Although there is an increased need for novel antibacterial compounds, a regress in developing new antibiotic drugs has been registered in the past decades, as a result of economic, medical, social and political factors. The present paper aims to bring together and to discuss the wealth of information in the subject by presenting both traditional and new approaches for antibiotic drug discovery. The route starting from analogues derived from well-known antibiotics seems that will be the one to offer the great part of new antibiotics having the potential to enter the marketplace. The target-based approach, well-validated biomolecular targets and new potential targets emerging from complex resistance mechanisms of bacteria and bacterial virulence, are disscused. Moreover, strategies based on the multiplicity of targets to be addressed by an antibacterial agent in order to limit the problem of antibiotic resistance are highlighted in the present paper. Challenging sources for developing new antibacterial agents, e.g. bacteriophages, non-multiplying and non-culturable bacteria are also considered.

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