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Swedres-Svarm Summary 2017

The situation in Sweden regarding antibiotic resistance in bacteria from humans and animals is still favourable from an international perspective. This confrms that our strategies to promote the rational use of antibiotics and to limit the spread of antibiotic resistance are effective. In the last decades the consumption of antibiotics in Sweden has decreased in both humans and in veterinary medicine. Despite this, most of the monitored types of antibiotic resistance in bacteria from humans have continued to increase since national surveillance began in the late 1990s. This is, in some cases, also true for bacteria from animals.

The key fndings in this year’s report are a lower number of cases of methicillin-resistant Staphylococcus aureus (MRSA) and ESBL, that the cases of carbapenemase-producing Enterobacteriaceae (ESBLCARBA) in humans remains at around 120 cases per year, several outbreaks of VRE in hospitals, as in previous years, and a continuing decrease in the occurrence of Clostridium diffcile infections. Previous years increased number of cases of MRSA and ESBL associated with the high number of refugees seeking asylum highlights the importance of travelling for the spread of these resistant bacteria. This increase in MRSA has not led to an increased spread in hospitals, and future risk of such spread is considered small, as preventive measures during several years has succeeded in maintaining the spread of MRSA in health care at a low level.

The extremely resistant bacteria ESBLCARBA are so far uncommon in Sweden, and it is important to detect them early and prevent dissemination in health care.

In the veterinary sector, MRSA is rare in both farm and companion animals in Sweden. ESBL-producing Enterobacteriaceae are, with the exception of broilers, rare among animals in Sweden and ESBLCARBA has not been reported.

This year’s report also show that the consumption of antibiotics has continued to decrease in human medicine. Within veterinary medicine has the consumption of antibiotics also decreased over time.

Consumption of antibiotics

Antibiotic consumption in humans

The total antibiotic sale (including outpatient care and hospital care) decreased by 1.9% in 2017 compared with 2016 (from 12.5 to 12.3 DDD per 1 000 inhabitants and day).

Outpatient care
In outpatient care (including prescription sales), antibiotic sales decreased by 2.8% from 318 to 309 prescriptions per 1 000 inhabitants. The sales decreased in all age groups with the greatest decrease seen among children 0-6 years. The sales in this age group decrease by 7.2% compared with 2016. The decrease encompasses most antibiotic groups with the exception of combinations of penicillins, trimethoprim with sulphonamides, macrolides and nitrofurantoin. Overall, women are prescribed more antibiotics than men.

Beta-lactamase sensitive penicillins, along with tetracyclines and beta-lactamase resistant penicillins, were the most commonly used antibiotics in outpatient care in 2017. Antibiotics commonly used to treat respiratory tract infections were the most frequently sold antibiotics. These substances have decreased most over time out of all types of antibiotics. In 2017 the trend continued with a decrease in sales of these drugs of 4.1% compared with 2016. Cephalosporins decreased by 41% between 2016 and 2017.

Treatment of lower urinary tract infections (UTIs) in women appears to be following national treatment recommendations. In 2017, the total sale of antibiotics commonly used to treat UTIs in women aged 18–79 years decreased by 1.1% compared with 2016. Sales increased for the recommended drug, nitrofurantoin, and decreased for trimethoprim and fluoroquinolones. These trends are also seen when it comes to UTI antibiotics to men with decreasing sales over time.

In 2017, the total sales of antibiotics commonly used to treat UTIs in men 65 years and older remained the same as in 2016. However, the sales of fluoroquinolones decreased by 4.3% compared with 2016, while the sales of pivmecillinam and nitrofurantoin both increased, by 4.1% and 10.3% respectively (measured as prescriptions per 1 000 men per year).

The sales of antibiotics decreased in 19 of Sweden’s 21 counties. There are still major regional differences within Sweden and the number of prescriptions per 1 000 inhabitants ranges from 353 in Gotland County to 246 in Västerbotten County.

Dentists account for approximately 6% of all antibiotics prescribed in outpatient care in Sweden. In 2017 the sales of J01 and metronidazole (P01AB01) prescribed by dentists continued to decrease, from 22 to 21 prescriptions per 1 000 inhabitants.

