Table 6 Examples of study types evaluating the human health risk posed by antimicrobial resistance genes that emerged in animal pathogens or commensal bacteria
Reference | Study | Key findings relevant to antimicrobial resistance | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|
Typea | subjects | country | time period | bacterial target | relevant study outcomes | sample size | controls | comments | ||
GRADE level: Controlled trial | ||||||||||
Not available | ||||||||||
GRADE level: observational study | ||||||||||
[100] | CC | poultry workers | Nigeria | published in 1989 | E. coli, nalidixic acid resistant | colonization of poultry workers with challenge E. coli strain | Complex study design: - Birds were experimentally inoculated with challenge strain of E. coli (n = 36 birds on university farm, and n = 16 on commercial farm) - Poultry works in direct contact with challenged birds were sampled for colonization with challenge strain - This was compared to control workers with or without direct contact to control birds, and to samples collected from the exposed workers prior to exposure - birds were sampled for colonization | after birds were challenged, the poultry workers in direct contact with challenged birds were colonized; results were similar on the university and commercial farm | ||
[101] | CC | poultry farmers | U.S. | published in 1978 | aerobic bacterial cultures, tetracycline resistance | resistance in bacterial microflora of chicken and contact farmers | Complex study design: - RCT of chicken, n = 50 chicken per group, test chicken were exposed to tetracycline in feed, controls were not; emergence of resistance was tested in commensal bacteria - farm family in contact with chicken was tested for emergence of resistance in background microflora - farm family was compared to other farm families in proximity, and to medical students | antimicrobial resistance emerged in exposed chicken and farm contacts | ||
[102] | cohort | poultry farmers | U.S. | published in 1976 | intestinal bacterial flora, tetracycline resistance | resistance in bacterial microflora of chicken and contact farmers | n = 11 farm members, 24 neighbors | neighbors | birds were exposed to tetracycline in feed, emergence of resistance was traced in birds and contact humans, and compared to neighbors | antimicrobial resistance emerged under exposure on the farm; the prevalence of antimicrobial resistance was higher in bacteria from exposed farm families than in neighbors; |
[103] | CS | pig farmers and abattoir workers | Netherlands | published in 1994 | E. coli | Prevalence of resistance | n = 290 pig farmers; n = 316 abattoir workers; n = 160 urban/suburban residents | urban/suburban residents | fecal E. coli from the three human groups were tested for resistance to multiple antimicrobial drugs | Pig farmers had the highest percentage of resistant E. coli, and urban/suburban residents had the lowest |
[104] | CC | turkey, broiler and layer farmers and slaughterers | Netherlands | published in 2001 | E. coli | Prevalence and degree of resistance | n = 47 turkey farmers and their flocks; n = 51 broiler farmers and n = 50 broiler flocks; 25 layer farmers and their flocks; n = 46 poultry slaughterers | comparison across human (and corresponding animal) populations; ciprofloxacin-resistant isolates were further subtyped; meat samples were collected immediately after slaughter | humans and birds sampled; antibiotic use on farms recorded | Prevalence of resistance significantly higher in turkey and broiler samples than laying hens (which correlated with antibiotic use); prevalence of resistance was higher in turkey and broiler farmers and slaughterers than in laying hen farmers; isolates from farmers/ slaughterers and birds / meat seemed to match, despite variability across farms |
GRADE level: other | ||||||||||
[63] | correlation study | isolates from chicken meat and humans | Canada | 2003–2008 | Salmonella Heidelberg, E. coli | Prevalence of ceftiofur-resistance in chicken samples and human cases | Correlation across provinces and time periods | n/a | n/a | Statistically significant correlation between ceftiofur-resistant Salmonella Heidelberg on retail chicken and human infections; in Quebec, changing levels of ceftiofur use in hatcheries during study period seemed to impact dynamics from before voluntary withdrawal to reintroduction. |
[105] | uncontrolled transmission study | farmers, livestock and environment | U.S. | published in 1990 | E. coli | Spread of resistant bacteria on farm; emergence of resistance | 2 trials with n = 2 cattle each; n = 4 pigs, n = 5 mice per cage; bovine experiments repeated in indoor / outdoor settings one challenged pig exchanged with one unchallenged pig from unchallenged pen | N/A; study monitored contact animals, mice in pens of challenged and non-challenged pig or cow, environment including flies, and human caretakers study also evaluated impact of chlortetracycline use on emergence of resistance | one pig and one cow were inoculated with marked strains of E. coli with resistance; contact animals (pigs or cows and mice) were sampled for the E. coli strain, as were human caretakers and the environment | Contact animals, mice, flies and caretakers excreted challenge strain of E. coli; length of colonization varied, but in several cases exceeded 4 weeks; E. coli strain was found in environment and housing system impacted spread; chlortetracycline use led to increased resistance; transfer of resistance plasmid to other bacteria not detected |
[106] | uncontrolled transmission study | Consumer handling chicken carcasses | US | published in 1977 | E. coli | spread of resistant bacteria from contaminated carcass to volunteer handling it | 1 trial | N/A | Â | Bacterial strain with antibiotic resistance transferred from chicken carcass to human volunteer handling it |
