News

March 6, 2017

 

Microbe-2017-header-v3

 

ASM Microbe 2017 (June 1–5, 2017, New Orleans, LA) showcases the best microbial sciences in the world, and provides a one-of-a-kind forum to explore the complete spectrum of microbiology from basic science to translation and application.

The UNTHSC Pre-Clinical Services group will be in attendance at the first ASM Microbe meeting in New Orleans, LA (June 1-5, 2017) and welcomes the opportunity to meet with current as well as prospective collaborators to discuss ongoing and future projects. If interested, please contact William Weiss (817-735-2111 or william.weiss@unthsc.edu) to arrange for a convenient day and time to meet.

In addition, please plan to view the following posters / presentations:

 

Efficacy of Novel Cationic Peptide SPR741 and Gyrase Inhibitor SPR720 Combinations Against Carbapenem-resistant K. pneumoniae in a Murine UTI Model

W. J. Weiss*1, M. Pulse1, P. Nguyen1, T. R. Parr Jr2, T. Lister2 and A. Rubio2

1UNT Health Science Center, Ft. Worth, TX, USA; 2 Spero Therapeutics, Cambridge, MA, USA

 

In vivo Efficacy of Combinations of Novel Antimicrobial Peptide SPR741 and Rifampin in a K. pneumoniae Murine Model of Urinary Tract Infection.

A Rubio*1, W Weiss2, M Pulse2, T Lister1 T R Parr Jr1

Spero Therapeutics, Cambridge, USA; 2. UNT Health Science Center, Fort Worth, TX, USA

 

The Novel Fluorocycline TP-271 is Efficacious in a Murine A. baumannii Pneumonia Model.

J. Newman1, T. H. Grossman2, M. E. Pulse3, W. J. Weiss3

Tetraphase Pharmaceuticals, Watertown, MA1; Consultant to Tetraphase Pharmaceuticals2, UNT Health Science Center, Fort Worth, TX3

 

PK/PD of the Novel Fluorocycline Eravacycline is Efficacious in a Murine E. coli Thigh Model.

J. Newman1, M. E. Pulse2, W. J. Weiss2

Tetraphase Pharmaceuticals, Watertown, MA1; UNT Health Science Center, Fort Worth, TX2

 

DAV131A prevents alterations of the intestinal microbiota and Clostridium difficile infection in hamsters treated with moxifloxacin and clindamycin

N. Saint-Lu1, T. Corbel1, F. Sablier-Gallis1, M. Pulse2, C. Burdet3, Céline Wahl4, T.T. Nguyen3, W. Weiss2, F. Mentré3, S. Ferreira4, A. Andremont3 and J. de Gunzburg1

1Da Volterra, Paris, France; 2UNT Health Science Center, Fort Worth, TX, USA; 3University Paris-Diderot Medical School and INSERM UMR 1137, IAME, Paris, France; 4GenoScreen, Lille, France

 

Development of OG716, a Novel Lantibiotic Against Clostridium difficile

A. DeFusco1, J. Ngoje1, G. Phillips1, M. Sivaram1, J. Park1, B. Tilley1, E. Richeson1, V. Sylva1, Z. Lamon1, F. Anazco1, M. Pulse2, W. J. Weiss2, M. Handfield1 1Oragenics, Inc., Alachua, FL, 2Univ. of North Texas Health. Sci. Ctr., Fort Worth, TX

 

March 1, 2017

 

Antimicrob Agents Chemother. 2017 Feb 6. pii: AAC.02243-16. doi: 10.1128/AAC.02243-16. [Epub ahead of print]

Can ceftazidime/avibactam and aztreonam overcome β-lactam resistance conferred by metallo-β-lactamases in Enterobacteriaceae?

 

Marshall S1, Hujer AM1,2, Rojas LJ1,2,3, Papp-Wallace KM1, Humphries RM4, Spellberg B5, Hujer KM1,2, Marshall EK1, Rudin SD1,2, Perez F1,2, Wilson BM1, Wasserman RB6, Chikowski L7, Paterson DL8, Vila AJ9, van Duin D10, Kreiswirth BN11, Chambers HF12, Fowler VG Jr13, Jacobs MR14, Pulse ME15, Weiss WJ15, Bonomo RA16,2,3,17.