Hospital care
The total antibiotic sale to hospital care in Sweden has been relatively stable since 2007. During 2017 the sales decreased slightly compared with 2016, from 1.58 DDD per 1 000 inhabitants and day to 1.53 DDD per 1 000 inhabitants and day. In acute care hospitals, there has been a signifcant increase in sales of beta-lactamase resistant penicillins, betalactamase sensitive penicillins and combinations of penicillins the last years. Carbapenems decreased slightly in 2017, which might indicate a change of the former increasing trend of this substance. After many years of increase, sales of Combinations of penicillins (in which Piperacillin with tazobactam (J01CR05) represents the biggest proportion) decreased for the frst time in several years (7%). This can be explained by shortages of these substances. In general, the sales of narrow spectrum antibiotics have increased in the last years and are the groups that are used the most in hospital care in Sweden.

Sales of antibiotics for animals

In 2017, reported sales of antibiotics for animals were 10 310 kg, of which 57% were for benzylpenicillin. The corresponding fgures for 2008 were 16 364 kg and 47%, respectively. These fgures include products for intramammary treatment. Since the withdrawal of growth-promoting antibiotics from the market in 1986, the total sales of antibiotics have decreased by two thirds when corrected for different population sizes over time. During the 1990s, sales of veterinary products for medication of groups of animals decreased, and in the past decade there has also been a decrease in sales of products for use in individual animals.

Comparing consumption of antibiotics in human and veterinary medicine

In 2017, a total of 60.8 tonnes of antibiotics were sold for human use and 10.2 tonnes were sold for animal use. Measured as milligrams of active substance per kilogram biomass, the consumption was 90.5 and 12.8 milligrams per kilogram, respectively. Consumption by humans still dominates for all classes of antibiotics except for trimethoprim-sulphonamides and aminoglycosides.

Notifiable resistance

ESBL

A total of 10 084 human cases of extended spectrum betalactamase (ESBL)-producing Enterobacteriaceae were reported in 2017, a decrease with 5% compared to 2017, and 11 of Sweden’s 21 counties reported less cases. The most commonly reported species was Escherichia coli with 86% of all cases followed by Klebsiella pneumoniae with 10%. Most ESBL-producing bacteria were found in urine samples. Invasive infections with ESBL-producing bacteria were reported in 594 cases in 2017 compared to 609 cases in 2016.

A special type of ESBLs, so-called ESBLCARBA, confers resistance to carbapenems as well as other classes of betalactam antibiotics. Bacteria with this extended resistance mechanism are notifable for both clinicians and laboratories since 2012. A total of 116 new cases were detected in 2017 compared to 127 cases 2016, and the two most common types of enzymes were OXA-48 and NDM. An hospital-related outbreak with an OXA-48 producing E. coli was detected during the year with fve cases. As the treatment alternatives for these infections are few if any, it is necessary to undertake active surveillance of these new and extremely resistant bacteria in order to detect them at an early stage and thereby prevent their spread within the health care system.

ESBL-producing Enterobacteriaceae are, with the exception of broilers, rare among animals in Sweden. In 2017, the occurrence of ESBL-producing E. coli in intestinal samples from pigs, samples of pork and beef, and in intestinal samples from broilers was investigated with screening methods. Such bacteria were isolated from 4% of the intestinal samples from pigs, 0 and <1% of the pork and beef samples of Swedish origin, and 34% of the intestinal samples from broilers. The occurrence in intestinal samples from broilers was comparable with previous years. Changes in the screening methodology prevent any direct comparisons with the fgures from previous years.

MRSA

The total number of human cases of MRSA was 3 375 in 2017, a decrease with 15% compared to 2016. After the sharp increase of cases seen in 2015–2016 the rate of increase seems to decline to the slower rate seen in previous years. The increase during 2015–2016 was mainly comprised of cases among persons seeking asylum and was likely due to higher prevalence, increased need for medical care, and increased sampling in this group. No increased spread of MRSA in hospitals has been reported in connection with this increase among persons seeking asylum, nor has there been a progressive increase in domestic cases of MRSA in the general population.

A nearly equal number of MRSA infections were acquired in Sweden and abroad. Community-acquired infections dominated among domestic cases (72%) and were less frequent among imported cases (53%). Hospital-acquired infections were comparatively more common in imported cases (22%) than among domestic cases (7%). Fifty-fve invasive isolates of MRSA were reported in 2017.

MRSA is notifable in animals in Sweden. The occurrence is still low, which limits the spread from animals to humans. In 2017, MRSA was isolated from the animal species horse, dog, cat, rabbit, cattle, goat and sheep. MRSA with mecC was isolated from several animals in a goat herd. In companion animals, the same types of MRSA as in humans dominate, indicating a human source of MRSA in these animals. In horses, livestock-associated MRSA CC398 is the most common type but other types occur. At two occasions in 2017, spread of MRSA was suspected between horses in equine clinic facilities.

