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Latest in Antimicrobial Agents: Novel Drugs, Mechanisms, and Clinical Trials

Stay updated with cutting-edge antimicrobial agents showcased at the 2006 ICAAC conference. Discover new drugs exclusively effective against Staphylococcus, targeting bacterial fatty acid synthesis. Explore potential game-changers like PZ-601 and LN-1-255, designed to combat drug-resistant bacteria effectively. Uncover insights into innovative approaches, such as AR-709, offering improved antimicrobial activity with lower resistance development. Delve into the world of natural antimicrobial peptides, including ceraginins, and their diverse roles in host defense mechanisms and innate immunity. Stay informed about promising candidates like HCV-796 against Hepatitis C Virus. Learn the latest advancements in antimicrobial research and potential therapeutic interventions with a focus on novel drug classes and mechanisms.

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Latest in Antimicrobial Agents: Novel Drugs, Mechanisms, and Clinical Trials

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  1. 2006 Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC)

  2. What is New in Antimicrobials? Drug - API-1252 • Exclusively against Staphylococcus. • Targets bacterial fatty acid synthesis • “Exceptionally active” against MRSA • Administered orally or IV (in mice) • Narrow Spectrum = “no off-target killing” • Human trials in 2007

  3. More against Staph Drug - PZ-601 • A Carbapenum drug • Active against drug-resistant gram (+) and some gram(-) bacteria. • Bactericidal against MRSA • Not active against PA, unless used in conjunction with aminoglycosides

  4. Against Gram(-) Drug – LN-1-255 • A penicillin-derived sulfone • Resembles the substrate of serine beta lactamase

  5. Against Streptococcus Drug – AR-709 • A diaminopyrimidine • Narrow spectrum • Inhibits dihydrofloate reductase (like trimethroprim) • Advantages over Trimethorpin are: • Better antimicrobial and bactericidal activity • A “low propensity “ to develop resistance

  6. Against Staph? • Drug – Hygromycin –A • An inhibitor of protein synthesis • Against gram(+) including MRSA • Similar to Linezolid an oxazolidinone antibiotic (Pfizer’s trade name Zyvox)

  7. Against Mycobacterium Drug – DC-159a • An 8-methoxy derivative of fluroquinoline • Orally available • Broad Spectrum - gram (+) and (gram (-) • Active against M. tuberculosis and its multiple drug resistant isolates

  8. Propionibacteria acnes Drug – BAL 19403 • A macrolide antibiotic • Antibacterial and anti-inflammatory • “wide safety margin” • Little systemic absorption • Strong candidate for topical treatment of acne

  9. Hepatitis –C Virus • Drug – HCV-796 • A selective, non-nucleoside inhibitor • A modified benzofuran • “Very Potent” against HCV in mammalian cells • Advances to Phase II clinical trials

  10. Natural Antimicrobial Peptides • Part of the Host defense system • Broad ability to kill microbes • Large peptides (over 100 a.a) are often lytic, nutrient binding proteins or specifically target microbial macromolecules • Small peptides disrupt the structure or function of microbial cell membranes • Found in epithelial cells, phagocytes and body fluids • They are endogenous antibiotics • Help in inflammation, wound repair and regulation of the adaptive immune system

  11. Ceraginins • Intriguing class of membrane-active mimics of antimicrobial peptides • Broad spectrum • Rapid in killing action • Very potent • Topical application to control eye infections • Useful to prevent biofilm contamination from catheters

  12. Antimicrobial Peptides • Cationic peptides- plants, insects& others • Disrupt plasma membrane integrity • Megainin –from skin of frogs • Squalamine – from spiny dogfish shark • Protegrins – from pigs

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