No 42-43 - 2014

DANMAP 2013: Antimicrobial consumption and resistance

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 follows the development of resistance in bacteria collected from animals, food and humans. The 2013 DANMAP report is available at www.danmap.org. The present issue of EPI-NEWS describes the main characteristics and trends in antimicrobial consumption and resistance in humans.

Total antimicrobial consumption

From 2012 to 2013, the total consumption of antimicrobials for systemic use (primary healthcare and the hospital sector taken together) increased by 1.2% in Denmark. As previously, 90% of the total antimicrobials were consumed in primary healthcare (general practices and medical specialists). Over a ten-year period (2004 to 2013), the total consumption of antimicrobials in Denmark has increased by 20%.

Antimicrobial consumption in primary healthcare

Compared with 2012, the total antimicrobial consumption in primary healthcare increased by 1.2%. Over the past decade, the consumption of antimicrobials in primary healthcare has increased by 19%. This increase may, in part, be explained by a higher dose (defined daily dose (DDD)) per treated patient and in part by an increased dose per medicine package prescribed.

The most prominent increases from 2012 to 2013 were observed for tetracyclines, "combination penicillins" (penicillin in combination with enzyme inhibitors), beta-lactamase-resistant penicillins and extended-spectrum penicillins. In contrast hereto, the consumption of macrolides decreased by 12%, which is a continuation of a decreasing trend that began in 2011.

Compared with 2012, the total consumption of broad-spectrum antimicrobials rose by 5.7%. From 2005 to 2013, the total consumption of tetracyclines increased by 54%. The largest increase was seen among the 10-14-year-olds (86%) and among the 15-19-year-olds (58%). That means that 5,400 more adolescents were treated with tetracyclines in 2013 than in 2005 (adjusted for population changes).

The majority of the prescriptions were probably for treatment of acne. GPs prescribed tetracyclines more frequently than dermatologists, and considerable geographical variation was observed in the prescription of tetracyclines.

Antimicrobial consumption in the hospital sector

At somatic hospitals, the total antimicrobials consumption stated as DDD per 100 bed days increased by 1.4% from 2012 to 2013.

Compared with 2013, a rise was observed in the consumption of "combination penicillins" and in the combination of sulphonamide and trimethoprim, beta-lactamase-resistant penicillins, extended-spectrum penicillins and carbapenems A decrease was observed in second-generation cephalosporines, fluoroquinolones, macrolides and tetracyclines. From 2004 to 2013, the total antimicrobials consumption in hospitals increased by 66%, and the consumption of broad-spectrum antimicrobials rose by 114% stated as DDD per 100 bed days. This increase is attributed to a combination of an increase in DDDs and a decrease in the number of bed days.

Resistance

Among E. coli blood infections and urinary tract infections from patients in hospitals and in practices, respectively, the occurrence of resistance in 2013 was in line with that observed for 2012, except for ciprofloxacine resistance in E.coli from blood infections, which decreased to 12% in 2013 compared with 14% in 2012.

In 2013, a total of 18 carbapenemase-producing Enterobacteriaceae (CPE) were detected compared with 19 CPE in the entire 2008-2012 period. In 2013, spreading of NDM-1-producing Citrobacter freundii occurred between four patients. None of the patients had recently returned from travels, and the infection source of the C. freundii was unknown. Two of the four C. freundii patients also had NDM-1-producing K. pneumoniae. The spreading of the NDM-1-producing C. freundii continued to a fifth patient in 2014.

In addition to the 18 CPE, 12 cases of carbapenemase-producing Acinetobacter baumannii and five carbapenemase-producing bacteria Pseudomonas aeruginosa were detected. In two cases, spreading of OXA-23-producing A. baumannii between two patients was seen. In 2013, three cases of OXA-40-like-producing A. baumannii were observed. This cluster also included infection spreading from one patient to another.

Additionally, two NDM-1-producing A. baumannii cases were detected. Three VIM-producing, one NDM- and VIM-producing and, for the first time ever in Denmark, an IMP-producing P. aeruginosa were detected. The patients with the two latter P. aeruginosa had both previously been admitted to hospitals abroad.

As in previous years, the occurrence of resistance to ciprofloxacin was higher in Salmonella Typhimurium and Campylobacter jejuni isolates from patients with infections acquired abroad than in isolates from patients with infections acquired in Denmark.

In 2013, the Reference Laboratory for Antimicrobials Resistance and Staphylococci at the SSI received the greatest number to date of vancomycin-resistant enterococci (VRE); 248 isolates from infections and 168 from faecal screenings EPI-NEWS 16-17/14. For comparison, in the 2005-2011-period, less than 30 clinical VREs were received annually, whereas the number increased to 52 VREs in 2012. Nearly all VRE were vanA Enterococcus faecium isolates.

The VRE isolates were primarily from hospitals situated in the Capital Region of Denmark, but there were also isolates from hospitals in Region Zealand and the Central Denmark Region. VRE was also found in the two remaining regions, but the numbers were considerably lower. Typing of isolates from 2012 and 2013 show that several strains are spreading. However, the same clonal types also spread both within hospitals and between hospitals.

