2^nd World Congress and Exhibition on Antibiotics and Antibiotic Resistance October 13-15, 2016 Manchester, UK

Biography:

Richard W Titball is Professor of Molecular Microbiology at the University of Exeter, and was previously a Senior Fellow at the Defence Science and Technology Laboratory. He is a founder of Biosystems Technology, which specialises in alternative infection models. He has published more than 300 peer reviewed papers, filed 20 patents and currently serves as an Editor of Vaccine and an Editorial Board member of NPJVaccines.

Abstract:

  Galleria mellonella (wax moth) larvae have been used as an infection model to understand microbial pathogens since the 1980’s and are susceptible to a broad range of bacteria and fungi which cause disease in humans. The use of larvae for infection studies is not subject to home office regulation in UK and G. mellonella larvae are generally considered to be an ethical alternative to studies in mammals. The larvae have the advantage that they can be infected at 37 °C, allowing the expression of temperature-regulated virulence genes. A defined infection site allows larvae to be injected with precise doses of bacteria and/or drugs. Drawbacks of this model include the lack of an adaptive immune response and a lack of mammalian target organs. During the past 5 years there have been reports of the testing of at least existing 22 antibiotics and 5 existing antifungal compounds for their abilities to control infections caused by 17 pathogens in Galleria. There is good agreement between drug efficacy data obtained in G. mellonella and efficacy data previously obtained in mammalian models or in human trials. These findings have generated confidence in the value of G. mellonella for antimicrobial drug screening and more recently there has been a shift towards using this model to screen new drugs and approaches for disease control.

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, where he is now a 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:

Carbapenems are among the most potent antimicrobial β-lactams available today. Emerging evidence indicates that, unlike other subclasses of β-lactams, carbapenems inhibit non-classical transpeptidases (L, D-transpeptidases) that generate 3→3 linkages in the bacterial peptidoglycan. Five different L,D-transpeptidases form part of the cell-wall biosynthesis machinery in Mycobacterium tuberculosis (Mtb), being Ldt_Mt2 the most consequential for mycobacteria survival. Homologous enzymes have been found in ESKAPE pathogens. Evidences show that the peptidoglycan structure produced by these enzymes confers antibiotic-resistant to strains of Enterococcus Faecium and Clostridium difficile. Biapenem, tebipenem and panipenem exhibit therapeutically valuable potencies against drug resistant pathogens. These three different carbapenems inactivate these enzymes by forming adducts with their catalytic cysteine and two other carbapenems, imipenem and meropenem docks to one of the two (inner and outer) cavities that access the catalytic site. The complexes of biapenem, tebipenem and panipenem with Ldt_Mt2 provide evidence that the dock to the outer cavity as a preferred binding mode. Unexpectedly, biapenem and tebipenem result in the same adduct resulted by an enzyme-catalyzed decomposition of the carbapenem resembling the S-conjugate elimination by β lyases. This elimination could be used to our advantage to the targeted delivery and release of the additional antimicrobial compounds. The binding mode and adduct stability are important factors to be considered in any antibiotic design based on the carbapenem scaffold. The potential correlations between these factors and carbapenems affectivity as antibiotics will be reviewed under the light of the structures of complexes of these carbapenems with Ldt_Mt2.

Biography:

Marc Devocelle has completed his PhD at the University of Lille, France under contract with a Pharmaceutical Company. He subsequently joined RCSI in 1999 as a Postdoctoral Researcher and became Manager of the Peptide Synthesis Laboratory in 2000. He has since been appointed as a Lecturer in 2004, a Senior Lecturer in 2008 and an Associate Professor of Chemistry in 2014. His laboratory is involved in over 25 collaborations with 14 academic groups across 8 HEIs in Ireland, 2 SMEs and 1 MNC.

Abstract:

For millions of years, the first line of defense against infections in multicellular organisms has relied on peptides with cationic and amphipathic properties. These Antimicrobial Peptides (AMPs) represent promising leads for the development of antibiotics delaying the emergence of resistance in bacteria. However, their clinical applications have been limited by inadequate margins of safety. A prodrug approach can overcome a toxicity barrier in drug delivery. With AMPs, prodrugs can be generated by reducing their net positive charge, through a modification which can be selectively removed by an enzyme (bacterial or human) confined to sites of infection. For example, neutrophil elastase (NE), a human protease involved in chronic airway inflammation and infections associated with cystic fibrosis (CF) can disconnect an oligo-glutamate promoiety masking the net positive charge and therefore activity of AMP candidates (Bac8c, P18, HB43, WMR and WR12). Their bactericidal activities against reference and clinical isolates of the CF pathogen P. aeruginosa are restored by NE in CF bronchoalveolar lavage fluids. Toxicity differentials are also achieved with the active peptides consistently more hemolytic and cytotoxic against representative epithelial and immune cells than their prodrug forms with the exception of WMR. While no toxicity was observed in vitro with both active and prodrug forms of this candidate, in vivo studies indicated that the prodrug was better tolerated than the active peptide. Finally, an in vitro nebulization study performed with a vibrating mesh nebulizer showed that a high level of dosing in the lung can be achieved for this AMP prodrug

Biography:

Oleg N Reva has completed his PhD from the Institute of Microbiology and Virology in Kyiv, Ukraine. He did his Postdoctoral studies on Bioinformatics in the Medical High School of Hanover, Germany. Currently he is an Associated Professor of Bioinformatics at the University of Pretoria, South Africa. He has published 83 papers and book chapters cited more than 1500 times.

