Flemming Bager

Effect of Abolishment of the Use of Antimicrobial Agents for Growth Promotion on Occurrence of Antimicrobial Resistance in Fecal Enterococci from Food Animals in Denmark

ABSTRACT From 1995 to 2000, a total of 673 Enterococcus faeciumand 1,088 Enterococcus faecalis isolates from pigs together with 856 E. faecium isolates from broilers were isolated and tested for susceptibility to four classes of antimicrobial agents used for growth promotion as part of the Danish program of monitoring for antimicrobial resistance. The four antimicrobials were avilamycin, erythromycin, vancomycin, and virginiamycin. Major changes in the use of antimicrobial agents for growth promotion have occurred during the last 6 years in Denmark. The government banned the use of avoparcin in 1995 and of virginiamycin in 1998. Furthermore, the producers have voluntarily stopped all use beginning in 1999. The avoparcin ban in 1995 was followed by a decrease in the occurrence of glycopeptide-resistant E. faecium (GRE) in broilers, from 72.7% in 1995 to 5.8% in 2000. The occurrence of glycopeptide resistance among isolates from pigs remained constant at around 20% from 1995 to 1997. It was shown that, in GRE from pigs, the genes encoding macrolide and glycopeptide resistance were genetically linked and that, following the decrease in the use of tylosin during 1998 and 1999, the occurrence of GRE in pigs decreased to 6.0% in 2000. From 1995 to 1997 the occurrence of erythromycin resistance among E. faecium and E. faecalis isolates from pigs was almost 90%. Use of tylosin decreased considerably during 1998 and 1999, and this decrease was followed by decreases in the occurrence of resistance to 46.7 and 28.1% among E. faecium and E. faecalis isolates from pigs, respectively. Erythromycin resistance among E. faecium isolates from broilers reached a maximum of 76.3% in 1997 but decreased to 12.7% in 2000 concomitantly with more limited use of virginiamycin. Use of virginiamycin increased from 1995 to 1997 and was followed by an increased occurrence of virginiamycin resistance among E. faecium isolates in broilers, from 27.3% in 1995 to 66.2% in 1997. In January 1998 the use of virginiamycin was banned in Denmark, and the occurrence of virginiamycin resistance decreased to 33.9% in 2000. Use of avilamycin increased from 1995 to 1996 and was followed by an increase in avilamycin resistance among E. faeciumisolates from broilers, from 63.6% in 1995 to 77.4% in 1996. Since 1996 avilamycin usage has decreased, followed by a decrease in resistance to 4.8% in 2000. Our observations show that it is possible to reduce the occurrence of antimicrobial resistance in a national population of food animals when the selective pressure is removed. Cases in which resistance to vancomycin was linked to resistance to erythromycin were exceptions. In such cases resistance did not decrease until the use of both avoparcin and tylosin was limited.

Avoparcin used as a growth promoter is associated with the occurrence of vancomycin-resistant Enterococcus faecium on Danish poultry and pig farms

We determined the association between the use of the glycopeptide antibiotic avoparcin as a growth promoter and the occurrence of Enterococcus faecium (VREF) with high-level resistance to vancomycin (MIC > or = 64 micrograms ml-1) on poultry and pig farms. The investigations were conducted as retrospective cohort studies, where groups of farms exposed or not exposed to avoparcin between September 1994 and April 1995 were compared. In poultry, the association between the use of avoparcin and the occurrence of VREF was confounded by the use of broad-spectrum antibiotics, and the adjusted relative risk was 2.9 (1.4-5.9). In pigs, the association had a similar magnitude with a non-adjusted relative risk of 3.3 (0.9-12.3). The similar findings in the two studies provide evidence in favour of a causal association between the use of avoparcin and the occurrence of VREF on farms, and suggest that food animals constitute a potential reservoir of infection for VREF in humans.

The serological response to Salmonella serovars typhimurium and infantis in experimentally infected pigs. The time course followed with an indirect anti-LPS ELISA and bacteriological examinations

