Development and persistence of multi-resistance to antibiotics in bacteria; an analysis and a new approach to this urgent problem.

The intestinal microflora may have more influence on infectious diseases, than the mere control of growth of opportunistic micro-organisms by colonisation resistance (CR) and unspecific stimulation of the immune system. In compromised patients the CR may become decreased for several reasons but mostly because antibiotics reach the intestine during treatment. The consequence of a CR-decrease is that antibiotic-resistant opportunistic micro-organisms may increase in numbers in the gut. In this context, it is hypothesised that if the CR could be maintained at a normal level, the risk for maintenance and spread of resistant strains could be mitigated. Such maintenance requires absence of active antibiotic substance in the gut. This might be brought by the inactivation of antimicrobial agents by intestinal contents. Intra-intestinal inactivation has been described to occur along two possible routes: (1) inactivation by chemical binding or absorption and (2) by enzymatic destruction. Secondly, the composition of the intestinal microflora should be maintained at a normal level in case of other reasons for CR-decrease than antibiotic activity. Comprehensive study of the composition of normal microflora and the strains of species which play a role in CR with techniques which have become available during last decade, is recommended as well as the application of certain pre- and probiotics. It is concluded that antibiotic inactivation may be an ancient strategy of nature which should become incorporated in antibiotic treatment. Antibiotic use and development of resistance may have occurred when ecosystems formed several billions of years ago. Protection against antibiotics produced by newcomers into the ecosystem may have developed as it was necessary to maintain locally available nutrients for the inhabitants of the ecosystem. Should this hypothesis be correct, it is plausible that antimicrobial inactivation by antibiotic inactivating molecules is ubiquitous. In the ecosystem of the digestive tract, molecules involved in inactivation may predominantly be formed by microorganisms.