Table 2 Examples of studies evaluating the emergence of resistance in foodborne pathogens after food producing animals were exposed to antimicrobial drugs

[46]

RCT

broiler chicken

Campylobacter experimental infection with 5 susceptible strains on day 16 or 24 of life

fluoroquinolones enrofloxacin, sarafloxacin, ciprofloxacin; treated for 5 days, starting on day 30 of life

drinking water

emergence of resistance

2 groups; 25 or 50 chicks per group (half treated)

Phenotypic agar dilution

negative controls

resistance emerged rapidly in isolates from treated birds and, for birds treated with enrofloxacin, resistance was retained throughout the sampling period; resistance remained low in untreated controls throughout the study

[47]

RCT

pigs

Salmonella Typhimurium DT104; native E. coli population monitored; experimental infection with 5 strains isolated from apparently healthy pigs (pentaresistant phenotype)

aureomycin, standard or subtherapeutic dose, treated for 7 days starting 48 h after inoculation

feed

emergence of resistance

3 groups; 6 pigs per group

Phenotypic agar dilution

negative controls

resistance emerged in native E. coli populations from treated animals and increased resistance persisted for 2 weeks after treatment; treated pigs shed higher numbers of Salmonella Typhimurium DT104 than untreated pigs.

[48]

RCT

pigs

Salmonella Typhimurium; native E. coli population;

experimental challenge of piglets 2 days after weaning

aparamycin in different dosing schemes, in some cases followed by sulfamethazine and carbadox or gentamicin and neomycin; treatment initiated 7 days after infection, for 14 days

feed or drinking water

emergence of resistance

2 trials; 6 groups of 8 pigs each

Phenotypic dilution test

negative controls

resistance of Salmonella isolates was not impacted by treatment regimen; resistance emerged in native E. coli populations and was effected by treatment regimen; use of similar antibiotics in rotation resulted in greater resistance than if dissimilar antibiotics were used

[49]

CT

broiler chicken

Campylobacter; experimental infection with susceptible strain on day 19 of life

fluoroquinolones: enrofloxacin or flumequine in different concentrations; treated for 4 days, beginning 7 days after infection (or on day 1 of the experiment for one group)

drinking water

emergence of resistance

8 groups; 15 chicks per group

Phenotypic disc diffusion

negative controls

resistance emerged in Campylobacter isolates from enrofloxacin treated birds (isolates from all other groups remained susceptible)

[50]

CT

beef cattle

Campylobacter; naturally occurring bacterial populations

chlortetracycline with or without

sulfamethazine; virginiamycin; monensin; or tylosin; treated for 56 days, starting 18 days after arrival at feedlot; antimicrobials removed for 91 days, reintroduced for 42 days

feed

emergence of resistance

30 groups; 10 steers per group

Phenotypic agar dilution

negative controls

administration of antimicrobial drugs increased the carriage rate for resistant isolates, but results differed by antimicrobial drug and Campylobacter species

[51]

RCT

pigs

Salmonella Typhimurium with nalidixic acid resistance; native E. coli population; experimental challenge of piglets (from treated or untreated sows)

oxytetracycline, aparamycin; sows treated prior to farrowing

feed

emergence of resistance (in piglets after treatment of sows)

3 groups of pigs

Phenotypic dilution test Genotypic PCR-based

negative controls

Exposure of sows to oxytetracycline associated with increased resistance in bacterial isolates from pigs

[52]

RCT

Pigs

Campylobacter; naturally occurring populations

enrofloxacin; treated with standard therapeutic dose for 5 days

per os

emergence of resistance

2 groups of pigs; 6 pigs per group

Phenotypic agar dilution

negative controls

exposure to enrofloxacin resulted in Campylobacter isolates resistant to nalidixic acid and ciprofloxacin (no quinolone resistance detected prior to antibiotic exposure); resistant isolates detected for up to 35 days

[53]

RCT

Pigs

Salmonella Typhimurium; experimental challenge with marked strain containing nalidixic acid resistance marker

ceftiofur, aparamycin, or carbadox, followed by oxytetracycline; Treated starting 2 days post inoculation

feed (i.m. for ceftiofur)

emergence of resistance

4 groups of pigs; 12 pigs per group

Phenotypic Disc diffusion

negative controls

frequency of antimicrobial resistance varied over time – resistance was lowest on day 4 post inoculation but increased steadily afterwards and was highest on the last day of sampling; continued increase of select antimicrobial resistance after exposure was discontinued

[54]

Cohort period: 2000–2001

dairy cattle

Salmonella

various used on conventional farms

n/a

antimicrobial resistance levels

95 farms: 26 organic and 69 conventional

Phenotypic broth dilution

organic vs. conventional

results differed by antibiotic; for most antimicrobial drugs, resistance levels were not significantly different; resistance to streptomycin and sulfamethoxazole was greater on conventional farms.

