Bacterial Infection Program Summary

AMRI has completed the following in its Bacterial Infection Program:

  • Screening of AMRI’s natural product libraries for activity against Staphylococcus aureus (“S. aureus”) and Escherichia coli (“E. coli”).
  • Screening hits were prioritized for identification of their active component(s) based on predetermined criteria with the objective of selecting classes of antibiotic that have not already been fully researched. Selected active wells were prioritized. Purification and identification of active components was completed. Structure elucidation is complete for the actives prioritized to date.
  • Following characterization of the active samples from the screens, both broad and narrow spectrum antibiotics with relatively large in vitro therapeutic indices (relative to mammalian cell-lines) and cidal activity have been identified.

  • AMRI has focused its optimization efforts on AMR-BAC-1 (Table 1). AMR-BAC-1 exhibits efficacy in vivo at lower doses than vancomycin and an in vivo therapeutic index equal to and potentially better than vancomycin in a murine model of sepsis (Table 2).

History of Antibacterial Resistance

Despite recent successes, antibiotic therapy remains in a precarious position due to the growing trend of antibiotic resistance. A recent release by the National Institute of Allergy and Infectious Diseases (April 2006) reported that:

  • More than 70% of the bacteria that cause hospital-acquired infections are resistant to at least one of the drugs most commonly used to treat them.
  • Strains of S. aureus resistant to methicillin (MRSA) are endemic in hospitals and are increasing in non-hospital settings.
  • A number of cases of community-associated MRSA have been reported, including cases in patients without established risk factors.
  • Increasing reliance on vancomycin has led to the emergence of vancomycin-resistant enterococci infections.

Since vancomycin resistance now exists in S. aureus, it is expected to increase at rates similar to those witnessed for vancomycin-resistant enterococci, becoming endemic in U.S. hospitals by 2015. Studies in Europe show similar findings.

The incidence rate of infections caused by community-acquired, methicillin-resistant S. aureus (CA-MRSA) has also risen, increasing 17-fold in AIDS patients between 2003 and 2005 (Infectious Disease News, October 2006).