[107] | Conjugation study | Transfer of resistance genes among bacteria of different origin | Norway | Published in 1994 | E. coli as well as Vibrio, Aeromonas | Conjugation frequencies across bacteria and environmental settings | Conjugation was studied in multiple environments (e.g., seawater, hand towel, meat) | N/A | Â | Plasmids were readily transferred from one bacterium to another, across bacterial species and in a number of different environments |
[108] | Conjugation study | Transfer of resistance genes between Enterobacteriaceae | UK | Published in 2003 | Commensal E. coli, E. coil O157, Salmonella | Conjugation across bacterial species | Conjugation across a number of bacterial pairs was evaluated under conditions in the gut (i.e., ileum) | N/A | Â | Antibiotic resistance genes were readily transferred from one bacterial strain to another |
[109] | Conjugation study | Transfer of resistance genes among Enterococci in the mouse gut | France | Published in 2003 | Enterococcus faecium isolates from humans and pigs | Conjugation across Enterococci of different origin | In the gut of mice | N/A | mice were gnotobiotic (i.e. reared under conditions so that colonization with bacteria is fully known) | Vancomycin resistance was readily transferred from porcine to human isolates in the gut of mice; tylosin exposure (through drinking water) favored colonization due to conjugation. |
[110] | Conjugation study | Transfer of resistance genes between Enterococci strains | Sweden | Published in 2006 | Enterococci faecium of human and animal origin | Conjugation across Enterococci of different origin | In vitro and in the gut of mice | N/A | Mice were germ-free | Vancomycin resistance was readily transferred among Enterococci of different origin; conjugation frequency was higher in the mouse gut than in the environment; in most cases resistance disappeared within 3Â days but one of the bacterial strains persisted for more than 20Â days without antibiotic selection |
[111] | Conjugation study | Transfer of resistance genes in the gut of human volunteer | Denmark | Published in 2006 | Enterococcus faecium | Conjugation between Enterococcus faecium of chicken and human origin | n = 6 volunteers | n/a | In the gut of human volunteers | Resistance genes were readily transferred from chicken to human isolates in the gut of human volunteers; in one volunteer, additional resistance genes were transferred |
[112] | Conjugation study | Transfer of resistance from Klebsiella to E. coli in the mouse intestine | Denmark | Published in 2008 | Klebsiella and E. coli | Conjugation between Klebsiella and E. coli | In vitro and in the gut of mice | n/a | Some mice were exposed to antimicrobial treatment | Resistance genes were readily transferred in vitro and in vivo. Antimicrobial treatment selected for resistant strains, which rapidly disappeared in the guts of mice not exposed to antibiotics. |
[113] | uncontrolled transmission study | Calves and humans in contact with them | US | published in 1978 | E. coli | Spread of resistant bacteria from calves to human contacts, and impact of tetracycline exposure on risk | 1 trial repeated 3 times | N/A | calves were inoculated with rare E. coli strain carrying resistance genes | Bacteria were transferred from calves to human contacts; no statistically significant impact of tetracycline exposure on transmission risk; exposure of calves to tetracycline did not result in statistically significant differences in resistance levels of bacteria in human volunteers |
[114] | correlation study | Cattle and human contacts | Norway | 1996 | E. coli | Presence of drug-resistant E. coli in animals and human contacts | n = 13 cattle; n = 3 family members; n = 1 veterinarian (sampling of humans repeated after 1 year, and samples from 4 other veterinarians added) | N/A | study of concurrence of E. coli strains | Multi-drug resistant E. coli were found in the animals and human contacts. |
[115] | correlation study | Poultry farmers and their birds | Norway | 1998 | Enterococcus faecium (VRE) | Genetic relatedness of human and animal isolates | n = 5 farmers and n = 7 broiler chicken | N/A | study of concurrence of E. coli strains | On one of the farms, human and animal bacteria were genetically closely related; genetically unrelated strains shared related vancomycin resistance genes, suggesting HGT |
[116] | correlation study | farm families and their animals (i.e., cattle or swine) | US | Published in 1975 | E. coli | Genetic relatedness of human and animal isolates | n = 14 farm families | N/A | Farm families in Missouri; impact of factors such as animal contact | Frequency of animal contact was not significantly correlated with genetic relatedness of human and animal isolates; consumption of home-raised beef appears to be associated with concordance between human and animal isolates |
[118] | Conjugation study | Transfer of resistance genes from E.coli from pig to those from human gut | Denmark | 2007–2008 | E. coli | Conjugation between resistance genes among E.coli of pig and human origin | n = 9 human volunteers; | n/a | donor strain of E.coli from Danish pig; recipient strain E.coli of human origin | Transfer of resistance genes between E.coli bacteria in human intestine |
[119] | Conjugation study | Transfer of mobile genetic elements associated with MRSA | UK | Published in 2014 | Staphylococcus aureus bacterial populations | Frequency of horizontal gene transfer of pig and human origins | Gnotobiotic piglets | n/a | Co-colonization with human and pig associated variants of MRSA | High frequency of horizontal gene transfer; transfer of mobile genetic elements from pig to human within 4Â h of co-colonization |
[120] | Phylogenetic study | Presence of tetQ resistance gene in different bacteria | US | Published in 1994 | Bacteroides | Sequence comparison for tetQ resistance gene | n/a | n/a | Presence of identical or closely related resistance genes across distantly related bacteria | Virtually identical resistance genes found in different bacterial species and isolates of different geographic origin |