrobial effect. Recently, we demonstrated that nonthermal plasma (plasma) -treated solutions acquire strong stable antimicrobial activity, and these solutions have a rapid and broad spectrum activity against multidrug resistant bacterial pathogens. This activity is retained for at least two years at room temperature, and the solution(s) exhibit appreciable toxicity. The proposed research presents the understanding of the mechanisms underlying the bactericidal effect of one of the plasma-activated antimicrobial solution, using E. coli’s physiological responses as the probe
Douglas Burgoyne
VRx Pharmacy Services, USA
Title: Antibiotic stewardship – A role for managed care
Time : 15:10-15:35
Biography:
Dr Douglas Burgoyne is President of VRx Pharmacy Services, a pharmacy benefits management company, and was President of the Academy of Managed Care Pharmacy for 2012-2013, where he supported AMCP’s advocacy for managed care pharmacy principles at both state and federal levels, including presentations to the FDA. Dr Burgoyne is a founding member of UtahAWARE, an antibiotic resistance education program for Utah. In this role, he was influential in reducing inappropriate antibiotic use in pediatrics and adults through public awareness campaigns and physician education programs. Dr Burgoyne was a speaker at many appropriate-use meetings, including the CDC ‘Get Smart’ conference.
Abstract:
Antibiotic resistance (AMR) is a major global health concern according to WHO, CDC, and governments worldwide. Resistant infections kill 23,000 Americans annually. Upper respiratory tract infections (URTIs) are mostly viral (60%-90% non-bacterial) and self-limiting, yet inappropriate antibiotic prescription is common, especially in primary care, which drives AMR. Even for bacterial URTIs antibiotics offer little or no immediate benefit; patients still need symptomatic therapy, which should always be utilized to minimize inappropriate use of antibiotics. The Global Respiratory Infection Partnership (GRIP) was initiated in 2011 to promote rational antibiotic stewardship for URTIs by focusing on symptomatic therapies and reducing inappropriate antibiotic use. The organization has developed the ‘5P’ framework to promote change and appropriate management of URTIs. Most antibiotics are low-cost drugs and provide little financial incentive for improving rational prescribing, compared to the expense of biologics and other novel drugs. However, there is an overwhelming public health imperative for reducing antibiotic resistance and promoting responsible antibiotic stewardship. What can be done? Strategies are required that increase access to symptomatic therapies and incentivize their use, including over-the-counter products. Different reimbursement approaches could also be considered. Ways to achieve these goals will be discussed, including potential roles for primary care and pharmacies. Managed Care can also influence patient education, especially concerning misperceptions about antibiotic use. Conclusions Managed Care could potentially reduce inappropriate antibiotic prescribing and increase use of symptomatic therapies to reduce AMR. This would support the goals of GRIP for responsible antibiotic stewardship and promotion of symptomatic therapies for URTIs.
Sedigheh Rafiei Tabatabaei
Shaheed Beheshti University, Iran
Title: The first report of CMY, aac (6′)-Ib and 16S rRNA methylase genes among Pseudomonas aeruginosa isolates from Iran
Time : 15:50-16:15
Biography:
Sedighe Rafiee Tabatabaei is working in Pediatric Infectious Research Center in Mofid Children Hospital at IRAN
Abstract:
Background:: Serious infections by Pseudomonas aeruginosa are commonly treated with the combination of a beta-lactam antibacterial and an aminoglycoside. Therefore, production of a 16S rRNA methylase may result in an extremely important antibacterial resistance profile. Objectives:: The present study was conducted to determine the prevalence of Cephamycinase (CMY), aminoglycoside 6'-N-acetyltransferase (aac(6′)-Ib) and 16S rRNA methylase genes among Pseudomonas aeruginosa isolates from Iran. Patients and Materials:: This descriptive study was performed on hospitalized burnt patients during 2011and 2012. Antibiotics susceptibility tests were performed by disc diffusion and broth microdilution methods. CMY, aac(6′)-Ib, 16S rRNA methylase genes were detected by PCR method. Results:: Seventy-seven (77%) of 100 isolates were resistant to Imipenem and Ceftazidime. aac(6)-Ib, Cephamycinase (CMY), and rRNA methyltransferase (rmtB and rmtD) were detected in 57 (74.02%), 7 (9.09%), 11 (14.28%), and 9 (11.68%) isolates, respectively. PCR results for aminoglycoside resistance methyltransferase (armA) and rRNA methyltransferase (rmtC) were all negative. Aminoglycoside resistance methyltransferase (armA), and rRNA methyltransferase (rmtC) were not detected. Conclusions:: This study detected multiple drug resistance in Pseudomonas aeruginosa including resistance to β-lactams, Aminoglycosides, and Fluoroquinolones. Therefore, identification of drug resistance patterns in P. aeruginosa and detection of pan-resistant producing isolates are of great importance in prevention and control of infections in burn center ward.
Gannu Praveen Kumar
Sahasra Institute of Pharmaceutical Sciences, India
Title: Tackling Antibiotic Resistance for Global Health: Future Challenges
Time : 16:15-16:40
Biography:
Dr. Gannu Praveen Kumar is currently working as Professor and Principal in Sahasra Institute of Pharmaceutical Sciences, India. Since 2009, he was appointed as an external examiner for PhD and post graduate students and has guided 30 M. Pharm students. He published in both National and International journals and compiled few chapters for text books. He received Gem of India award in the year 1999. He attended international conferences of repute and visited London, Dubai, Singapore, Malaysia and Spain as invited speaker. He was selected as a best academician of Vaagdevi college of Pharmacy in 2002 and of Talla Padmavathi college of Pharmacy in 2011
Abstract:
In the last 60 years, major improvements in the early recognition and the treatment of infectious diseases have resulted in an extraordinary reduction in the morbidity and mortality associated with these illnesses. This has been due, in part, to better understanding of the fine molecular biological mechanisms of these diseases and to improved understanding of their pathophysiology and their epidemiology but, most notably, to the rapid development of safe and effective new antimicrobial treatments that have been able to attack the specific agent causing the infection, thus helping the infected host to eliminate the infection being treated. Seen initially as truly miraculous drugs, access to the first available systemic antibiotics (sulfonamides and penicillin) was not immediately available for the general public. In fact, these drugs were scarce and very expensive and were initially reserved for use by the military during World War II. The discovery of antibiotics revolutionized medicine transforming often fatal diseases into curable, or at least manageable, problems. They were viewed as a panacea. Unfortunately, antibiotic drug resistance has gradually become a major health risk potentially compromising gains made in public health worldwide and is currently considered one of the greatest threats to public health. Although not a new phenomenon, resistance has become a more pressing issue over recent years as approximately 70% of known bacteria have developed resistance to one or more antibiotics, threatening a return to the pre-antibiotic era. Resistance has been reported for entire classes of antibiotics, and untreatable multi-drug resistant bacteria are increasingly documented. The causes of antibiotic resistance are complex and include human behaviour at many levels of society of which the consequences affect everybody in the world. Similarities with climate change are evident. Many efforts have been made to describe the many different facets of antibiotic resistance and the interventions needed to meet the challenge. Although antibiotics paved the way for unprecedented medical and societal developments, today they have become indispensible in all health systems. Achievements in modern medicine, such as major surgery, organ transplantation, treatment of preterm babies, and cancer chemotherapy, which we today take for granted, would not be possible without access to effective treatment for bacterial infections. Within just a few years, we might be faced with dire setbacks, medically, socially, and economically, unless real and unprecedented global coordinated actions are immediately taken. Finding a solution to the problem of antibiotic resistance is an urgent global healthcare priority. Life threatening infections such as MRSA, tuberculosis and E. coli are all developing resistance to commonly prescribed antibiotics and very few new are currently under development. Overcoming the ability of bacteria to develop resistance could potentially prevent thousands of needless deaths per year worldwide and reduce the burden on healthcare systems around the globe. Nanoscience is a relatively new field of research, yet our growing ability to build at the molecular level allows for the creation of customised structures which have the potential to transform medicine. It is hoped that new antibiotics, identification of sensitive microbial targets and design of novel drug delivery systems will enable the development of an urgently needed new generation of antibiotic treatments. Here, we describe the global situation of antibiotic resistance, its major causes and consequences, and identify key areas in which action is urgently needed
Rehab K. Alhajjar
King Saud University, Saudi Arabia
Title: Comparative Study of Antimicrobial Activities of two type of TiO2 Nanoparticles Against the Pathogenic Strain of Escherichia coli
Time : 16:40-17:05
Biography:
2012/2013: M. Sc. Microbiology in King Saud University, Riyadh, Saudi Arabia, Excellence with first class honor and ranked first in class. 2013-2015: Lecturer in University of Princess Noura bint Abdul Rahman. 2013-2015: Visiting Lecturer for King Abdullah Institute for Nanotechnology for Training Course for University of Princess Noura bint Abdul Rahman.Teach Lecture and Practical [lab] in Biology College also in College of Pharmacy, College of Nursing and Preparatory Year for College of Medicine. Scholarships and Awards from King Abdullah Scholarship Program (2015). Author of several articles in the magazine “World of Food”. Issue 162 - November 2011 etc….