The number of new methicillin-resistant Staphylococcus aureus (MRSA) cases (both colonised and infected persons) increased to 2,094 compared with 1,556 cases in 2012, EPI-NEWS 24b/14. The increase was primarily observed for pig MRSA (MRSA CC398), where a total of 643 cases were observed in 2013 compared with 232 cases in 2012.

A considerable share of this increase was probably due to the fact that contact to pigs was made a risk factor as from December 2012 from which point everyone with contact to pigs were to be screened for MRSA when admitted to hospital. In 2013, CC398 comprised 31% of all new MRSA cases.

The majority (87%) of the persons who had CC398 (both infection and colonisation) had been in contact with pigs or lived with persons who had contact to pigs. Among all MRSA cases, the occurrence of infections was lower in 2013 than in 2012 (45% versus 57%), reflecting the increased screening intensity for pig MRSA. The number of hospital-acquired cases (HA) remained very low in 2013 (4%).

Commentary

The increased consumption of tetracyclines in younger persons gives cause for concern. Acne treatment with tetracycline is frequently prolonged (> 3 months). This means that the bacteria found in the gastrointestinal tract and on the skin of the young persons are exposed to prolonged selection pressure, which entails an increased risk of development of resistance.

As there are only few treatment options for serious VRE infections, the described increase and spreading of VRE constitutes a problem.

Experiences from both Denmark and abroad demonstrate that VRE can only be controlled through prolonged and intensified focus, including screening and isolation of VRE patients. This is probably associated with the fact that VRE can persist for prolonged periods of time in hospital environments, particularly if the cleaning is not very thorough, and that VRE may be carried asymptomatically in the intestine. No treatment is available for the carrier state in the intestine.

The known screening methods are time- and resource-demanding, and initiation of supplemental infection hygiene precautions is therefore a major challenge for hospitals and for the nursing sector. Local awareness of the VRE carrier state and infections is essential in limiting further transfer as much as possible.

Carbapenems are one of the only classes of antimicrobials that can be used for treatment of infections with multi-resistant bacteria such as ESBL-producing E. coli. Treatment of infections caused by carbapenem-resistant bacteria is difficult, as only a limited number of frequently non-optimal antibiotics (tigecycline, colistin) is available. The increasing occurrence of carbapenem-resistant bacteria therefore gives cause for considerable concern.

It is important to pay particular attention to any occurrence of multi-resistant bacteria in patients who are transferred following admission to hospitals abroad, and to patients who have visited countries with a high prevalence of carbepenem-resistant bacteria (Greece, India, Pakistan, etc.).

An increased risk of infection with ciprofloxacine resistant Salmonella and Campylobacter in connection with travels abroad is still observed. Ciprofloxacine-resistant bacteria may be associated with an increased risk of treatment failure, and it is therefore important to take into account any travelling activity before choosing any antimicrobial treatment of suspected Salmonella and Campylobacter infections.

The number of new MRSA cases continued to increase and was higher in 2013 than in any other year since the mid-1970s. Despite this trend, the number of hospital-acquired cases remained low, which indicates that the Danish Health and Medicines Authority's 2006 guideline revised in 2012 remains effective.

A continued increase in the number of pig MRSA (CC398) cases was observed, EPI-NEWS 24a/14. An increase in the number of cases was, in part, expected owing to the revision of the MRSA guideline whereby contact to pigs was added as a risk factor, EPI-NEWS 47/13.

This means that persons working with pigs and their households are tested for MRSA when admitted to hospital and in connection with any infections that may have been caused by staphylococci. Consequently, more samples will be taken from asymptomatic carriers. The share of cases with a clinical infection among MRSA CC398 cases thus decreased from 40% in 2012 to 24% in 2013.

Regardless of this, the total number of infections with pig MRSA increased (92 in 2012 versus 157 in 2013) which indicates a continually expanding reservoir. Pig MRSA is now the most frequently observed type of MRSA in Denmark.
(L. Skjøt-Rasmussen, A. M. Hammerum, S.S. Olsen, K.G. Kuhn, F. Hansen, L. Jakobsen, B. Kristensen, M. Torpdahl, E.M. Nielsen, A.R. Larsen, A. Petersen, R.L. Skov, Microbiology and Infection Control, M. Laursen, Data Delivery and Medicinal Product Statistics)

SSI vaccines expected to be included again in the childhood vaccination programme as from 1 January 2015

We expect that both the SSI's primary vaccine (DTaP-IPV/Hib) and the booster vaccine (DTaP-IPV Booster) will once again be on stock for use in the childhood vaccination programme as from 1 January 2015.

Until then, children initiating the vaccination programme should still be vaccinated with Infanrix hexa®, EPI-NEWS 3/14, and the 5-year-olds should receive their booster vaccination as a DTaP vaccine and IPV vaccine in two separate syringes, EPI-NEWS 18/14.

A more detailed description of the return to the SSI's vaccines will be published in a later issue of EPI-NEWS.
(Department of Infectious Disease Epidemiology)

Link to previous issues of EPI-NEWS

22 October 2014