Abstract:

Reversion of resistance to traditional antibiotics in pathogenic bacteria is just beginning to be realized as a prospective approach to combat the drug resistance in hospitals. Little is known about mechanisms of the drug resistance reversion. In a recent review by Baym et al., several theoretical models were proposed to explain the phenomenon by an active counter-selection of resistant strains from the population. A new nanomolecular anti-tuberculosis drug FS-1 has been registered recently in Kazakhstan. It was found in clinical and in vitro studies that FS-1 caused a reversion of sensitivity to traditional antibiotics in multidrug resistant isolates of M. tuberculosis (MDR-Mtb). In this study a recently sequenced MDR-Mtb strain SCAID 187.0 (NCBI acc. CP012506) was used in an in vivo experiment on Guinea pigs to study changes in the genetic composition of the Mtb population during treatment of the infected animals by different combinations of traditional anti-tuberculosis antibiotics with FS-1. In total, 11 Mtb isolates where fully sequenced by Illumina and aligned against the reference genome for variant calling. Treatment with FS-1 increased the genetic heterogeneity of the Mtb population by counter-selecting from the population of the most virulent MDR clones, which were genetically barcoded in this study. Drug resistance in the remaining clones was seriously compromised by a disruption of the genetic context required for drug resistance. In result, the therapy of a MDR-Mtb infection by traditional antibiotics enforced by FS-1 became effective again. To our best knowledge, this was the first experimental assertion of the drug resistance reversion by the theoretically predicted suppressive drug interaction mechanism.

Biography:

Anna Malm has completed her PhD in 1989 from Medical University in Lublin, Poland. She is the Head of Department of Pharmaceutical Microbiology in Medical University in Lublin. She works as a full Professor position and is a Specialist in Medical Microbiology. She has published more than 200 papers mainly in reputed journals in the field of medical microbiology, including studies on antibacterial/antifungal activity in vitro of the compounds of plant or synthetic origin.

Abstract:

The spread of bacterial resistance is an increasingly serious threat to global public health, being a worldwide problem. There are high proportions of resistant bacteria that cause not only serious nosocomial diseases but also common community acquired infections. The dual-action/targeting concept can be regarded as one of the solutions to overcome the problem of growing bacterial resistance. The various hybrid antibacterial agents have been developed and described, including a series of 1, 2, 4-triazole-ciprofloxacin hybrids obtained by a molecular hybridization of ciprofloxacin and different 1, 2, 4-triazole derivatives. These hybrids showed good inhibitory effect against Gram-positive bacteria such as Staphylococcus aureus ATCC 25923, S. aureus ATCC 6538, methicillin-resistant S. aureus MRSA Microbank 14001, Staphylococcus epidermidis ATCC 12228, Micrococcus luteus ATCC 10240, Bacillus subtilis ATCC 6638 and Bacillus cereus ATCC 10876 as well as Gram negative bacteria, including Escherichia coli ATCC 25922, Klebsiella pneumoniae ATCC 13883, Proteus mirabilis ATCC 12453, Pseudomonas aeruginosa ATCC 9027 and Haemophilus influenzae ATCC 10211. A number of these compounds displayed enhanced potency as compared with ciprofloxacin. The results of enzymatic assays have proven that stronger antibacterial activity of novel 1, 2, 4-triazole-ciprofloxacin hybrids (as compared to ciprofloxacin) cannot be caused by the increased affinity towards bacterial type II topoisomerases; the analyzed compounds demonstrated other preferences towards primary and secondary molecular targets than ciprofloxacin. These hybrids were found to be active not only against planktonic cells but also against biofilm forming cells of Haemophilus spp. The 1, 2, 4-triazole-ciprofloxacin hybrids may be considered as starting compounds for designing of the agents with improved antibacterial activity, including anti-biofilm properties

Biography:

Byungse Suh has completed his BS in Pharmacy from Chungang University, Seoul, Korea; PhD from University of Kansas; Postdoctoral studies from University of Iowa and MD from University of Miami, USA. He has completed his Residency and Fellowship from University of Wisconsin Hospital. He is also a Professor of Medicine and published more than 110 papers

Abstract:

