AimsThe objective of this study was to determine the effect of lysozyme and antibiotics on zoonotic pathogen shedding in faeces from nursery pigs housed without and with an indirect disease challenge. Methods and ResultsTwo replicates of approximately 650 pigs each were weaned and randomly assigned to one of 24 pens in either a nursery room that had been fully disinfected or a nursery room left unclean. Pigs were randomly assigned to control diet (Control), control diet+antibiotics (Antibiotic; chlortetracycline and tiamulin), or control diet+lysozyme (Lysozyme; 100mgkg(-1) diet). Rectal swab samples were collected on day 0 and 28 of treatment, and enriched and cultured for Campylobacter spp. and shiga-toxigenic Escherichia coli (STEC). Enrichments from rectal swab samples also were analysed for presence of enterohaemorrhagic E.coli (EHEC) virulence genes (hlyA, eae, stx1 and stx2). Room hygiene had little effect on day 28 results. Percentage of samples culture positive for Campylobacter spp. was lowest for lysozyme diets (P<001), but similar for control and antibiotic diets (432, 837, and 848 respectively). Diet had little effect on the EHEC virulence genes hlyA or eae (P>01), but there was a tendency for fewer samples positive for stx1/stx2 in antibiotic or lysozyme diet groups (P<007) compared to control diet (12, 21 and 58% respectively). Salmonella spp. and specific STEC types tested were rarely detected in the study. ConclusionsIn nursery swine, room hygiene had little effect on pathogen shedding. Dietary chlortetracycline and tiamulin did not reduce pathogen shedding but dietary lysozyme reduced faecal shedding of Campylobacter. Significance and Impact of the StudyLysozyme can effectively replace antibiotics in the diet of nursery swine and can be effective for pathogen control.