Investigation into the Effects of Zinc Oxide in Pig Starter Rations on the Persistence of Antibiotic Resistance28 May 2014
University of Guelph research reveals that high levels of zinc oxide in the diet of young pigs may be causing selective pressure for multidrug-resistant bacteria such as MRSA, delegates heard at the 33rd Centralia Swine Research Update in January 2014.
High levels of zinc oxide (ZnO) is commonly used as an alternative to antibiotics in the starter ration, Mackenzie J. Slifierz of the Department of Pathobiology told the conference. It is well documented that zinc oxide will inhibit enterotoxigenic E. coli and thus is useful in helping to control diarrhoea and therefore is widely used in the Ontario industry.
The action of zinc oxide as a therapeutic agent and its effect on the bacterial population of the gut is not well understood and needs further investigation. In addition, it has recently been demonstrated that some bacteria carry resistance to zinc. From a severe case of greasy pig disease in weaned pigs, the researchers have identified Staphylococcus hyicus carrying zinc resistance genes.
It appears that at least in the case of staphylococci, the genetic material that confers resistance to zinc is carried in combination with the genetic material associated with multidrug resistance including methicillin resistance.
It is possible that feeding high levels of zinc oxide in starter rations creates selective pressure so that multidrug resistant bacteria predominate, for example bacteria like methicillin-resistant Staphylococcus aureus (MRSA).
From a public health standpoint it is important we identify why drug resistance persists and spreads in the absence of antibiotics and therefore we should look at this possible link with zinc oxide. But also for the sake of pig health it is important that the value of antibiotics as therapeutic agents be preserved by minimizing the presence of multi-drug resistant bacteria on pig farms.
The objective of this study was to determine if a high level of in-feed zinc oxide is associated with increased prevalence of antibiotic-resistant staphylococci.
A randomised-controlled trial was completed using 110 pigs from 23 sows from a herd naturally colonized with czrC-positive MRSA.
The pigs were enrolled into the trial at birth (day 0) and followed for 49 days. At weaning (day 21), stratified randomisation was used to ensure pigs testing positive for MRSA prior to weaning were equally distributed among eight pens. The pens were located within the same nursery room, containing individual feeders and solid partitions.
Four pens (n=49 pigs) received a starter ration containing 100ppm zinc oxide and the remaining four pens (n=50 pigs) received an identical ration containing 3,000ppm zinc oxide. All pigs were raised without exposure to any other antimicrobial agents.
Nasal swabs were taken from each pig on days 1, 3, 7, 14, 21, 28, 35, 42 and 49. Samples were transported at 4°C in transport broth to laboratory facilities at the Centre for Public Health and Zoonoses at the University of Guelph where microbiological analysis was performed.
The samples were tested for the presence of MRSA using selective plates, coagulase testing, agglutination tests and PCR. Isolates of MRSA were also tested for the presence of the methicillin-resistance gene (mecA), the zinc-resistance gene (czrC), and the Staphylococcal Cassette Chromosome mec (SCCmec) using PCR. The statistical analysis was performed in STATA 10.0 (College Station, TX).
In this trial, diarrhoea was absent in both the treatment (3000ppm zinc group) and the controls (100ppm zinc group).
There was no difference in growth rate or feed intake between the two groups (Table 1).
|Table 1. Growth performance and feed intake between groups|
|Parameter||Pigs fed 100ppm ZnO||Pigs fed 3,000ppm|
|- 2 weeks post-weaning||9.25||9.39|
|- 4 weeks post-weaning||17.5||17.25|
|Average daily gain (g/day)|
|- pre-weaning (d1-21)||241.2||242.0|
|- early nursery (d21-35)||205.6||210.1|
|- late nursery (d35-49)||589.1||561.7|
|Average feed intake (g/day)||578.7||595.2|
|Average zinc intake (g/day)||0.052||1.786|
The prevalence of MRSA in suckling piglets was low (5.6 per cent) but increased rapidly after weaning, particularly in the piglets receiving 3,000ppm zinc oxide (Figure 1).
MRSA prevalence was statistically higher at one and two weeks post-weaning (P<0.01) for pigs fed 3,000ppm zinc oxide compared to those fed the minimal dietary levels of 100ppm zinc oxide.
Take Home Message
The use of high levels of zinc oxide, often considered as an alternative to antibiotics, may be causing selective pressure for multidrug resistant bacteria such as MRSA.
Acknowledgements: Research support was received from Ontario Pork and from the University of Guelph-OMAF research partnership and from NSERC.
Slifierz M.J., R. Friendship and J.S. Weese. 2014. An investigation into the effects of zinc oxide in pig starter rations on the persistence of antibiotic resistance. Proceedings of 33rd Centralia Swine Research Update. II-20-II-21.