C. Reduced efficacy to related antibiotics used in human medicine
Vancomycin-resistant Enterococci (VRE)
Enterococci are members of the normal gut flora for most warm-blooded animals, including humans. However, they are sometimes problematic nosocomial infections in hospital settings where the use of antibiotics is believed to contribute to the emergence of multiple antibiotic resistant genes in this organism. Vancomycin is considered the treatment of choice for many resistant organisms, so the emergence and subsequent spread of VRE became a significant public health concern.
Before the 1990s, it was thought that VRE were present only in hospitals where vancomycin had been used for many years15. However, epidemiological and molecular studies have shown that the use of avoparcin in farm animals can result in carriage and dissemination of VRE by these animals and in humans in close contact with these animals15, 16. Because of public health concerns about resistance to these glycopeptide antibiotics, avoparcin was banned in Denmark in 1995, in Germany in 1996, and eventually by all EU member states15. Subsequent reduction in prevalence of VRE in poultry, swine and humans in the later years were reported17.
Although vancomycin is frequently used in the hospital setting in the USA, avoparcin was never used in livestock and poultry in the US. This may be the reason why, in spite of the relatively high rates of VRE in U.S. hospitals, there is less evidence of a community reservoir for VRE in this country18.
Antimicrobial resistance due to a particular antibiotic used in food animals may result in reduced efficacy of most or all members of that same antibiotic class, some of which may be extremely important for human medicine. This occurs because of the similarity of the antibiotic’s related structural components, which causes cross-recognition and cross-resistance for all or most of the antibiotics within the same antibiotic class. An example is the emergence and spread of vancomycin resistant enterococci (VRE) in hospitals following the extensive use of avoparcin in animals, a glycopeptide antimicrobial agent that is structurally similar to vancomycin. Another example is virginiamycin resistance cross-reacting with resistance to the human streptogramin, quinupristin-dalfopristin14.
Streptogramins were developed for use in animals at a time when there was no interest in using this class of antibiotics for human medicine. Virginiamycin had been used subtherapeutically for growth promotion in livestock and poultry since 1974. However, after using virginiamycin in animals for many decades, researchers went back and re-visited the streptogramin class of antibiotics and developed quinupristin-dalfopristin for human usage. It was very disheartening in 1999 when this newly licensed human antibiotic was immediately met with AMR in Enterococcus faecium due to many years of using virginiamycin in animals.
The Avoparcin-Vancomycin Story
Avoparcin is a glycopeptide antibiotic in the same antibiotic class as vancomycin. Although structurally related, these two antibiotics differ in usage and application. Vancomycin is clinically important for humans and often serves as a drug of last resort for Gram-positive infections. Avoparcin, however, was used in animals as a growth promotant in Europe and elsewhere (but not in the US). Strong evidence later linked vancomycin resistance in human pathogens with subtherapeutic usage of avoparcin in food animals, which led to the banning of the use of avoparcin in the EU in 1997.