Abstract:
The current study investigated the antibacterial properties 0.25%, 0.50% and 1% of two different types of nano-TiO2 against a selection of pathogenic bacteria (Escherchia coli) isolated from a sample of wastewater from Riyadh, for the purposes of further application to time and cost effective water purification in Saudi Arabia. A commercial sample of nanoparticles metal oxide containing 98% titanium dioxide (TiO2) that was brown in colour – hereinafter (T2B). Another commercial sample of nanoparticles metal oxide was obtained containing 99% titanium dioxide (TiO2) that was white in colour – hereinafter (T2W). Pathogenic bacteria were cultured in liquid nutrient medium to evaluate the antibacterial effects of 0.25%, 0.50% and 1% of both types of nano-TiO2 . Electron microscopy was also used to observe the effect of both nanoparticles on the pathogenic bacterial cells in the liquid media specimens. For both nano-specimens significant results were seen for 0.25%0.50% and 1% concentration. The bacterial number substantially decreased with 0.25%, 0.50% and 1% of both nanoparticles. However, better results were obtained with 0.50% and 1% of (T2B), where bacterial inhibition was greater in both media. With (T2B), bacterial clearance was observed in nearly half the time needed (T2W). This has been observed in both media. In the liquid medium, complete cell death was seen with 1% (T2B) after 4 hours compared with 6 hours with 1% (T2W). Electron microscopy showed bacterial samples completely destroyed with 1% (T2B). E. coli appeared to be sensitive bacteria to the presence of both (T2W) and (T2B) nanoparticles, as they experienced significant bacteria disruption and damage
Jayanta Haldar
Jawaharlal Nehru Centre for Advanced Scientific Research (JNCASR), India
Title: Strategies to combat bacterial resistance: Towards development of future antibacterial drugs
Time : 17:05-17:30
Biography:
Jayanta Haldar is an Assistant Professor at New Chemistry Unit, Jawaharlal Nehru Centre for Advanced Scientific Research (JNCASR), Bangalore, India since October 2009. His undergraduate training was at the Presidency College, University of Calcutta and he received his Master of Science and PhD from Indian Institute of Science, Bangalore in 2005. He did Postdoctoral Research from Department of Chemistry, Massachusetts Institute of Technology, USA. His research interests are towards the development of molecular strategies for the prevention and treatment of infectious diseases. He has published more than 30 international peer-reviewed papers, many book chapters and review articles. He has filed various national and international patent applications from 10 different inventions on the development of new drugs and new materials to tackle drug resistance and infections. His research work has been featured in Scientific American, Chemical Engineering News, American Chemical Society, BBC News, Times of India, The Hindu, Rajya Sabha TV, DD India TV etc. He has been awarded as a Ramanujan Fellow from the Department of Science and Technology, Government of India, in 2010. He is an Editorial Board Member of the journal “Microbial Pathogenesis” of Elsevier
Abstract:
Multi-drug resistant Gram-positive bacteria like vancomycin resistant Enterococci (VRE) and Staphylococci (VISA and VRSA); as well as pan-drug resistant New Delhi metallo-β-lactamase-1 (NDM-1) producing Gram-negative bacteria have become a threat to the global public health. The perennial persistence of bacterial resistance, calls for urgent need to develop more potent drugs having new mode of action, which would make bacterial resistance difficult to develop. Recently, we have developed novel vancomycin analogues, which could not only overcome, acquired resistance against VRE, VISA and VRSA but also took care of the inherent vancomycin resistance towards Gram-negative bacteria. Unlike vancomycin, these vancomycin analogues showed the ability to stop the development of bacterial resistance due to incorporation of novel membrane disrupting mechanism. I will also present another strategy where the membrane-active molecules were found to re-sensitize the tetracycline antibiotics to colistin-resistant NDM-1 producing Gram-negative clinical isolates. It was observed that the membrane activity of the molecules provided a backdoor entry to the otherwise excluded antibiotics due to efflux pumps
- Young Research Forum
Session Introduction
Richa Bhardwaj
Guru Gobind Singh Indraprastha University, India
Title: Emergence of Multi Drug Resistance Escherichia coli strains against clinically significant antibiotics from river system, India
Time : 17:30-17:55
Biography:
Richa Bhardwaj is pursuing Ph.D. under the supervision of Prof. J.K. Garg and Co-supervision of Dr. Anshu Gupta. Her area of research is Environmental microbiology wherein the work involves the study of Antibiotic and Heavy metal pollution of River Yamuna using microbiological indicators. She has her masters as a gold medallist throughout in scientific fields of Environment and Microbiological sciences as well as administration fields of Disaster management and NGO management. She graduated as honours in Microbiology from Delhi University as university topper. She has been associated with organizations as National Centre of Disease Control (Ministry of Home Affairs), Red Cross Society (Ministry of Health and Family Welfare), and Samsung Electronics (Corporate Social Responsibility). She has been associated with several projects including KAP studies for Disasters in Delhi, Psycho-social impacts of quality of work life in Multinational corporations, Quality standards for various Bio-safety levels as an integral part of epidemiological significance
Abstract:
Escherichia coli is an emerging pathogen of the greatest concern as it is the leading cause of various severe infections of stomach, urinary tract, ear, wound etc. in humans. Increasing rates of antimicrobial resistance among E. coli is another furthermost fret worldwide. This problem is more traumatic when water bodies are getting contaminated with faecal pollution and inappropriate use of antibiotics that led to emergence of multi-drug resistant strains of this normal microbiota of human intestine. The current study dealt with the isolation of twenty-eight E. coli strains from water samples collected from River Yamuna in Delhi stretch of India. E. coli was tested for antibiotic susceptibility by Kirby Bauer disc diffusion method as per Clinical and Laboratory Standard Institute (CLSI) guidelines using 24 different antibiotics belonging to three different modes of action namely β-lactams, aminoglycosides, phenicols, tetracyclines and quinolones. Most evident finding of the study was that none of antibiotic used in the study was 100% effective. In total, 100% of the isolates exhibited multi drug resistance (MDR) character and all the isolates had a very high multiple antibiotic-resistance (MAR) index, suggesting the origin of the isolates to be of high antibiotic usage. MAR index for all the isolates were calculated on the basis of resistance patterns. It has been observed all the strains were having the MAR value > 0.2 and up to 1, showing very high degree of multi-drug resistance. Therefore, the analysis is highly informative in terms of assessing the faecal contamination of river water, determining resistance of E. coli against the commonly available significant antibiotics and prediction of future emergence of MDR strains.
- Exclussive Session
Session Introduction
John M. Clerici
Tiber Creek Partners, USA
Title: Development and procurement of biotechnology for emerging disease and engineered threats in the public health preparedness sector
Biography:
John Clerici is a founding Principal of Tiber Creek Partners, LLC and a Partner in the Life Sciences Practice at Dentons LLP. For over 16 years, John has been at the forefront in the creation of the public health preparedness sector, including helping large pharmaceutical and emerging biotechnology companies develop creative approaches to access non-dilutive capital to fund the development of biotechnology for emerging disease and engineered threats. Since 1999, John has assisted over three dozen companies in obtaining nearly $4 billion in funding for research, development and procurement of public health countermeasures to the Federal government, including the majority of the awards made under Project Bioshield, the U.S. Government’s initiative for preparing the Nation against a bioterrorist attack. In 2006, John was instrumental in the passage of legislation creating the Biomedical Advanced Research and Development Authority (BARDA), which builds upon and improves Project BioShield. John began his career as a judge advocate with the U.S. Air Force where, among other assignments, he advised the Air Force Research Laboratory on the procurement of technology from research institutions throughout the United States, Europe and Asia. John earned his Juris Doctor from the University of North Carolina at Chapel Hill. He did his undergraduate work at the Catholic University of America, graduating summa cum laude.
