Day 2 :
Keynote Forum
Glenn S Tillotson
TranScrip Partners, USA
Keynote: Antibiotic resistance: The holistic viewpoint of outcomes and costs
Time : 10:00-10:30
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:
Antibiotic resistance is an increasing phenomenon in clinical practice with most common pathogens exhibiting one form of resistance or another. However it is the emergence of multi-drug resistant (MDR) pathogens that are grabbing the headlines. Moreover unlike cancer drugs antibiotics can save lives as has been demonstrted over the past 6 decades with pneumonia. This familiarity with antibiotics has led to a “generalization” of the class by the public. It is this conundrum which underpins the current paucity of new antibiotics being developed. The immediate clinical impact of these MDR infections is clear with the use of more drugs, longer hospital and intensive unit stays occurring widely. Moreover the financial impact of multi-drug resistant Gram negative infections has recently been analyzed. P aeruginosa was reported by Morales et al. that MDR PA infections cost 15,265 Euros compared with 4,933 for a susceptible strain of PA. This increase is particularly important when considering infections such as nosocomial pneumonia of which 30% are due to PA and of these >40% are MDR P. aeruginosa is the 3rd most common causative agent of nosocomial infections. These individualistic data should be part of the over-arching calculation for the value of new antibiotics, indeed a recent evaluation by ERG indicates the overall costs of certain infections indicate that a bigger financial and social impact is due to MDR pathogens. These data cover the totality of costs or holistic outcomes. Unfortunately these important data are not widely known nor appreciated by many stakeholders involved in drug formulation processes. As O’Neill et al. describe the critical need for new antibiotics but with the likely strict stewardship applied to new agents their use is likely to be highly controlled. This situation is a dis-incentive to pharmaceutical companies who are considering investing in this space. Although the overall numbers of MDR infections are relatively low their clinical and financial impact is escalating with costs growing beyond mere drug budgets. As we wait the O’Neil team’s recommendations being implemented it is imperative that the holistic impact of antibiotic resistance be assimilated and integrated into decision making. We need a realistic price to be assigned to new life-saving antibiotics so that essential resources will be invested
Keynote Forum
Martin Duerden
Bangor University, UK
Keynote: Antibiotic prescribing for respiratory tract infections in primary care
Time : 10:30-11:00
Biography:
Martin qualified in medicine from Newcastle University in 1982 and has worked as a GP since 1986. He obtained a Masters qualification in public health at Cambridge University in 1997. He has had a longstanding interest in applying evidence-based medicine to prescribing and therapeutics. He has previously worked for the National Prescribing Centre and the Department of Medicines Management at Keele University. From 1999 he has worked as a part-time GP in Conwy, North Wales, and initially worked as Medical Director for Conwy Local Health Board. Following the reorganisation of health services in Wales in 2009 he became Deputy then Acting Medical Director for the Health Board which manages all primary and secondary care NHS services in North Wales. He helped to organise and run the Diploma in Therapeutics at Cardiff University between 2005 and 2010. He chaired the New Medicines Group for Wales from inauguration in 2007 through to 2010. He is a Clinical Adviser on prescribing and evidence-based medicine for the Royal College of GPs, and is member of one of NICE's technology appraisal committees
Abstract:
In the UK 60% of all antibiotic prescriptions are for upper respiratory tract infections (URTIs), although for 60 - 90% of these an antibiotic will not provide resolution or symptom relief. Inappropriate prescribing contributes to antibiotic resistance (AMR), a WHO-recognised urgent issue threatening global health.We conducted an online multinational study of URTI patients in 33 countries (~500 in each). In the UK 68% of healthcare practitioner encounters for URTI in the last year were with a GP; of these 24% resulted in antibiotic prescription. Comparable rates of GP prescribing were seen in several other countries; e.g. USA (24%), Mexico (23%), and South Africa (26%), underscoring the global dimension of inappropriate prescribing. In the UK concerns around AMR have been raised by the Prime Minister and the Chief Medical Officer with forthcoming reports on antibiotic stewardship and risk-related behaviours from The National Institute for Health and Care Excellence (NICE). The Global Respiratory Infection Partnership (GRIP), a group of international experts, was established in 2011 to promote rational antibiotic use and stewardship for URTIs. Practical steps at national and local levels are urgently needed to bring about change, especially in behaviours. GRIP have created useful resources for multiple stakeholders to identify high risk patients and promote symptomatic relief for others.Despite considerable efforts, these UK data show continuing inappropriate antibiotic prescribing for URTIs, especially in primary care. Further education of GPs and patients is required. This is recognised as paramount and, based on its ‘5P’ framework, GRIP is committed to promoting non-antibiotic, symptomatic relief for self-limiting conditions.
- 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.