1Louis Stokes Cleveland Department of Veterans Affairs Medical Center, Cleveland, OH. 2Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, OH. 3Department of Molecular Biology and Microbiology, Case Western Reserve University School of Medicine, Cleveland, Ohio. 4Department of Pathology and Laboratory Medicine, University of California, Los Angeles, CA. 5Division of Infectious Diseases, Keck School of Medicine at USC and the Los Angeles County-USC Medical Center, Los Angeles, CA. 6Infectious Disease Doctors Medical Group, Walnut Creek, CA. 7John Muir Health, Walnut Creek, CA. 8The University of Queensland, UQ Centre for Clinical Research, Brisbane, Queensland, Australia. 9Instituto de Biología Molecular y Celular de Rosario Consejo Nacional de Investigaciones Científicas y Técnicas de Argentina, Universidad Nacional de Rosario, Argentina. 10Division of Infectious Diseases, University of North Carolina, Chapel Hill, NC. 11Public Health Research Institute Center, New Jersey Medical School-Rutgers University, Newark, NJ. 12University of California, San Francisco General Hospital, San Francisco, CA. 13Division of Infectious Diseases, Department of Medicine, and Duke Clinical Research Institute, Duke University Medical Center, Durham, NC. 14Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, OH. 15University of North Texas Health Science Center, Fort Worth, TX. 16Louis Stokes Cleveland Department of Veterans Affairs Medical Center, Cleveland, OH 17Departments of Pharmacology, Biochemistry, and Proteomics and Bioinformatics, Case Western Reserve University School of Medicine, Cleveland, OH.

Abstract Based upon knowledge of the hydrolytic profile of major β-lactamases found in Gram negative bacteria, we tested the effectiveness of the combination of ceftazidime/avibactam (CAZ/AVI) with aztreonam (ATM) against carbapenem-resistant enteric bacteria possessing metallo-β-lactamases (MBLs). Disk-diffusion and agar based antimicrobial susceptibility testing were initially performed to determine the in vitro efficacy of a unique combination of CAZ/AVI and ATM against 21 representative Enterobacteriaceae isolates with a complex molecular background that included blaIMP, blaNDM, blaOXA-48, blaCTX-M, blaAmpC, and combinations thereof. Time-kill assays were conducted, and the in vivo efficacy of this combination was assessed in a murine neutropenic thigh infection model. By disk diffusion assay, all 21 isolates were resistant to CAZ/AVI alone, and 19/21 were resistant to ATM. The in vitro activity of CAZ/AVI in combination with ATM against diverse Enterobacteriaceae possessing MBLs was demonstrated in 17/21 isolates, where the zone of inhibition was ≥ 21 mm. All isolates demonstrated a reduction in CAZ/AVI agar dilution MICs with the addition of ATM. At 2 h, time-kill assays demonstrated a ≥ 4 log10 CFU decrease for all groups that had CAZ/AVI plus ATM (8 μg/ml) added, compared to the CAZ/AVI alone group. In the murine neutropenic thigh infection model, an almost 4 log10 reduction in CFUs was noted at 24 h for CAZ/AVI (32 mg/kg q8h) plus ATM (32 mg/kg q8h) vs. CAZ/AVI (32 mg/kg q8h) alone. The data presented herein, requires us to carefully consider this new therapeutic combination to treat infections caused by MBL-producing Enterobacteriaceae.

Copyright © 2017 American Society for Microbiology.

 

 February 21, 2017

 FDA

 

FDA Workshop – March 1, 2017: Silver Springs, MA

Current State and Further Development of Animal Models of Serious Infections Caused by Acinetobacter baumannii and Pseudomonas aeruginosa

Meeting Summary: The Food and Drug Administration (FDA) is announcing this public workshop regarding the current state and further development of animal models for serious infections caused by Acinetobacter baumanii and Pseudomonas aeruginosa. FDA is conducting this workshop in order to facilitate the development of narrow-spectrum antibacterial drugs, such as those that are active against only a single species of bacteria that may not occur frequently. When the species occurs infrequently, performing clinical trials can be extremely challenging. Therefore, animal models of infection may be useful to explore the activity of a candidate antibacterial drug and may help to predict whether the drug will be efficacious in humans. A discussion of the additional scientific work needed to evaluate current animal models of infection and evaluate potential animal models that may predict response in humans could advance the development of antibacterial drugs targeting a single species. The input from this public workshop will also help in developing topics for future discussion. The Agency encourages health care providers, other U.S. Government Agencies, academic experts, contract research organizations, industry and other interested persons to attend this public workshop.

