The resistance pathways that have been discussed are not necessarily new mechanisms that have recently evolved among bacteria. By definition, antibiotics originate from microorganisms. Therefore, antibiotic resistance mechanisms have always been part of the evolution of bacteria as a means of survival among antibiotic-producing competitors. However, with the introduction of antibiotics into medical practice, clinically relevant bacteria have adopted resistance mechanisms as part of their survival strategy. As a result of the increased use of antimicrobial agents, a survival of the fittest strategy has been documented as bacteria adapt to the pressures of antimicrobial attack (Figure 1).
Fig1. Factors contributing to the emergence and dissemination of antimicrobial resistance among bacteria.
All bacterial resistance strategies are encoded on one or more genes. These resistance genes are readily shared between strains of the same species, between species of different genera, and even between more distantly related bacteria. When a resistance mechanism arises, either by mutation or gene transfer, in a particular bacterial strain or species, it is possible for this mechanism to be passed on to other organisms using commonly described paths of genetic communication. Therefore, resistance may spread to a wide variety of clinically relevant bacteria, and any single organism may acquire multiple genes and become resistant to the full spectrum of available antimicrobial agents. For example, strains of enterococci and P. aeruginosa already exist for which there are few effective therapeutic choices. Also, a gene encoding a single, very potent resistance mechanism may mediate multiple resistances. One such example is the mecA gene, which encodes staphylococcal resistance to methicillin and to all other beta-lactams currently available for use against these organisms; this leaves vancomycin as the only available and effective cell wall–inhibiting agent.
In summary, antibiotic use, coupled with the formidable repertoire bacteria have for thwarting antimicrobial activity and their ability to genetically share these strategies, drives the ongoing process of resistance emergence and dissemination (see Figure1). This has been manifested by the emergence of new genes of unknown origin (e.g., methicillin-resistant staphylococci and vancomycin-resistant enterococci), the movement of old genes into new bacterial hosts (e.g., penicillin resistant N. gonorrhoeae [PPNG]), mutations in familiar resistance genes that result in greater potency (e.g., beta lactamase–mediated resistance to cephalosporins in Escherichia coli), and the emergence of new pathogens for which the most evident virulence factor is intrinsic or natural resistance to many of the antimicrobial agents used in the hospital setting (e.g., Stenotrophomonas maltophilia).
Because of the ongoing nature of the emergence and dissemination of resistance, reliable laboratory procedures to detect drug resistance serve as crucial aids to managing patients’ infections and as a means of monitoring changing resistance trends among clinically relevant bacteria.
