Development and transfer of resistance to coccidiostats in bacteria
The number of scientific publications on the effect of ionophores on the development of antimicrobial resistance is small for lasalocid and maduramicin, and lacking for
semduramicin. More data is available for narasin, monensin and salinomycin. Since narasin and monensin are used in Norwegian poultry farming the panel considers the scientific basis strong enough to conclude that anti-microbial resistance is induced by ionophores in
conditions found in Norway.
The panel has chosen to consider it likely that horizontal transfer of resistance against coccidiostats may occur since transfer of a large variety of other antibacterial resistance genes is known to occur in bacteria. However, only one scientific study describes such transfer, reporting horizontal transfer of resistance against narasin in vitro. Furthermore, as none of the a coccidiostat resistance genes have been described in scientific literature, it is not known to which degree these genes are located on tansferrable gene
elements.Consequently the frequency of such gene transfer is not known.
Cross- or co-resistance between coccidiostats and other antimicrobials in bacteria A statistical association was found between resistance against narasin and bacitracin, and between narasin and vancomycin. In addition, two publications report laboratory studies that may support these data; one studying narasin resistance and vancomycin resistance and enterococci, and one studying lasalocid resistance and bacitracin resistance in Clostridium aminophilum. However, the amount of data is very limited, and the level of uncertainty is high. More studies are needed before any firm conclusions can be drawn, and especially the characterization of resistance gene(s) against narasin would elucidate a possible link
between resistance against narasin and resistance against bacitracin or vancomycin in enterococci.
Probability of increased use of therapeutic antibacterials in poultry production under current production practices if coccidiostats with antibacterial effects are replaced by coccidiostats without such effects, or replaced by anticoccidial vaccines
The conclusion that this probability is high is based on the assumption that other
predisposing factors for necrotic enteritis than coccidiosis are important and prevalent in the broiler environment. Our knowledge about the relative importance of coccidia and other predisposing factors for necrotic enteritis is limited. Although this risk is high, the degree of increase in use of therapeutic antibacterials is uncertain as data on this is limited. Also, if the
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use of therapeutic antibacterials increases significantly, other management changes are likely to be implemented in the field in order to counteract such a development.
Human exposure to coccidiostat resistant bacteria
Estimation of probability levels of exposure to resistant bacteria are based on data from the Norwegian surveillance program NORM-VET. Concerning data from faeces of live animals, the sampling unit of concern is flock. The Panel has assumed that the prevalence of positive farms equels that of positive flocks. In addition, there may have been relatively large
differences between the age of the chicken flocks at the time of sampling, and sampling procedures have been changed over the years; all adding to the uncertainty of the estimated prevalences.
Furthermore, the estimated prevalences of resistant bacteria, both in faeces and on raw meat, are based on investigations on two species of bacteria only, i.e. E. faecium and E faecalis. There are no surveillance data on prevalences in other bacterial species of the normal microbiota of poultry. Thus, the prevalences of may be underestimated.
Probability of human exposure and resistance development among endogenous microbiota of workers and consumers exposed to coccidiostats
Real life exposure probabilities in humans handling coccidiostats (feed mill workers, farmers etc.) has not been quantified because such exposure will to a large extent depend on the use of protective measures. The Panel does not have information on the actual use of protective measures. Therefore the probabilities are given according to a worst case scenario. In real life where people are likely to use some kind of protective measures the probabilities will be lower. Without such measures, absorption across the skin and mucous membranes of the respiratory tract may occur, but the subsequent risk to development of antibacterial resistant strains of bacteria among endogenous bacterial populations is not known.
Nor have the consequences of intermittent, low level exposure of coccidiostats by consumers at or somewhat above MRLs in poultry products for development of antibacterial resistant strains of bacteria among endogenous populations been investigated. The temperature stability of various coccidiostats merit documentation as well, as does the ability of
denaturation products following heat treatment to induce the development of antibacterial resistant strains of bacteria in consumers.
These uncertainties do not allow the Panel to conclude more specifically regarding the probabilities and risks of human coccidiostat exposure among workers or consumers with subsequent resistance development among their respective endogenous microbiota.
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Probability of exposure of coccidiostats for workers handling poultry manure Several studies confirm residual coccidiostats in poultry exctreta and manure. The concentration levels depend on numbers of factors; e.g. the age and treatment of the manure, the properties of the substances and the environmental conditions. The risk for exposure of workers handling manure is higher in contact with fresh or short-time stored manure than composted manure. A study performed by Ghent University on request by EFSA gives a reliable indication of the residue levels which is expected to find in excreta and
manure during storage, composting and transfer to certain crops of the studied coccidiostats.
However, due to differences in practical apects and the high variation in disappearence fate, the concentration levels the workers might be exposed for can be either lower or higher than observed in this study. The challenge of sampling of non-homogenous matrix, such as
manure, might influence the results, and should be considered during interpretation of data.
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