A 51 yom with COPD was hospitalized for pneumococcal pneumonia and sepsis requiring mechanical ventilation and glucocorticoid treatment for 30 days. One week later, he developed right hemiplegia and confusion. MRI of brain demonstrated two left parietal lesions with edema. A brain biopsy fungal stain showed non-septate, right angle branching hyphae consistent with mucormycosis; fungal culture was negative. Treatment was initiated with high dose LAMB (10 mg/kg/day), and by day 9 the patient showed improvement in mentation and the ability to lift his right arm. LAMB was decreased (5 mg/kg) and oral posaconazole (PCZ) (400 mg BID) was added. He continued to improve and was discharged on this combination therapy (day 28). On day 38, chemical hepatitis was observed, presumably due to PCZ. PCZ was discontinued while continuing LAMB. On day 51, PCZ was re-introduced in an attempt to convert to oral therapy. On day 166, LAMB was discontinued; PCZ was continued alone. He was readmitted with another episode of pneumonia (day 221) and repeat MRI demonstrated significant enlargement of the known parietal lesions and a new enhancing right parietal lesion. PCZ was discontinued and LAMB was restarted (day 229). On day 541, LAMB was discontinued due to acute renal failure and PCZ was reintroduced. On day 576, LAMB was resumed due to progression of brain lesions while on posaconazole. The patient was continued on LAMB until day 978 when he expired due to respiratory failure. In this patient, LAMB appeared more efficacious in controlling cerebral mucormycosis than posaconazole.

Biography:

Mymoona Akhter holds Ph.D. Pharmaceutical Sciences, M. Pharma in Pharmaceutical Chemistry from Jamia Hamdard (Hamdard University) New Delhi. Akhter is working as an Associate Professor of Medicinal Chemistry in Faculty of Pharmacy and is Deputy Co-ordinator of the Bioinformatics Facility Jamia Hamdard. Akhter has been bestowed with several honors like the SERB- fast track research project award for young scientists by Department of Science and Technology, Govt. of India (2012), the Career award for young Teachers by All India Council of Technical Education (2010), SERC Visiting Fellowship by DST (2005). She is supervising scientific research of the post-graduation and the doctoral level. She has guided/under guidance about 20 theses of M. Pharm. and M.Tech Bioinformatics and 5 theses of Ph. D. She has presented his research work in 43 conferences held in India and abroad. She has a list of more than 50 manuscripts in journals of repute and has co-authored a book on Practical Pharmaceutical Analytical Chemistry. She is Editor-in-Chief of International journal of Pharmaceutical Chemistry and Analysis.

Abstract:

Dihydrofolate reductase (DHFR) is one of the validated drug targets in Mycobacterium tuberculosis infection. DHFR inhibitors have been used to treat various life threatening diseases such as cancer, malaria and several bacterial infections. However, all clinically effective DHFR inhibitors are non-selective and inhibit both human and pathogenic DHFR more or less to a similar extent. The crystal structures of DHFRs are validated and have been used for new drug design. Mycobacterium and human (h)-DHFRs show 26% structure similarity but their active sites are not identical and this information forms the basis of our study. Since most of the reported inhibitors of Mtb DHFR are pteridine based and are non-selective in nature therefore this study is aimed at to design and develop selective non-pteridine Mtb DHFR inhibitors. In the ternary complex of MTX with Mtb DHFR, in addition to MTX a glycerol “A” molecule is found in a depression nearby which shows interaction with the side-chains of Trp22, Asp27 and Gln28 which form a pocket in Mtb DHFR while glycerol is absent in h-DHFR. The h-DHFRs glycerol is absent and the site is packed with three hydrophobic residue side chains, Leu22, Pro26 and Phe31, which correspond to Leu20, Arg23 and Gln28 in Mtb DHFR. A compounds with side chain which could mimic the binding mode of glycerol to protein, may bind to Mtb DHFR selectively. Such a derivative should be sterically and chemically hindered from forming a complex with h-DHFR. This assumption forms the basis of present study and these understandings have been used for designing of selective inhibitors of Mtb DHFR. Number of novel non-pteridine based molecules has been identified through virtual screening of three databases. The synthesis of best hit has been carried out and tested for anti-tubercular activity. The results are promising and require further work in this direction

Biography:

Andrew Cross specializes in exploiting copper's intrinsic antimicrobial properties to reduce infection risk from touch surfaces. He offers product advice and consultancy to healthcare providers, architects/designers, construction professionals and helps manufacturers to develop new products. He has also helped the Copper Development Association develop educational materials on the scientific, practical and economic aspects of deploying copper for infection control. His long-term experience with the use of copper alloys for specialist engineering and architecture provides a sound practical foundation, combining this with the latest published research enables successful translation of a concept into healthier buildings with tangible benefits for people and organizations.