 

February  2, 2017

 

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Translatable Therapeutic Effects of Extracellular Superoxide Dismutase (ecSOD) in the Treatment of Staphylococcus aureus Infections

M. E. Pulse, W. J. Weiss, L. Dory, J. W. Simecka

UNTHSC, Fort Worth, TX,

Objectives: Alternatives to antibiotics is an expanding area of research that focuses on non-traditional approaches to treating bacterial infections, which includes approaches that target various host responses during an infection. Extracellular superoxide dismutase (ecSOD) has previously been proposed as possible target since it regulates the amount of reactive oxygen and nitrogen species generated during an immune response. In an effort to further validate ecSOD as a potential therapeutic target, mice expressing varying amounts of ecSOD were used in experimental models of bacterial sepsis, pneumonia, and skin-associated abscess infections caused by Staphylococcus aureus. Additionally, a non-specific SOD inhibitor was used to therapeutically treat wild-type mice that had skin-associated abscess infections.

Methods: C57BL/6 mice that either did not express ecSOD (ecSOD-KO) or expressed wild-type levels of ecSOD (ecSOD-WT) were used in the experimental infection models. The sepsis model involved intraperitoneal (IP) injection with 7 log10 CFU of S. aureus and monitoring survival for 5 days post-infection. The pneumonia model involved intranasal infection of anesthetized mice with 8 log10 CFU of S. aureus and harvesting lungs for CFU counts 26 hours post-infection, or monitoring survival for 5 days post-infection. The skin-associated abscess model involved subcutaneous infection of anesthetized mice with 8 log10 CFU of S. aureus, diluted in sterile dextran beads, recording abscess severity and harvesting abscesses 4 days post-infection for CFU enumeration. Additional skin abscess studies involved treating infected ecSOD-WT mice with vancomycin and/or diehtyldithiocarbamate (DDTC), an SOD inhibitor, (600-1200 mg/kg, IP or topically) for 4 days post-infection, with abscess severity and CFU recovery being accessed.

Results: All of the ecSOD-KO mice survived lethal sepsis infections with S. aureus, while only 40% of the ecSOD-WT mice survived in the same studies. Between 40-80% of the ecSOD-KO mice survived lethal pneumonia infections with S. aureus and had about 7.5 log10 CFU in their lungs 26 hours after infection. In contrast, only 20% of the ecSOD-WT mice with S. aureus pneumonia infections survived, and they had approximately 9 log10 CFU in their lungs 26 hours after infection. The amount of S. aureus recovered from skin-associated abscesses 4 days after infection was approximately equal for both infected ecSOD-WT and ecSOD-KO mice. However, between 80% of the abscesses formed in ecSOD-WT mice were severely cavitated, while only 22% of abscesses formed in ecSOD-KO mice were cavitated. Abscess studies with DDTC generated similar results to the ecSOD-KO mice, in that S. aureus CFU abscess counts remained relatively unchanged but abscess severity was noticeably better with DDTC treatment.

Conclusion: The described results clearly suggest that inhibition of ecSOD is a potential path for treating various infectious diseases; additional investigations are needed to fully determine if this is an attainable target for drug development.

January 7, 2017

SMI 2017

SMi is proud to present the 2017 19th annual Superbugs & Superdrugs conference, taking place on 20th and 21st March in Central London.
Expanding horizons on the growing threat of anti-microbial resistance for almost two decades, the flagship show in the global Superbugs portfolio of events will once again play host to an international audience of scientific leaders, funding bodies and drug discovery specialists, providing a focal point to push industry collaboration through updates on clinical advancements and investment opportunities.

Each year, around 2 million people are taken ill in the US from antibiotic-resistant bacteria and kills at least 23,000, according to estimates by the Centers for Disease Control and Prevention. The threat is so high that in September 2014 President Barack Obama issued an executive order Combating Antibiotic-Resistant Bacteria. *

The threat is the same in Europe, big pharmaceutical companies are re-entering the space into development of new antibiotics after decades. In January 2016, more than 80 pharmaceutical, biotechnology and diagnostics companies including Roche, Pfizer, Novartis AG and GlaxoSmithKline pledged at the World Economic Forum to fight the threat of antimicrobial resistance.*

The industry’s premier event on antibiotic resistance will provide a perfect platform for its growing “superbugs” community to network, exchange novel solutions and consolidate current strategies. A must attend for both new and seasoned stakeholders involved in AMR and infectious disease.

