Outbreak of quinolone-resistant, multiresistant Salmonella typhimurium DT104, Denmark

Since the beginning of the 1990s infection with the zoonotic Salmonella type S. typhimurium DT104 has been recognized as a health problem in several industrialized countries.¹ S. typhimurium DT104 has a broad spectrum of hosts and can easily spread to a large number of domestic animals, as well as to wild animals. Because of its extensive reservoir, S. typhimurium DT104 is difficult to control in animal farming. It is often resistant to ampicillin, chloramphenicol, streptomycin, sulphonamides and tetracycline. In addition, the organism can acquire resistance to other antibacterial agents, including quinolones. As a fluoroquinolone is the drug of first choice for treating extra-intestinal and serious intestinal complications of human salmonellosis, this can cause therapeutic problems. In England, multiresistant S. typhimurium DT104 is the second most common Salmonella sero- and phage type after S. enteritidis DT4.

¹ For more information on the use of quinolones in food and their potential impact on human health, please refer to: The medical impact of the use of antimicrobials in food animals (document WHO/EMC/ZOO/97.4), The use of quinolones in food animals and potential impact on human health (document WHO/EMC/ZDI/98.10) and Multidrug resistant salmonella typhimurium (Fact Sheet No. 139, January 1997), all available from the Division of emerging and other communicable diseases surveillance and control, World Health Organization, 1211 Geneva 27, Switzerland; and website www.who.int/emc/diseases/zoo.

In Denmark, the proportion of S. typhimurium DT104 infections had hitherto been less than 1% of total human Salmonella infections, and apart from a small hospital outbreak in 1996, only sporadic cases had been recorded. From 1995 to 1997 there had been no increase in human cases, and no quinolone-resistant strains had been isolated.²

² Annual report on zoonoses in Denmark 1997. Copenhagen, Danish Zoonosis Centre, 1998.

The outbreak

In the summer of 1998, the first community outbreak of multidrug-resistant S. typhimurium DT 104 was registered, the source being pork meat of Danish origin. Most cases occurred during the week starting 1 June. This coincided with the identification of the same type of Salmonella in meat at a slaughterhouse on 25 May. The cases reported from 29 June onwards are presumably due to the use of frozen meat.

The organism involved showed the classic resistance pattern, but was also resistant to a quinolone, nalidixic acid. This outbreak constitutes an example to illustrate that problems with the treatment of human infections can be related to the occurrence of quinolone-resistant bacteria in live animals and food products.

Investigation of the outbreak

The outbreak was confirmed at Statens Serum Institut on 18 June 1998. Isolates from 5 patients with S. typhimurium DT104 infection showed the unusual resistance pattern (nalidixic acid resistance) which exactly corresponded to that found in isolates from a slaughterhouse in Zealand, as well as in isolates collected by food inspection agencies in Copenhagen and Roskilde. This resistance profile had not been detected in Danish food animals or food previously, and only rarely in humans. Subsequent investigations confirmed that all isolates were of phage type 104 and had the same DNA-fingerprinting pattern.

A connection between the finding of nalidixic acid resistant S. typhimurium DT104 both in fresh pork and in these patients was further supported by patient interviews, which revealed that patients had bought and eaten pork from shops that had received deliveries from the slaughterhouse in question. Furthermore, the farm that had sent the pigs to the slaughterhouse was identified, and Salmonella isolates from the same herd were found to be identical to isolates from the slaughterhouse, the pork and the patients. This strain was also found in another herd of pigs from which the index stock had received piglets.

All 22 cases were probably part of the same outbreak, as the resistance profile of the 22 isolates was very unusual. This conjecture has been supported by molecular epidemiological investigations carried out in collaboration with the Danish Veterinary Laboratory. Eighteen of the 22 patients were interviewed, and 9 provided information that directly revealed that they had eaten pork originating from the slaughterhouse concerned. One of the patients was a slaughterhouse employee who was presumably infected at work, and another was a hospital employee who had had contact with one of the other patients. It should be stressed that none of the patients had been abroad. Of the 7 patients admitted to hospital, 6 were treated with antibiotics, including fluoroquinolones. Several of the cases have had severe intestinal disease and fluoroquinolone treatment has been reported to lack clinical effect in at least 4 cases.

A previously healthy 62-year-old woman died from the complications of intestinal perforation. The patient had been treated with fluoroquinolone for 5 days before operation and was treated per- and postoperatively with ceftriaxone and gentamicin. In addition, Bacteroides fragilis, which was resistant to the antibiotics given, was isolated from blood culture.

(Based on reports from Statens Serum Institut and the Danish Veterinary Laboratory.)