Abstract:

Antimicrobial resistance threatens the viability of many recent medical advances such as organ transplants, hip replacements, cancer therapy, etc. Development of new antibiotics cannot keep up with resistance, partly because the “easy” antibiotics have already been developed, partly because the funding model does not incentivize companies to develop new antibiotics and partly because of the huge cost of validating new antibiotics nowadays. So what can we do? It is easy to say “use fewer antibiotics” but effective antibiotic stewardship requires control to be consistent around the world. Also, human behavior is hard to change; patients are accustomed to being prescribed antibiotics, even for self-limiting conditions and the number of patients with long-term conditions (e.g., diabetes, asthma) that merit antibiotic prescription is raising. Agriculture and aquaculture need to adapt, yet antibiotics have helped these industries provide low-cost food for the world's fast-growing population. Should we all eat less meat and fish? At work, employees can be under pressure to be at work rather than rest when unwell. 'Presenteeism' can not only worsen an illness or infection but also help it spread to colleagues and customers. In hospitals, approximately 25% of Intensive Care (ICU) patients acquire an infection (HCAI). Among other patients, the HCAI rate is around 6%. HCAIs typically require not only antibiotics but a prolonged stay in ICU. Globally, huge numbers of healthcare patients acquire avoidable infections that need antibiotics. Achieving even a modest reduction in HCAI rates will help to preserve our dwindling antibiotic stock.

Biography:

Sitah N Alzuman has earned her Bachelor degree in Pharmaceutical Science in 2004 and Postgraduate Residency in Clinical Pharmacy Practice in 2009. She has worked in many big hospitals in the Saudi Arabia before joining King Khaled Eye Specialist Hospital in 2010. She has gained more experience in ophthalmic field and established the medication refill clinic for ophthalmic patient.

Abstract:

Antibiotics were considered “miracle” drugs when they were presented in the middle of the 20th century. However, excessive use of antibiotics has long been a worry in the medical community-most specifically the development of antibiotic resistant especially against a systemic medicine (OR medication OR antibiotic?), but is it less problematic in ophthalmic field? Bacterial infections of the eye are common and ophthalmologists are spoilt (little harsh word) for choice with a variety of antibiotics available in the market which are mainly used topically, thereby help ophthalmologist to achieving high concentrations; often much above the minimum inhibitory concentration (MIC) of antibiotics in ocular tissues during therapy. These high concentrations are effective in treating bacteria that are deemed resistance using standard interpretations of susceptibility. But the important question is whether systemic in vitro susceptibility standards accurately interpret for ocular infection as well. Until recently, ocular pathogens resistant to fluoroquinolones have been minimal but the pattern is currently alarming. Among the most common types of ocular infections, we need to know which one reflects arise in resistance. Also, if the current practice is enough to manage the ocular infection or reconsideration is required for future.

Biography:

Bing Xie has completed his PhD from East China Normal University and Postdoctoral studies from Hongkong University School of Ecology Diversity. He is the Director of Shanghai Society of Environmental Microorganism Association. He has published more than 100 papers in reputed journals and has been serving as an Editorial Board Member of international journal

Abstract:

The anthropogenic sources wastes, including domestic sewage and husbandry wastewater, to and sludge to garbage and municipal solid waste are regarded as main contributors to the elevated level of antibiotics in the environment. This paper introduces recent studies on the occurrence and dynamic models of antibiotics in anthropogenic wastes, their effects on wastes bio-processing and the corresponding risk assessment methodology. Our results show that removal of antibiotics is more dependent on their sorption potential than on their biodegradability within a treatment system. Furthermore, the presence of antibiotics at trace levels is reportedly inhibitory to bio-treatment systems particularly to nitrification. However, after prolonged acclimatization microorganisms may come to the fore that can subsist on antibiotics, while these inhibitory effects can also be alleviated as a consequence of the evolution of antibiotic resistance genes (ARG) and/or succession of a microbial community that is gradually dominated by antibiotic insensitive microorganisms. The spread of ARGs and their recruitment by clinically important bacteria have not been studied in enough detail to allow assessment of the related risks. Defining risk determinants and proposing validated risk quantification models are imperative as necessary steps towards a comprehensive risk assessment framework for the presence of antibiotics and antibiotic resistance in anthropogenic wastes.

Biography:

Christof Berberich has completed his PhD in Molecular Biology from the University of Heidelberg, Germany. After several years of Postdoctoral research in infectious diseases, he has moved to the health care industry. In his current position as Head of Medical Training at Heraeus Medical, Germany, he educates surgeons, microbiologists and infectious disease specialists on the appropriate use of antibiotic-loaded bone cement for PJI prophylaxis and treatment support. He has published 28 papers in reputed journals and books and has lectured at more than 150 educational events and congresses.