MRSP

In 2017, the number of notifed cases of methicillin-resistant Staphylococcus pseudintermedius (MRSP) was on the same level as 2016. In total, 47 cases were notifed in 2017, which can be compared to 55 cases in 2016 and 60 cases in 2015. All cases in 2017 were dogs. In previous years, the clone ST71 has dominated among Swedish cases, but now the picture is becoming more diverse. The clones ST71 and ST258 are most common but several other types were also detected in 2017. MRSP in humans is not notifable.

PNSP

Sixty-one cases of pneumococci with reduced susceptibility to penicillin (PNSP, defned as MIC > 1 mg/L) were reported in 2017, and in 2016 there were 67 reported cases. Five invasive cases were reported.

VRE

In 2017, a total of 244 new cases of vancomycin-resistant enterococci (VRE) were reported compared to 165 cases in 2016. Enterococcus faecium carrying the resistance gene vanA (161 cases) was more common than those carrying vanB (68 cases). In 2017 there were four large hospital outbreaks reported. During earlier years with large hospital outbreaks, vanB has been the most common resistance gene. Two invasive VRE infection were reported in 2017.

Zoonotic pathogens

Salmonella is rare in animals in Sweden, and few incidents involve antibiotic-resistant strains. Strains with ESBL resistance have never been found in isolates from animals in Sweden, and resistance to fluoroquinolones is rare. Usually humans diagnosed with Salmonella in Sweden has contracted the infection abroad or through imported foodstuffs. This is most likely the explanation to the higher levels of resistance, e.g. to fluoroquinolones, in isolates from humans than in isolates from Swedish animals.

Campylobacter from animals in Sweden are mostly susceptible, and resistance to erythromycin, for example, is most uncommon.

Infections, either in humans or in animals, caused by Salmonella and Campylobacter are usually not treated with antibiotics. See the “Comparative analysis” section of each bacterium.

Human clinical isolates

In this Swedres-Svarm report almost all data on clinical isolates from humans have been collected through Svebar. This is an automated system that collects all culture results from participating laboratories. Currently 19 laboratories deliver data to Svebar. In contrast to previous years, the data for this year will contain all culture results from different individuals, e.g. duplicate fndings from blood cultures. This is expected to cause some differences in resistance levels, especially for species isolated less frequently and for unusual resistance types.

In E. coli and K. pneumoniae from blood, the levels of resistance to third-generation cephalosporins has increased continually, and is now approximately 6% and 5.4%, respectively. MRSA isolates accounted for 1.8% of S. aureus from skin and soft tissue infection, which is low from a European perspective. The rate of non-susceptibility to penicillins in Streptococcus pneumoniae from nasopharynx (referred to as PNSP) was 12% in 2017. For invasive E. faecalis the rate of vancomycin resistance was 0.5 % and no vancomycin resistance was found among invasive E. faecium.

Other bacterial species are included in special surveillance programmes and are often referred to special laboratories, including C. diffcile, Mycobacterium tuberculosis, Neisseria gonorrhoeae, and N. meningitidis.

In 2017, 6 466 new CDI cases were reported corresponding to an incidence of 64 cases per 100 000 inhabitants, a little less cases than in 2016. No isolates resistant against metronidazole or vancomycin were found in 2017.

In 2017, 2 531 cases of gonorrhea were reported. Resistance to cefxime was 0.6%, and no resistance to ceftriaxone was detected. This is a very positive result because ceftriaxone is the last available agent for the empirical treatment of gonorrhoea.

Animal clinical isolates

Bacteria causing clinical disease in animals are mostly susceptible to antibiotics relevant for treatment. Respiratory pathogens from farm animals and horses are generally susceptible to benzylpenicillin, but penicillin resistance is common in Staphylococcus pseudintermedius from dogs and occurs in S. aureus from horses and Staphylococcus felis from cats. Resistance in E. coli occurs in all animals but is most prominent in enteric isolates from young calves. Susceptibility testing for guidance in antibiotic therapy is warranted, especially for staphylococci, E. coli and Brachyspira spp.

Indicator bacteria from healthy animals

Antibiotic resistance in E. coli from the intestinal flora of healthy animals serves as an indicator for the presence of resistance in an animal population. The prevalence of acquired resistance in such commensal bacteria also indirectly indicates the magnitude of the selective pressure from the use of antibiotics in an animal population. The prevalence of resistance in indicator bacteria from animals in Sweden is low, and the situation is favourable in an international perspective. 

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