Recent advances and challenges in antibacterial drug development


Special issue guest edited by Lynn Silver

There is a continuing need for new antibacterial drugs to deal with the burgeoning of bacterial pathogens resistant to the existing armamentarium of antibacterial drugs, compromising their effectiveness; furthermore, emerging pathogens are now considered to be a major microbiologic public health threat. Over the years, these issues have been addressed with modification of existing antibiotic classes or the search for new structural classes. The latter approach has not been particularly successful, as evidenced by the fact that the last novel antibacterial class to be developed was discovered in 1984. Today the clinical pipeline is predominantly occupied by derivatives of established classes, although there are some novel entries in development [1].   

Since the beginning of the century, Big Pharma began exiting antibacterial drug discovery despite a growing clinical need [2]. Apart from financial issues and regulatory hurdles, antibacterial discovery research, especially target based approaches, has not been productive. The current preclinical pipeline has high diversity, with > 40% of the projects representing new classes, new mechanisms of action or new targets [3]. However, this has generally been true of the preclinical pipeline all along (even when it was largely the domain of Big Pharma). Now, these projects are most often developed by SMEs residing in North America or Europe.  The problem arises in the validation and successful development of these preclinical projects into actual clinical candidates – and that is where most projects fail. Clearly focused efforts toward overcoming the obstacles to antibacterial discovery are needed [4]. Research and resources are essential to progress novel approaches to clinical practices in order to sustainably fight against antibacterial resistance and emerging bacterial pathogens.

This special issue of ADMET and DMPK is guest-edited by Lynn Silver, LL Silver Consulting. It will critically address challenges in antibacterial drug development, translational hurdles, innovative approaches and advances in preclinical pipelines. The topics of the special issue include but are not limited to:

-           Antibacterial drug resistance,
-           Novel targets,
-           Multi-targeting agents,
-           Repurposed drugs,
-           Derivatives of existing classes,
-           Potentiators (e.g. efflux pump inhibitors),
-           Antibodies, vaccines and immune-modulators.

The special issue is planned for January 2022. The deadline for manuscript submission is November 15, 2021. During article submission please select “Antibacterial special issue” as a section.


  1. Theuretzbacher, U.; Gottwalt, S.; Beyer, P.; Butler, M.; Czaplewski, L.; Lienhardt, C.; Moja, L.; Paul, M.; Paulin, S.; Rex, J. H.; Silver, L. L.; Spigelman, M.; Thwaites, G. E.; Paccaud, J.-P.; Harbarth, S., Analysis of the clinical antibacterial and antituberculosis pipeline. The Lancet Infectious Diseases 2019, 19 (2), e40-e50.
  2. Projan, S. J., Why is big Pharma getting out of antibacterial drug discovery? Curr Opin Microbiol 2003, 6 (5), 427-30.
  3. Theuretzbacher, U.; Outterson, K.; Engel, A.; Karlen, A., The global preclinical antibacterial pipeline. Nat Rev Microbiol 2020, 18 (5), 275-285.
  4. Silver, L. L., Challenges of antibacterial discovery. Clin Microbiol Rev 2011, 24 (1), 71-109.