Microbial development of drug resistance: mechanisms and clinical significance

Bacteria have demonstrated a disconcerting ability to develop resistance to antimicrobial agents nearly as quickly as new compounds become available. During the past two decades the molecular bases of several types of resistance have been elucidated. Mechanisms of resistance include the transference of genetic material either through conjugation (involving direct contact between microorganisms), or indirectly through transduction (involving bacteriophages). In addition to this "infectious" drug resistance, genetic mutations which permit the utilization of new metabolic pathways, and the production of enzymes which can inactivate the antimicrobic have been described. One particularly complex problem has been the ability of many Enterobacteriaceae to develop resistance to multiple antimicrobials simultaneously. The possible effect of such an occurrence is illustrated by the recent epidemic of multiply resistant Salmonella typhi in Mexico. Because the typhoid bacilli shared an identical resistance pattern to an epidemic Shigella dysenteriae type 1 the in vivo interspecies transmission of resistance has been postulated. Understanding the various mechanisms of resistance development should allow more rational use of antimicrobial agents.