No 48 - 2016

DANMAP 2015

The annual DANMAP report (Danish Integrated Antimicrobial Resistance Monitoring and Research Programme) provides an overview of the Danish consumption of antimicrobial agents used for animals and humans and the development of resistance in bacteria collected from animals, food and humans.

The report is the result of the collaborative efforts of DTU Food, DTU Vet and Statens Serum Institut.

The report has been published annually since 1995 and it is the most comprehensive source of monitoring of antibiotic resistance in Denmark. The DANMAP 2015 report is an anniversary edition, which – apart from the normal chapters - also describes the DANMAP collaboration in a historical perspective.

The 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.

Consumption

Total consumption of antimicrobials for patients

In 2015, the total human consumption of antimicrobials for systemic use (primary healthcare and hospitals pooled) was 18.5 DID (Defined Daily Doses per 1,000 inhabitants), which is nearly identical to the 18.6 DID recorded in 2014.

Primary healthcare accounted for nearly 90% of the consumption with 16.5 DID and the hospitals generated the remaining 2 DID. 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. Within the past ten years, the consumption first increased by 12% from 2006 to 2011, but then decreased by 4% in the subsequent period.

Antimicrobial consumption in primary healthcare

Penicillins constitute the largest group of antimicrobials in primary healthcare, and in 2015 penicillins accounted for 65% of the total consumption. This group 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 9% of the total consumption, respectively. Inversely, the use of beta-lactamase-sensitive penicillins (phenoxymethylpenicillin) has now declined to 26% of the total consumption.

Ten years ago, the beta-lactamase-sensitive penicillins accounted for 35% 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 urinary tract infections and airway infections (including treatment of acute bronchitis/COLD). Nevertheless, the increased use of combination penicillins may also reflect a shift in the attitude among prescribing doctors towards more broad-spectrum penicillins.

Children and elderly people account for the greatest antimicrobial consumption. This year, the consumption of children and adolescents aged 0-18 years was presented separately. The consumption shows an overall decrease in the course of the past ten years in the use of the four primary antibiotic drug groups; beta-lactamase-sensitive penicillins, extended-spectrum penicillins, macrolides and tetracyclines. The total consumption in this age group decreased from 32.3 DID in 2006 to 26.1 DID in 2015 (-19%).

The antimicrobial consumption in primary healthcare may also be stated as the total number of prescriptions dispensed. In the course of the past ten years, the total number of prescriptions dispensed has decreased from 604 prescriptions per 1,000 inhabitants in 2006 to 531 prescriptions per 1,000 inhabitants in 2015.

Antimicrobial consumption in the hospital sector

The hospital consumption is typically stated as defined daily doses per 100 bed-days (DBD) or per 100 admissions (DAD).

When stated as DBD, the antimicrobial consumption at somatic hospitals decreased for the first time in ten years, from 104.3 DBD in 2014 to 103.0 DBD in 2015. In the course of 10 years, the total consumption of antimicrobials increased by as much as 52% as the use in 2006 was 67.7 DBD. This increase may, in part, be accounted for by shorter treatment courses.

The average number of bed days per treatment has therefore now been reduced compared with previously, and hospitals have simultaneously increased their activity. When stated as DAD, the antimicrobial consumption decreased from 324.1 DAD in 2014 to 313.5 DAD in 2015. In the ten-year period from 2006 to 2015, the consumption increased by 9% when stated as DAD.

As for primary healthcare, the penicillin group constituted the greatest share, a total of 51%, including beta-lactamase-sensitive and beta-lactamase-resistant penicillins with each 9%, extended-spectrum penicillins with 16% and combination penicillins with 17% of the total hospital consumption.

Thus, for the first time, the combination penicillins comprised the largest of the penicillin groups at the hospitals.
Just like for primary healthcare, the considerable increase in the consumption of combination penicillins at the hospitals is remarkable; from 2014 to 2015, the consumption of this drug group rose by 11% (from 16.0 DBD in 2014 to 17.8 DBD in 2015).

This substantial increase is mainly due to the fact that piperacillin/tazobactam has become an important part of empirical sepsis treatment at the hospitals.

Consumption of critically important antimicrobials

Since 2011, a slight decrease has been recorded in the use of fluoroquinolones following the trend in the total antimicrobial consumption in the same period. In primary healthcare, fluoroquinolones comprised an unchanged 3% of the total consumption in 2015, whereas this group comprised 9% of the consumption at hospitals.

The consumption of cephalosporines at hospitals peaked in the 2009-2011 period and has subsequently decreased, but comprised 15% of the total antimicrobial consumption at hospitals in 2015 (compared with 11% in 2014). The consumption of carbapenems has increased steadily over the past decade, but remained nearly unchanged from 2014 to 2015 (4% of the total consumption).