 

THE USE OF IN VIVO MODELS FOR INFECTIOUS DISEASE RESEARCH

 

William Weiss, Director of Pre-Clinical Services, University of North Texas Health Science Center

  • Experimental Design of Animal Models
  • Bridging the gap – in vitro activity to in vivo effi cacy
  • Where to start / What model to use
  • What does the data tell us

 

WORKSHOP PROGRAMME
William Weiss, Director of Pre-Clinical Services, University of North Texas Health Science Center

Mark Pulse, Assistant Director , University of North Texas Health Science Center

PRECLINICAL DRUG DEVELOPMENT

Overview of preclinical testing
Discovery to lead selection
The development model: then and now
Antibacterial research efforts

EXPERIMENTAL DESIGN AND METHODOLOGY

Experimental design profoundly influences the outcome of a research study
Clearly define the question or problem being studied
Realistic objectives (achievable)
Choose the best research model

ANIMAL MODELS – EXAMPLES

Acute infection models – Bacteremia, Sepsis
Chronic infection models – Pneumonia, skin, abscesses
GI related – C. difficile, H. pylori
Device related – Biofilm, endocarditis, prosthetic joint

ANIMALS IN RESEARCH

Institutional Animal Care and Use Committee (IACUC)
Justify why animals are necessary, minimize pain and distress, husbandry and care
Use of appropriate euthanasia methods
The 3 R’s

November 17, 2016

 

Dr. William Weiss is the Director of Pre-Clinical Services at University of North Texas in Fort Worth, working to develop animal models in infectious disease for the evaluation of new and novel therapies in antibacterial, antifungal and antiviral research. He has been using a Don Whitley Scientific DG250 and an A35 anaerobic workstation for about 2 decades.

Read more about his research on novel antibiotics for the treatment of Clostridium difficile infectionhere.

http://800ezmicro.com/Univ-North-Texas-Interview.html

 

September 7, 2016

SMI-USA

 

Broadening horizons on the growing global threat of Antimicrobial resistance (AMR) for almost two decades at the sell-out Superbugs & Superdrugs conference in Europe, SMi is thrilled to announce the expansion of its antimicrobial portfolio of events across the Atlantic with the release of Superbugs & Superdrugs USA. This year’s show in Iselin, New Jersey, will play host to an audience of scientific leaders, funding bodies and drug discovery specialists, providing a focal point to discuss the latest clinical advancements and funding opportunities.

With huge interest from leaders in the field including PAHO/WHO, BARDA, NIH, Pfizer, AstraZeneca, Janssen and other senior industry representatives, we have worked closely with an expert panel of speakers to present an agenda that is shaping up to be the best Superbugs & Superdrugs event to date.

The program will hone in on key topics such as public private partnerships, collaboration, R&D, scientific priorities for antibiotic discovery, novel antibacterial therapeutic approaches, antibiotic stewardship, rapid diagnostic tools, combination therapies, resistance prevention, plus much more!

 

ANTIMICROBIAL COMBINATION THERAPY: USE AND DISUSE
William Weiss, Director of Pre-Clinical Services, University of North Texas Health Science Center

Rationale for the use of antibiotic combinations
Advantages / disadvantages of combining antimicrobial agents
Currently used antibiotic combinations
Novel and non-traditional antimicrobial combinations

 

WORKSHOP PROGRAMME
William Weiss, Director of Pre-Clinical Services, University of North Texas Health Science Center

Mark Pulse, Assistant Director , University of North Texas Health Science Center

 

PRECLINICAL DRUG DEVELOPMENT

Overview of preclinical testing
Discovery to lead selection
The development model: then and now
Antibacterial research efforts

EXPERIMENTAL DESIGN AND METHODOLOGY

Experimental design profoundly influences the outcome of a research study
Clearly define the question or problem being studied
Realistic objectives (achievable)
Choose the best research model

ANIMAL MODELS – EXAMPLES

Acute infection models – Bacteremia, Sepsis
Chronic infection models – Pneumonia, skin, abscesses
GI related – C. difficile, H. pylori
Device related – Biofilm, endocarditis, prosthetic joint

ANIMALS IN RESEARCH

Institutional Animal Care and Use Committee (IACUC)
Justify why animals are necessary, minimize pain and distress, husbandry and care
Use of appropriate euthanasia methods
The 3 R’s

 

 

April 15, 2016

 

FINAL_ASM_web_banner_V2

The UNTHSC Pre-Clinical Services group will be in attendance at the first ASM Microbe meeting in Boston, MA (June 16-20, 2016) and welcomes the opportunity to meet with current as well as prospective collaborators to discuss ongoing and future projects. If interested, please contact William Weiss (817-735-2111 or william.weiss@unthsc.edu) to arrange for a convenient day and time to meet.

