Anette M. Hammerum

Use of antimicrobial growth promoters in food animals and Enterococcus faecium resistance to therapeutic antimicrobial drugs in Europe.

Supplementing animal feed with antimicrobial agents to enhance growth has been common practice for more than 30 years and is estimated to constitute more than half the total antimicrobial use worldwide. The potential public health consequences of this use have been debated; however, until recently, clear evidence of a health risk was not available. Accumulating evidence now indicates that the use of the glycopeptide avoparcin as a growth promoter has created in food animals a major reservoir of Enterococcus faecium, which contains the high level glycopeptide resistance determinant vanA, located on the Tn1546 transposon. Furthermore, glycopeptide-resistant strains, as well as resistance determinants, can be transmitted from animals to humans. Two antimicrobial classes expected to provide the future therapeutic options for treatment of infections with vancomycin-resistant enterococci have analogues among the growth promoters, and a huge animal reservoir of resistant E. faecium has already been created, posing a new public health problem.

Detection of mcr-1 encoding plasmid-mediated colistin-resistant Escherichia coli isolates from human bloodstream infection and imported chicken meat, Denmark 2015.

The plasmid-mediated colistin resistance gene, mcr-1, was detected in an Escherichia coli isolate from a Danish patient with bloodstream infection and in five E. coli isolates from imported chicken meat. One isolate from chicken meat belonged to the epidemic spreading sequence type ST131. In addition to IncI2, an incX4 replicon was found to be linked to mcr-1. This report follows a recent detection of mcr-1 in E. coli from animals, food and humans in China.

Human health hazards from antimicrobial-resistant Escherichia coli of animal origin.

Because of the intensive use of antimicrobial agents in food animal production, meat is frequently contaminated with antimicrobial-resistant Escherichia coli. Humans can be colonized with E. coli of animal origin, and because of resistance to commonly used antimicrobial agents, these bacteria may cause infections for which limited therapeutic options are available. This may lead to treatment failure and can have serious consequences for the patient. Furthermore, E. coli of animal origin may act as a donor of antimicrobial resistance genes for other pathogenic E. coli. Thus, the intensive use of antimicrobial agents in food animals may add to the burden of antimicrobial resistance in humans. Bacteria from the animal reservoir that carry resistance to antimicrobial agents that are regarded as highly or critically important in human therapy (e.g., aminoglycosides, fluoroquinolones, and third- and fourth-generation cephalosporins) are of especially great concern.

In Vivo Transfer of the vanA Resistance Gene from an Enterococcus faecium Isolate of Animal Origin to an E. faecium Isolate of Human Origin in the Intestines of Human Volunteers

ABSTRACT Transient colonization by vancomycin-resistant enterococci of animal origin has been documented in the intestines of humans. However, little is known about whether transfer of the vanA gene occurs in the human intestine. Six volunteers ingested a vancomycin-resistant Enterococcus faecium isolate of chicken origin, together with a vancomycin-susceptible E. faecium recipient of human origin. Transconjugants were recovered in three of six volunteers. In one volunteer, not only was vancomycin resistance transferred, but also quinupristin-dalfopristin resistance. This study shows that transfer of the vanA gene from an E. faecium isolate of animal origin to an E. faecium isolate of human origin can occur in the intestines of humans. It suggests that transient intestinal colonization by enterococci carrying mobile elements with resistance genes represents a risk for spread of resistance genes to other enterococci that are part of the human indigenous flora, which can be responsible for infections in certain groups of patients, e.g., immunocompromised patients.

Danish Integrated Antimicrobial Resistance Monitoring and Research Program

This program has led to changes in the use of antimicrobial agents in Denmark and other countries.

Human and Swine Hosts Share Vancomycin-Resistant Enterococcus faecium CC17 and CC5 and Enterococcus faecalis CC2 Clonal Clusters Harboring Tn1546 on Indistinguishable Plasmids

ABSTRACT VRE isolates from pigs (n = 29) and healthy persons (n = 12) recovered during wide surveillance studies performed in Portugal, Denmark, Spain, Switzerland, and the United States (1995 to 2008) were compared with outbreak/prevalent VRE clinical strains (n = 190; 23 countries; 1986 to 2009). Thirty clonally related Enterococcus faecium clonal complex 5 (CC5) isolates (17 sequence type 6 [ST6], 6 ST5, 5 ST185, 1 ST147, and 1 ST493) were obtained from feces of swine and healthy humans. This collection included isolates widespread among pigs of European Union (EU) countries since the mid-1990s. Each ST comprised isolates showing similar pulsed-field gel electrophoresis (PFGE) patterns (≤6 bands difference; >82% similarity). Some CC5 PFGE subtype strains from swine were indistinguishable from hospital vancomycin-resistant enterococci (VRE) causing infections. A truncated variant of Tn1546 (encoding resistance to vancomycin) and tcrB (coding for resistance to copper) were consistently located on 150- to 190-kb plasmids (reppLG1). E. faecium CC17 (ST132) isolates from pig manure and two clinical samples showed identical PFGE profiles and contained a 60-kb mosaic plasmid (repInc18 plus reppRUM) carrying diverse Tn1546-IS1216 variants. The only Enterococcus faecalis isolate obtained from pigs (CC2-ST6) corresponded to a multidrug-resistant clone widely disseminated in hospitals in Italy, Portugal, and Spain, and both animal and human isolates harbored an indistinguishable 100-kb mosaic plasmid (reppRE25 plus reppCF10) containing the whole Tn1546 backbone. The results indicate a current intra- and international spread of E. faecium and E. faecalis clones and their plasmids among swine and humans.