Resistance

As in the previous years, the occurrence of ciprofloxacine-resistant Salmonella Typhimurium was higher among the travel-associated infections (20%) than among infections acquired in Denmark. Eleven S. Typhimurium isolates (5% of the cases) were resistant to 3rd generation cephalosporines.

None of the Salmonella isolates, where the resistance pattern has been established, from animals, meat or humans, exhibited carbapenemase activity (meropenem resistance).

Among Campylobacter jejuni detected in patients with travel-associated infections, the occurrence of fluoroquinolone resistance (79%) was also higher than in isolates from patients whose infections had been acquired in Denmark (42%).

Among the approx. 4,600 isolates of Escherichia coli from blood cultures, the occurrence of resistance to 3rd-generation cephalosporines was 7% and for ciprofloxacin it was 12%. Both remained unchanged compared with 2014.

This year, DANMAP presents resistance data for E. coli covering all of the 20 years during which monitoring has been in place. Generally, the occurrence of resistance in E. coli has followed an increasing trend from around 2003 and until 2011, after which resistance has stagnated. For ampicillin, these 20 years have brought an increase from 35% at the end of the 1990s to 45% from 2007 onwards.

For Klebsiella pneumoniae isolates from blood cultures (n=943), the occurrence of resistance to 3rd-generation cephalosporines was 8% and for ciprofloxacin it was 6%. Generally, the occurrence of resistance in K. pneumoniae has followed a decreasing trend since it peaked in 2009 at e.g. 12% for 3rd-generation cephalosporines and 18% for ciprofloxacin.

For E. coli, Denmark is now closing in on the occurrence of resistance in the remaining Nordic countries after recording considerably lower Danish occurrences in the period from about 2007 to 2013.

Thus, the resistance to, e.g. 3rd-generation cephalosporines in E. coli was 6% in Norway, 6.2% in Sweden and 6.1% in Finland, whereas resistance to 3rd-generation cephalosporines in K. pneumoniae remained somewhat lower in the remaining Nordic countries; 5% in Norway, 3.3% in Sweden and 3.0% in Finland (EarsNet data for 2015). The resistance of both bacterial species to meropenem remains at <1%.

Among Streptococcus pneumoniae isolates from blood and spinal fluid, the occurrence of penicillin and erythromycin resistance remained low in 2015 (5% and 5%, respectively).

Ciprofloxacin resistance among Neisseria gonorrhoeae was 29% in 2015 compared with 46% in 2014 and 56% in 2013. The occurrence of resistance has decreased steadily since 2009 where it peaked at 75%.

In 2015, a total of 1,973 cases of bacteraemia with Staphylococcus aureus were reported. This corresponds to an annual incidence of 36.7 cases per 100,000 inhabitants. The number of methicillin-resistant S. aureus (MRSA) was 29 (1.5%) compared with 57 (2.9%) in 2014. The number of MRSA bacteraemias was at par with the level observed the previous years, which is still very low compared with the other European countries.

The number of new MRSA cases in 2015 was 2,972 (infections and carrier state); for comparison, 2,965 cases were observed in 2014, EPI-NEWS 23/16. Infection was detected in 39% of all new MRSA cases, but only in 18% in the group that was infected with livestock MRSA CC398.

This is mainly owed to the special efforts made to screen people who work with pigs, causing this group to be over-represented among the screened persons.

Increases in the occurrence were mainly recorded among community-acquired MRSA cases (1,057 in 2015; 945 in 2014) and imported (500 in 2015; 411 in 2014) MRSA cases, whereas a slight decrease was recorded for livestock MRSA CC398 (1,173 in 2015; 1,277 in 2014). The occurrence of hospital-acquired cases remained very low at only 40 recorded cases in 2015.

In 2015, an increase was once again seen in the number of patients who had infections with the multi-resistant bacteria vancomycin-resistant enterococci (VRE) and carbapenemase-producing organisms (CPO) in Danish hospitals. 2015 saw a total of 372 reported clinical VRE cases compared with 303 cases in 2014 and 235 cases in 2013. The increased occurrence of VRE was primarily associated with hospital outbreaks, and the occurrence was most prominent in the Capital Region of Denmark and in Region Zealand.

In 2015, a total of 91 carbapenemase-producing organisms (CPO) were detected in specimens from 85 patients. Previously, findings of CPO have been travel-associated, but in 2014 and 2015, the source for several of the CPO findings remained unknown or was related to Danish outbreaks.

Commentary

The total human antimicrobial consumption has increased markedly compared with the consumption recorded at the end of the 1990s. Even though a slight decrease in consumption has been observed since 2011 in primary healthcare, and the first ever decrease in the hospital consumption was seen in 2015, it is estimated that an overconsumption of antimicrobials occurs in both healthcare sectors.