Abstract:
Biotechnology companies are increasingly seeking to use non-dilutive capital from the U.S. Government, foreign governments, and non-governmental organizations as part of their commercialization objectives. Companies must have a full understanding of funding and procurement opportunities and help communicate the advantages and the state of development of its technology so that it resonates most effectively with funding and purchasing decision-makers. Private equity and venture capital firms are increasingly aware of the fact that legislation and policies established in the US and the EU directly influence the value of their investments. It is critical for companies undertake an effort in identifying and analyzing global government procurement trends as well as assessing the risks associated with investing in companies that receive U.S. federal and state funding and government contracts. In the specific area of emerging disease and engineered threats , including antibiotics, this approach is more important than any other area of biotechnology given the risks of development and the pricing pressure on new drugs, as well as the limited market for many of these products. Thus, access to non-dilutive capital becomes critical. This talk will explore the sources of such capital, the experience of past applicants (both successful and unsuccessful) and prospects for future funding in this age of government austerity.
- Antibiotics in Prevention and Treatment of Inflammatory and Infectious Diseases
Antibiotics: Water Born Diseases
Antibiotics and Allergies: Clinical Update
Antibiotics: Agriculture, Veterinary and Aquaculture
Antibiotics in Child care, Dental and Oral care
Antibiotics for Emerging and Re-emerging Diseases
Session Introduction
Tsung Hsing Chen
Chang Gung University College of Medicine, Taiwan
Title: Analysis of ascitic fluid lactoferrin levels in the diagnosis of spontaneous bacterial peritonitis after systemic antibiotic treatment
Time : 12:15-12:40
Biography:
Tsung Hsing Chen is working in the department of Gastroenterology and Hepatology in Linkou Chang Gung Memorial Hospital of Chang Gung University College of Medicine in Taiwan
Abstract:
Aim: Spontaneous bacterial peritonitis (SBP) is one of the most frequent complication of liver cirrhosis. Ascitic fluid lactoferrin has been proved to be a good diagnostic tool for SBP. However, lactoferrin in ascites may be checked after antibiotic used in some of these patients. Our study is to assess the utility of ascitic fluid lactoferrin levels for the diagnosis of SBP after antibiotic treatment. Materials & Methods: Twenty-two ascites samples were collected from patients with cirrhosis. Samples were examined for bacterial culture, lactoferrin concentration, and polymorphonuclear leukocyte count. Clinical symptoms and indications for ascites paracentesis were obtained from medical records. The diagnosis of SBP was made based on an elevated ascitic fluid polymorphonuclear leukocyte count of ≥250 cells/mm3. Results: Four (18.1%) samples fulfilled the diagnostic criteria for SBP. There were 3 ascites samples with a positive result for bacterial culture. Patients who received antibiotics other than those for treatment for SBP were classified as group B (n=9), whereas those who did not receive any antibiotics comprised group A (n=9). Lactoferrin concentration was significantly elevated (mean: 261.69±145.5 ng/mL) in the 3 cases with a positive bacterial culture compared with those without SBP, in both group A (mean: 4 19.64±6.32 ng/mL, p = 0.002) and group B (mean: 23.64 ± 9.53 ng/mL, p=0.001). Conclusion: After systemic antibiotic treatment, elevated lactoferrin levels in the ascites of cirrhotic patients appear to be a promising predictor for the presence of SBP with a positive ascitic bacterial culture.
Yuxiu Lei
Lahey Hospital & Medical Center, USA
Title: Earlier Appropriate Antibiotics Treatment of Ventilator Associated Tracheaobronchitis: Now or Wait?
Time : 12:40-13:05
Biography:
Yuxiu Lei has completed her PhD in Chemical Physics in 2002 from University of Puerto Rico and Postdoctoral studies from University of Pennsylvania and University of Kentucky. She has completed a master of art in clinical investigation from Boston University School of Medicine. She has published more than 15 papers in chemistry and physics journals and more than 15 papers in medical journals. She is a clinical research scientist and biostatistician at Lahey Hospital and Medical Center
Abstract:
Ventilator-associated tracheobronchitis (VAT) may be a presursor to ventilator-associated pneumonia (VAP). Studies have demonstrated that patients diagnosed with VAT have increased ventilator days, length of intensive care unit stay and associated healthcare costs. Initiating early targeted antibiotic treatment may improve patient outcomes and prevent VAP. Intravenous and/or aerosolized antibiotic therapy for VAT has been shown to reduce VAP and improve outcomes. Nseir and coworkers showed that appropriate antibiotic therapy was the only risk factor independently associated with reduced risk of transition to VAP (p=0.009). Bouza and coworkers conducted a study where 40 patients were randomized to a 3-day course of linezolid and meropenem versus 38 control patients. The antibiotic treated group had significantly lower rates of VAT/VAP and a longer time to the first episode of VAT/VAP (9 vs 4.5 days, p=0.02). Data from several randomized clinical trials and a meta-analyses support the use of pre-emptive, appropriate antibiotic therapy for VAT to reduce progression to VAP and improve clinical outcomes. Our hospital is one of the sites to conduct the clinical trials of aerosolized amikacin and fosfomycin delivered via the eFlow inline nebulizer system in mechanically ventilated patients. Assessing serial endotracheal aspirate cultures allows identification of bacterial pathogens and antibiotic sensitivity needed to initiate appropriate, “targeted” intravenous and/or aerosolized antibiotic therapy, especially for infections due to S. aureus, P. aeruginosa, Acinetobacter species or other multi-drug resistant Gram-negative pathogens. We recommend use of pre-emptive, appropriate antibiotic therapy for VAT be considered a new “standard of care”.
Khine SweSwe- Han
University of KwaZulu-Natal, National Health Laboratory service ( NHLS) , IALCH Academic complex , South Africa
Title: The prevalence of Carbapenem Resistant Gram Negative Bacteria (CRGNB) and Methicillin Resistant Staphylococcus aureus (MRSA) in a central referral hospital, Durban, South Africa between 2010-2014
Time : 13:50-14:15
Biography:
K Swe Swe Han has completed her MBBS from Myanmar Medical University and FC Path, MMed (Medical Microbiology), Post graduate studies from South Africa University School of Medicine. She is a Senior Consultant/Lecturer of NHLS, University of KwaZulu Natal, IALCH academic Hospital. She is a chair person of Infection Control Committee and participates as a major role for Antibiotics stewardship programme. She has published 11 papers, 23 oral/ poster presentations and also a reviewer . She participated as an Editorial Board Member of SASCM, a member of FIDSSA and senate of UKZN.
Abstract:
Introduction: Antibiotic resistance poses a serious challenge to public health worldwide, including South Africa. This problem has been exacerbated by the emergence of carbapenem resistant Gram-negative bacteria belonging to the Enterobacteriaceae, Acinetobacter and Pseudomonas aeruginosa (CRE/CRNE), as well as the presence of methicillin resistant Staphylococcus aureus (MRSA). This study was conducted to determine the prevalence of CRE/CRNE and MRSA at a central referral hospital within a 5 year period. Methods: The laboratory data and hospital admission data were reviewed between 2010 and 2014. The identification and drug susceptibility test results were interpreted by using the automatic system (Vitek 2) and the clinical laboratory standards institute (CLSI) guidelines. The prevalence of the patients infected with MRSA/CRE/CRNE was determined. Results: The prevalence of the patients with MRSA decreased from 47% (421/889) to 22% (172/770) from 2010 to 2014. This was probably due to the implementation of strict infection control measures. CRNE was fluctulated between 39% (368/941) to 48% (331/689) during the same period, with A. baumannii being the predominant organism among the CRNE. However, the prevalence of the CRE (K. pneumoniae and E. coli) increased from 0% (0/1110) to 2% (20/1265) during the study period. Conclusion: Although the prevalence of MRSA was significantly reduced, the challenge remains for the total elimination of these resistant pathogens, as well as the highly prevalent CRNE and the newly emerging CRE before this spirals out of control. Additional resources, antibiotic stewardship and aggressive infection control programs are urgently needed to prevent and control the spread of these resistant organisms in the hospital setting.
