Thursday, March 22 

7:30 Morning Coffee 
(Breakfast Workshop Sponsorship Available) 

8:10 Chairperson’s Opening Remarks 
Scott D. Mills, Ph.D., Principal Scientist, Infection Discovery, AstraZeneca R&D

9:00 Overcoming the Challenge of Gram-Negative Resistance: New, or Improved Antibacterials? 
Nafsika Georgopapadakou, Ph.D., Consultant, MethylGene, Inc.
Over the past two decades, gram-negative pathogens-most notably Klebsiella pneumoniae but also other Enterobacteria-have become increasingly resistant to multiple antibiotics due to their extensive use in the hospital and in the community. In addition, intrinsically multi-resistant, opportunistic gram-negative pathogens-notably Acinetobacter and Pseudomonas species-have increased in frequency. These developments have come at a time when very few new antibacterial agents have been identified and underscores the urgent need for new antibiotic classes. Recently introduced gram-negative antibacterials will be reviewed, as well as agents in clinical development. Prospects and challenges for new drugs-as well as improved drugs-will be discussed from the perspectives of research efforts, progress to date, the pleiotropic nature and mechanistic complexity of multidrug resistance. The talk will conclude with a realistic roadmap for overcoming the multidrug resistance challenge. 

9:30 Novel Approach to Preserving Longevity of New and Current Beta-Lactam Antibiotics
Nora Kaarela, M.Sc.,Chief Executive Officer, IPSAT Therapies Ltd.
Intestinal commensal microflora is a rich source of microbial genetic diversity; it contains over 800 microbial species. Antibiotic influence has been shown to alter the proportions of and, by selective pressure, the genetic make-up of the microbes populating the gut. The consequences of altered gut microflora are altered resistance patterns of the microbes, reduced resistance to infection (colonizationresistance), local and systemic infections with potential spread to the local environment. The infections involved can be Clostridium difficile, ESBL-Klebsiella, Candida infections, Vancomycin-Resistant Enterococcal infections and changes in the resistance-sensitive ratios of common bacteria in the gut, such as E.coli. Ipsat’s products are bioengineered enzymes, beta-lactamases, which inactivate unabsorbed beta-lactam antibiotics in the lower gastro-intestinal tract. This prevents the earliest step in the cascade of events leading to the complications described above. 

9:45 Networking Coffee Break, Poster and Exhibit Viewing

10:20 Rethinking Antibacterial Targets 
Lynn L. Silver, Ph.D., LL Silver Consulting, LLC 
The standardly used monotherapeutic antibacterial agents have a limited number of targets. One strategy for the discovery and development of agents to overcome the problem of increasing resistance to antibacterials is exploitation of novel targets, since inhibitors of such targets should not be subject to existing resistance mechanisms. However, over the past fifteen or so years, very little progress has been made in this endeavor. The multi-targeting characteristics of the successful antibacterials and implications for discovery of inhibitors of novel targets will be discussed. 

10:50 Pigment Inhibition as a Target for Staphylococcal Therapy 
Victor Nizet, M.D., Ph.D., Associate Professor/Chief, Division of Pharmacology & Drug Discovery, University of California, San Diego
Molecular genetic studies coupled with tissue culture and small animal models of infections demonstrate that the eponymous golden pigment of Staphylococcus aureus is a virulence factor. Through its antioxidant properties, the pigment protects the pathogen from killing by host neutrophils. We have gone on to show that small molecule inhibitors of pigment production can be used to protect against infection in the murine model. This offers an alternative approach to MRSA therapy, instead of directly killing the bacteria, rendering it susceptible to killing by our own innate immune defenses. 

11:20 Chairperson’s Opening Remarks 
Michael J. Pucci, Ph.D., Senior Director, Discovery, Achillion Pharmaceuticals 

11:25 Novel Technologies and Approaches to Antibacterial Drug Discovery 
Michael J. Pucci, Ph.D., Senior Director, Discovery, Achillion Pharmaceuticals 
The discovery of new and effective antibacterials has proven to be a challenging task in recent years with relatively few novel drugs introduced into clinical use. Entry into the era of genomics has spurred the development of a number of novel technologies applicable to the drug discovery process. Several of these technologies will be profiled in regard to their use in antibacterial research. In addition, some newer approaches to discover and develop new compounds will be reviewed. The potential impact of these novel technologies and approaches on the future of antibacterial drug discovery will be discussed. 

11:55 Identifying & Improving Nature’s Defenses 
Hans-Henrik Kristensen, Ph.D., Senior Manager, Anti-infective Discovery, Novozymes A/S 
Antimicrobial peptides (AMPs) are a recently discovered group of antimicrobial agents. They are simple peptides but are widely distributed in animals and plants and show activity against a broad range of pathogens. They have a number of characteristics that make them interesting candidates for pharmaceutical development. Notably they are fast-acting, microbicidal rather than microbiostatic and with little observed resistance development - a key property in an age of multiresistant bacteria as represented by MRSA. 

12:25 Lunch on Your Own 
(Lunch Workshop Sponsorship Available) 

1:40 Understanding Efflux: An Asset for Drug Discovery 
Herbert Schweizer Ph.D., Professor, Department of Microbiology, Immunology and Pathology, Colorado State University 
Bacterial drug efflux pumps have traditionally been regarded as almost insurmountable challenges of antibacterial drug development. Recent research efforts, however, clearly demonstrated that an understanding of structure, function and regulation of bacterial efflux systems can actually serves as an important asset for drug discovery. 

2:10 In Search of a Novel Antibacterial Agent 
Mira Hinman, Ph.D., Associate Research Investigator, Target and Lead Discovery, Global Pharmaceutical R&D, Abbott Laboratories 
I will describe the synthesis and antibacterial activity of a series of naphthyridones. The members of this series act primarily via inhibition of bacterial translation and belong to the class of novel ribosome inhibitors (NRIs). I will discuss the structure-activity relationships (SAR) of these compounds to measure their ability both to inhibit bacterial translation and also to inhibit the growth of bacterial cells in culture. The most active of these compounds inhibit Streptococcus pneumoniae translation at concentrations of <5 uM and have minimum inhibitory concentrations (MICs) of <8 ug/mL against clinically relevant strains of bacteria. 

2:40 Refreshment Break, Poster and Exhibit Viewing 

4:40 End of Conference