Food-borne salmonella infections have become a major problem in many industrialized countries (1, 2). Salmonella enterica serotype typhimurium (DT104) is now resistant to five drugs: ampicillin, chloramphenicol, streptomycin, sulfonamides, and tetracycline. An increasing proportion of DT104 isolates also have reduced susceptibility to fluoroquinolones. The concomitant use of these and other antimicrobial agents at sub-therapeutic concentrations to enhance growth in animals and for farming purposes is causing obvious concern and national and international recommendations on the use of antimicrobials for disease control in humans and animals have been proposed (3, 4).
A recent study in Denmark has demonstrated the spread of an unusually resistant strain of typhimurium, through the food chain, from food-producing animals to humans (5). The surveillance of salmonella in farms in Denmark covers nearly all commercial food-producing animal facilities and slaughterhouses. In 1998, the first community outbreak of quinolone-resistant salmonella occurred. The outbreak included 25 culture-confirmed cases which were difficult to treat: eleven patients were hospitalized and two died. The investigators succeeded in tracing the source of infection in most of the 25 cases. During microbiological investigation, an unusual resistance pattern was found in isolates from all patients, the slaughterhouse, two samples of pork originating from food inspection agencies and two swine herds. Nine patients had eaten pork originating from a slaughterhouse where two herds tested positive for multidrug-resistant salmonella. The molecular epidemiological data from patients confirmed that the primary source of all cases was a Danish swine herd.
Fluoroquinolones were licensed in Denmark for veterinary use in 1993 and by 1998 accounted for 400 kg of a total of 57 300 kg of antimicrobial agents consumed by food-producing animals. No indication of fluoroquinolone use was found in the implicated herds. It is therefore suggested that resistant salmonella may have originated as a result of use of fluoroquinolones prior to 1998 or through introduction from pigs not bred in Denmark, and thereafter spread through wild animals or equipment.
A further case of ceftriaxone resistant salmonella infection acquired by a child from cattle has also been reported from the United States (6). The ceftriaxone-resistant isolate from the child was indistinguishable from one of the isolates from cattle, which was also resistant to ceftriaxone. Furthermore, both isolates were resistant to 13 antimicrobial agents; all but one of the resistance determinants were on a conjugative plasmid of 160 kb that encoded the functional group 1 beta-lactamase CMY-2. This study provides additional evidence that antibiotic-resistant strains of salmonella evolve primarily in livestock. Resistance to ceftriaxone is a concern, especially with respect to children, since fluoroquinolones are not approved for use in children in the United States.
Fluoroquinolones remain the empirical treatment for suspected intestinal salmonella infection. They are crucial for the treatment of severe concomitant diseases and health conditions. The increased presence of quinolone-resistant salmonella strains in food producing animals is therefore of public health concern. Fluoroquinolones should not be used in food-producing animals to enhance growth or for other purposes. They should be used in veterinary practice for therapeutic indications only when other options are not possible.
Antimicrobial resistance was the topic of a conference of Health Ministers from the European Union countries in 1998 (4, 7). The majority of participants considered the use of antimicrobials as growth promoters in animals unjustified and recommended that safer alternatives such as improved farming practices should be developed. The follow-up of these recommendations is increasingly important.
1. Threlfall, E.J., Frost, J.A., Rowe, B. Increasing spectrum of resistance in multiresistant Salmonella typhimurium. Lancet, 347: 1053-1054 (1996).
2. Glynn, M.K., Bopp, C., Dewitt, W. Emergence of multidrug resistant Salmonella enterica serotype typhimurium DT104 infections in the United States. New England Journal of Medicine, 338: 1333-1338 (1998).
3. WHO Drug Information, 12: 142-143 (1998).
4. WHO Drug Information, 13: 12-13 (1999).
5. Molbak, K. An outbreak of multidrug resistant, quinolone resistant Salmonella enterica serotype typhimurium DT104. New England Journal of Medicine, 341: 1420-1425 (1999).
6. Fey, P.D., Safranek, T.J., Rupp, M.E. et al. Ceftriaxone-resistant salmonella infection acquired by a child from cattle. New England Journal of Medicine, 342: 1242-1249 (2000).
7. Ministry of Health & Ministry of Food, Agriculture and Fisheries, Denmark. Europe Union Conference. The Microbial threat. The Copenhagen Recommendations, 10 September 1998.