In addition, please plan to view the following posters:

Monday June 20 at 12:30 – 2:30pm

In Vivo Efficacy of Dual-Action Molecule TNP-2092 in Mouse H. pylori Infection Model as Compared to Triple Therapies and Distribution within the Gastric Mucosal Layer

W. J. Weiss,1 M. Pulse,1 P. Nguyen,1 Z. Ma;2

1UNT Health Science Center, Fort Worth, TX; 2TenNor Therapeutics Ltd, Suzhou, China

 

In Vivo Efficacy of Dual-Action Molecule TNP-2092 in Mouse H. pylori Infection Model: Dose Relationship and Impact of Proton Pump Inhibitor

M. Pulse,1 W. J. Weiss,1 P. Nguyen,1 Z. Ma;2

1UNT Health Science Center, Fort Worth, TX; 2TenNor Therapeutics Ltd, Suzhou, China

 

In Vivo Efficacy of Dual-Action Molecule Tnp-2092 in Hamster and Mouse Clostridium difficile Infection Models

X. Xu1, W. J. Weiss2, G. T. Robertson3, F. Guo4, C. Li4, J. Zhang4, L. Jiang4, M. Yang4, D. Xu4, X. Wang1, Z. Ma1;

1TenNor Therapeutics Ltd, Suzhou, China, 2UNT Health Science Center, Fort Worth, TX, 3Colorado State Univ., Fort Collins, CO, 4WuXi AppTec (Shanghai) Co., Ltd, Shanghai, China

 

Late breaker:

Extended protection by DAV131 against antibiotic-induced Clostridium difficile infection in hamsters

Saint-Lu1, S. Sayah-Jeanne1, F. Sablier-Gallis1, M. Pulse2, C. Burdet3, T.T. Nguyen3, W. Weiss2, F. Mentré3, E. Chachaty4, A. Andremont3 and J. de Gunzburg1

1Da Volterra, Paris, France; 2UNT Health Science Center, Fort Worth, TX, USA; 3University Paris-Diderot Medical School and INSERM UMR 1137, IAME, Paris, France; 4Institut Gustave-Roussy, Villejuif, France

 

April 5, 2016

 

Unknown

 

TP-6076 is efficacious in a mouse pneumonia model with carbapenem-resistant Acinetobacter baumannii (CRAB) and retains potency against common tetracycline-resistance mechanisms

T. Grossman, C. Fyfe, K. Kerstein, X. Xiao, C. Sun, J. Newman, P. Nguyen, M. Pulse, W. Weiss, J. Dumas, J. Sutcliffe

Tetraphase Pharmaceuticals, Watertown, MA, UNT Health Science Center, Fort Worth, TX

 

 

 

November 5, 2015

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The Use of Combination Antibiotic Therapy

  • History of antibiotic combinations
  • Rationale for combination therapy
  • Advantages / disadvantage of combining antibiotics
  • Testing regimens for combination therapy

William Weiss, Director, Pre-Clinical Services,

UNT Health Science Center

 

 

September 1, 2015

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The University of North Texas Health Science Center Pre-Clinical Services group has recently become a part of the UNT System College of Pharmacy.

 

Myron Jacobson, PhD., Dean of the College of Pharmacy, said “I am delighted to announce that Jerry Simecka and William Weiss will be joining the faculty of the College of Pharmacy effective September 1, 2015. Additionally, the outstanding staff of the Pre-Clinical Services Program that they lead will also be joining the College. The staff members of the team include Mark Pulse, Assistant Director, David Valtierra, Kelly Peterson, Kiahrae, Carter, Phung Nyugen, Jessica Silva and Monica Castillo. Both Jerry and Bill have already been making high quality teaching contributions to our doctor of pharmacy program and we look forward to their continued involvement. Additionally, the outstanding Pre-Clinical Sciences Program integrates perfectly with the translational research efforts of the College of Pharmacy.”

 

The PreClinical Services group will continue to function as before, providing guidance and support for the research and development of new and novel therapies with an emphasis on infectious disease.