[55]

CS

dairy cattle

Campylobacter

various used on conventional farms

n/a

antimicrobial resistance levels

60 farms: 30 organic and 30 neighboring conventional

Phenotypic disk diffusion

organic vs. conventional

no statistically significant difference in resistance rates for organic vs. neighboring conventional dairy herds

[56]

CS

broiler chicken and turkey

Campylobacter

various used on conventional farms (gentamicin, lincomycin, bacitracin, virginiamycin, etc.)

feed and water

antimicrobial resistance levels

30 farms: 10 organic, 20 conventional

Phenotypic agar dilution

organic vs. conventional

antimicrobial resistance rates were significantly higher in isolates from conventional than organic farms, and conventional isolates were significantly more likely to be multi-drug resistant; resistance levels varied across antimicrobial drugs

[57]

Longitudinal study

broiler chicken

Campylobacter

fluoroquinolones; difloxacin or enroflaxcin; treatment for 5 days to treat clinically relevant infection; bacterial samples taken before, during and after treatment of flocks

drinking water

prevalence of antimicrobial resistance

5 commercial flocks

Phenotypic

agar dilution Genotypic PCR-based

resistance before, during and after treatment

prevalence of resistant strains increased during treatment and remained elevated after treatment

[58]

bacterial samples at slaughter

broiler chicken

Campylobacter

various used on conventional farms

various

prevalence of antimicrobial resistance at slaughter

n = 600 ceacal samples from chicken

Phenotypic dilution method

resistance levels at slaughter as a function of production type and antimicrobial use history

antimicrobial resistance levels differed significantly by production type and antimicrobial administration history

[59]

bacterial samples of retail meats

Chicken meat

Campylobacter

fluoroquinolone

presumably water

Prevalence of resistance

5 producers, meats sampled at retail for 20 consecutive weeks in 2004 and 15 consecutive weeks in 2006

Phenotypic

NAE vs. conventional

No statistically significant difference in fluoroquinolone resistance levels after use was reportedly discontinued (no sample collection or validation at the farm or producer level)

[60]

bacterial samples

chicken and turkey meat; healthy human volunteers

Enterococci; VanA-type vancomycin resistant (VRE)

avoparcin use for growth promotion phased out during study period

various

levels of VRE prevalence

convenience samples

N/A

VRE carrier rates before and after the ban

VRE detection in poultry meat and intestinal bacteria of healthy volunteers decreased after the ban

[61]

bacterial samples

humans and poultry products

Campylobacter

fluroquinolones

n/a

prevalence of resistance

convenience sample, collected from 1982 to 1989

Phenotypic disk diffusion

prevalence of resistance over time

prevalence of quinolone resistance increased from 0 to 14% in poultry products and from 0 to 11% in human samples

[62]

bacterial samples at slaughter

broiler chicken

Campylobacter

various used on conventional farms; 1992–1996 time period falls before ban for antibiotic growth promoters, 2001–2002 period does not

various

prevalence of antimicrobial resistance at slaughter

22 flocks; 10 chickens per flock

Phenotypic agar dilution

resistance levels at slaughter as a function of production type (free-range or standard) and study period

antimicrobial resistance was more likely in isolates from standard than free-range chicken, differed by Campylobacter strain, and for many antimicrobial drugs and strains resistance increased over time

[63]

correlation study

isolates from chicken meat and humans

Salmonella Heidelberg, ceftiofur resistant commensal E. coli

2003–2008

n/a

prevalence of ceftiofur-resistance in bacterial isolates from chicken meat and human cases

Correlation across provinces and time periods

Phenotypic broth dilution

Resistance levels before, during, and after a voluntary discontinuation of ceftiofur use in hatcheries in Quebec

Statistically significant correlation between prevalence of ceftiofur-resistant Salmonella Heidelberg on retail chicken and human infections; in Quebec, levels of ceftiofur use in hatcheries during study period seemed correlated with ceftiofur resistance in chicken Salmonella and E. coli isolates.

[64]

Longitudinal study

pigs

Enterococcus faecium

tylosin; resistance to erythromycin, spiramycin, clindamycin, penicillin, tetracycline, chloramphenicol, streptomycin, gentamycin

feed

prevalence of antimicrobial resistance

16 farms; 13 farms were examined again 183 to 287 days later

Phenotypic disk diffusion

resistance before and after the ban of tylosin as a growth promoter

Resistance to macrolides, lincosamides and tetracyclines decreased after the use of tylosin for growth promotion was banned.