Methods for Evaluating the in vitro-in vivo Activity Relationship of Antibacterial Compounds

At a Glance

Researchers at Colorado State University have developed patented methods for evaluating the in vitro-in vivo activity relationship of antibacterial compounds to better prioritize and advance drugs through the drug discovery pipeline for treatment of several bacterial infections, including M. tuberculosis, F. tularensis, and B. pseudomallei.

The drug discovery strategy developed here is incorporated into all of the team’s drug discovery programs, NIH funded drug assessment contracts, and industrial drug discovery partnerships, amounting to at least 5 different programs and thousands of tests. The approach describes prioritized progression of compounds into efficacy studies using animal models of infection.


Bacterial infections are a leading cause of mortality worldwide. Burkholderia pseucomallei, the causative agent of melidoidosis, has mortality rates as high as 40%. Franciscella tularensis is often fatal when inhaled, and it is estimated that a third of the world’s population is infected with Mycobacteria tuberculosis, the causative agent of tuberculosis (TB), and between 5-10% of those infected individuals will develop the active disease over their lifetime. In addition to the global burden of these diseases, the increasing rates of multi-drug resistant strains (MDR) that require extensive treatment regimens with second line drugs impacts disease management.

Therefore, there is a need to develop new therapeutics with unique modes of action that can be used to treat these types of bacterial infections or that can be co-administered with existing antitubercular drugs.


Cell division is an attractive under-exploited target for the development of new chemotherapeutics against pathogenic bacteria, which are often medically important, difficult to treat, and drug resistant. Developing small molecule inhibitors with specificity for these targets through rational drug design has demonstrated potency with low or negligible cytotoxicity. However, the determination of in vivo efficacy cannot be determined by analysis of minimal inhibitory concentrations (MIC) alone, and adequate in vitro methods for determining in vivo efficacy are urgently needed.


  • Better/faster identification of lead compounds for treating bacterial diseases
  • Application to a wide range of therapeutic candidate drugs


  • Modern drug discovery protocols do not adequately find new compositions because they rely primarily on the MIC – these methods are far more advanced
  • Discovery of new lead compounds from chemical libraries can be determined to have high efficacy in vivo, even though they may demonstrate poor MIC
Last Updated: February 2024
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​Susan E Knudson
Richard A Slayden

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