Glenn S Tillotson
TranScrip Partners, USA
Title: The impact of substandard antibiotics, is it beyond the individual?
Time : 14:15-14:40
Biography:
Glenn Tillotson has 30+ years pharmaceutical experience in early pre-clinical and clinical research, commercialization, medical affairs, scientific communications including publication planning strategic drug development, life cycle management and global launch programs. Dr Tillotson has been instrumental in the development and launch of ciprofloxacin, moxifloxacin, gemifloxacin and other antibacterials. Glenn has held several key committee positions at the American College of Chest Physicians, he is on the Scientific Steering Committee for the GTCBio. Annual Summit on Anti-infective Partnering. Currently Dr Tillotson has published >140 peer-reviewed manuscripts, presented >270 scientific posters and is on several journal Editorial Advisory Boards including the Lancet Infectious Disease, eBioMedicine and F1000.
Abstract:
There is a growing body of evidence that as much as a third of anti-malaria drugs in emerging markets are substandard, in some way such products may cause 100,000 deaths (primarily by not curing the disease) a year, as well as immeasurable suffering. Drug quality in malaria is analyzed far more than other infectious diseases, but even for malaria no estimations of the contribution of poor quality medicines to resistance have been undertaken. Another global infectious disease of major importance is tuberculosis with at least two billion possible incubators for resistant strains. Over 700 treatment packs in Central Africa, of isoniazid or rifampicin were tested using standard physical chemistry methods. Failures occurred in 16.6% of drugs in Africa. In the same location approximately 10% of the 1,500 samples of the broad spectrum antibiotic ciprofloxacin also failed basic content assays - the vast majority of substandard products were sloppily produced with a few being counterfeit. Drugs which have active pharmaceutical ingredient within the margins of 80-125% of innovator activity are considered bioequivalent, but many are not truly therapeutically or biologically equivalent. Antimicrobials are unique among the many drugs available that substandard versions cause harm to the patient and to society in terms of resistance. Lack of equivalence is true across a range of antibiotic agents including vancomycin, the β-lactam; ampicillin, piperacillin, oxacillin and meropenem; gentamicin and ciprofloxacin eye drops. Bioequivalence as measured pharmacologically is not truly representative of antibacterial activity. It is therefore important to use other more biologically appropriate discriminatory assays such as MIC, MBC, kill curve assays, and appropriate animal infection models. In vivo animal model studies with Staphylococcus aureus and vancomycin have shown that some generic versions enriched for resistant subpopulations. The use of copy products (those that had not established bioequivalence) of vancomycin could contribute to resistance and therapeutic failures as even minor MIC increments can have a huge impact on clinical impact especially in the frail or compromised patient. Indeed in the instance of vancomycin it was postulated that a potential therapeutic failure of the generic agent had led to MRSA peritonitis and bacteremia. The key issue is that some antibiotics have marginal activity, as measured by MIC, against some critical pathogens. Thus by using target attainment pharmaco-dynamic approaches it is possible to estimate the likelihood of clinical and bacterial failure by exposing organisms with MICs close to the breakpoint to ≤80% activity of key drug can drive resistant selection and therapeutic failure. In summary, it is clear that a number of generic antibiotic preparations are of a poor standard and this can be deleterious to the patient but as significant is the impact, this formulation may have on the wider bacterial population in terms of resistance selection and dissemination. Tighter measures are needed to avoid the emergence of the untreatable bacterium.
Marco Manfredi
University of Parma, Italy
Title: Changes in antibiotic sensitivity in children with Helicobacter pylori infection
Time : 14:40-15:05
Biography:
Marco Manfredi MD, PhD carried out his education at Parma University, Italy (Medical Degree, post graduate degree in General Pediatrics and in Gastroenterology) where also completed his PhD in Pediatric Gastroenterology. By now he is Assistant Manager in Pediatrics and in Pediatric Gastroenterology at Azienda Ospedaliero- Universitaria of Parma, University Hospital, Parma, Italy. His main fields of interest are Helicobacter pylori infection, Celiac Disease, acid-related gastrointestinal diseases, IBD. He has published more than 60 papers, included chapters of textbooks and is a scientific reviewer for several reputed medical journals. He is member of Italian Society of Pediatric Gastroenterology and Nutrition (SIGENP)
Abstract:
Helicobacter pylori (H. pylori) infection is one of the most common infections in humans. Although many efforts have been made in trying eradication, several difficulties remain to be overcome both in children and adults. During the last years, the widespread use/abuse of antibiotics led to the emergence of increasing resistances of H. pylori infection to common antibiotics. ESPGHAN/NASPGHAN guidelines recommend antibiotic susceptibility testing for Clarithromycin before starting Clarithromycin-based triple therapy in areas/populations with a known high resistance rate. In Italy Clarithromycin resistance rate is around 25%. We evaluated the variations in primary antibiotic sensitivity over last 13 years in children with H. pylori infection in Parma, northern Italy comparing with our previous results obtained in 1998/99. Throughout the last 13 years, we obtained a significant reduction in Metronidazole resistant (57% vs 33%) (p=0.014), while the Clarthromycin resistance evidently increased although with no statistically significant value (16% vs 26%) (p=0.142). During these years resistance to ampicillin has been confirmed very low or absent (3% in 1998/99 and none in 2011/2012) as well as that to tetracyclines (2% in 1998/99 and none in 2011/12); in the same way the combined resistance to Metronidazole and Clarithromycin together has not been changed, staying very low (8% in 1998/99 and 7% in 2011/12). The eradication of H. pylori infection represents an enormous challenge in gastroenterology. Considering this organism lives in an environment not easily accessible to many drugs, the increasing antibiotic resistance is a burden that we must fight every day. To know the local prevalence of antibiotic resistance is important also for choosing the better therapy mainly if the antibiotic sensitivity does not develop from the culture, therefore we must use an empirical eradication treatment. Comparing our study with the previous one (executed in 1998/99), we obtained some changes in antibiotic resistance rate over the last 13 years. Metronidazole resistance significantly decreased and that to Clarithromycin increased although with no statistically significant value. Furthermore we confirmed that the resistance rate of H. pylori to amoxicillin is very rare around the world. Therefore before recommending H. pylori eradication therapy, we should know either the antibiotic susceptibility of patient or the local distribution of antibiotic resistance rates to have higher successful probabilities
Kenneth Bischoff
National Center for Agricultural Utilization Research, USA
Title: A novel oil produced by Aureobasidium pullulans has antibacterial activity with specificity for species of Streptococcus
Time : 15:05-15:30
Biography:
Kenneth Bischoff received his PhD. in biochemistry from Purdue University in 1995. He joined the USDA Agricultural Research Service in 1998 as a microbiologist investigating antimicrobial resistance in food-borne pathogens. In 2004, he relocated to the USDA National Center for Agricultural Utilization Research (NCAUR), Peoria, IL and redirected his research toward improving the biochemical processes for the biorefining industry. He is currently a lead scientist for biobased products research in the Renewable Product Technology Research Unit at NCAUR
Abstract:
Liamocins are a heterogeneous mixture of polyol-lipids produced by the fungus Aureobasidium pullulans. When grown on sucrose, A. pullulans strain NRRL 50380 produces four types of liamocins with chemical structures consisting of a single mannitol headgroup partially O-acylated with polyester tails containing three or four 3,5-dihydroxydecanoic ester groups, some of which are acetylated. Liamocins possessed antibacterial activity with specificity against Streptococcus species with MICs ranging from ≤10 µg/ml to 78 µg/ml for the following: S. agalactiae, S. infantarius, S. mitis, S. mutans, S. pneumonia, S. salivarius, S. suis, and S. uberis. Enterococcus faecalis and Bacillus subtilis were less susceptible, while the following bacteria were not susceptible: Staphylococcus aureus, Lactobacillus fermentum, Escherichia coli, and Pseudomonas aeruginosa. In an effort to improve yields (typically 0.5-6.0 g liamocin/L), different growth media and strains of A. pullulans were tested. Selective growth on different polyols resulted in considerable structural variation of liamocins including some with galactitol, sorbitol, D-arabitol, D-xylitol, and D- or L-threitol headgroups. Liamocins with D-arabitol or D/L-threitol headgroups were active but to a lesser extent than the mannitol liamocins. The components of mannitol liamocins were separated by HPLC and assayed by MALDI-TOF/MS, and a fraction that was enriched for liamocin B1 (the non-acetylated type with four 3,5-dihydroxydecanoic acid groups) had the highest antibacterial activity against S. agalactiae (MIC = 16 µg/ml). Liamocins have potential application as a narrow spectrum antimicrobial agent that targets streptococcal pathogens, but avoids disruption of normal flora and reduces selection for antibiotic resistance in commensal bacteria.