 

 

July 17, 2015

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Dav132, an Adsorbent-Based Product, Protects the Gut Microbiome and Prevents Clostridium difficile Infections during Moxifloxacin Treatments

Jean De Gunzburg, PhD1, Amine Ghozlane, PhD2, Annie Ducher, MD1, Xavier Duval, MD, PhD3, Etienne Ruppé, PharmD, PhD2, Mark Pulse, MS4, Caroline Chilton, PhD5, Laurence Armand-Lefevre, PharmD, PhD6, Elisabeth Chachaty, PharmD, PhD7, Sakina Sayah-Jeanne, PhD1, Joël Doré, PhD2, Emmanuelle Le Chatelier, PhD2, Florence Levenez, BS2, Sean Kennedy, PhD2, Nicolas Pons, PhD2, William Weiss, MS4, Mark Wilcox, MD5,8, France Mentré, MD, PhD6, Antoine Andremont, MD, PhD6 and Stanislav Dusko Ehrlich, PhD2

(1)Da Volterra, Paris, France, (2)Metagenopolis, INRA, Jouy-en-Josas, France, (3)Bichat Claude Bernard Hospital; Paris 7 University, Paris, France, (4)UNT Health Science Center, Fort Worth, TX, (5)University of Leeds, Leeds, United Kingdom, (6)University Paris-Diderot Medical School and INSERM, UMR 1137, IAME, Paris, France, (7)Institut Gustave-Roussy, Villejuif Cedex, France, (8)Leeds Teaching Hospitals, Leeds, United Kingdom

 

 

June 24, 2015

ICAAC2015_Fina2l

The UNTHSC Pre-Clinical Services group will be in attendance at the 55th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) meeting in San Diego, CA (September 17 – 21, 2015) and welcomes the opportunity to meet with current as well as prospective collaborators to discuss ongoing and future projects. If interested, please contact William Weiss (817-735-2111 or william.weiss@unthsc.edu) to arrange for a convenient dayand time to meet.

 

Efficacy of Carbavance (Meropenem-RPX7009) against Carbapenem-resistant E. coli in a murine UTI infection model

 W. J. Weiss1, M. Pulse1, P. Nguyen1, K. Peterson1, J. Silva1, J. W. Simecka1, D. Valtierra1, M. Sabet2, D. C. Griffith2

 1UNT Health Science Center, Ft. Worth, TX, 2 The Medicines Company, San Diego, CA

 

Efficacy of a Bacteriophage Cocktail in a Staphylococcus aureus Mouse Pneumonia Model is Comparable to Vancomycin

J. Shaw1,3*, W. J. Weiss2, M. E. Pulse2, S. M. Lehman1, F. Smrekar1, S. P. Morales1

1AmpliPhi Biosciences Corporation, Richmond, VA; 2 UNT Health Science Center, Fort Worth, TX; 3Hearts Consulting Group, Poway, CA.

 

 

January 30, 2015

WH seal

President’s 2016 budget proposes historic investment to combat antibiotic-resistant bacteria to protect public health.

“We now have a national strategy to combat antibiotic-resistant bacteria, to better protect our children and grandchildren from the reemergence of diseases and infections that the world conquered decade ago”

– President Barack Obama’s remarks at the Global Health Security Agenda Summit, regarding the Executive Order to Combat Antibiotic Resistance, September 26, 2014.

http://www.whitehouse.gov/the-press-office/2015/01/27/fact-sheet-president-s-2016-budget-proposes-historic-investment-combat-a

January 27, 2015

eccmid image

The 25th European Congress of Clinical Microbiology and Infectious Disease (ECCMID) meeting will be held from April 25-28, 2015 in Copenhagen, Denmark. The meeting will feature a series of keynote lectures, symposia, educational workshops and meet-the-experts sessions on parallel tracks, covering the entire field of infectious diseases and clinical microbiology. Among the presentations will be:

Evaluating the induction potential of three antibiotics in the hamster Clostridium difficile infection model.

M. Pulse, T. Murphy, P. Nguyen, K. Peterson, J. Silva, J. Simecka, D. Valtierra, W. Weiss, S. Sayah-Jeanne, J. de Gunzburg

UNT Health Science Center, Fort Worth, TX & Dalvolterra, Paris, France

Efficacy evaluation of TP-271, a novel fluorocycline, in a neutropenic murine pneumonia model against susceptible and resistant gram-positive pathogens

W. Weiss, T. Murphy, M. Pulse, P. Nguyen, D. Valtierra, K. Peterson, J. Silva, J. Simecka, J. Sutcliffe, T. Grossman

UNT Health Science Center, Fort Worth, TX & Tetraphase Pharmaceuticals, Watertown, MA

Synthetic novel host defense protein mime tics for the treatment of gram-negative bacterial infections

S. Ram, K. Menon, R. Scott, D. Weaver, K. Freeman, G. Tew, W. Weiss, W. DeGrado, K. Fadela, A. Kumar, D. Brennan, S. Holden

Fox Chase Chemical Diversity Center, Doylestown, PA & UNT Health Science Center, Fort Worth, TX

www.eccmid.org

January 15, 2015

SMI

UNTHSC PreClinical Services to present at the SMI 17th Annual conference on SuperBugs & SuperDrugs, March 25-26, 2015 in London, UK.

