Antimicrobial Use and Antimicrobial Resistance: A Population Perspective

Marc Lipsitch, Matthew H. Samore


Emerging Infectious Diseases. 2002;8(4) 

In This Article

Indirect Effects on Resistance

For any infectious disease, the infection or colonization status of any one (index) patient affects the risk of infection or colonization of others. Measures (such as vaccination or antibiotic treatment) that change the incidence or duration of infection in one person will affect that person's contacts [13,14]. Just as vaccination programs benefit those who are not vaccinated because of the phenomenon of herd immunity, antibiotic usage by some persons may increase the risk of colonization or infection with resistant organisms in people who have not received antibiotics. Members of a population experience indirect effects of antimicrobial use, defined as the enhancement of risk for acquiring a resistant organism, because of the use of antimicrobials by other persons in the group or population.

For example, simply by eradicating susceptible organisms, and thereby reducing the opportunities for transmission of susceptible strains, antibiotics received by treated hosts can increase the probability that other hosts will acquire resistant variants (Figure, B; Table). For many pathogens, acquisition of one strain reduces a person's chances of acquiring other strains, either via immune responses, via direct interference [15,16,17], or both. These inhibitory interactions create competition between resistant and susceptible strains. As a result, treatment of some patients, by eradicating susceptible strains and thereby reducing their ability to transmit to other hosts, is advantageous to resistant strains in the population. Mathematical models [18,19,20,21,22] and epidemiologic studies [23] suggest that this mechanism of shifting the competitive balance in favor of resistant strains can increase the prevalence of resistant organisms in the community, alone or in combination with other mechanisms. An important feature of this kind of indirect effect is that it need not involve an increase in a patient’s own risk of carrying resistant organisms, only a reduction in the duration or probability of carrying susceptible ones.

In these organisms, the increase in transmission of resistant pathogens is a consequence of successful treatment of the infected host, resulting in the eradication of drug-susceptible pathogens that colonize or infect that host. As a consequence, the more effective a treatment is at eradicating drug-susceptible populations of these organisms, the more it will promote the spread of resistant ones. This spread contrasts with TB, in which treatment failure is often associated with the emergence of resistance in treated hosts, so unsuccessful treatment is seen as a factor promoting the spread of resistance (although, over a time scale of decades, this type of indirect mechanism described here may play a role even in tuberculosis [21]).


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