Antimicrobial Use and Antimicrobial Resistance: A Population Perspective

Marc Lipsitch, Matthew H. Samore


Emerging Infectious Diseases. 2002;8(4) 

In This Article

Abstract and Introduction

The need to stem the growing problem of antimicrobial resistance has prompted multiple, sometimes conflicting, calls for changes in the use of antimicrobial agents. One source of disagreement concerns the major mechanisms by which antibiotics select resistant strains. For infections like tuberculosis, in which resistance can emerge in treated hosts through mutation, prevention of antimicrobial resistance in individual hosts is a primary method of preventing the spread of resistant organisms in the community. By contrast, for many other important resistant pathogens, such as penicillin-resistant Streptococcus pneumoniae, methicillin-resistant Staphylococcus aureus, and vancomycin-resistant Enterococcus faecium resistance is mediated by the acquisition of genes or gene fragments by horizontal transfer; resistance in the treated host is a relatively rare event. For these organisms, indirect, population-level mechanisms of selection account for the increase in the prevalence of resistance. These mechanisms can operate even when treatment has a modest, or even negative, effect on an individual host’s colonization with resistant organisms.

The growth of antimicrobial resistance has prompted calls to reduce unnecessary antibiotic use and to improve treatment protocols to maximize the lifespan of these drugs. These calls rest on the well-supported idea that the use of antimicrobial agents is a powerful selective force that promotes the emergence of resistant strains.

To reduce antimicrobial resistance, multiple, and often conflicting recommendations, have been made. For example, strategies to minimize the burden of resistance in hospitals have included reduction of all antimicrobial classes, increased use of prophylactic antimicrobials to reduce colonization, rotation of different antibiotic classes in a temporal sequence, and simultaneous use of different antimicrobials for different patients [1,2,3,4,5,6].

Underlying these often varying recommendations for improving antimicrobial use is frequently conflicting evidence about the relationship between antibiotic treatment and antibiotic resistance. In some pathogens, showing that antibiotic treatment puts treated persons at a greater risk for acquiring resistant organisms has been difficult [7,8]; nonetheless, the cumulative effect of using these antibiotics has clearly been to increase the prevalence of resistance in the population as a whole.

For many pathogens of current concern, especially organisms for which asymptomatic colonization typically precedes infection (e.g., Streptococcus pneumoniae, Staphylococcus aureus, Enterococcus spp., and the gram-negative enteric bacteria), the relationship between antimicrobial use and resistance differs in fundamental ways from the relationship found in Mycobacterium tuberculosis, for which many modern principles of chemotherapy were developed. Furthermore, we argue that the selective effects of antibiotic use on these organisms are poorly understood, and we make specific suggestions for studies that could improve understanding of the mechanisms by which antibiotics exert natural selection on these organisms. Such an understanding will be crucial for the design of rational policies of antibiotic use to maximize the lifespan of existing drugs and to minimize the impact of resistant infections.


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