- Video Presentation
Session Introduction
Alessandra Piccitto
Durham University, UK
Title: New Strategies to develop antibiotics for treatment of Pseudomonas aeruginosa and Leishmania infections
Biography:
Alessandra Piccitto is a registered Pharmacist in the United Kingdom. She received her MPharm degree from the University of Turin (Italy) after completing a research project at Durham University Department of Chemistry (UK) in 2010. She has been teaching Human Anatomy, Physiology and Pathology at IIS Q. Sella of Biella (Italy). She is member of the General Pharmaceutical Council (GPhC) since 2013 and member of the Royal Pharmaceutical Society of Great Britain based in London since 2014. She published her research work entitled “New Strategies to develop Antibiotics – for treatment of P. aeruginosa and Leishmania spp infections” for the category of biochemistry and biophysics, one book (ISBN 978-3-659-48170-3) of 72 pages in English language, on Amazon at International Editor – Lambert Publishing Academic House in Germany in 2013. She is now working on a research project financed by the Italian Ministry of University and Research at Politecnico di Torino, Turin (Italy) that focuses on the design of scaffolds and their functionalization with peptides or proteins for Myocardial Tissue Engineering and in general Regenerative Medicine.
Abstract:
The current available therapy against Pseudomonas aeruginosa and Leishmania spp infections for the well-known diseases such as cystic fibrosis and leishmaniasis (cutaneous, mucocutaneous and visceral) is far from satisfactory. It has been reported that established infections caused by P. aeruginosa are notoriously difficult to treat because this bacteria is usually resistant to many broad-spectrum antibiotics commonly used in hospitals and it may also acquire resistance to these drugs. Furthermore, a similar situation has been reported for leishmaniasis a complex of diseases caused by the protozoan parasite Leishmania spp in humans and dogs. In fact only a limited number of expensive drugs are available for the treatment of this disease and resistance to them is still increasing day by day in endemic regions. It is also well-known that AMPs (or antimicrobial peptides) can play a very important role in host defense against these multi-drug resistant pathogens. Hence the aim of this project is firstly to find a synthetic peptide able to target the protein-protein interaction of an essential P. aeruginosa protein known as PA-Fur, and secondly to create a group of new anti-leishmanial synthetic peptides derived from natural AMPs. To satisfy the targets of this double project a number of synthetic peptides were manufactured following a structure-based rational design and a selection of peptides from libraries with varying sequence composition were also synthesized. Synthetic peptides of this kind, with broad range activity and which might be produced industrially by chemical synthesis, have attracted the interest of many pharmaceutical companies as a possible new generation of antibiotics able to kill highly resistant pathogens. At present they have a realistic potential for overcoming the growing problems of antibiotic resistance.
- Poster Presentations
Session Introduction
Woo-Jung
Gyeonggi Institute of Science and Technology Promotion (GSTEP) South korea
Title: Liquid Chromatography-Mass Spectrometry-based Rapid Secondary-Metabolite Profiling of Marine Pseudoalteromonas sp. M2
Biography:
Woo Jung Kim received the PhD degree from the Catholic University of Korea in Biotechnology. He is currently Gyeonggi Institute of Science and Technology Promotion (GSTEP) in Korea. His research interests include structure and bioactivities of polysaccharides and oligosaccharides and related enzymology. He has published more than 22 papers in journals and been a member of the Korean Society for Glycoscience and The Korean Society for Applied Biological Chemistry
Abstract:
The ocean is a rich resource of flora, fauna, and food. A wild-type bacterial strain showing confluent growth on marine agar with antibacterial activity was isolated from marine water, identified using 16S rDNA sequence analysis as Pseudoalteromonas sp., and was designated as strain M2. This strain was found to produce various secondary metabolites including quinolone alkaloids. Using high-resolution mass spectrometry (MS) and nuclear magnetic resonance (NMR) analysis, we identified 9 secondary metabolites of 4-hydroxy-2-alkylquinoline (pseudane-III, IV, V, VI, VII, VIII, IX, X, and XI). Additionally, this strain produced 2 novel closely related compounds, 2-isopentylqunoline-4-one and 2-(2,3-dimetylbutyl)qunoline-4-(1H)-one, which have not been previously reported from marine bacteria. From the metabolites produced by Pseudoalteromonas sp. M2, 2-(2,3-dimethylbutyl)quinolin-4-one, pseudane-VI, and pseudane-VII inhibited melanin synthesis in melan-a cells by 23.0%, 28.2%, and 42.7%, respectively, wherein pseudane-VII showed highest inhibition at 8 µg/mL. The results of this study suggest that liquid chromatography (LC)-MS/MS-based metabolite screening effectively improves efficiency of novel metabolite discovery. Additionally, these compounds are promising candidates for further bioactivity development.
Kevin K Schrader
University of Mississippi, USA
Title: Antibacterial activities of metabolites from Platanus occidentalis (American Sycamore) against fish pathogenic bacteria
Biography:
Kevin K Schrader completed his PhD in 1995 from Auburn University, AL, and Postdoctoral studies with Mississippi State University in 1996-1997. He is a Research Microbiologist at the USDA, ARS, Natural Products Utilization Research Unit, National Center for Natural Products Research. He has authored and co-authored more than 80 papers in peer-reviewed journals, one U.S. patent, an edited book, and over 10 invited book chapters, and he has been serving as an Editorial Board Member of repute.