Abstract:

Prosthetic joint infection (PJI) is a rare pathology of joint replacement surgery. However, as a consequence of the growing number of joint replacement procedures worldwide, the incidence of PJI cases is projected to increase sharply in future. Treatment of PJI is often complex and challenging in multi-morbid patients and in presence of multi-resistant pathogens. In order to prevent bacterial colonization and biofilm formation on the “vulnerable” prosthesis or to support the septic treatment of a PJI, a combination of systemic and local antibiotics has become surgical standard. The best studied and most widely used delivery system for local antibiotics is bone cement (BC). Pharmocokinetic studies have shown that the level of antibiotics released from BC may reach bactericidal in situ-concentrations which are 100-1000 fold higher compared to concentrations of systemically administered antibiotics. Typically, this is not associated with a higher burden of systemic side effects. According to several arthroplasty registries the combined use of systemic and local antibiotics may reduce the risk for PJI and/or the incidence of PJI relapses up to 50%. Gentamicin is the prophylactic local antibiotic of choice, because of its broad-spectrum and strict concentration-dependant bactericidal effect. To support eradication of an already established PJI, an antibiogram-adapted combination of two or more antibiotics in a cement spacer should be considered after surgical debridement of the infected tissue. However, not any antibiotic is suitable for using with bone cement. For the microbiologist and orthopedic surgeon it is therefore important to know which basic chemical and physical requirements an antibiotic chosen for admixing to bone cement powder must fulfill. These include often not easily predictable parameters such as water-solubility, heat-stability, no chemical interaction with cement polymerization etc. The available literature does not support concerns on the promotion of relevant bacterial resistance, if the when and how of antibiotic-loaded bone cements are followed

Biography:

Prof Samir Kumar-Singh is a certified medical doctor with a doctorate in Pathology and a Master degree in Laboratory Animals. He is a full-time research professor of Molecular Pathology at the Faculty of Medicine, University of Antwerp, Belgium and is affiliated to the Vaccine and Infectious Disease Institute, Belgium. He has published a well-cited body of work on molecular pathology of cancer and neurodegeneration involving patient studies and mouse modelling. Professor Kumar-Singh serves on several review and editorial boards and international consortia. Since 2012, his group is engaged in studying the pathomechanism of hospital acquired pneumonia especially ventilator-associated pneumonia (VAP) and has developed several authentic rat and mouse VAP as well as acute and chronic pneumonia models to study disease pathogenesis and for biomarker discovery as well as high-throughput in vitro screens for new antimicrobial targets.

Abstract:

P. aeruginosa is a unique organism able to grow in the harshest environments and is characterized by both a large genome as well as unique mechanisms that allow for enhanced genomic and metabolic plasticity making this organism a robust nosocomial pathogen equipped with a myriad of virulence factors as well as antibiotic resistance adaptations. Low-level exposure to antibiotics, both in hospital settings as well as from livestock and wastewater pollution showed that resistance selection and phenotypic alterations could already occur at sub-inhibitory concentrations. Using a multiplex labeling strategy followed by mass spectrometry, we showed a differential response of P. aeruginosa when challenged with sub-inhibitory concentrations of imipenem, colistin, cefepime and tobramycin by both laboratory strains as well as clinical isolates recovered from ventilator-associated pneumonia (VAP) patients. Low-level exposure to imipenem induced expression of AlgR and AlgC proteins that are known to be involved in biofilm formation as well as in regulating virulence and were observed to be most elevated in the laboratory strains. Moreover, Hcp1 and ClpV1, both main components of H1-type-6 secretion system were increased following imipenem exposure in all isolates used. Tobramycin on the other hand induced marked up-regulation of proteins involved in branched amino acid metabolism, electron transport chain proteins and superoxide dismutase indicating that tobramycin induces oxidative stress, a mechanism previously observed with E. coli. Cefepime and colistin only showed a marginal effect on protein expression at sub-inhibitory concentrations. The demonstration of a differential response of P. aeruginosa towards different antibiotic classes at sub-inhibitory concentrations gives us further insights in the potential resistance mechanisms and cellular physiology of this highly pathogenic bacterium and will be the focus of the talk.

Biography:

Khine Swe Swe Han has completed her MBBS from Myanmar Medical University and FC Path, MMed (Medical Microbiology), Post graduate degree studies from South Africa University School of Medicine. She is a Senior Consultant/Lecturer of NHLS, University of KwaZulu Natal and IALCH Academic Hospital. She is a chair person of infection control committee and participates as a major role for antibiotics stewardship program. She has published 14 papers, 27 oral/ poster presentations and she is also a Reviewer. She has participated as an Editorial Board Member of SASCM, a Member of FIDSSA and senate of UKZN.

Abstract:

Introduction: Antibiotic resistance Acinetobacter baumannii (A. baumannii) is a serious problem in clinical settings worldwide, including South Africa. It significantly affects the optimal use of antibiotics. Differentiating colonization from infection/sepsis is also problematic and indiscriminate unnecessary treatment with colistin will induce colistin resistance A. baumannii.