The Changing Role of Academia in Drug Discovery

  • Historical perspective of academic involvement in drug development
  • Growth of the modern pharmaceutical industry and detachment from academia
  • Downturn in antibacterial discovery and development and current needs
  • Collaboration of industry and academia in drug discovery
  • Novel partnering models to increase innovation

William Weiss, Director of PreClinical Services, UNT Health Science Center

www.smi-online.co.uk/pharmaceuticals/uk/superbugs-superdrugs

July 3, 2014

IC14

The UNTHSC Pre-Clinical Services group will be in attendance at the 54th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) meeting in Washington DC (September 59, 2014) and welcomes the opportunity to meet with current as well as prospective collaborators to discuss ongoing and future projects. If interested, please contact William Weiss (817-735-2111 or william.weiss@unthsc.edu) to arrange for a convenient dayand time to meet.

In addition, please plan on attending the following presentations:

Poster Session 172 New Spins on Protein Synthesis Inhibitors

Monday, Sept. 08, 2014; 11:00am – 1:00pm

Pharmacodynamic evaluation of TP-271, a novel fluorocycline, in a neutropenic murine lung model infected with Streptococcus pneumoniae presentedby Tim Murphy

Pharmacodynamics of the fluorocycline TP-271 in a neutropenic murine lung infection model with methicillin-resistant Staphylococcus aureus presentedby Bill Weiss

Slide Session 200Clostridium difficile : Pathogenesis, Immune Response and Therapy

Monday, Sept. 08, 2014; 4:00pm – 4:15pm

Epidemic Clostridium difficile ribotype 027 strains are more virulent than other non-epidemic strains in the hamster CDAD model presented by MarkPulse

April 24, 2014

ESMID

The UNTHSC Pre-Clinical Services group will be attending the 24th ECCMID meeting in Barcelona, Spain from May 9-14 and welcomes the opportunity to meet with interested parties. Please contact William Weiss (817-735-2111 or william.weiss@unthsc.edu) to arrange for a convenient day and time tomeet.

In addition, please stop by the following poster presentations:

Saturday May 10th 3:30pm: Poster P0112 Ileal Dosing of Nisin and Miconazole Combination is Efficacious in the Hamster Clostridium difficile Associated Disease Model (Presented by Mark Pulse, Assistant Director UNTHSC Pre-Clinical Services).

Sunday May 11th 1:30pm: Poster 0804 DAV131, an oral absorbent-based product, exerts dose-dependent protection of hamsters againstmoxifloxacin-induced Clostridium difficile lethal infection (Presented by DaVolterra in conjunction with UNTHSC).

March 1, 2014

SMI presents Superbugs & Superdrugs A Focus on Antibacterials

May 5 6, 2014, London, UK

“Research and Development in Neglected Diseases” (presented by William Weiss, Director of UNTHSC Pre-Clinical Services)

Overview and Clinical Relevance

Current therapies and issues

Why pursue research of neglected diseases?

New efforts and treatment options

June 7, 2013

The UNTHSC Pre-Clinical Services group will be in attendance at the 53rd Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) meeting in Denver, Colorado (September 10-13, 2013) and welcomes the opportunity to meet with current Sponsors as well as prospective collaborators to discuss ongoing and future projects. If interested, please contact William Weiss (817-735-2111 or william.weiss@unthsc.edu) to arrange for a convenient day and time to meet.

In addition, please plan on attending the following presentations by Mark Pulse, Assistant Director of the Pre-Clinical Services group:

Wednesday, Sept 11. – Slide Session 066 – Clostridium difficile: Pathogenesis

10:00 – 10:15 am : Dosing clindamycin before and after infection dramatically impacts disease outcome in the hamster Clostridium difficile -associated disease model

Thursday, Sept. 12 Poster Session 143 Antimicrobial Resistance and Immune Therapy

11:00am1:00 pm : Characterization of the programmed death 1 (PD1) and its ligand, PD-L1, in a murine cecal ligation model of sepsis