Abstract:
One approach to the management of common fish diseases in aquaculture is the use of antibiotic-laden feed. However, there are public concerns about the use of antibiotics in agriculture and the potential development of antibiotic resistant bacteria. Therefore, the discovery of other environmentally safe natural compounds as alternatives to antibiotics would benefit the aquaculture industries. Four natural compounds, commonly called platanosides, [kaempferol 3-O-α-L-(2",3"-di-E-p-coumaroyl)rhamnoside(1), kaempferol 3-O-α-L-(2"-E-p-coumaroyl-3"-Z-p-coumaroyl)rhamnoside (2), kaempferol 3-O-α-L-(2"-Z-p-coumaroyl-3"-E-p-coumaroyl)rhamnoside (3) and kaempferol 3-O-α-L-(2",3"-di-Z-p-coumaroyl)rhamnoside (4)] isolated from the leaves of the American sycamore (Platanus occidentalis) tree were evaluated using a rapid bioassay for their antibacterial activities against common fish pathogenic bacteria including Flavobacterium columnare, Edwardsiella ictaluri, Aeromonas hydrophila and Streptococcus iniae. The four isomers and a mixture of all four isomers were strongly antibacterial against isolates of F. columnare and S. iniae. Against F. columnare ALM-00-173, 3 and 4 showed the strongest antibacterial activities, with 24-h 50% inhibition concentration (IC50) values of 2.13±0.11 and 2.62±0.23 mg/L, respectively. Against S. iniae LA94-426, 4 had the strongest antibacterial activity, with 24-h IC50 of 1.87±0.23 mg/L. Neither a mixture of the isomers nor any of the individual isomers were antibacterial against isolates of E. ictaluri and A. hydrophila at the test concentrations used in the study. Several of the isomers appear promising for the potential management of columnaris disease and streptococcosis in fish
Sanjay Biswas
Tata Memorial Centre, India
Title: Efficacy of ceftriaxone-sulbactam-EDTA combination in immuno compromised patients in a tertiary care cancer centre
Biography:
SANJAY BISWAS is a Professor & Microbiologist in the Dept of Microbiology in Tata Memorial Hospital, Mumbai completed his M.B.B.S in Sambalpur University 1992 and M.D (Microbiology), Bombay University, October 1998
Abstract:
Introduction: The resistance to the antimicrobials has been increasing over the years and is varying from country to country. Among the causes of β-lactam antibiotic resistance, the production of ESBLs appeared to be most common. The ESBLs are plasmid mediated and can be easily transmitted among members of Enterobacteriaceae, thus facilitating the dissemination of resistance, not only to β-lactam, but to other commonly used antibiotics including aminoglycosides and quinolone. To overcome ESBLs resistance, carbapenem drugs have been introduced in clinical settings, although carbapenems resistance has been reported increasingly worldwide. Resistance in bacteria to carbapenems is due to the production of carbapenem hydrolyzing enzymes called carbapenemases, which is encoded by KPC, VIM and IMP genes. The aim of the present study was to compare the susceptibility pattern of ceftriaxone-sulbactam-EDTA(CSE) combination with other routinely used antibiotics in immunocompromised patients. Materials and Methods: A total of 33930 clinical samples were received in the Dept. of Microbiology in 2014. All the samples were processed as per standard microbiological methods. Antimicrobial susceptibility testing of cefoperazone-sulbactam , ceftriaxone-sulbactam-EDTA , piperacillin-tazobactam, imipenem and meropenem of 195 Gram negative isolates, included in this study, were carried out by disc diffusion method as per CLSI guidelines. ATCC strains were used as standards. Interpretative criteria of Ceftriaxone were used for interpretation of CSE. Results: Of the 33930 samples received, only 195 Gram negative isolates, from different clinical samples, were included in this study. Blood was the most common isolate followed by broncho- alveolar lavages, wound swabs and drain fluids. Escherichia coli was the commonest isolate followed by Klebsiella pneumoniae, Pseudomonas aeruginosa and Acinetobacter spp. Carbapenems were the most sensitive antimicrobial followed by cefoperazone-sulbactam, ceftriaxone-sulbactam-EDTA and piperacillin-tazobactam. Conclusions: Results obtained in the current study clearly demonstrates the good in-vitro activity of ceftriaxone plus sulbactam plus EDTA as compared to other beta-lactam beta-lactamase inhibitor combinations.The enhanced susceptibility of ceftriaxone+EDTA+sulbactam against different clinical isolates is likely to be associated with synergistic activity of ceftriaxone+sulbactam+EDTA. EDTA chelates the divalent ions, thus enhancing the susceptibility of ceftriaxone plus EDTA plus sulbactam towards different microorganisms. The EDTA also enhances the susceptibility by altering the outer membrane permeability, which in turn increased penetration of drugs inside the bacterial cells
Juhee Park
Health Insurance Review and Assessment Service, South Korea
Title: Systemic antibiotic consumption in a population of South Korea between 2009 and 2013
Biography:
Soo-Ok Lee has completed biostatistics coursework from Yeonsei University. She is the senior researcher of Health Insurance Review and Assessment Service. She belong to pharmaceutical assessment research team and her main research area is pattern of drug prescription and drug cost containtment policy. Juhee Park is a PhD student in biostatistics at the Catholic University of Korea. She is researcher of Health Insurance Review and Assessment Service. She belong to pharmaceutical assessment research team and her main research area is DUR(drug utilization review) and use of drugs.
Abstract:
Systemic antibiotic consumption in a population of South Korea between 2009 and 2013: This study was conducted to investigate overall systemic antibiotic consumption levels and specific patterns using standardized Anatomical Therapeutic Chemical/Defined Daily Dose (ATC/DDD) methodology. The administrative data from South Korean Health Insurance Review & Assessment (HIRA) were used to examine trends in antibiotic consumption. Antibiotic usage data were collected for systemic antibacterial (ATC category J01). Total consumption was slightly increased from 25.8DID (the number of DDD per 1,000 inhabitants per day) to 26.7DID from 2009 to 2013 slightly. These values are higher than the average (21.2DID) of OECD 2012. Consumption figures under 10 years of age (44.8DID and 51.5DID in 2009 and 2013, respectively) were even higher than figures in aged 60-69 (34.0DID and 33.4DID in 2009 and 2013, respectively), especially the measure of average in aged 2-5 was very high (65DID). The most frequently prescribed antibiotic was combinations of penicillins (J01CR, 24.32%, in 2013), followed by second-generation cephalosporins (J01DC, 18.24%) and macrolides (J01FA, 13.82%). 49.4%(6.6DID) among the outpatients of acute upper respiratory infections and 54.6%(5.8DID) among the outpatients of other acute upper respiratory infections were prescribed antibiotics. Overall antibiotic prescription usage have increased slightly. However, use of cephalosporins is gradually increasing, except first-generation cephalosporins and the amount of antibiotics in children is still a high level, which can affect to antibiotic resistance. Efforts to increase prudent antibiotic use, especially for upper respiratory system infections and for younger children, should be made to decrease antibiotic use
Karol RodrÃguez-Peña
Universidad Nacional Autónoma de México, México
Title: The potential of endophytic actinomycetes of Amphipterygium adstringens as producers of novel antibiotics
Biography:
Karol Rodríguez-Peña is a PhD student in Biomedical Sciences at UNAM. He has 40 years experience leading the Industrial Microbiology Laboratory at the Biomedical Research Institute at UNAM. He carried out his Postdoctoral studies at MIT in Cambridge MA. He is Member of the American Academy of Microbiology and has published more than 150 papers in reputed journals. He is the Editorial Board Member of Applied Microbiology and Biotechnology and Editor in Chief of Biotechnology
Abstract:
Endophytes are microorganisms that inhabit plants without causing apparent damage. It has been found that the interaction between the host plant and endophyte is based on both physical and chemical mechanisms. The secondary metabolism of these microorganisms which allows them to defend themselves or communicate with their host, as well as their unique habitat make them a very interesting source of new molecules with biological activity. Actinomycetes are a group of Grampositive bacteria that have been extensively studied for their ability to produce a variety of secondary metabolites, especially the genus Streptomyces. However, it has recently been found by genome mining studies among some others, that other genera of actinomycetes that have hardly been studied are also capable of producing a large number of compounds. In this study, endophyte isolation was made from the medicinal plant Amphipterygium adstringens. Four actinomycetes were isolated: one of the genus Streptomyces and three others closest to the genus Actinoplanes. Phylogenetic studies place the latter three strains as potential new species. Sequential extracts were conducted, first with dichloromethane (DCM) and then with ethyl acetate (EtAc). The minimum inhibitory concentration was determined with Gram-positive, Gram-negative and a yeast. Extracts from the strain NF3 showed significant activity against the Gram-positive bacteria tested at 0.1μg/mL with DCM and 6.3 μg/ mL with EtAc, making it a very attractive strain for further elucidation of bioactive molecules. The extracts from strain TFC3 meanwhile, showed activity against Bacillus subtilis with 200 μg/mL in both DCM and EtAc. These same extracts were tested against cancer cell lines MCF7 and HeLa, as well as with with HaCaT as a healthy cell line. The extract from the NF3 strain produced mortality higher than 80% with 0.4 μg/mL in MCF7, 0.8 μg /mL for HeLa and 1.6 μg/mL for HaCaT. The putative Actinoplanes extracts had moderate activity only at 200 μg/mL with different cell lines. However, genomic studies of closely related strains indicate that these strains have enormous potential due to the large number of clusters that encode various cryptic secondary metabolite pathways.
- Modern antibiotics: Emerging trends, Barriers and Opportunities
Antibiotics: Market Analysis & Business Opportunities
Antibiotic Regulatory Affairs
Antibiotics and Mechanism
Drug Discovery and Novel Delivery Technologies
Session Introduction
Glenn S Tillotson
TranScrip Partners USA
Title: Fluoroquinolones-A maligned class being re-discovered?
