No 42-43 - 2015
The annual DANMAP report (Danish Integrated Antimicrobial Resistance Monitoring and Research Programme) summarises the Danish consumption of antimicrobial agents used for animals and humans and describes the development of resistance in bacteria collected from animals, food and humans.
The report has been published annually since 1995 and is the most comprehensive source of monitoring of antibiotic resistance in Denmark. The 2014 DANMAP report is available at www.danmap.org. In the following, we summarise the main points concerning consumption and development of resistance in relation to patients.
Total consumption of antimicrobials for patients
In 2014, the total human consumption of antimicrobial agents for systemic use (primary healthcare and hospitals pooled) was 18.6 DID (Defined Daily Doses per 1,000 inhabitants) as opposed to 19.1 DID in 2013. Primary healthcare accounted for nearly 90% of the consumption with 16.4 DID, and the hospitals generated the remaining 2.2 DID. Whereas the total consumption in primary healthcare has remained stable since 2011, the consumption at hospitals has followed an increasing trend. In 2011, when the highest ever consumption was recorded, the consumption reached 19.3 DID, which is a nearly 40% increase from the first report published in 1997.
In 2014, a total of 52,819 kg of active substance was employed.
Antimicrobial consumption in primary healthcare
Penicillin constitutes the largest group of antimicrobials in primary healthcare and accounts for 65% of the total consumption. This group has also recorded the largest changes in consumption as the use of penicillins with an extended spectrum (particularly pivmecillinam) and combination penicillins (amoxicillin with clavulanic acid) has increased in the course of the past 10 years and now comprises 22% and 8% of the total consumption, respectively.
Inversely, the use of beta-lactamase-sensitive penicillins (phenoxymethyl penicillin) has now declined to 27% of the total consumption. Ten years ago, the beta-lactamase-sensitive penicillins accounted for 37% of the total consumption in primary healthcare, whereas extended-spectrum penicillins and combination penicillins accounted for 19% and <1%, respectively. This marked shift reflects changed guidelines on the treatment of airway infections in particular (including treatment of acute bronchitis/COLD), but it may also reflect a shift in the attitude among prescribing doctors towards more broad-spectrum penicillins.
Antimicrobial consumption in the hospital sector
Stated as defined daily doses per 100 bed days (DBD), the consumption of antimicrobials at somatic hospitals increased from 99.9 DBD in 2013 to 104.3 in 2014 (4%). In the course of 10 years, the total consumption of antimicrobial agents increased by as much as 57% as the use was 66.3 DBD in 2005. Nevertheless, this increase may, in part, be accounted for by shorter admission courses.
The average number of bed days per treatment is shorter compared with previously, and hospitals have simultaneously increased their activity. The penicillin group comprised 50%, including broad-spectrum penicillins and combination penicillins which comprised 15% and 16% of the total hospital consumption, respectively.
As in primary healthcare, the consumption of combination penicillins increased from 13.6 DBD in 2013 to 16.0 DBD in 2014 (18%). This substantial increase is due to the fact that piperacillin/tazobactam has become an important part of empirical sepsis treatment at most hospitals.
Consumption of critically important antimicrobials
Since 2011, a limited decrease in the consumption of fluoroquinolones has been observed. However, this decrease is not statistically significant. In primary healthcare, fluoroquinolones comprised 3% of the total consumption, whereas this group comprised 9% of the consumption at hospitals.
The consumption of cephalosporins at hospitals has also decreased. Nevertheless, cephalosporins comprised 11% of the total antibiotic consumption (as opposed to 12% previously recorded). The consumption of carbapenems has increased steadily in the course of the past 10 years, but did not increase significantly from 2013 to 2014.
In 2014, there were not a higher prevalence of multidrug-resistance in isolates of Salmonella Typhimurium acquired abroad than acquired in Denmark; this is in contrast with previous years. This may primarily be explained by the increasing share of mono-phasic variants of Salmonella Typhimurium in clinical isolates, EPI-NEWS 11/14; this type is frequently multidrug-resistant.
In contrast hereto, fluoroquinolone resistance remained more frequent in travel-associated infections than in Danish infections. In seven S. Typhimurium isolates (2% of cases), co-resistance to ciprofloxacin and 3rd generation cephalosporins was found. This warrants increased attention as these two antimicrobial agents are critical in the treatment of serious and invasive salmonella infections. None of the resistance-determined Salmonella isolates from animals, meat or humans exhibited carbapenemase activity (meropenem resistance).
As for Salmonella, a higher occurrence of fluoroquinolone resistance was observed among Campylobacter jejuni found in patients with travel-associated infections (81%) than in isolates from patients whose infection had been acquired in Denmark (35%). The occurrence of resistance in C. jejuni and C. coli from Danish meat and poultry for human consumption remains among the lowest in Europe.
In clinical isolates from patients with bacteraemia, 2014 recorded no increasing occurrence of resistance for critical antimicrobials. Among the approx. 4,500 isolates of Escherichia coli from blood cultures, the occurrence of resistance to 3rd generation cephalosporins was 7% and for ciprofloxacin it was 12%. Both remained unchanged compared with 2013.
