JAC Advance Access originally published online on August 12, 2004
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Journal of Antimicrobial Chemotherapy 2004 54(3):693-694; doi:10.1093/jac/dkh400
JAC vol.54 no.3 © The British Society for Antimicrobial Chemotherapy 2004; all rights reserved.
Correspondence |
Reply
1 Division of Farm Animal Science, Department of Clinical Veterinary Science, University of Bristol, Langford BS40 5DU; 2 Department of Food and Environmental Safety, Veterinary Laboratories Agency (Weybridge), Woodham Lane, Addlestone, Surrey KT13 3NB, UK
Keywords: food safety , enrofloxacin , resistance , zoonotic , pig model
Silley & Froyman1 have raised a number of issues regarding our study2 into the effect of enrofloxacin treatment on S. Typhimurium in a pig model. Many of these issues are misunderstandings due to the presentation of data in graphical rather than tabular form. It should be pointed out that the paper was provisionally accepted after peer review with the suggestion that the paper be reduced in scale to a brief report. Whilst every effort was made to retain all relevant data in the paper, it is possible that brevity and exclusion of certain information from the full paper may have contributed to the issues raised.
In their first comment, Silley & Froyman have misquoted a sentence and taken it out of context: "Treated pigs inoculated with cyclohexane-resistant S. Typhimurium DT104 (group 2) and treated pigs inoculated with gyrA mutant S. Typhimurium DT104 (group 3) consistently shed higher numbers than the untreated pigs from their respective control groups (P<0.01 for both)". Silley & Froyman argue this "cannot be true" but state this without any statistical validation. In the publication, the very next sentence explains by how much and how long the pigs treated with enrofloxacin (Baytril, Bayer) were shedding higher numbers of S. Typhimurium: 100-fold for 2 weeks in group 2 (for day 14, the exact values have already been given to Dr P. Silley in a personal communication confirming the accuracy of the statement) and 10-fold for 2 weeks post-treatment in group 3. In addition, the graphs show clearly the period during which the treated pigs were shedding higher levels of salmonella than the untreated pigs. Thus we contend that the data are sound and we have reported the facts accurately, and these have been analysed appropriately.
Silley & Froyman suggest that our conclusion that "our study has provided direct evidence that enrofloxacin-treated pigs could be entering abattoirs with higher numbers of quinolone-resistant zoonotic bacteria than untreated pigs" cannot be supported by our data. They suggest that we have overlooked three issues: (1) the levels of S. Typhimurium colonization at the end of the study period did not appear to differ between controls and treated animals; (2) the age of the animals was not relevant to the age at slaughter; (3) the endogenous gut flora of the pigs was not as mature as it would be at the commercial slaughter age.
These issues are, in our view, spurious. Our study investigated the effect of enrofloxacin treatment on organisms that possessed mechanisms of resistance to quinolones, namely gyrA and multiple antibiotic resistance (MAR) in a pig model. Our data are irrefutable that on and after treatment these mutants were present in significantly higher numbers in treated pigs than untreated pigs. Our main conclusion is that the use of enrofloxacin in the pig increases the number of resistant bacteria beyond the current withdrawal time and in turn increases the risk of these moving up the food chain. This point was clearly stated in the first paragraph of the discussion.
Antibiotics are powerful selective agents and we contend that the effect we observed in the model system employed in this study may apply equally at other ages. It is difficult to see how an altered flora or more mature flora would obviate the powerful selective effects of the antibiotic. Indeed, in Silley & Froyman's discussion, not a single reference relates to the response of the native flora in pigs to antibiotic treatment and thus it is likely that the issues raised are speculative, if not unfounded. The Bel
il et al.3 paper comments on the serological response to Salmonella enterica in growing pigs, whilst the Katouli et al.4 paper specifically deals with the role of zinc oxide on stabilizing the gut flora of pig and states "there was a significant increase in both variety (P=0.019) and diversity (P
0.001) of coliforms in control pigs compared with the ZnO treated group". We question the relevance of these studies on Salmonella strains that are resistant to quinolones in the pig when subjected to selective pressure. If Silley & Froyman are questioning the presence of quinolone-resistant salmonella in pigs at slaughter, it should be pointed out that the prevalence of quinolone resistance in salmonellas from pigs in the UK is currently running at 19.8% (VLA, Salmonella reference laboratory, 2002).
We do not attempt to simplify the complexities of the gut flora dynamics in pigs of differing ages under differing dietary regimes but we contend that the data are unequivocal regarding the positive selective pressure mediated by the use of antibiotics. We have demonstrated that enrofloxacin positively selects for gyrA and MAR salmonella, and importantly that this effect outlasts the withdrawal time currently employed by the industry. Therefore, treatment with enrofloxacin increases the risk of resistant salmonellas moving up the food chain. We argue that the withdrawal time should reflect the hazard posed by resistant bacteria to meat safety, and in the case of enrofloxacin our data indicate this withdrawal time should be increased.
Footnotes
* Corresponding author. Tel: +44-117-928-9478; Email: a.a.g.delsol{at}bris.ac.uk
References
1 . Silley, P. & Froyman, R. (2004). Comment on: Effect of a 5 day enrofloxacin treatment on Salmonella enterica serotype Typhimurium DT104 in the pig. Journal of Antimicrobial Chemotherapy 54, DOI: 10.1093/jac/dkh370.
2
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Delsol, A. A., Woodward, M. J. & Roe, J. M. (2004). Effect of a 5 day enrofloxacin treatment on Salmonella enterica serotype Typhimurium DT104 in the pig. Journal of Antimicrobial Chemotherapy 53, 396–8.
3
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Belil, P. A., Chauvin, C., Proux, K. et al. (2003). Longitudinal serological responses to Salmonella enterica of growing pigs in a subclinically infected herd. Preventive Veterinary Medicine 60, 207–26.[Medline]
4 . Katouli, M., Melin, L., Jensen-Waern, M. et al. (1999). The effect of zinc oxide supplementation on the stability of the intestinal flora with special reference to composition of coliforms in weaned pigs. Journal of Applied Microbiology 87, 564–73.[CrossRef][Medline]
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