Biography:
Glenn Tillotson has 30+ years pharmaceutical experience in early pre-clinical and clinical research, commercialization, medical affairs, scientific communications including publication planning strategic drug development, life cycle management and global launch programs. Dr Tillotson has been instrumental in the development and launch of ciprofloxacin, moxifloxacin, gemifloxacin and other antibacterials. Glenn has held several key committee positions at the American College of Chest Physicians, he is on the Scientific Steering Committee for the GTCBio. Annual Summit on Anti-infective Partnering. Currently Dr Tillotson has published >140 peer-reviewed manuscripts, presented >270 scientific posters and is on several journal Editorial Advisory Boards including the Lancet Infectious Disease, eBioMedicine and F1000.
Abstract:
Background: Fluoroquinolones were discovered in the early 1980’s with norfloxacin and ciprofloxacin being early class members. In the intervening 30 years the group has expanded and contracted mainly due to a series of adverse events. The class was “cutting edge” due to the breadth of activity, the oral and IV formulations and significant tissue distribution. Indeed these characteristics enabled courses of therapy to be shortened with all those attendant benefits. In the past decade no further quinolones have been approved, why? A combination of safety worries association with Clostridium difficile infection and emergence of resistance among the pathogens for which the class was developed. Current status: The current global situation of antibiotic resistance among many pathogens is alarming and alternative agents are being sought, these include new members of the quinolone class. These agents are being developed based on either a novel mode of action or an expanded spectrum of activity. The local environment in an infected lesion or space is approximately pH 5 which can have adverse effect on some conventional antibiotics including current quinolones. The fluoroquinolones, delafloxacin and finafloxacin have better activity at the lower pH compared with MICs at pH 7.0. These two agents are being developed based on their enhanced activity against gram-positive and gram-negative pathogens, e.g. delafloxacin [MIC MRSA 0.5 mg/l] and finafloxacin [E. coli MIC 0.12 mg/l]. Thus these are being developed for acute bacterial skin and skin structure and complicated urinary tract infections respectively. The respiratory fluoroquinolones were vanguards of the shorter course therapy in respiratory infections based on many characteristics , most of which are harnessed by zabofloxacin which is highly active against an array of Streptococcus pneumoniae strains and penetrates lung compartments very well. Thus this drug is being examined for mild-moderate community acquired bacterial pneumonia with a 3 day course. This presentation will review the three new fluoroquinolones from microbiological, pharmacological and clinical perspectives with regard to the 3 different indications being studied
Mario A Bianchet
Johns Hopkins University School of Medicine, USA
Title: Mycobacterium tubercolosis cell-wall biosynthesis as target of Carbapenems
Biography:
Mario A Bianchet has completed his PhD from The University of La Plata, Argentine, and performed Postdoctoral studies at Johns Hopkins University School of Medicine in where he is now Assistant Professor of Neurology since 2011. He has published 65 papers in reputed journals. As structural enzymologist and expert in ligand recognition, he has participated in several seminal structural and mechanistic studies of macromolecules and ligand/macromolecule interactions of biomedical interest. He has important contributions to different fields, including bioenergetics: F1-ATPase, xenobiotic-response: NADPH:Quinone oxidoreductases, DNA-repair: Uracyl-Glycosylase/inhibitors, carbohydrate-recognition: animal lectins, and late stage cell-wall biosynthesis: LD-transpeptidases and their complexes with substrates and carbapenems
Abstract:
Transpeptidases play essential roles in the bacterial cell-wall biosynthesis. Inter-stems cross-links made for these enzymes assemble the peptidoglycan mesh that confer mechanic stability to the bacteria. β-lactam antibiotics, penincillin, inactivates (4-3) DD-transpeptidases. These transpeptidases also called penincillin-binding proteins,cross-linked-centers of the fourth residue main-chain with that of the third residue side-chain of adjacent peptidoglycan stems. Most bacteria utilize(4-3) crosslinks to build their peptidoglycan layer. However, the Mycobacterium genus and some penicillin-resistant bacteria—involved in nosocomial infections—majoritarily utilize the (3,3)-crosslinks carried out by (3,3) LD-transpeptidases. This (3,3)-crosslink joins the L-center of the third residue main-chain and the D-center of the another third residue main-chain of an adjacent stem. The use of this crosslink and the presence of a potent β-lactamase (BlaC) confers to mycobacteria resistance to penicillin and other antibiotics that mimic the D-Ala4-D-Alanyl5 terminal region of the pentapeptide donor stem recognized by DD-transpeptidases. LD-transpeptidases are resilient to this type of inhibition because they exclusively recognize a tetrapeptidedonor stem lacking the D-alanyl terminal. Carbapenems are β-lactam antibiotics that have a carbon atom replacing the sulphur atom at position1 of the penicillin core. This class of antibiotics inactivate LD-transpeptidases by a quasi-irreversible acylation of the enzyme catalytic cysteine, resulting in a effective agent to treat these penicillin-resistant bacteria. We are going to discuss our recent structural, biophysical, and biochemical characterization of members of this family of enzymes and their complexes with a series of carbapenemsin medical use.
Michael kelso
University of Wollongong, Australia
Title: Biofilm Dispersing NO-Donor Cephalosporins Activated by b-Lactamase
Biography:
Kelso graduated from the University of Wollongong with a B. Medicinal Chemistry (1996) and received his PhD (Peptidomimetics, 2002) from the University of Queensland (Australia). After a 1-year postdoc with Prof Claudio Palomo (Universidad del Pais Vasco, Spain) studying catalytic asymmetric synthesis he moved to The Scripps Research Institute (CA, USA), where he studied medicinal chemistry as an NHMRC CJ Martin Fellow under Professor Dale Boger. Upon returning to Australia in 2006 he completed his Fellowship under Prof John Bremner at the University of Wollongong, where he was subsequently appointed as a lecturer (2008) and promoted to A/Prof (2014). His research group focuses on the design, synthesis and biological evaluation of antibacterials acting via novel mechanisms
Abstract:
Low concentrations of nitric oxide (NO) have been shown to act as a signal that induces biofilm bacteria to disperse and revert to the free-swimming (planktonic) form. This finding unveiled an exciting new anti-biofilm paradigm; i.e. use of NO-donor compounds in combination with antibiotics to clear chronic biofilm infections, sinceit is well-known that planktonic bacteria are up to 1000x more susceptible to antibiotics and host immune defences than their better-protected biofilm counterparts. Based on this discovery, we have designed, synthesized and provided in vitro proof-of-concept validation for a novel class of cephalosporin-based NO-donor prodrugs (DEA-CPs) that can provide biofilm-targeted NO delivery. The targeted NO signal from DEA-CPs (activated by ß -lactamases) induces biofilms to disperse and when used in combination with clinical antibiotics the compoundsare able to clear biofilms. The seminar will highlight key results in this area, including our latest efforts to translate DEA-CPs for use against chronic respiratory P. aeruginosa biofilms in cystic fibrosis patients.
Ganjun Yuan
Jiangxi Agricultural University, China
Title: Anti-methicillin-resistant Staphylococcus aureus assay of azalomycin F and its derivatives
Biography:
Ganjun Yuan has completed his PhD from Hainan University and has been researching on pathogenic microbe in Luisana State University Health Sciences Center for six months. He is the Director of Analysis & Test Center, Jiangxi Agricultural University. He has published more than 40 papers in reputed journals and has been serving as a Council Member of Jiangxi Pharmacological Society in China and a Senior Member of Chinese Pharmaceutical Association
Abstract:
To discover anti-methicillin resistant Staphylococcus aureus (anti-MRSA) compounds, the anti-MRSA activities of many natural products from plants and microorganisms were evaluated in my lab, and even those of some known medicines were deduced from their structures and proved by reasonable experiments. Azalomycins F5a, F4a and F3a, three main components of azalomycin F with broad-spectrum antimicrobial activity, were 36-membered polyhydroxyl macrolides produced by Streptomyces hygroscopicus var. azalomyceticus or Streptomyces sp. 211726. After their relative configurations were reported by us, their anti-MRSA activities were first assayed with agar diffusion and broth microdilution methods. The results showed that their minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations against MRSA ATCC33592 and eight clinical isolates MRSA 01-08 were 3.0-8.0 and 8.0-16.0 μg/mL, respectively. To further improve their anti-MRSA activity, stability and water solubility, eleven azalomycin F derivatives were synthesized through direct hydrolysis with NaOH in MeOH or through hydrocarbylation in hydrocarbyl alcoholic-AcOH and subsequent demalonylation with KOH in MeOH-H2O. The antimicrobial assays of these derivatives showed that the anti-MRSA activities of demalonylazalomycin F and 17-alkyl demalonylazalomycin F5a derivatives were respectively 8-16 and 4-6 times those of azalomycin F and azalomycin F5a, while those of the 17-alkyl azalomycin F5a derivatives showed no enhancement. Moreover, the checkerboard assays indicated that azalomycin F5a, F4a or F3a combined with vitamin K3 showed synergistic activities against MRSA and their fractional inhibitory concentration indices were 0.25-0.50. With remarkable anti-MRSA activity, stronger stability, moderate water solubility and antifungal activity indicated that demalonylazalomycin F had a high potency as anti-MRSA agents.
