Alternatives to conventional antimicrobial drugs: a review of future prospects.

BACKGROUND: Growing antimicrobial resistance poses the threat that before long no suitable drugs will be available for treatment of common infections. This review examines promising new strategies for treatment and control of microbial diseases, with an emphasis on staphylococcal infection. NEW DRUGS AND TARGETS: Advances in microbial genomics have provided tools identifying many new targets for antimicrobial drugs. Of particular interest amongst these are inhibition of microbial efflux pump activity, interruption or diversion of riboswitches controlling bacterial metabolism, and metagenomics, which allows analysis of genes from unculturable organisms. BIOLOGICAL APPROACHES: Advances are also being made in biological systems for disease control, with the exploitation of antimicrobial peptides to attack micro-organisms and modulate immune responses, and the use of bacteriophages or their lysins to eliminate bacteria. There are new approaches in the development and targeting of vaccines and immunoglobulin preparations based on advanced knowledge of microbial physiology and immunoregulation. WORKING WITH THE BIOME: With increasing recognition of the value of the normal microbiota in modulating immunity and the establishment of pathogens, there is growing interest in understanding the mammalian microbiome. Strategies are being developed to promote or maintain the normal microbiota, including the use of probiotics, and there is re-evaluation of the potential of bacterial interference. LOOKING AHEAD: Whilst these approaches are likely to generate new methods of disease control, few will yield usable products within the near future. There will be a continuing need for careful use of existing drugs based on firm diagnosis, rigorous hygiene and prudent antimicrobial stewardship.