For 943 isolates of Klebsiella pneumoniae, the occurrence of resistance to 3rd generation cephalosporins was 8% (9% in 2013) and for ciprofloxacin it was 7% (9% in 2013). Generally, resistance has followed an increasing trend in the years leading up to 2011. After 2011, it has stagnated or followed a slightly decreasing trend.
Compared with the remaining Nordic countries, Denmark has been recording a slightly higher occurrence of cephalosporin resistance for several years. However, the 2014 figures indicate that Denmark is now reaching a level comparable to that of our Nordic neighbours. Thus, 2013 data from the European network EARS-Net showed 5-6% cephalosporin resistance in E. coli from our neighbouring countries. The only significant increase in E. coli was observed for piperacillin/tazobactam where resistance increased from 4% to 5%. The resistance of both bacterial species to meropenem remains at <1%.
In 2014, the occurrence of resistance to penicillin and erythromycin remained low among Streptococcus pneumoniae in isolates from blood and spinal fluids (5% and 7%, respectively).
The prevalence of ciprofloxacin resistance among Neisseria gonorrhoeae was 46% in 2014, thus showing a steady decline since a peak of 75% in 2009. Penicillinase production among gonococci varied between 24% in 2005 and 11% in 2014. As in the previous years, no ceftriaxone-resistant isolates were reported.
In 2014, a total of 1,964 cases of bacteraemia with Staphylococcus aureus were reported. This corresponds to an incidence of 34.9 cases per 100,000 inhabitants. The number of methicillin-resistant S. aureus (MRSA) was 57 (2.9%) compared with 30 in 2013. Despite the substantial increase, the number of MRSA bacteraemias remains very low compared with the remaining European countries.
In 2014, a considerable increase was seen in the number of patients who had infections with the multidrug-resistant bacteria vancomycin-resistant enterococci (VRE) and carbapenemase-producing organisms (CPO) in Danish hospitals. In 2014, a total of 303 cases were reported in which VRE had been detected, which is a 30% increase with respect to 2013 (235 cases). The number of VRE-positive blood cultures increased in 2014 to 33 compared with 23 in 2013. The increased occurrence of VRE was primarily associated with hospital outbreaks, and the occurrence was more prominent in the Capital Region of Denmark and in Region Zealand.
In 2014, a total of 55 carbapenemase-producing organisms (CPO) were isolated from 48 patients. Previously, findings of CPO have been travel-associated, but in 2014 the source for several of the CPO-findings remained unknown or was related to Danish outbreaks.
The number of new MRSA cases increased in 2014 to 2,965; for comparison, 2,092 cases were observed in 2013, EPI-NEWS 23/15. Most detections were carriers. A total of 30% of those positive with common MRSA had symptomatic infections whereas only 19% of those positive with livestock associated MRSA showed symptoms.
Increases in the occurrence were more prominent in livestock associated MRSA, here particularly type CC398, with 1,277 cases in 2014 compared with 643 cases in 2013. This corresponds to a total share of 43% in all cases detected in 2014. The majority (89%) of the persons who were found positive for CC398 had close contact to livestock (70%) or were living in households with persons who had close contact to livestock (17%). As in previous years, no signs of spreading to urban areas were seen. This underlines that foods have no appreciable impact on the spreading of livestock MRSA.
Overall, the antibiotics consumption for humans has remained constant since 2011. A decrease was observed in the number of prescriptions issued in primary healthcare and in the consumption among some age groups (not shown in the report). Furthermore, in primary healthcare and at hospitals alike, a shift in consumption of penicillins was observed as the consumption of beta-lactamase-sensitive penicillins decreased, whereas the consumption of broad-spectrum penicillins and combination penicillins increased.
Even though this occurs in the context of unchanged antimicrobial guidelines, it raises a suspicion that antibiotics are used for conditions where this is not indicated. Thus, there is a need for further analysis of the consumption in both healthcare sectors.
In primary healthcare as well as in the hospital sector, the use of fluoroquinolones and cephalosporins decreased, but both types of antimicrobials remain widely used.
The increased consumption of broad-spectrum antimicrobials (ciprofloxacin, 2nd generation cephalosporins and carbapenems) recorded at hospitals in recent years coincides with an increased occurrence of resistant E. coli and K. pneumoniae. It is worrying that the occurrence of these resistant bacteria is higher in Denmark than in the other Nordic countries. At the same time, an increasing occurrence of VRE and CPE was observed.
The occurrence of MRSA also increased. Nevertheless, these increases should be considered in light of comprehensive screenings of persons with contact to pigs in recent years, EPI-NEWS 23/15. The share of MRSA-positive piggeries has increased to approx. 60-70%, and up to 80% of employees with contact to MRSA-positive pigs may test positive to livestock associated MRSA. This means that the carrier state is very prevalent in some parts of the population, which - of course - causes concern.
It is important to continually strive for a more rational antimicrobial consumption at hospitals as well as in primary healthcare. Furthermore, there is a need for additional testing of the spreading of the resistant K. pneumoniae, E. coli, VRE and MRSA and for comprehensive initiatives aiming to curb the spreading of infection.
(U.W. Sönksen, S.S. Olsen, K.G. Kuhn, A. Petersen, A.R. Larsen, E.M. Nielsen, S. Hoffmann, T. Dalby, A.M. Hammerum, R.L. Skov, Microbiology and Infection Control, M. Laursen, Data Delivery and Medicinal Product Statistics)
21 October 2015