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April 24, 1999
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Danish Antimicrobial Resistance Monitoring and Research Programme Issues New Report
April 23, 1999 / WEEKLY EPIDEMIOLOGICAL RECORD / No. 16, 125 / -- DANMAP (the Danish Antimicrobial Resistance Monitoring and Research Programme) has issued its second report. The programme collects data on human and animal antibiotic consumption and antibiotic resistance in bacteria from humans, animals and foodstuffs. In addition to human and zoonotic pathogens, normally-occurring bacteria (indicator bacteria) that permit a direct comparison of resistance levels are collected from the 3 sources. The programme has now been in existence for 3 years and has received considerable international attention. A selection of results from the report are presented below.

Antibiotic consumption
The consumption of antibiotics in human treatment continues to be low in Denmark in comparison with other countries. There was a definite drop in consumption from 1995 to 1996. Contributing factors could be the extra focusing on antibiotic use that took place during that period, and the change in health services prescription subsidies from 1 January 1996. In comparison with other countries, the distribution of consumption over different groups of antibiotics has been favourable for the avoidance of resistance problems. There is, however, some variation between counties. In 1997 consumption of penicillins made up 65% of the total anti-biotic consumption in the primary sector. In the period 1994-1997, consumption of the broad-spectrum quinolones and cephalosporins fell by 39% and 13% respectively. In 1997 these accounted for only 2% and < 1%, respectively, of total consumption. The first 9 months of 1998, however, have seen a 5% rise in antibiotic consumption in the primary sector, with increases in quinolone and cephalosporin consumption of 2.9% and 9.5% respectively. This calls for increased vigilance. Antibiotic use in animals, whether as therapy or to promote growth, rose in 1997. A direct comparison of antibiotic consumption in animals and humans requires the conversion of animal consumption into defined daily doses. This is difficult, however, both because there are no defined daily doses for animals and because no information is available on the distribution of consumption between animal species and age groups.

Antibiotic resistance
Four indicator bacteria have been chosen because they are readily isolated from humans, foodstuffs and animals. These are Enterococcus faecium, E. faecalis, coagulase-negative staphylococci and Escherichia coli. Bacterial zoonoses are represented by the most commonly occurring: Salmonella enteritidis, S. typhimurium and Campylobacter spp. The pathogenic bacteria have been chosen for their frequent occurrence and virulence in either humans or animals. For the human pathogens, data are collected both nationally and from Aarhus and Roskilde counties, which have been chosen as key counties.

Indicator bacteria
Enterococci. Baseline material has been collected, consisting of isolates from army recruits, nurses, slaughterhouse workers and pig farmers. Isolates from pig farmers show a higher frequency of resistance to macrolides and nitro-furantoin than those from the other groups, a difference that is statistically significant. This is probably because pig farmers are exposed both to large amounts of antibiotics and to many resistant bacteria from their animal stock. Even with a sensitive method, only 1 enterococcus isolate was shown to have acquired vancomycin resistance. This may indicate that Denmark has a lower faecal carrier frequency for vancomycin-resistant enterococci than some other countries. E. coli. The resistance level was generally low. No differences in resistance were found between strains isolated from the different occupational groups: 31% of strains were resistant to sulphonamide, 19% to ampicillin and < 1% to gentamicin or quinolones.

Zoonotic bacteria
Campylobacter jejuni. Resistance levels were generally low. However, a 12% resistance to quinolones (ciprofloxacin) is giving rise to concern, as quinolones are usually the preparations of first choice for treating complicated gastrointestinal infections in humans. Quinolone resistance was lower in isolates from live chickens than from Danish and foreign poultry meats or from humans. This is probably due to resistant Campylobacter from imported poultry and/or to the fact that about 20% of human infections are associated with travel.

Salmonella. Resistance levels in S. typhimurium and S. enteritidis were low and unchanged. There was a correspondingly good agreement between the occurrence of resistance in S. typhimurium from pigs and from humans. No quinolone resistance was found in human isolates during 1997. Typing of Salmonella from animal production and human infections shows that pigs and pork are probably the principal source of foodborne S. typhimurium infection in Denmark.

Pathogenic bacteria
E. coli is a frequent cause of both bacteraemia and urinary tract infections. There are resistance data for isolates from both hospitals and general practice. In isolates from blood the occurrence of ampicillin and cefuroxime resistance was generally higher in Aarhus county than in Roskilde county. This may be explained by the different hospital structures in the 2 counties. Some hospitals in Aarhus county have a regional function and thus a higher degree of specialization. This could be the reason for a higher use of broad-spectrum antibiotics. Despite a fall in the use of cephalosporins in Aarhus county there was a rise in resistance to ampicillin and cefuroxime. This may be due to a conjoint selection of bacteria that are resistant to several antibiotics at the same time, or to the fact that changes in antibiotic use are first reflected as changes in resistance rates after some time. The changes in resistance rates of blood isolates in Roskilde county are not statistically significant, probably because of the low number of isolates. In isolates from urine, the resistance of E. coli from urinary tract infections diagnosed in either general practice or hospitals was nearly identical, and ampicillin resistance was similar to that of blood isolates. This may be due to the fact that the vast majority of urine specimens from the primary sector are sent in because of treatment failure, so that the source material has undergone a preselection. The rise in the occurrence of quinolone-resistant E. coli calls for increased vigilance. In this case data from the Roskilde county primary sector are not comparable with those from Aarhus, as the samples from Roskilde were collected to assess the resistance of E. coli from untreated urinary tract infections in the primary sector.

Streptococcus pneumoniae. Penicillin-resistant pneumococci constitute an ever-growing problem on a world scale. There has been a rise in erythromycin and penicillin resistance from 1990 to 1997, with the proportion of strains with reduced sensitivity to penicillin doubling over this period. In Denmark, however, resistance remains low in comparison with other countries. It is still of great importance to monitor the resistance of pneumococci, and the Statens Serum Institut is investigating which factors have contributed to this rise.

Coagulase-negative staphylococci. There were no appreciable differences between resistance rates in the 2 counties.

Summary
In the human isolates, resistance levels were generally low in comparison with those from other countries. There is nevertheless a need in several areas for an increased drive to curtail the rise in the number of penicillin-resistant pneumococci and quinolone-resistant E. coli. In the veterinary sector of medicine, guidelines have now been drawn up for the treatment of animals with antibiotics, as has been the case for many years in human medical care. In addition work is in progress to facilitate a better registration of antibiotic consumption in the treatment of animals. DANMAP has been able to demonstrate that the banning in May 1995 of the use of avoparcin as a growth promotor has resulted in a fall in resistance rates to this agent. Resistance in E. faecium from chickens fell from 52% in the first half of 1996 to 12% in the second half of 1997. A less significant fall has been seen in E. faecium from pigs, which may be connected to the fact that the pig stock is maintained by continuous breeding, whereas chickens for slaughter are bred by a batchwise all in - all out process. On the basis of data including those from DANMAP, the use of a further 4 growth promoters has been prohibited. The DANMAP 97 report can be obtained from the Statens Serum Institut; e-mail: tls@ssi.dk. (Based on 2 articles published in EPI-NEWS No. 3 and No. 4, 1999, Statens Serum Institut, Copenhagen, Denmark.)

Source: AnimalNet