No 43 - 2013

DANMAP 2012: 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 2012 DANMAP report is available at www.danmap.org. The report describes the main characteristics and trends in antimicrobial consumption and resistance in humans.

Total antimicrobial consumption

In 2012, total consumption of antimicrobials for systemic human treatment in primary and secondary healthcare decreased by 2% compared with 2011. As previously, primary healthcare (general practice and medical specialists) accounted for 90% of the total consumption. Over a ten-year period (2002 to 2012), the total consumption of antimicrobials in Denmark rose by 23%.

Antimicrobial consumption in primary healthcare

The consumption of antimicrobials in primary healthcare decreased by 3% compared with 2011. For some groups of antimicrobials, including "combination penicillins" and tetracyclines, an increase was observed. Many of the prescriptions for tetracycline were prescribed for treatment of skin disorders such as acne in adolescents.

In 2012, penicillins comprised 65% of the total consumption in primary healthcare. In the past decade, the consumption of antimicrobials in primary healthcare rose by 22%. Part of this increase coincides with changed guidelines according to which the individual patient receives a higher dose per treatment than was previously the case. In November 2012, a website was launched targeting citizens www.antibiotikaellerej.dk with information about antimicrobials.

Antimicrobial consumption in the hospital sector

In hospitals, the total antimicrobial consumption increased by 3% from 2011 to 2012. The consumption of "combination penicillins", beta-lacmatase-resistant penicillins and beta-lacmatase-sensitive penicillins increased, whereas a decrease was observed in the consumption of second and third generation cephalosporins, carbapenems and fluoroquinolones.

The changes were in accordance with the National Danish guideline on prescription of antimicrobials, published by the Danish Health and Medicines Authority in November 2012.

Resistance

In 2012, a total of 1,556 new cases of methicillin-resistant Staphyloccocus aureus (MRSA) were detected, compared with 1,292 in 2011. This corresponds to a 20% increase. The increase initiated in 2010 thus continued in 2012. The increase was primarily due to community-acquired cases and it includes both colonised persons and patients with clinical infection.

The share of infected patients in 2012 was at par with that of 2011 (54% versus 53%). The number of hospital-acquired cases remained low and only comprised 4% of the total number of MRSA cases in 2012. A total of 232 new human cases of CC398 MRSA (an MRSA type associated with contact to pigs) were observed in 2012, and this type thus comprised 15% of all cases. The number observed in 2012 equals a 41% increase relative to 2011 (164 cases).

In 2012, the occurrence of resistance to third-generation cephalosporins for both Klebsiella pneumoniae (9%) and Escherichia coli (7%) from blood was in line with that observed in 2011. Resistance to third-generation cephalosporins may be used as a marker for ESBL production in bacteria. In comparison, the occurrence of resistance was below 5% for both types of bacteria in 2006.

Resistance to third-generation cephalosporins in E. coli urine isolates from patients admitted to hospital increased from 5% in 2011 to 6% in 2012. Similarly, the occurrence of resistance to third-generation cephalosporins in E. coli from urinary tract infections in primary healthcare increased from 3% in 2011 to 4% in 2012. Ciprofloxacin resistance among E. coli isolates from urinary tract infections in patients from primary healthcare increased from 2% in 2003 to 10% in 2012.

In 2012, a total of four new cases of carbapenemase-producing Enterobacteriaceae, and another four cases of carbapenemase-producing (VIM) Pseudomonas aeruginosa were identified. Furthermore, a cluster of multi-resistant carbapenemase-producing (OXA-23) Acinetobacter baumanii was observed in 2012 at a hospital in the Capital Region of Denmark.

Additionally, a limited number of cases of OXA-23-producing A. baumanii were reported from three other DCMs. As carbapenemase-producing bacteria are not notifiable in Denmark, more cases may have occurred.

In 2012, two DCMs reported outbreaks with vancomycin- and ampicillin-resistant Enterococcus faecium (vanA). These outbreaks are currently being investigated.

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.

Commentary

Despite a considerable focus on resistance problems, the past ten years have seen an increased consumption of critically important antimicrobials at hospitals (ciprofloxacin, second- and third-generation cephalosporins and carbapenems) and in part also in primary healthcare (ciprofloxacin). The same period has seen an increased occurrence of infections with bacteria that are resistant to the critically important antimicrobials, e.g. E. coli which is resistant to third-generation cephalosporins.

The new guidelines from the Danish Health and Medicines Authority and the efforts targeting citizens seek in particular to reduce the consumption of these antimicrobials. It is too early to determine if these initiatives will have an effect on the consumption of antimicrobials and the occurrence of resistance.

The increased consumption of tetracyclines in adolescents is worrying as tetracycline is a broad-spectrum antimicrobial capable of exerting a selection pressure on bacteria that are also resistant to the critically important antimicrobials.

Acne treatments with tetracycline are frequently prolonged treatment courses (≥ 3 months). The normal flora in the young persons is therefore exposed to antimicrobials during a prolonged period of time which carries an increased risk that bacteria occur that are resistant to several different antimicrobials.

The low occurrence of hospital-acquired MRSA shows that Danish MRSA guidelines are effective at hospitals. The continued increase in the number of community-acquired MRSA cases is probably associated with travel activity to other countries and visits from abroad with subsequent spreading in the community.

Additionally, the number of persons infected with MRSA of the type associated with contact with pigs (CC398) continues to rise. As a consequence of the continued increase in the occurrence of community MRSA, the MRSA guideline from the Danish Health and Medicines Authority was revised in November 2012.

Contact to pigs was introduced as a risk factor for MRSA, and patients admitted to hospital should be asked if they have been in contact with pigs. It is remarkable that the type associated with contact with pigs now comprises 15% of all MRSA cases.

Carbapenems are one of the only classes of antimicrobials that can be used for treatment of infections with heavily multi-resistant bacteria such as ESBL-producing E. coli. Frequently, no or only suboptimal antimicrobials (tigecycline, colistin) are available for treatment of infections with carbapenem-resistant organisms.

The growing occurrence of carbapenem-resistant organisms is therefore cause for grave concern. Not only are these infections extremely difficult to treat with antimicrobials, the bacteria carry the potential to establish and spread at hospitals – including in the form of outbreaks – and in the community. This is in line with what is seen for ESBL-producing bacteria.

Due to the seriousness of this issue, the ECDC (European Centre for Disease Prevention and Control) encourages systematic monitoring of carbapenem-resistant bacteria in all European countries.

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 multi-resistant bacteria.
A. M. Hammerum, L. Skjøt-Rasmussen, S. S. Olsen, K. G. Kuhn, M. Torpdahl, E. M. Nielsen, A. R. Larsen, A. Petersen, R. L. Skov, Department for Microbiology and Infection Control, M. Laursen, Department for Data Delivery and Medicinal Product Statistics.

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23 October 2013