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

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.