http://jac.oxfordjournals.org/cgi/content/full/49/1/25
Journal of Antimicrobial Chemotherapy (2002) 49, 25-30
© 2002 The British Society for Antimicrobial Chemotherapy
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The 2000 Garrod Lecture
Factors impacting on the problem of antibiotic resistance
Stuart B. Levy,*
Center for Adaptation Genetics and Drug Resistance, Tufts University School of Medicine, Boston, MA 02111, USA
Abstract
Antibiotic resistance has become a major clinical and public health problem within the lifetime of most people living today. Confronted by increasing amounts of antibiotics over the past 60 years, bacteria have responded to the deluge with the propagation of progeny no longer susceptible to them. While it is clear that antibiotics are pivotal in the selection of bacterial resistance, the spread of resistance genes and of resistant bacteria also contributes to the problem. Selection of resistant forms can occur during or after antimicrobial treatment; antibiotic residues can be found in the environment for long periods of time after treatment. Besides antibiotics, there is the mounting use of other agents aimed at destroying bacteria, namely the surface antibacterials now available in many household products. These too enter the environment. The stage is thus set for an altered microbial ecology, not only in terms of resistant versus susceptible bacteria, but also in terms of the kinds of microorganisms surviving in the treated environment. We currently face multiresistant infectious disease organisms that are difficult and, sometimes, impossible to treat successfully. In order to curb the resistance problem, we must encourage the return of the susceptible commensal flora. They are our best allies in reversing antibiotic resistance.
Today we can list a number of organisms in both hospitals and the community that thwart treatment because they are resistant to not one, but to many different antibiotics (Table).1 The term multidrug resistance (MDR), which initially described resistant mammalian tumour cells, and later strains of Mycobacterium tuberculosis, now describes multidrug resistance in any microorganism—bacterium, fungus or parasite. The emergence of MDR is clearly related to the quantity of antibiotics and how they are being used.2,3 It may reflect acquisition of different resistance determinants on the same DNA molecule, or single determinants, such as multidrug pumps, that specify efflux activity against different antibacterials.4 Besides the known pathogens, the relatively recent appearance of opportunistic organisms, intrinsically resistant to many drugs, is now complicating the advances that we have made in medical technologies. With a larger number of immunocompromised patients and longer time periods spent in an immunocompromised state, these organisms have become ‘specialized’ pathogens—typically attacking only the most vulnerable patients. Among these opportunistic pathogens are the enterococci, the coagulase-negative staphylococci, Pseudomonas aeruginosa and Acinetobacter baumanii. Those physicians attending medical school 20–30 years ago probably did not even discuss these organisms as important pathogens, though today they cause prominent, even potentially lethal, problems in hospitals worldwide