[Antibiotics and phages: effects of combined therapy on susceptibility and resistance of bacterial pathogens].

Abstract

The increasing use of antibiotics both in human therapy and for non-therapeutic applications with simultaneous reduction in antibiotic drug development have led to a world-wide rise in antibiotic resistance. Before the age of antibiotics, bacteriophages (phages) were already used initially in France and Georgia and later in the USA and Russia. Today, phages are increasingly being used to treat infections caused by antibiotic-resistant bacteria either alone or in combination with antibiotics.Combining phages with antibiotics reduces the likelihood of simultaneous resistance development against both agents. In contrast to chemically defined antibiotics, phages have the ability to adapt to resistant host cells through genetic mechanisms. However, bacterial mutants that confer antibiotic resistance could simultaneously limit the effectiveness of phages. To avoid such effects, detailed knowledge of the mechanism of action and resistance of the antibiotic as well as the replication strategy of the phage is required. For the individual steps in the replication cycle of the lytic phages, the possible effects on resistance to the corresponding phages are analyzed for host cell factors associated with antibiotic resistance. Based on selected combinations, it becomes evident that resistance to one component is often accompanied by increased sensitivity to the other, which significantly reduces the likelihood of simultaneous resistance to both. Particularly efficient appear to be synergistic combinations, such as those consisting of an antibiotic and endolysin, a bactericidal phage enzyme.