Subtherapeutic antibiotics have been used for decades as growth promotants and prophylactic agents. The following antibiotics are approved for use a feed additives in swine: tetracyclines, roxarsone, hygromycin, tylosin, oleandomycin, penicillin G, sulfathiazole, carbadox, sulfamethazine, erythromycin, flavomycin, bacitracin, virginiamycin, lincomycin, apramycin, tiamulin, eftromycin, neomycin, tilmicosin, and florfenicol.
A recent study indicates that subtherapeutic chlortetracycline can be associated with an increase in multiple antibiotic resistance for swine intestinal microbes. Other studies also suggest that subtherapeutic antibiotics can lead to the propagation of an antibiotic resistant “superbug” (Enterococcus) in swine (Poole, et al., 2001). On the other hand, some subtherapeutic antibiotics have not yet been associated with this problem (Donabedian, et al., 2003). These three studies do not, however, address gene transfer events that precipitate resistance and virulence. That is, little is known about the effects of these antibiotics on gene transfer events in enteric bacteria.
The overall objective was to determine which subtherapeutic antibiotics contribute to the transfer of antibiotic resistance and virulence genes while also identifying the subtherapeutic antibiotics that do not contribute to this problem in swine. Three main objectives involved assessing various transfer events mediated by subtherapeutic antibiotics in the laboratory and in swine. These three transfer events involved determining the relative rates of transfer of two different types of antibiotic resistance gene “clusters” (plasmids and integrons) and one type of virulence gene cluster. Transfer was measured from a normal non-virulent (commensal) intestinal bacteria (E. coli) to six different pathogenic bacteria- Salmonella, Yersinia, Pseudomonas, Shigella, ETEC, and Proteus.
Results from these studies revealed that certain antibiotics were more likely to mediate gene transfer events. Our studies revealed numerous subtherapeutic antibiotic-mediated transfer events. The worst offending antibiotics were, in order of rank, lincomycin > apramycin = neomycin = > tylosin = florfenicol.
The results indicate that certain subtherapeutic antibiotics have a higher risk for mediating unwanted gene transfer into pathogenic bacteria. These six antibiotics include apramycin, lincomycin, neomycin, sulfamethazine, tylosin, and florfenicol. Other subtherapeutic antibiotics appear to have a less significant risk.