May 3, 2002 (CIDRAP News) – In a Danish study, patients who had infections with a common drug-resistant type of Salmonella enterica were significantly more likely to die within 2 years than were either patients infected with drug-susceptible variants of the same strain or matched controls from the general population.
Patients who had infections with S Typhimurium DT104 (S enterica serotype Typhimurium definitive phage type 104) were 4.8 times more likely to die within the ensuing 2 years than age-matched controls were, according to the report in the May issue of Emerging Infectious Diseases. This strain is usually resistant to ampicillin, chloramphenicol, streptomycin, sulfonamides, and tetracycline (resistance type [R-type] ACSSuT). By contrast, patients who had infections with "pansusceptible" S Typhimurium were 2.3 times more likely to die within 2 years than age-matched controls were.
"We associated resistance in S Typhimurium with excess mortality, and the demonstration of a hazard to human health underscores the need for restrictions in the use of antimicrobial drugs in the production of food from animals," states the report by Morton Helms and colleagues at the Statens Serum Institut in Copenhagen, Denmark. The investigators adjusted their data for differences in underlying illness rates between patients and controls, but they were not able to assess the contribution of reduced drug efficacy to deaths in the salmonellosis patients.
The researchers gathered data on all S Typhimurium infections reported in Denmark from January 1995 through October 1999. The Danish Civil Registration System, which includes demographic data on all Danish citizens, was used to link each S Typhimurium patient with 10 randomly selected people matched to the patient by age, sex, and county of residence. To control for preexisting illness, the authors obtained data on hospital admissions and discharge diagnoses from the Danish National Patient Registry and the Cancer Registry. They assigned severity scores to underlying illnesses and added them to develop a comorbidity index.
In the study period, there were 2,059 cases of S Typhimurium infection in which antimicrobial susceptibility of the isolate was determined. Of these, 2,047 patients were successfully matched with 10 controls from the registration system. Fifty-nine of the S Typhimurium patients and 221 of the 20,456 control group members died in the period up to 2 years after entry into the study.
After adjustment for comorbidity, patients with any S Typhimurium infection were 2.3 times (95% confidence interval [CI], 2.2 to 4.0) more likely to die within 2 years than controls. Likewise, patients with pansusceptible S Typhimurium infections had mortality 2.3 times (95% CI, 1.5 to 3.5) higher than that of controls.
R-type ACSSuT was found in 13.8% of the isolates, and patients infected with this type were 4.8 times (95% CI, 2.2 to 10.5) more likely to die, compared with the controls. For patients infected with quinolone-resistant strains (resistant to nalidixic acid, a first-generation quinolone), mortality was 10.3 times (95% CI, 2.8 to 37.8) higher than in controls. Quinolone resistance was found in 4.1% of the isolates. No ciprofloxacin-resistant strains were found.
In other antimicrobial susceptibility findings, 46.6% of the isolates were pansusceptible, 53.4% were resistant to at least one of the 13 drugs tested, and 30.8% were resistant to at least two drugs. Resistance levels for some specific classes or drugs included sulfonamides, 47.3% of isolates; tetracycline, 25.1%; streptomycin, 22.4%; ampicillin, 19.2%; chloramphenicol, 17.0%, and kanamycin, 9.6%.
The researchers had no data on treatment with antimicrobial drugs and hence could not examine the possible contribution of drug resistance to mortality. However, citing previous research, they state, "We estimate that approximately 20% of the patients were prescribed empiric treatment in connection with the collection of specimens and that some of the deaths may have been associated with reduced efficacy of fluoroquinolones."
Helms M, Pernille V, Gerner-Smidt P, et al. Excess mortality associated with antimicrobial drug-resistant Salmonella Typhimurium. Emerg Infect Dis 2002;8(5)