<UL> <LI> To assess at the national level the farm prevalence of fluoroquinolone resistant Campylobacter and E. coli in pigs and poultry on-farm under different production systems. <LI> To try and identify risk factors associated with fluoroquinolone resistance. <LI> To characterise selected resistant organisms from the surveys in terms of the proportion of the population in the sample they represent, relatedness to strains infecting humans and ability to be selected for or withstand disinfectants.<LI> Produce draft guidance pamphlets for veterinarians and farming company livestock managers on the optimum use of fluoroquinolones to reduce the problem of antimicrobial resistance.
Final report summary: Fluoroquinolones (FQ) are an important class of antimicrobial drugs available to treat human infections. This class is effective against a wide range of human diseases and is used in both treatment and prophylaxis of bacterial infections. <P>
Fluoroquinolones have been particularly important in the treatment of foodborne infections often resistant to other antimicrobials. The introduction of quinolone and fluoroquinolone antimicrobials for use in food animals has been followed by a rise in first stage resistance to the quinolone antimicrobial nalidixic acid. There is concern that use of fluoroquinolone antimicrobials in food animals may lead to fluoroquinolone resistance in bacteria causing foodborne infections in man, resulting in failure of antimicrobial therapy in man. <P>
The main objectives of this project, as stated in the CSG7, were as follows:
<OL> <LI> To assess at the national level the farm prevalence of fluoroquinolone resistant Campylobacter and E. coli in pigs and poultry on-farm under different production systems.
<LI> To identify risk factors associated with fluoroquinolone resistance.
<LI> To carry out work on selected samples and E.coli or Campylobacter isolates:
<uL> <LI>to assess the proportion of the total population of organisms in the sample that they represent;
<LI>to evaluate disinfectant resistance and effect of exposure to disinfectants on fluoroquinolone resistance, and selection of resistant organisms, and;
<LI>to further characterise organisms to identify molecular mechanisms of resistance and similarity to those involved in human disease. </ul>
<LI>To produce draft guidance pamphlets for veterinarians and farming company livestock managers on the optimum use of fluoroquinolones to reduce the problem of antimicrobial resistance. </ol>
Summary of work and findings :
The work carried out, and the findings, in relation to each objective, are as summarised below. <P>
Objective 01 <BR>
To estimate the proportion of farms on which near-to-slaughter poultry or pigs are shedding fluoroquinolone-resistant bacteria in their faeces a sample of farms was identified and then farm-level sampling was carried out in order to classify each farm as either ‘positive’ (shedding animals detected) or ‘negative’ (shedding animals not detected). Randomly selected, pooled, freshly passed faeces were collected from near-to-slaughter animals on 89 poultry farms and 108 pig farms for isolation of fluoroquinolone-resistant E.coli and Campylobacter. Measured aliquots were plated directly onto Chromagar ECC (for isolation of E.coli) and BASAC (for isolation of Campylobacter) each containing 1mg/l ciprofloxacin. Enrichment cultures in buffered peptone water (for E.coli) and Exeter's broth (for Campylobacter) were plated onto the same media.
Briefly, the survey indicated that: <BR>
• faecal shedding of FQ-resistant E.coli occurred on over half of all poultry and pig farms (around 60%); <BR>
• faecal shedding of FQ-resistant Campylobacter occurred on about a quarter of all poultry farms (around 22%);
<BR> • faecal shedding of FQ-resistant Campylobacter occurred on about three quarters of all pig farms (around 75%); <BR>
• the proportion of turkey farms on which faecal shedding of FQ-resistant organisms occurred was about twice the proportion of broiler farms. <BR> <BR>
Objective 02 <BR>
To provide information on possible risk factors, data about husbandry practices, performance, disease and drug use were collected using detailed questionnaires. The analysis showed that use of FQ is by far the most important factor influencing occurrence of FQ-resistant bacteria on farms, and it seems hard for farmers to avoid resistance when FQ are used. It needs to be stressed that the organisms studied are commensal organisms in these animals and resistance in these is not necessarily associated with loss of therapeutic effect of FQ. <BR> <BR>
Resistant organisms can also be spread from farm to farm, which means that FQ-resistant bacteria can be found on farms where FQ are never used. The factors affecting this spread are the same factors as would be associated with biosecurity and prevention of disease caused by any bacterial agent. However, there are slight differences in the importance of various factors between the two organisms, E.coli and Campylobacter.