Clinical and Epidemiological Aspects of Invasive Streptococcus pyogenes Infections in Denmark during 2003 and 2004

ABSTRACT Active surveillance of invasive group A streptococcal (GAS) infections was conducted in Denmark during 2003 and 2004 as a part of the Strep-EURO initiative. The main objective was to improve understanding of the epidemiology of invasive GAS disease in Denmark. During the 2 years, 278 cases were reported, corresponding to a mean annual incidence of 2.6 cases per 100,000 inhabitants. The vast majority of isolates, 253 (91%), were from blood, with the remaining 25 (9%) being from cerebrospinal fluid, joints, or other normally sterile sites. The mean case fatality rate (CFR) was 20%, with the rate being higher in patients more than 70 years of age (36.5%). For streptococcal toxic shock syndrome (STSS) and necrotizing fasciitis the CFRs were 53% and 25%, respectively. Out of 16 T types recorded, three predominated: T28 (23%), T1 (22%), and the cluster T3/13/B3264 (14%). Among 29 different emm types, emm28 and emm1 accounted for 51% of strains, followed by emm3 (11%), emm89 (7%), and emm12 (5.5%). Low resistance rates were detected for macrolide-lincosamide-streptogramin B (MLSB) antibiotics (3%) and tetracycline (8%); two isolates exhibited coresistance to tetracycline and macrolides. Of nine pyrogenic exotoxin (superantigen) genes examined, speA and speC were identified in 58% and 40% of the strains, respectively; either of the genes was present in all strains causing STSS. Most strains harbored speG (99%). ssa was present in 14% of the isolates only. In Denmark, as in comparable countries, GAS invasive disease shows a sustained, high endemicity, with involvement of both established and emerging streptococcal emm and T types.

Enterococci of animal origin and their significance for public health

Enterococci are commensal bacteria in the intestines of humans and animals, but also cause infections in humans. Most often, Enterococcus faecium isolates from clinical outbreaks belong to different types than E. faecium from animals, food, and humans in the community. The same variants of the vanA gene cluster (Tn1546) encoding vancomycin resistance can be detected in enterococci of both human and animal origin. This could indicate horizontal transfer of Tn1546 between enterococci of different origin. E. faecium isolates of animal origin might not constitute a human hazard in themselves, but they could act as donors of antimicrobial resistance genes for other pathogenic enterococci. Enterococcus faecalis of animal origin seems to be a human hazard, as the same types can be detected in E. faecalis from animals, meat, faecal samples from humans in the community, and patients with bloodstream infections.

Human Health Hazard from Antimicrobial-Resistant Enterococci in Animals and Food

The use of antimicrobial agents in the modern farm industry has created a reservoir of resistant bacteria in food animals. Foods of animal origin are often contaminated with enterococci that are likely to contribute resistance genes, virulence factors, or other properties to enterococci IN humans. The potential hazard to human health from antimicrobial-resistant enterococci in animals is questioned by some scientists because of evidence of host specificity of enterococci. Similarly, the occurrences of specific nosocomial clones of enterococci in hospitals have lead to the misconception that antimicrobial-resistant animal enterococci should be disregarded as a human health hazard. On the basis of review of the literature, we find that neither the results provided by molecular typing that classify enterococci as host-specific organisms nor the occurrence of specific nosocomial clones of enterococci provide reasons to change the current view that antimicrobial-resistant enterococci from animals pose a threat to human health. On the contrary, antimicrobial resistance genes appear to spread freely between enterococci from different reservoirs, irrespective of their apparent host association.

Escherichia coli Isolates from Broiler Chicken Meat, Broiler Chickens, Pork, and Pigs Share Phylogroups and Antimicrobial Resistance with Community-Dwelling Humans and Patients with Urinary Tract Infection

Escherichia coli is the most common cause of urinary tract infection (UTI). Phylogroup B2 and D isolates are associated with UTI. It has been proposed that E. coli causing UTI could have an animal origin. The objective of this study was to investigate the phylogroups and antimicrobial resistance, and their possible associations in E. coli isolates from patients with UTI, community-dwelling humans, broiler chicken meat, broiler chickens, pork, and pigs in Denmark. A total of 964 geographically and temporally matched E. coli isolates from UTI patients (n = 102), community-dwelling humans (n = 109), Danish (n = 197) and imported broiler chicken meat (n = 86), Danish broiler chickens (n = 138), Danish (n = 177) and imported pork (n = 10), and Danish pigs (n = 145) were tested for phylogroups (A, B1, B2, D, and nontypeable [NT] isolates) and antimicrobial susceptibility. Phylogroup A, B1, B2, D, and NT isolates were detected among all groups of isolates except for imported pork isolates. Antimicrobial resistance to three (for B2 isolates) or five antimicrobial agents (for A, B1, D, and NT isolates) was shared among isolates regardless of origin. Using cluster analysis to investigate antimicrobial resistance data, we found that UTI isolates always grouped with isolates from meat and/or animals. We detected B2 and D isolates, that are associated to UTI, among isolates from broiler chicken meat, broiler chickens, pork, and pigs. Although B2 isolates were found in low prevalences in animals and meat, these sources could still pose a risk for acquiring uropathogenic E. coli. Further, E. coli from animals and meat were very similar to UTI isolates with respect to their antimicrobial resistance phenotype. Thus, our study provides support for the hypothesis that a food animal and meat reservoir might exist for UTI-causing E. coli.