Emergence, Spread, and Environmental Effect of Antimicrobial Resistance (O'Brien)

Antimicrobial use selects for resistant bacterial strains as well as genetic vectors specifying resistance genes.

Antimicrobial use anywhere, at any time, can increase resistance in microbes anywhere else. A bacterial isolate may be resistant not only because nearby use of antimicrobials has amplified genetic constructs locally, but also because distant use may have affected the evolution and spread of the construct or its components. Therefore, levels of resistance in a given isolate may, in part, reflect the total number of bacteria in the world ever exposed to antimicrobials.

Generally Overlooked Fundamentals of Bacterial Genetics and Ecology (Summers)

Propagation of antimicrobial resistance is an ecological problem.

Ameliorating resistance requires an understanding of the commensal microbiota of mammals as well as genetic vectors involved in the movement of resistance genes and the linkage of resistance genes on these vectors.

Treatment with any given antimicrobial can result in selection for resistance to not only that specific agent, but also, by genetic linkage of resistance genes, to other antimicrobials.

Antimicrobial Use and Resistance in Animals (McEwen and Fedorka-Cray)

Most food animals in the United States are exposed to an antimicrobial via feed, water, or injection at some point during their lives. This medication is used to treat or prevent infectious disease, promote growth, or enhance feed efficiency.

Many antimicrobials used in food animal production are the same as, or closely related to, drugs used in human medicine.

Precise figures describing the extent and quantity of antimicrobial use in animals are not publicly available, and estimates vary widely.

There is considerable evidence that antimicrobial use in food animals selects for antimicrobial resistance in commensals and in zoonotic enteropathogens.

Intended purpose of use, dose, duration, and route of administration can influence the degree to which antimicrobial use exerts a selective pressure for resistance as well as the spread of resistance among bacterial populations.

Fecal waste from food animals is often composted and spread as fertilizer. Swine operations typically construct lagoons to hold such waste. These practices are implicated in contamination of the environment with resistant bacteria.

Antimicrobial resistance is also a concern for animal health, but little is known about the magnitude of this problem because surveillance of resistance in exclusively animal pathogens is poor relative to that of zoonotic enteropathogens.

Uses of Antimicrobials in Plant Agriculture (Vidaver)

Only streptomycin and oxytetracycline are currently approved for treatment of bacterial diseases in plant agriculture. Use is primarily prophylactic, and most applications are by spray treatments in orchards.

Because monitoring and surveillance are not routine, the effect of antimicrobial use in plant agriculture on antimicrobial resistance is unknown.

Human Diseases Caused by Foodborne Pathogens of Animal Origin (Swartz)

Several lines of evidence may link antimicrobial-resistant pathogens in humans to the use of antimicrobials in food animals. These include the following: (i) direct epidemiological studies, (ii) temporal evidence for emergence of resistance among animal-associated bacteria before related human pathogens, (iii) additional circumstantial evidence, (iv) trends in resistance among Salmonella; Campylobacter; and Escherichia coli isolates, and (v) studies suggesting that farmers and family members may be more likely than the general population to acquire antimicrobial-resistant bacteria.

Evidence also suggests a link between enterococci of food animal origin (particularly strains that are vancomycin resistant) and strains found in the human gastrointestinal tract.

The latent period between the introduction of an antimicrobial and the emergence of resistance varies considerably, but once the prevalence of resistance in a population reaches a certain level, reversal of the problem becomes extremely difficult. The time to act is therefore limited.

Mechanisms of Increased Disease in Humans from Antimicrobial Resistance in Food Animals (Barza)

There are at least five potential mechanisms by which antimicrobial resistance can have adverse effects on human health: (i) the “attributable fraction,” or proportion of infections caused by pathogens that are resistant to antimicrobials taken for unrelated reasons; (ii) linkage of variable traits to resistance traits; (iii) ineffective treatment due to choice of a drug to which pathogens are resistant; (iv) the attributable fraction in food animals, which increases the numbers of resistant foodborne pathogens; and (v) the acquisition of resistance by commensal flora of food animals, which serve as a reservoir of resistance traits that can find their way to commensals and pathogens of people.

Excess Infections Due to Antimicrobial Resistance: The “Attributable Fraction” (Barza and Travers)

Paradoxically, antimicrobial use can increase vulnerability to infection upon exposure to a resistant foodborne pathogen by up to 3-fold (the “attributable fraction”), because it causes a transient decrease in an individual's resistance to colonization.

Calculations based on estimates of annual rates of nontyphoidal Salmonella and Campylobacter jejuni infections suggest that resistance to antimicrobial agents results annually in 29,379 additional nontyphoidal Salmonella infections, leading to 342 hospitalizations and 12 deaths, and 17,668 additional C. jejuni infections, leading to 95 hospitalizations.

Morbidity of Infections Caused by Antimicrobial-Resistant Bacteria (Travers and Barza)

Antimicrobial resistance can affect the outcome of infection in 2 ways: (i) virulence of the pathogen may be increased, and (ii) treatment may be less effective as a result of choosing an antimicrobial drug to which the pathogen is resistant.

Data for Salmonella and Campylobacter infections suggest that antimicrobial resistance strains are somewhat more virulent than susceptible strains, either via prolonged or more severe illness.

Fluoroquinolone-resistant infections (stemming from administration of antimicrobials to food animals) lead to an estimated 400,000 excess days of diarrhea per year in the United States relative to fluoroquinolone-susceptible infections.

Review of Assessments of the Human Health Risk Associated with the Use of Antimicrobial Agents in Agriculture (Bailar and Travers)

Published risk assessments of antimicrobial use in agriculture are likely to underestimate risk to human health because they are subject to multiple limitations in scope.

Two of the most serious limitations include (i) a tendency to limit the scope of analysis to what has happened in the past, ignoring the potential for cumulative effects in the future; and (ii) a tendency to examine the effect of resistance on only one species of microorganism, ignoring the potential for transfer of resistance.