Methods: A 5 year retrospective study of critically injured patients requiring mechanical ventilation is presently ongoing at our Level 1 Trauma Unit in South Africa. Endotracheal (ETA) samples from patients with suspected VAP are processed using the automatic system (Vitek 2) and as per the Clinical, Laboratory Standards Institute (CLSI) guidelines. The laboratory data and hospital admission data were reviewed between 2011 and 2015. The prevalence of the patients infected or colonization with A. baumannii and outcomes were determined.

Results: To date a total of 119 patients had A. baumannii isolate cultured from ETA who were suspected VAP in 24 (20%) of whom was significance of VAP. All isolates were susceptible only to colistin and 96 isolates were susceptible to Amikacin. The prevalence of Multidrug resistant A. baumannii (MRDAB) was 75% and 60% in significant infection and colonized patients respectively. The patients with signs of sepsis and a sole isolate of A. baumannii received inhaled nebulization with Amikacin. All deaths of which were directly related to injuries sustained rather than infection with A. baumannii during the study period.

Conclusion: Our study supported the current individual specific antibiogram approach and continued collaboration between clinicians and clinical microbiologists in order to achieve the effective antibiotic stewardship programs in the hospital setting

Biography:

Jebananthy Anandaselvam Pradeepan has graduated from University of Jaffna as a MBBS in 2004 and successfully completed MD in Internal Medicine in 2009 from University of Colombo, Sri Lanka. She proceeded for overseas training at Queensland Health, Australia. She has assumed her duties as a Consultant Physician and Lecturer at the University Medical unit, Teaching Hospital, Jaffna in September 2014. Her current interests are tropical infectious diseases, in particular Rickettsial outbreaks in Sri Lanka. She has published papers related to typhus in peer reviewed journals.

Abstract:

Scrub typhus is a zoonotic disease caused by a subtype of Rickettsiae; Orientia tsutsugamushi. It has significant prevalence in Eastern and Southeast Asia, usually presenting as an acute febrile illness. The diagnosis is often missed due to similarities with other tropical febrile infections, such as dengue and leptospirosis. The presence of typical eschar of scrub typhus infection aids the clear diagnosis. However, its painless and covert nature makes it difficult to diagnose clinically, when present with devastating complications like pneumonitis, meningoencephalitis and shock. Prompt therapy with highly sensitive antibiotics such as chloramphenicol, tetracycline, doxycycline and azithromycin in pregnancy and lactation shortens the course of the disease, lowers the risk of complications and in turn reduces morbidity and mortality due to rickettsial diseases. We conducted a retrospective study in 64 adult patients at Teaching Hospital, Jaffna during an epidemic in Northern Sri Lanka during March 2012-2013. They presented with acute fever (<14 days) and a clinical profile of typhus, without an obvious focus of infection. They were treated with a 7 day course of doxycycline monotherapy or azithromycin as per indication. All patients responded to monotherapy. Fever defervescence was noted on day 2 or 3 in majority of patients and complete recovery observed on day 7. Subsequently, 54 cases (84.4%) were found to be positive for scrub typhus with specific IgM and IgG ELISA (ImBios, USA). Typical eschar was identified in 49 cases among positives.

Biography:

Fanyana Mtunzi has completed his PhD from University of North-West, South Africa. He is the Senior Lecturer and Researcher at Vaal University of Technology. He has published more than 30 papers in reputed journals and has been serving as an Editorial Board Member of repute.

Abstract:

limit. Carissa bispinosa hexane fraction displayed the lowest activity of 467.7 mg/L within 264.0 to 828.5 at 95% confidence limit. Highest ABTS^●+ radical scavenging was demonstrated by Pomaria sandersonii DCM, (1.273 mg/L at 0.9439 to 1.719 within 95% confidence limit) for the Ethyl acetate, (5.973 mg/L at 4.722 to 7.555 within 95% confidence limit while the lowest activity was displayed by hexane fraction from Eucomis autumnalis (929.4 mg/L at 557.5 to 1550 within 95% confidence limit). The activity of Pomaria sandersonii extracts and fractions demonstrated that the plant contains antioxidants that react with both DPPH and ABTS radicals although higher activities were shown by ABTS as displayed by the lower EC₅₀ values. All of the crude fractions and extracts displayed high to moderate anti-bacterial activity (20-625 µg/ml) and anti-fungal activity (20-2500 µg/ml). P. sandersonii crude and fractions demonstrated highest antimicrobial activity compared to other plants. Some MIC values P. sandersonii DCM and ethyl acetate (80 µg per ml in each case) compared well with gentamycin (4 µg per ml) same value against S. aureus, E. faecalis, E. coli and P. aeruginosa. Anti-fungal activities of the DCM, acetone and methanol fractions were also highly active (20 µg per ml) for both Candida albicans (C. a.) and Aspergillus. fumigatus (A. f.) Inhibition of pathogen growth demonstrated by the polar fractions indicates that most of the active compounds would be soluble in water. P. prunelloides, crude methanol extract produced 60% sucrose component and G. perpensa, 36% was glucose. Three compounds isolated from Alepidea amatymbica and three from Pomaria sandersonii which displayed high antimicrobial activities.

