Origin of transferable drug-resistance factors in the enterobacteriaceae.

The observation of a rise in multiple resistance to antibiotics in shigellae by Japanese workers, and their demonstration that this resistance could be transferred to other Enterobacteriaceae by conjugation (Ochiai et al., 1959 ; Akiba et al., 1960 ; Watanabe, 1963), opened a new phase both in bacterial genetics and in the study of drug resistance in this group of organisms. Briefly, this type of resistance is transferred from cell to cell by resistance factors (R-factors), which have been postulated to consist of the genetic determinants for drug resistance (R-determinants), and resistance transfer factors (R.T.F.s). It has been assumed that the R-factors are cytoplasmic in location and that the communicability of the complex is dependent on the R.T. F.s, which are episomal in nature. The drug resistance is usually multiple and is directed against the antibacterial drugs commonly used in human and veterinary medicine? for example, ampicillin (A), chlor amphenicol (C), neomycin (N), kanamycin (K), streptomycin (S), sulphonamides (Su), and tetracycline (T). Work in the Enteric Reference Laboratory has been concerned particularly with transferable resistance in Salmonella typhimurium. Common resistance patterns currently found in this organism are: S T Su ; A S T Su ; and S T N K Su. To these combinations furazolidone resistance is now usually added in cultures of both animal and human origin. Anderson and Lewis (1965a) recently drew attention to the disturbing rise of multiple drug resistance in S. typhimurium. Of 450 cultures of this serotype examined in the Enteric Reference Laboratory between December 1964 and February 1965 273 (61%) showed drug resistance, mostly multiple, and one particular phage-type, 29, predominated with 168 cultures? 61.5% of the total number of resistant strains. At the time of the survey almost all cultures of type 29 examined were drug-resistant. We have continued monitoring this situation and will publish a detailed analysis of our results later. However, it can be stated that of approximately 4,700 cultures of S. typhimurium received between December 1964 and October 1965 1,700 (36%) belonged to phage-type 29 ; that only 40 (2.4%) of. the type 29 cultures were completely sensitive to drugs ; that 500 of the 1,700 cultures were of human and 1,200 of animal origin ; that the overwhelming majority of animal cultures were isolated from calves ; and that many of the human infections were directly related to bovine disease. The principal reservoir of type 29 is thus bovine. The prevalence of furazolidone resistance in cultures of human origin was similar to that in bovine cultures, an indication that most human infections of undetermined source were bovine in origin, since furazolidone is most widely used in efforts to prevent and treat calf scours. Only a small minority of the drug-resistant cultures of phage type 29 have so far been tested, but all those examined could transfer at least part of their drug resistance to suitable recipient cultures, and there is no reason to doubt that the great majority will behave similarly. We have already pointed out (Anderson, 1965a ; Anderson and Lewis, 1965a, 1965b, 1965c) that the high incidence of drug-resistant phage-type 29 in calves is probably due to a combination of poor conditions of hygiene in animal husbandry, especially in the intensive farming, transport, and marketing of calves, and the distribution of infected stock by dealers ; and by the too free use of antibacterial drugs in efforts to control the resultant salmonellosis.