Reduction of human exposure to resistant micro-organisms: a Pragmatic approach - the RedRes-study

Intensively reared farm animals (veal calves, pigs and poultry) form a
reservoir for antimicrobial resistant bacteria and antimicrobial resistance
genes. Antimicrobial use is generally regarded as one of the main reasons for
the selection and spread of resistant bacteria. In order to reduce the
prevalence of resistant bacteria in farm animals, and thus to reduce this
public health threat, interventions should be implemented at farm level and
should be aimed at reduction of antimicrobial use, improving hygiene, and
changing animal contact structure. It is hypothesized that these measures will
limit transmission of antimicrobial resistant organisms between different
compartments, similar to infection control measures in (human) health care
settings, and subsequently will result in a significantly reduced prevalence of
resistant bacteria on farms. So far, no research has been done on the possible
effect of these potential intervention measures. Therefore, it is unclear what
the quantitative effect of possible intervention measures is on the level of
antimicrobial resistance on the farm, both in animals and in humans. In order
to create an adequate and effective control and intervention protocol for
antimicrobial resistance, this quantitative knowledge is essential.

Primary objectives:

1. To determine the effect of the use of a tailored intervention protocol
(regarding reduced antimicrobial use, improving hygiene and changing the animal
contact structure) on pig and veal farms on the degree of antimicrobial
resistance and the prevalence over time of MRSA, ESBLs and CD in people working
and/or living on these farms.

2. To determine the effect of the use of a tailored intervention protocol
(regarding reduced antimicrobial use, improving hygiene and changing the animal
contact structure) on pig and veal farms on the degree of antimicrobial
resistance and the prevalence over time of MRSA, ESBLs and CD in animals on
these farms.

3. To determine the effect of the use of a tailored intervention protocol
(regarding reduced antimicrobial use, improving hygiene and changing the animal
contact structure) on pig and veal farms on the degree of antimicrobial
resistance and the prevalence of MRSA, ESBLs and CD in the stables and living
environment.


Secondary objectives:

1. To determine the prevalence of LA-MRSA in pigs and veal calves as well as in
humans at the beginning of the study using nose swabs.

2. To determine the prevalence of ESBLs, CD and the degree of antimicrobial
resistance in pigs and veal calves as well as in humans at the beginning of the
study by using faecal samples.

3.To determine the prevalence of LA-MRSA, ESBLs, CD and the degree of
antimicrobial resistance in the stables and living environment at the beginning
of the study using electrostatic dust cloths.

4. To describe associations between antimicrobial resistance in animals and
antimicrobial resistance in humans by means of (dynamic mathematical) modelling.

5. To predict antimicrobial resistance throughout the pig- and veal production
chain under different intervention scenarios.

We will perform a pragmatic intervention study which makes use of repeated
measurements to determine the effect of a reduction in antimicrobial use on 40
pig farms and 51 veal farms on the level of antimicrobial resistance in humans
and animals on these farms. This reduction in antimicrobial use will be
indirectly achieved by influencing animal contact structure and hygiene
protocols, and directly by reducing antimicrobial use.
The farms and the individual participants will be monitored during 18 months.
There will be 4 sampling moments. At each sampling moment a nasal swab and a
faecal sample will be taken by all the participants themselves. Also, at each
sampling moment a questionnaire will be filled out by the participants. MRSA
will be determined in the nasal swabs and ESBLs, CD, and the degree of
antimicrobial resistance will be determined in the faecal samples.

In this study, interventions on reduced antimicrobial use, improved hygiene and
changed animal contact structures will take place at farm level and therefore
in the animals.

Participation in the study does not take much time and there will be no
invasive procedures used. In a study period of 18 months there will be 4
sampling moments. At each sampling moment a nasal swabs and a faecal sample
will be taken by all the participants themselves, which should not be
considered to be much discomfort to the participants. Also, at each sampling
moment a questionnaire will be filled out by the participants. The risks of
participation in this study can be considered negligible and the burden can be
considered minimal. To estimate prevalence within one household, it is
necessary that all household members and employees of the included pig and veal
farmers (inclusive minors and incapacitated individuals) will be examined for
colonization of MRSA, the degree of antimicrobial resistance and the occurrence
of ESBLs and CD.