Biography:

Apurba Dey has completed his PhD from IIT Delhi and Postdoctoral studies from University of Malaya, Malaysia. He is having 22 years of teaching, 2 years industrial and 25 years of research experience. Presently he is working as a Professor in the Department of Biotechnology, National Institute of Technology Durgapur, India. He has published more than 45 research papers in reputed journals and supervised 10 PhD students.

Abstract:

An extensive mutation work has been carried out to improve the rapamycin (antibiotic) yield by Streptomyces ghanaensis MTCC 4003. Mutational approach i.e., sequential UV mutagenesis was applied to the spores with an aim of increasing the stability along with higher rapamycin synthesis. 30 watt lamp with 254 nm UV-C category light was used for mutagenesis experiment. Around 6% survival rate (94% killing ratio) was achieved after final spore count by Haemocytometer on 21^st day of incubation. Numerous colonies were obtained after primary screening of mutants, of which some were deteriorating in nature and rest maintained rapamycin producing activity. Preliminary experiments were carried out by Agar disc diffusion method using Candida albicans MTCC 227 as test organism and validation/purification was performed with HPLC. Concentration of rapamycin from fermentation broth was calculated using standard curve prepared between known concentration of rapamycin vs inhibition zone diameter. Average rapamycin production by different UV mutants were found as follows: UV-30-17 127.73 mg/L, UV-45-11 89.66 mg/L, UV-60-9 84.33 mg/L and UV-90-5 76.33 mg/L. Among all UV induced mutants, UV-30-17 showed highest rapamycin yield which is 1.61 fold higher than that of the wild type or untreated strain (79.23 mg/L). The strain was further selected for higher production using statistical design approach

Biography:

Carolina dos Santos Vinagreiro is a Medicinal Chemistry PhD Student. In 2015, she has completed her Msc from Coimbra University under the supervision of Mariette M Pereira. She ranked first among her classmates and was awarded various prizes as the Best Student in High School (18.4/20), in the BSc (17/20) and in the MSc (19/20). Her outstanding performance was also remarked by Luzitin SA, which offered to pay her tuition feed, and in two congresses where her oral presentation was distinguished with an award. Moreover, she is the author of 6 oral communications, 3 posters and 2 papers.

Abstract:

The development of new molecular entities capable of promoting the inactivation of bacteria without developing drug resistance depends on finding alternative mechanisms of action for antibiotics. Photodynamic Inactivation of microorganisms (PDI) is emerging as an alternative to classical antibiotics because PDI is not associated with the development of microorganism resistance after treatment. This work presents new methods of synthesis of new chemical entities based on tetrapyrrolic macrocycles that can potentially target bacteria and act both as bacteriostatic and photosensitizing agents. Additionally, this work presents the fundamental photophysical assessment of the new photosensitizers, namely in terms of their electronic absorptions, singlet oxygen quantum yields and reactive oxygen species generation. The cytotoxicity of selected photosensitizers and its antibacterial activity assays will be presented. The presentation will discuss the future perspective of PDI as a promising approach for overcoming antibiotic resistance.

Biography:

Martina Kulen is a PhD student in Prof. Fredrik Almqvist group at the Department of Chemistry, Umeå University, Sweden.

Abstract:

The rapid emergence of bacterial resistance to antibiotics is a serious global problem and new therapeutic options to treat severe bacterial infections are therefore urgently required. The bacterium Listeria monocytogenes is a Gram positive saprophyte, responsible for the severe disease listeriosis in humans upon ingestion. It is one of the most problematic food borne pathogens due to its ability to grow at low temperatures, low oxygen conditions and in high salt concentrations. From a small in-house library, we have identified several ring fused 2-pyridone molecules that attenuate L. monocytogenes infectivity by reducing the expression of virulence genes, without compromising bacterial growth. The inhibitors bind to and prevent activation of PrfA, the central transcriptional virulence regulator in L. monocytogenes. The ring fused 2-pyridone C10 binds to PrfA with an IC50 ≈1 µM according to ITC measurements. The structural basis for inhibition was elucidated by the structurally resolved complex between C10 and PrfA. This represents the first structurally resolved complex between an inhibitor and a Crp family transcriptional regulator. Here, we will present a new generation of improved ring fused 2-pyridone molecules, which have been designed and developed based on the PrfA·C10 crystal structure. These demonstrate increased solubility and improved activity in our biological screen. Co-crystallization of the new structures with PrfA has also provided a more detailed illustration of the inhibitor mode of action.