April 27, 2013

23rd ECCMID Meeting, Berlin, Germany

Oral Session New Antibacterial agents

In vivo Efficacy of the novel monosulfactam BAL300072 alone and in combination with meropenem against clinically important gram-negative pathogens

William Weiss, Director of Pre-Clinical Services, University of North Texas Health Science Center

March 1, 2013


SMI Presents: Superbugs & SuperdrugsA Focus on Antibacterials
4th March to 5th March 2013, London, UK

AN UPDATE ON CURRENT ISSUES AND PROGRESS IN C. DIFFICILE DISEASE (CDAD)
William Weiss, Director of Pre-Clinical Services, University of North Texas Health Science Center

  • A brief history and review
  • The changing epidemiology and resistance development in CDAD
  • Transmission, Virulence factors and clinical manifestations
  • Surveillance, diagnosis and clinical testing
  • Prevention, emerging therapies and potential for efficacy

November 12, 2012

UNTHSC Pre-Clinical Services (PCS) is pleased to announce the recent hire of Timothy Murphy who joins the group as Project Manager.

Tim comes to the group with 16 years experience in the drug discovery and pharmacology industry. He has previously held positions of increasing responsibility in ViviSource Laboratories, Arpida Inc., Enanta Pharmaceuticals and Wyeth Research. Tim brings with him extensive experience and expertise in the design and performance of anti-infective efficacy models: antibacterial and antiviral, pharmacology and oncology studies as well asPK/PD evaluations and vaccine discovery research. He has earned both B.S. and M.S. degrees in biology and has co-authored or presented numerousmanuscripts and presentations.

UNTHSC PCS welcomes Tim and looks forward to the contributions that he will make along with expanding the expertise and scope of testing that thegroup has to offer to our Sponsors.

July 30, 2012

The UNTHSC Pre-Clinical Services group will be in attendance at the 52nd Interscience Conference of Antimicrobial Agents and Chemotherapy (ICCAC) inSan Francisco, CA (September 9 12, 2012) and welcomes the opportunity to meet with current collaborators as well as prospective Sponsors to discussongoing and future research projects, utilizing our expertise to meet your R & D requirements. If interested, please contact William Weiss (817-725-2111or william.weiss@unthsc.edu) to arrange for a convenient day and time to meet.

April 2, 2012

UNTHSC Pre-Clinical services, in conjunction with Affinium Pharmaceuticals, presented their findings on the effects of AFN-1252, a novel fatty acidbiosynthesis inhibitor antibacterial agent, on the in vitro and in vivo expression of S. aureus virulence genes at the 22nd European Congress of ClinicalMicrobiology and Infectious Disease (ECCMID) in London, UK.

Presentation Summary: (full details and time can be found on the ECCMID Congress website)

Poster P2058 AFN-1252 Alters In Vitro and In Vivo Staphylococcus aureus Gene Expression and Reduces Bacterial Counts in a Mouse GranulomaInfection Model

M. E. Pulse1, N. Kaplan2, J. Parsons3, C. O. Rock3, M. Kukula1, P. Nguyen1, J. Pierce1, D. Valtierra1, W. J. Weiss1, J. W. Simecka1

1UNTHSC, Fort Worth, TX, 2Affinium Pharmaceuticals, Toronto, Canada, 3St. Jude Children’s Res. Hosp., Memphis, TN

Exposure of S. aureus cultures to AFN-1252 resulted in the anticipated up-regulation of genes involved in the FAS II pathway associated with the FapRregulon and the unpredicted down-regulation of several virulence genes that are controlled by the SaeRS two-component regulator. In the MG infectionmodel, a single oral dose of AFN-1252 at 2 hours post-infection resulted in mean log10 CFU reductions of 2.9 3.1 in 24 48 hours after dosing. PKanalysis of this fluid revealed that the relative exposure (AUC) of AFN-1252 in the granuloma fluid was 85% of the corresponding plasma levels, andqRT-PCR of S. aureus RNA extracted from granuloma fluid indicated that fabH expression was up-regulated and virulence factor expression was down-regulated following the single dose of AFN-1252. AFN-1252 was also dosed consecutively (2, 26, 50 hours) in the MG model, which maximally reducedgranuloma-associated S. aureus counts by 5.3 log10 CFU within 72 hours of the first dose. AFN-1252 triggered the up-regulation of genes associated with the FASII pathway in S. aureus, and it simultaneously down-regulated virulence genes controlled by the SaeRS regulator. AFN-1252 not only alteredS. aureus gene expression in the granuloma fluid, but it also therapeutically reduced the CFU counts in the fluid as well.

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