A total of 43 pigs, inoculated with Salmonella typhimurium (O:1,4,5,12) and un-inoculated controls were followed weekly by blood and faecal samplings for up to 18 weeks post inoculation (p.i.). Three pigs, inoculated with S. infantis (O:6,7) were followed similarly for 9 weeks. All inoculated pigs, except one, were positive for Salmonella by traditional faecal culture on at least one occasion during the first week of infection, whereafter shedding of bacteria rapidly declined to < 10% of the pigs from week 7. All control pigs remained Salmonella negative by culture of faecal samples. When examined serologically in an indirect ELISA using mixed purified LPS from S. typhimurium and S. choleraesuis (O:6,7), all but one S. typhimurium infected pig and all S. infantis infected pigs produced significantly increased optical densities (OD) in the ELISA as compared to the control groups. The maximum anti-LPS response was observed at day 22, when 86% of the S. typhimurium inoculated pigs had seroconverted, while the frequency of seropositive pigs peaked at days 30 (92%) and 37 p.i. (92%). Large variations were found among pigs concerning time of seroconversion (between 6 and 37 days p.i.), maximum OD-level attained (between 8 and 130% of a reference serum) and persistence of reaction. At the time of necropsy, 18 weeks p.i., 67% of the S. typhimurium inoculated pigs were found seropositive, while 100% of the S. infantis inoculated pigs were found seropositive at necropsy, 9 weeks p.i. Salmonella in internal organs were detected at necropsy in 4/22 of the S. typhimurium inoculated pigs with persistent anti-LPS reaction and all 3 S. infantis inoculated pigs but in none of the antibody-negative pigs. The ELISA is therefore suitable for screening for the presence of infection with S. typhimurium or S. infantis on a herd basis. Its suitability for other serotypes of Salmonella will require further testing.

The seasonal distribution of campylobacter infection in nine European countries and New Zealand.

In all temperate countries campylobacter infection in humans follows a striking seasonal pattern, but little attention has been given to exploring the epidemiological explanations. In order to better characterize the seasonal patterns, data from nine European countries and New Zealand have been examined. Several European countries with weekly data available showed remarkably consistent seasonal patterns from year to year, with peaks in week 22 in Wales, week 26 in Scotland, week 32 in Denmark, week 30 in Finland and week 33 in Sweden. In Europe, the seasonal peak was most prominent in Finland and least prominent in Scotland and Austria. In New Zealand the seasonality was less consistent since the peak was more prolonged. Possible explanations for the seasonal peaks are discussed. Research into the causes of campylobacter seasonality should help considerably in elucidating the sources of human infection.

Danish Integrated Antimicrobial Resistance Monitoring and Research Program

This program has led to changes in the use of antimicrobial agents in Denmark and other countries.

Herd prevalence of Salmonella enterica infections in Danish slaughter pigs determined by microbiological testing

Abstract As a part of a nationwide programme to survey and control salmonella in pig herds, a microbiological survey of 1363 pig herds was performed in Denmark. A total of 13 468 slaughter pigs were examined at slaughter by culture of 5 g of caecal contents. Overall, 30 different serotypes of Salmonella enterica were isolated from 832 pigs (6.2%). The predominant serotype was S. Typhimurium, comprising 536 (64.4%) of the isolates. Four hundred and forty-eight isolates of S. Typhimurium were examined by phage typing, resulting in detection of 17 different phage types (definitive types, DT) with DT12 being the most frequent (49.1%). Salmonella enterica was found in 302 herds (22.2%), S. Typhimurium was found in 61.1% of these. 279 (23.1%) large herds (producing more than 2600 slaughter pigs per year) were found to be salmonella positive compared with 23 (14.7 %) small herds (annual production of 500 to 550 slaughter pigs). Practical constraints in the study design did not allow for a firm conclusion on the interplay among herd size, geographical location and occurrence of salmonella. In 284 of 302 infected herds (94.0%) only one serotype was detected. Infections with two different serovars were seen in 18 herds (6.0%).

Dealing with antimicrobial resistance – the Danish experience

Following the discovery in 1994 and 1995 that use of the glycopeptide antimicrobial avoparcin for growth promotion was associated with the occurrence of vancomycin resistant Enterococcus faecium in food animals and in food, the Danish Minister of Food, Agriculture and Fisheries banned the use of avoparcin in May 1995. The ban was later extended by the European Commission to include all EU member states. In May 1999, the EU Scientific Steering Committee recommended that use for growth promotion of antimicrobials, which are or may be used in human or veterinary medicine should be phased out as soon as possible and ultimately abolished. During the first half of the 1990s the consumption of tetracyclines, mainly in pig production, increased markedly. This was countered by severely reducing through legal means the financial enticement for veterinarians to prescribe medicines and by restricting the availability of tetracycline as non-registered speciality products. The focus on consumption of antimicrobials and...

Fluoroquinolone Resistance in Salmonella: A Web Discussion

Dr. Rich Carnevale of the Animal Health Institute (Washington, DC) was asked by Dr. Abigail Salyers, who runs the Reservoirs of Antibiotic Resistance (ROAR) web site, to comment on the article by Molbak et al. [1] published in the New England Journal of Medicine in November 1999. Dr. Salyers requested that the article in the New England Journal of Medicine [1] be discussed, since it may have demonstrated a bridge to clinical impacts in humans from antibiotic-resistant bacteria in animals.