The results of the survey suggest that Campylobacters need a living carrier, being carried as commensals in guts of live animals (wild birds into poultry houses or bought-in pigs into pig farms). Nevertheless, introduction of FQ-resistant Campylobacter to a poultry flock, that would be uncontaminated when coming on farm would perhaps be most likely by repeated entrance of staff, for example thinning crews, with dirty boots, or recently contaminated clothing.
In comparison, E.coli are more robust and may be transferred by any sort of fomites (animals’ feet, truck tyres etc.), therefore barrier biosecurity measures are important (fences, separation from other farms, staff hygiene and requirements for visitors). In particular, E.coli can survive routine cleaning and disinfection so this must be of a high standard to reduce the persistence of resistant organisms on the farm. <BR> <BR>
Objective 03 <BR>
Early in the project, the potential for dissemination and persistence of fluoroquinolone-resistant organisms within two integrated companies was studied. The finding of simultaneous distribution and persistence of numerous strains of fluoroquinolone-resistant E.coli, most of which were also multiresistant, suggested a complex multi-factorial problem which would merit more detailed epidemiological investigations.
Work on 23 pig and 23 poultry samples containing fluoroquinolone-resistant E.coli from the cross-sectional study indicated a wide range of proportions of resistant E.coli (ranging from 0.00045% to 52.9%) in ‘positive’ faeces samples. The proportion of FQ-resistant Campylobacter in 19 pig samples containing fluoroquinolone-resistant Campylobacter showed a wide range both within and between farms from <10% up to 100% of the total Campylobacter population.
Work on disinfectant resistance suggested that ciprofloxacin-resistant and ciprofloxacin-sensitive strains of E.coli have similar susceptibility to disinfectants. Work on the effect of exposure to disinfectants on fluoroquinolone resistance, and selection of resistant organisms suggest that exposure of E.coli to three unrelated classes of disinfectants can lead to increased selection of strains with the MAR phenotype and/or with reduced susceptibility to ciprofloxacin. <BR> <BR>
Among 235 ciprofloxacin-resistant E.coli tested, 53 different serotypes and 65 untypable strains were identified. Differences were found both between and within farms. All resistant Campylobacter and E.coli isolates tested had MICs >2mg/l (and the majority >8mg/l) and possessed mutations previously identified with fluoroquinolone resistance. A high percentage of Cip-resistant isolates, both E.coli and Campylobacter, were also resistant to other antibiotics.
It proved not possible to perform comparisons with isolates of E. coli from human cases. <BR> <BR>
Objective 04 <BR>
Based on the results of this project, advice to farmers can be summed up as:
<OL> <LI> avoid using fluoroquinolones by maintaining a clean and healthy farm environment
<LI> prevent entry of resistant bacteria with strong biosecurity measures
<LI> prevent carry-over of resistant bacteria by applying very high standards of farm hygiene and cleaning and disinfection </ol>
Relevance of these results to public health:
The survey detected FQ-resistant bacteria in animal faeces from high proportions of farms. The survey was not designed to estimate the proportion of animals going to slaughter which harbour FQ-resistant bacteria. This proportion depends also on the proportions of animals within a farm that harbour FQ-resistant bacteria. The probability that consumers may be exposed to FQ-resistant bacteria through contamination of carcases is further dependent upon other factors, including the proportion of the bacterial population that is resistant. Results from this survey show that this proportion can be very small, e.g. less than 1%. Further epidemiological studies, linked to risk modelling, would be required to fully assess the potential risk to public health posed by fluoroquinolone-resistant organisms of food animal origin.