Biography:
Andrei L Gartel, PhD is an Associate Professor in Department of Medicine at the University of Illinois at Chicago, and the academic editor of PLOS ONE. He is the author of 86 peer-review publications with more than 8500 citations and with H-index 35. His scientific interests are cancer, cell cycle, transcriptional gene regulation, cyclin-dependent kinase inhibitors including p21, regulation of oncogenic transcription factors FOXM1 and c-Myc. He showed that thiazole antibiotic thio-strepton targets FOXM1 and could be delivered in nanoparticles to cancer cells to suppress FOXM1.
Abstract:
The oncogenic transcription factor forkhead box M1 (FOXM1) is overexpressed in human cancer, while its expression is turned off in terminally differentiated cells. For this reason, FOXM1 is an attractive target for anticancer drugs. Using a high-throughput, cell-based assay system, we screened for and isolated the antibiotic thiazole compound Siomycin Aas FOXM1 inhibitor. Next, we found that structurally similar thiazole antibiotic, thiostrepton also inhibits the transcriptional activity and expression of FOXM1. The thiazole antibiotics efficiently inhibited the growth and induced strong apoptosis in human cancer cell lines of different origin. It turned out that Siomycin A and thiostrepton act as proteasome inhibitors in mammalian cells. In addition, we showed that thiostrepton, when formulated into nanoparticles, is highly suited for delivery to tumors. We decided to examine whether other known thiazole antibiotics such as berninamycin, micrococcin P1 and P2, thiocillin and YM-266183 (lacking the quinaldic acid ring B) also have this activity. Several thiazole antibiotics have a macrocyclic loop connecting thiazole rings at position 2 and 3 described as ring A, while thiostrepton and Siomycin A have in addition a quinaldic acid macrocycle also connected to thiazole on position 2 described as ring B. We found that berninamycin, micrococcin P1 and P2, thiocillin and YM-266183 do not act as proteasome inhibitors. Moreover, structural modification of thiostrepton to thiostrepton methyl ester (with open B ring) also did not show this activity. These data suggest that A and B rings are required for the proteasome inhibitory activity of these drugs.
Jorge Ernesto Guevara Vasquez
National University Mayor de San Marcos – Lima-Perú
Title: Use of Probiotics in Guinea Pigs (Cavia porcelllus)
Biography:
Jorge Guevara Vásquez completed his PhD at the National University Agraria La Molina, Lima – Perú. Currently he is working as a teacher and a member of the Research Group on Animal Nutrition (GINA) of the National University Mayor de San Marcos. He has published articles in various journals on research in the area of nutrition and animal production. Sponsor of his thesis are students of undergraduate and graduate degrees to obtain corresponding academic degree.
Abstract:
The objective is to isolate and identify the bacterial isolates by molecular techniques belonging to genera with potential for probiotics in the intestine of guinea pig (Cavia porcellus) and evaluate this productive parameters supplemented with this probiotics, the intestine was extracted from each sample were taken by scraping the intestinal mucosa, they were planted in different culture media in order to achieve isolated colonies with phenotypic characteristics of bacterial species of known potential probiotic (Lactobacillus, Enterococcus, Streptococcus, Bacillus, Bifidobacterium). We identified 27 representative isolates by amplification, sequencing and bioinformatic analysis of 16S rRNA gene. DNA sequences were compared with three different databases. It turned out that 85.18% obtain Lactobacillus, Enterococcus, Streptococcus and Bacillus, the 14.81% remaining bacterial species gram positive identified that are not objective of this study, but that however, contribute to the identification of guinea pig intestinal microbiota, was found Staphylococcus. Then it was to evaluate the productive parameters of guinea pigs supplemented with this probiotics. Five treatments with eight replicates per treatment were used: T1, T2 and T3 received 100, 150 and 200 ml of probiotic, respectively, and T4 and T5 were positive and negative controls, respectively. The dry matter intake, weight gain, feed conversion and carcass yield were evaluated. T2 had the lowest dry matter intake (2564 g) and the lowest feed conversion (3.90) and T5 increased consumption (3293 g) and increased feed conversion (5.04). Weight gain and carcass yield were not affected by the probiotic. The dietary inclusion of probiotic strains from guinea pig intestinal microbiota affected (p<0.05) feed conversion in growing and fattening guinea pigs.
- Video Presentation
Session Introduction
Baló-Banga J M
Medical Center of the Hungarian Defense Forces, Hungary
Title: Evaluation of antibiotic hypersensitivity in hospital setting. In vivo and in vitro testing by using standardized epicutaneous, intradermal, oral provocation tests and a rapid IL-6 release assay on the peripheral mononuclear cells
Biography:
Baló-Banga J M is working in Dermato-Allergy Unit at the Department of Dermatology Medical in Hungary
Abstract:
Background: Antibiotics are amongst the most frequent causes of drug hypersensitivity. Aim: To study the appearance of mostly skin related hypersensitivity events due to this very heterogeneous group of drugs in our hospitalized and out-patient material between 2007-2013 in order to analyze their culprit role. Methods: The total number of patients was 136 that of matching control 29. Most patients were seen at the Emergency Unit of our hospital and sent after consultation as in- or outpatient for further clarification. According their history and symptoms 45% were definitely, 19% probably, 19% possibly hypersensitive to one or more drugs. Within the control group in 67% drugs as causative agents could be ruled out and in 33% their role has emerged as possibility. All tests have been carried out between 2-8 months after the event. In vivo methods included patch testing by pure drugs (10% w/w in petrolatum), intradermal tests by 1 mM drug solutions and oral provocations introducing incremental doses over 3 hrs. In vitro tests were developed to exploit the rapid (20’) release of preformed IL-6 from ex vivo T-cells due to sensitizing drugs. Many in vivo-in vitro tests were run inparallel. Results: Fourty two patients and 5 controls were tested with various antibiotics according their histories. The number of positive in vitro tests was 31 and that of negative tests 29. Within the control group 9 negative tests were noted. Most tests (32/60=53%) were performed with ß-lactams (penicillins and cephalosporins), followed by clindamycin (8/60=13%), fluoroquinolones (5/60=8%) sulfametoxazole (4/69=7%), doxycycline (3/60=5%), metronidazole (3/60=5%) and clarythromycine (2/60=3%). The highest positivity rate was found to amoxicillin (8/14=57%) but both false negative and false positive results (1-1) relative to in vivo tests were noted. The lowest positivity rate (0/4=0%) could be found with sulfametoxazole. The intradermal tests with 10-3M vancomycin gave false positive results in 3 controls tolerating this drug. Therefore, its test concentration has been lowered to 10-4 M. The phenotypic expression of antibiotic hypersensitivity fell into the following categories: circumscribed (17%) and generalized (30%) maculopapular rash, severe perioperative angioneurotic edema with dyspnoea, cardiac arrest (6,4%), generalized hives , diffuse erythema + fever (4,3%) circumscribed angioneurotic edema or urticaria (27,6%), severe intertriginous and flexural exanthema(SDRIFE), induced asthma, fixed drug eruption, loss of consciousness; one case each (14,7%). Non-immediate reactions were more common. Conclusion: In vivo and in vitro tests carried out successively are needed to demonstrate drug induced hypersensitivity to antibiotics taking into account the clinical picture and differential diagnostic approach. IL-6 release assay has gained a solid place in the procedure.