Apr 30, 2002 (CIDRAP News) A new mathematical model of the spread of antimicrobial resistance suggests that the agricultural use of new antibiotics can introduce resistant microbes into humans but that continued farm use of the drugs has little further effect after a resistant strain is established in the human population.
"Our analysis demonstrates that AAU [agricultural antibiotic use] may hasten the appearance of AR [antibiotic resistance] and decrease the efficacy of the antibiotic in humans; prudent AAU after the development of AR in humans may have few medical impacts," states the report by David L. Smith of the University of Maryland and colleagues from there and from the Veterans Administration Medical Center in Baltimore.
"We conclude that agricultural use of antibiotics in new resistance classes should be delayed until the period of maximum medical utility has passed," they add. Their model suggests that this approach could postpone the development of significant resistance by several years. After that point, it may be safe to allow prudent agricultural use, they suggest. Their study was supported by a grant from Pfizer Corp.
The model predicts the prevalence of resistance in human commensal bacteria, such as enterococci, which are usually harmless but sometimes cause opportunistic infections in wounds or the bloodstream. With regard to resistant bacteria, the model classifies people in four categories: unexposed, exposed, colonized, or amplified (carrying a high load). The model includes many factors, such as the background rate of exposure to new AR strains, the increase in exposure due to AAU, medical antibiotic use, colonization rate, colonized loss rate, recolonization rate, and rates of contact between colonized persons and others. The model includes an equation that yields the person-to-person transmission rate of resistant bacteria.
The authors say the model predicts that the prevalence of antimicrobial resistance to a new medical drug will eventually stabilize at about the same level whether it is used in food animals or not, but that it will reach this level sooner with agricultural use. To illustrate this, they apply the model to current data on the relationship between the use of vancomycin in medicine, the use of avoparcin (the veterinary form of vancomycin) in farm animals, and the spread of vancomycin-resistanct enterococci (VRE) in hospitals. (Some of the estimates used in the calculation are not well supported by data, so the results represent a theoretical illustration, not a risk assessment, the article says.)
Because antibiotic resistance stems from natural sources and is magnified by medical antibiotic use, "VRE would eventually emerge without AAU, but it would reach equilibrium several years later," the article says. Using the VRE data, the model predicts that the total increase in antibiotic resistance prevalence over the first 10 years would be about the same as the increase that would be generated by a 30% increase in medical antibiotic use over the same period. Further, the model indicates that the excess prevalence resulting from agricultural use would dwindle almost to zero if agricultural use were delayed until 6 years after the beginning of medical use.
"Restricting AAU is most effective when AR bacteria remain rare," the authors state. "One solution might be to regulate AAU before AR becomes a problem in medicine and then allow prudent AAU once clinically significant resistance has already developed." This approach is the opposite of an approach suggested by the Food and Drug Administration, in which agricultural use would be allowed until antibiotic resistance exceeds a certain threshold, the article says.
"This threshold concept may be an ineffective tool for managing commensal AR bacteria because once AR bacteria are detected, much of the damage has been done," the authors state. They add that thresholds may be useful for pathogens like Campylobacter and Salmonella but not for resistance in enterococci. "In commensal bacteria with the potential for epidemic spread, small increases in prevalence when AR is extremely rare can initiate epidemics which may have large consequences. We are skeptical that a threshold in humans could be set low enough to prevent the adverse effects of AAU."
Smith DL, Harris AD, Johnson JA, et al. Animal antibiotic use has an early but important impact on the emergence of antibiotic resistance in human commensal bacteria. Proc Natl Acad Sci 2002;99(9):6434-9