SC12: CLINICALLY RELEVANT ANIMAL MODELING FOR THE EVALUATION OF NOVEL ANTIBACTERIAL APPROACHES
TUESDAY, SEPTEMBER 25, 6:00 - 8:30 PM

Course Objectives

  • The course will present a progression from small animal models (Galleria, mice) to more elaborate biofilm models (mice, rats, rabbits), and conclude with larger complicated models that include trauma reflective of where these infections cause hardware and implant problems (rats, pigs, goats).
  • Each instructor will present typical evaluations of antibacterial products, both successes and failures.
  • Each instructor will present examples of traditional small molecule antibiotic successes/controls and compare them to alternative antibacterial treatments such as vaccines, bacteriophage, etc.
  • Important considerations for model development will be addressed such as: strain selection, biofilm, method of delivery, dosing, PK/PD considerations.
  • The instructors will stress why the use of various models and species are required when evaluating different antibiotics.
  • Instructors will provide published examples as well as unpublished techniques, tips, and ideas.

Individual Lectures

1. Kamilia Abdelraouf, PhD, – Biofilm and polymicrobial models of infection – First 50 min

  • Introduction to animal modeling
    • IACUC considerations
    • in vitro correlation
    • clinical correlation
    • Antibiotic PK,
    • Biofilms – Polymicrobial consideration
    • Animal model success due to good models vs. failure due to poor models.
  • Murine tibial punch osteomyelitis model
  • Rabbit tibial punch osteomyelitis model
  • Rabbit endocarditis model
  • Cystic Fibrosis P. aeruginosa model
  • Examples of antibacterials tested:
    • S. aureus vaccine
    • Novel small molecules against S. aureus
    • Novel monoclonal antibodies against S. aureus

First Break – 5 minutes

2. Daniel Zurawski, Ph.D. - Small animal models – Evaluation of virulence and novel antibacterials – Second 45 min.

  • Galleria mellonella model of infection
    • evaluation of virulence
    • evaluation of antibacterials in this model.
  • Murine thigh model of infection – typical first step in antibacterial evaluation.
    • Description of CFU/g calculation
    • Example of novel approach utilizing this model.
  • Murine pulmonary model of infection
    • Description of different endpoints and uniqueness of model.
    • Examples of different bacterial species in this model and important considerations.
    • Examples of novel antibacterial approaches in this model to include: novel small molecules and antibodies
  • Murine wound model of infection
    • Description of different endpoints and uniqueness of model.
    • Examples of different bacterial species in this model and important considerations.
    • Examples of topical treatment: small molecules, gallium, phage, predatory bacteria

Second Break – 5 min

3. Joseph Wenke, Ph.D. – Biofilm and novel antibacterials in large mammals – Final 45 min.

  • Rat implant model
  • Rat trauma model
  • Goat polytrauma model
  • Examples of anti-infective strategies tested:
    • Irrigants
    • Conventional antibiotics
    • Antibiofilm agents.

Final Break – Time for questions – 10 min

Instructor Biographies:

Daniel V. Zurawski, Ph.D., Senior Scientist/Principal Investigator, Clinical RM, Inc., Walter Reed Army Institute of Research

From 2009 to present, Dr. Zurawski managed a laboratory in the Wound Infections Department (WID) at WRAIR. He is also an adjunct professor at the University of Maryland Dental School in the Department of Microbial Pathogenesis. His laboratory utilizes the disciplines of genetics, biochemistry, cell biology and animal modeling in order to design and test novel antimicrobial strategies against MDR-ESKAPE pathogens. Specifically, he and his group have developed useful genetic tools to better understand the pathogenesis of Acinetobacter baumannii and Klebsiella pneumoniae, which has led to the identification of new targets that can be exploited for drug design and therapeutic monoclonal antibodies. They also developed novel animal models in mice, rats, and swine that incorporate different infection sites, different drug deliveries, multiple endpoints, and bioluminescent bacteria to address the efficacy of any antimicrobial treatment. In addition to exploiting these models for his own research, Dr. Zurawski has ongoing extramural collaborations with industry, government, and academic partners to test their novel antibacterial strategies, where the animal models that were developed by his team provide crucial preclinical data on efficacy and toxicity. Dr. Zurawski has four patents on novel antibacterial approaches and has published over 30 papers on bacterial pathogens that cause wound infections and new treatments against these organisms. Dr. Zurawski received his B.A. from the University of Pennsylvania and his Ph.D. from the University of Vermont. After his thesis work on mechanisms of Salmonella pathogenesis, Dr. Zurawski did post-doctoral research at the Uniformed Services University of Health Sciences on novel effector proteins secreted by Shigella and was subsequently recruited by the WRAIR to develop Shigella vaccines.

Kamilia Abdelraouf, PhD, Associate Director, Center for Anti-Infective Research and Development, Hartford Hospital

Kamilia Abdelraouf, PhD serves as Associate Director for the Center for Anti-Infective Research and Development at Hartford Hospital in Hartford, Connecticut. She has broad experience in examining the pharmacokinetic and pharmacodynamic profiles of investigational agents as well as PK/PD modeling and simulations. Her research activities involve a wide range of preclinical drug development studies to assess the in vitro and in vivo activity of antibacterial agents, most prominently, the establishment and refinement of animal models of infection. She designs human-simulated regimens of antibacterial agents in murine infection models to assess efficacy at clinically achievable exposures, which improves the translational application of the outcomes from pre-clinical studies into clinical practice. Dr. Abdelraouf received a Bachelor of Science in Pharmaceutical Sciences from Alexandria University, Egypt in 2004 and a PhD in Pharmaceutics from University of Houston in 2012.  She completed a fellowship in Infectious Diseases at Hartford Hospital.


 

Joseph C. Wenke, Ph.D., U.S. Army Institute of Surgical Research

Joseph C. Wenke, PhD arrived at the US Army Institute of Surgical Research in San Antonio, TX as a National Research Council Postdoctoral fellow in 2003. The following year he accepted a position at ISR as a Research Physiologist and is now the manager for the Extremity Trauma & Regenerative Medicine Task Area. His primary research focus is improving outcomes of open fractures. Much of his previous the work has been focused on improving early therapies (e.g., wound irrigation techniques, negative pressure wound therapy and local delivery of antibiotics); current and future projects focus on regenerating bone in a contaminated bone defects and in polytrauma patients and targeted therapies for biofilm-related infections. Dr. Wenke spent the past six years as the government program manager for the Major Extremity Trauma Research Consortium (www.metrc.org), which is the largest orthopaedic trauma consortium ever. METRC has enrolled over 5,000 patients in prospective studies over the past four years. One of the main strengths of his research program is the ability to utilize or develop clinically-relevant orthopaedic trauma animal models to evaluate different therapies or develop clinical guidelines. Dr. Wenke received a Bachelor of Science from Baylor University in 1997 and a PhD from Texas A&M University in 2003. Skeletal muscle plasticity and injury was his main areas of research while in graduate school.

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