Epidemiology of antibiotic resistance

Three biological processes contribute to the accumulation of bacterial drug resistance: new selection, gene epidemics and strain epidemics. New resistance emerges by (i) the advantaging of entire species, (ii) by mutation, and (iii) by the escape of resistance genes to mobile DNA. Organisms to have 'benefited' from modern patterns of cephalosporins and quinolone use include enterococci, Clostridium difficile, coagulase-negative staphylococci and Enterobacter spp. Mutational resistance notoriously occurs with certain antibiotic/organsim combinations and allows rapid multifocal accumulation of resistance. At worst, therapy can fail when resistant mutants are selected in individual patients. Escape of new genes to mobile DNA is rare but, having occurred, permits massive 'gene epidemics', as the same genes and plasmids spread into diverse pathogens. Strain epidemics notoriously occur in individual units, reflecting break-downs of hygiene. Some strains achieve a much wider distribution: thus, much of the MRSA problem in the UK depends on the dissemination of two epidemic strains, EMRSA15 and 16; penicillin resistant pneumococci of serotypes 6 and 23 have disseminated internationally from Spain and a serotype K25 strain of Klebsiella pneumoniae with SHV-4 beta-lactamase has spread widely in France. It remains unknown why some strains and genes achieve wide spread whereas others, equally resistant, fail to do so. There is no simple cure for resistance but the best opportunities for control lie in lesser and better use of antibiotics backed by swifter and more accurate microbiology; in developing new antibiotics; and in protecting old ones from resistance determinants. All this must be supported by good local knowledge of the epidemiology of infections and resistance and of the likelihood of particular antibiotics to select resistance.