Alternative Approaches in Antibacterial Drug Discovery

All aspects discussed so far have centered mostly around classical broad-spectrum antibiotics aimed at in vitro essential targets. One simple reason for this is the outstanding success of this paradigm in the past together with the fact that only a small fraction of such targets has so far been exploited by marketed antibiotics, and that distinct classes of antibiotics can even interfere with the same target. Thus, in principle, there should be ample room for repeating that success story. However, the apparently slow pace at which novel antibiotics have been discovered and successfully developed in recent years, and the desire to at least partially circumvent the resistance development inherent in the classical approaches, have led many scientists, especially in the academic world, to come up with alternative strategies. These include:

1. Nonantibiotic strategies aiming to reverse the resistance against existing antibiotic classes

2. Extremely narrow-spectrum drugs

3. Phage therapies and other nonantibiotic bacteriolytic approaches

4. Strategies to reduce virulence and/or influence pathogenesis

5. Immunology-based approaches

We will review the general status of these alternative strategies in brief,11 as almost all of them are still at an early experimental stage and, with the exception of resistance breaker combination strategies, no clinical proof of concept is available yet.

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