This is clear both from the considerable increase in use of combination penicillins in both sectors over the past ten years and from a continued high consumption of critically important antimicrobials at the hospitals. The consumption is not due to an increased occurrence of resistant bacteria as a decrease was recorded for E. coli and K. pneumoniae in the occurrence of resistance to ciprofloxacine and 3rd generation cephalosporines since these peaked in 2011 and 2009, respectively.

Nevertheless, the occurrence of resistance in E. coli and K. pneumoniae remains markedly higher today than 20 years ago.

The increase in CPO and VRE causes grave concern as few antimicrobials are available for the treatment of infections with these bacteria.

The MRSA occurrence stagnated in 2015. The observed decrease in livestock MRSA CC398 may possibly have been recorded because most of the persons at risk (with contact to livestock) have already been registered. The same saturation is not likely to occur in the group with no livestock contact. In 2015, this group counted 77 cases who had infections compared with 72 in 2014. This indicates that secondary spreading to the general population is not increasing substantially.

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 CPO, VRE and MRSA and for comprehensive efforts aiming to curb the spreading of infection.

(U.W. Sönksen, S. Skovgaard, S.S. Olsen, K.G. Kuhn, A. Petersen, J. Larsen, A.R. Larsen, M. Torpdal, S. Hoffmann, T. Dalby, H. Hasman, A.M. Hammerum, Louise Roer, Microbiology and Infection Control, M. Laursen, Data Delivery and Medicinal Product Statistics)

Fighting discrimination of HIV positives

1 December is international World AIDS Day. The objective of the day is to create awareness of the global as well as local fight against HIV and AIDS. The theme of this year’s Danish AIDS Foundation campaign is anti-discrimination: “Meet people with HIV the same way you meet anyone else”

Worldwide, the number of new HIV cases and the number of AIDS fatalities are decreasing. But the number of people who are diagnosed exceeds the number who initiate treatment. In other words; the world's HIV-positive people are not provided with treatment as rapidly as they should be.

In Denmark, free HIV-testing and effective treatment have been available for many years. In the group that is most frequently diagnosed with HIV, i.e. men who have sex with men, an increasing number of people are being tested frequently, and therefore those who have become infected with HIV are diagnosed earlier.

Early diagnosis benefits the HIV-positive person owing to the health benefits associated with starting treatment immediately. It is also an advantage for society as a well-treated HIV-positive person will not pass on the infection.

Due to fear of stigma and discrimination, some of those who might suspect that they had become infected with HIV opt out of testing. The fear for discrimination is well-founded. Many Danes still believe that HIV can be transmitted through saliva, kissing, tears or hugs, even though this is incorrect.

This is so despite the fact that, thanks to modern medicines, well-treated HIV is no longer transmitted through sexual contact. This lack of knowledge therefore becomes a problem for HIV prevention in Denmark.

The Danish AIDS Foundation’s World AIDS Day campaign 2016 aims to make Danes abandon fear and invite people with HIV into their lives.

As the fear of HIV positives recedes, it is hoped that stigma and discrimination may be avoided and that more Danes will show courage and have HIV tests performed earlier and more frequently, which will allow more HIV positives to receive early treatment, which, in turn, will break more chains of infection.

Nevertheless, early testing and treatment alone are not sufficient if we are to markedly reduce the number of new HIV diagnoses. For that to happen, a strong focus on HIV prevention is needed.

In this year’s International World AIDS Day campaign, UNAIDS focuses on known as well as novel methods of HIV prevention. Particular attention is given to pre-exposure prophylaxis (PrEP). PrEP aims at treating the people who are at the greatest risk of contracting HIV with preventive HIV medicines.

This form of prevention has proven more effective than any other treatment, and it is recommended by the UNAIDS, the WHO, the ECDC and several other international organisations that focus on HIV. PrEP is suitable only for people who are at a specially high risk of contracting HIV, which in the Danish context in practice means men who have sex with men.

In addition to PrEP, other preventive methods are also a focus area, including: condoms, lubricants, clean syringes, needles and other injection gear and substitution treatment with e.g. methadone and (in Africa) voluntary male circumcision. As well-treated HIV positives do not transmit HIV, treatment for HIV is also an effective preventive method (treatment as prevention, TasP).

To offer treatment, the person's HIV status needs to be known and for that HIV testing is required. 
The Danish Health Authority's guideline on HIV testing ( identifies three main groups who should be offered testing:

• Men who have sex with men should be tested a minimum of once annually, and more frequently if they have condom-free sex.
• Immigrants from Sub-Saharan Africa, Asia and Eastern Europe should be tested upon arrival to Denmark or the first time they come into contact with Danish healthcare, regardless of the cause for such contact.
• Finally, patients who present with unexplainable symptoms or with signal conditions should also undergo HIV testing.

(S. Cowan, Department of Infectious Disease Epidemiology)

Link to previous issues of EPI-NEWS

30 November 2016