Biography:

Samar Said Mahmoud Mohamed Elbaramawi has completed her Master degree in 2014 from Faculty of Pharmacy, Zagazig University, Egypt. She is an Assistant Lecturer of Medicinal Chemistry, Faculty of Pharmacy, Zagazig University, Egypt. Currently, she is a PhD student at School of Pharmacy and Pharmaceutical Sciences, Cardiff University, Cardiff, United Kingdom through a joint supervision scholarship between Zagazig University and Cardiff University. She has published five papers in reputed journals.

Abstract:

Increased resistance of MRSA (multidrug resistance Staphylococcus aureus) to anti-infective drugs is a threat to global health. So anti-infectives with novel mechanisms must be developed. Aminoacyl-tRNA synthetases (aaRSs) are essential enzymes to protein biosynthesis as they catalyze the attachment of amino acid to its cognate tRNA molecule. Phenylalanine tRNA synthetase (PheRS) is a unique enzyme of aaRSs family, it is an (αβ)₂ tetrameric enzyme composed of two alpha subunits (PheS) and two larger beta subunit (PheT). Our potential target in the drug development for the treatment of MRSA infections is the phenylalanine tRNA synthetase alpha subunit that contains the binding site for the natural substrate. There is no crystal structure available to S. aureus PheRS enzyme, therefore comparative structure modeling is required to establish a putative 3D structure for the required enzyme enabling development of new inhibitors with greater selectivity. The S. aureus PheRS alpha subunit homology model was constructed using Molecular Operating Environment (MOE) software. Staphylococcus haemolyticus PheRS was the main template while Thermus thermophilus PheRS was utilized to predict the enzyme binding with tRNA. The model has been evaluated and compared with the main template through Ramachandran plots, Verify 3D and ProSA. The query protein active site has been predicted from its sequence using a conservation analysis tool. Docking suitable ligands using MOE into the constructed model was used to assess the predicted active site. The docked ligands involved the PheRS natural substrate (phenylalanine), several described S. aureus PheRS inhibitors and phenylalanyl-adenylate analogue.

Biography:

Jaimee George has completed her post graduation in Microbiology from the University of Mysore, Karnataka. She is currently pursuing her PhD from Central Food Technological Research Institute, Mysore, India. She is presently working on the topic “ Molecular assessment of aminoglycoside resistance in Enterococcus sp.” has published two papers in reputed journals. Her work highlights  the significance of aminoglycoside resistance in lactic acid bacteria isolated from farm animals and fermented food, its spread via horizontal gene transfer as well as its expression studies.

Abstract:

Low level resistance is associated with constitutive expression of aminoglycoside resistance genes. Nevertheless, treatment with specific aminoglycosides facilitates induction of mRNA expression as well as confers resistance to structurally related antibiotics of this class. As vital drugs in human therapy this cross resistance mechanism in bacteria may challenge the efficacy of the entire aminoglycoside class. In the presence of two or more aminoglycoside resistance genes viz. aac(6´)Ie-aph(2˝)Ia and aph(3˝)IIIa (kanamycin resistance) in E. faecalis 33-1, it was interesting to observe the pattern of expression levels of each gene upon individual induction with increasing concentrations of gentamicin, kanamycin and streptomycin (2048, 4096, 8192, 16384 µg/mL). The expression of the bifunctional and kanamycin resistance genes increased with the increase in gentamicin and kanamycin concentration, respectively. Upon streptomycin and gentamicin induction, the expression levels increased at a low concentration (2048 µg/mL) with gradual decrease at higher concentrations for aac(6´)Ie-aph(2˝)Iaand aph(3˝)IIIa, respectively. Similar observation was made for aph(3˝)IIIagene when induced with gentamicin at 8192 µg/mL. However, it was least expected to observe significant increase in expression of the aph(3˝)IIIa gene which is not known to induce when treated with streptomycin and may have a novel mechanism. Similarly, the genotypic and phenotypic effects of continuous induction with sub-inhibitory concentrations of gentamicin for 30 days in Lactobacillus plantarum C27b MCC3011 harboring aac(6´)Ie-aph(2˝)Ia gene were investigated. In addition, plasmid encoded horizontal gene transfer of the high level aminoglycoside resistance gene, aac(6´)Ie-aph(2˝)Ia from viz. Enterococcus avium, E. cecorum, E. faecalis species into the recipient strain E. faecalis JH2-2 by filter mating indicated the possibilities gene transfer into pathogenic strains in the gut. Thus, this investigation demonstrates that exposure to sub lethal aminoglycoside concentrations facilitate cross resistance mechanisms, biofilm formation, conjugal transfer and adaptive selection of resistance genes in commensal lactic acid bacteria which can have deleterious effects.