Recommended Readings: Vincent A. Fischetti, Ph.D. April 24, 2017

Monday Lectures

Monday, April 17, 2017  3:45 p.m.

Carson Family Auditorium

Vincent A. Fischetti, Ph.D.

Professor and Head,

Laboratory of Bacterial Pathogenesis and Immunology

The Rockefeller University

Exploiting phage evolution for the development of novel therapeutics

Recommended Readings:

David Bautz. March 20th 2017. CFRX: Phase 2 Trial of CF-301 to Initiate in mid-2017.

Czaplewski, Lloyd; Bax, Richard; Clokie, Martha; et al. (2016). Alternatives to antibiotics-a pipeline portfolio review. LANCET INFECTIOUS DISEASES. 16(2): 239-251

Diez-Martinez, Roberto; De Paz, Hector D.; Garcia-Fernandez, Esther; et al. (2015). A novel chimeric phage lysin with high in vitro and in vivo bactericidal activity against Streptococcus pneumoniae. JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY. 70(6): 1763-1773

Bikard, David; Euler, Chad W.; Jiang, Wenyan; et al. (2014). Exploiting CRISPR-Cas nucleases to produce sequence-specific antimicrobials. NATURE BIOTECHNOLOGY. 32(11): 1146-1150

Schuch, Raymond; Lee, Han M.; Schneider, Brent C.; et al. (2014). Combination Therapy With Lysin CF-301 and Antibiotic Is Superior to Antibiotic Alone for Treating Methicillin-Resistant Staphylococcus aureus-Induced Murine Bacteremia. JOURNAL OF INFECTIOUS DISEASES. 209(9): 1469-1478

Pastagia, Mina; Schuch, Raymond; Fischetti, Vincent A.; et al. (2013). Lysins: the arrival of pathogen-directed anti-infectives. JOURNAL OF MEDICAL MICROBIOLOGY. 62:1506-1516

Gilmer, Daniel B.; Schmitz, Jonathan E.; Euler, Chad W.; et al. (2013). Novel Bacteriophage Lysin with Broad Lytic Activity Protects against Mixed Infection by Streptococcus pyogenes and Methicillin-Resistant Staphylococcus aureus. ANTIMICROBIAL AGENTS AND CHEMOTHERAPY. 57(6): 2743-2750


How Pathogenic Bacteria Hide Inside Host Cells

A new study into Staphylococcus aureus, the bacterium which is responsible for severe chronic infections worldwide, reveals how the bacteria have developed a strategy of hiding within host cells to escape the immune system as well as many antibacterial treatments. The research, published by EMBO Molecular Medicine, demonstrates how ‘phenotype switching’ enables bacteria to adapt to their environmental conditions, lie dormant inside host cells and become a reservoir for relapsing infections.

British Medical Journal Editorial Outlines Need to Tackle Antibiotic Resistance

Professor Otto Cars from Infectious Diseases, Department of Medical Sciences, Uppsala University, Uppsala, Sweden, et al. present disturbing evidence that a well-coordinated global response is needed to prevent a pandemic of antibiotic resistance BMJ 2008;337:a1438In the September 18, 2008 publication, Cars unravels a story that began almost eight decades ago when the first antibiotics were used to treat infections.  The use and misuse of antibiotics threatens to take the world back to a pre-antibiotic era with sobering consequences that would impede surgery, organ transplantation, cancer chemotherapy, and a myriad of other healthcare advances.

Low income and middle income countries have poor treatment rates (e.g. 70% of nosocomial neonatal infections could not be successfully treated by using WHO’s recommended regimen).  In high income countries, the number of methicillin resistant Staphylococcus aureus related deaths has increased 30-fold between 1993 and 2006.  To overcome these statistics, the authors call for leadership on international and national levels, changes in consumer and provider behaviors, and better development of effective antibacterial agents to match current need.

The editorial also describes how fundamental problems in sanitation and the lack of safe water contribute to the overuse of antibiotics as a quick-fix solution to avoid disease.  And as existing antibiotics decline in their effectiveness, the discovery of new antibiotics is also declining.  Innovation and the discovery of new antibacterial agents has been meager in recent years; less than 2% of all drugs in development at the world’s largest pharmaceutical companies are antibiotics and there still remains unmet needs for treating some Gram negative infections.

Summary points listed in the article include:

  • “Antibiotics are a prerequisite for many of the advanced technologies in today’s healthcare”
  • “Although antibacterial resistance is growing, development of new antibiotics has declined”
  • “A new paradigm in which antibiotics are considered as a non-renewable resource is needed”
  • “The know-do gap in control of bacterial resistance to antibioticsmust be tackled on international, national, and individual levels”