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Swedres-Svarm Summary 2016

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 human and veterinary medicine. In addition, the sales of broad-spectrum antibiotics have decreased while the use of narrow-spectrum antibiotics has increased. Despite this, most of the monitored types of antibiotic resistance have continued to increase since national surveillance began in the late 1990s.

The key fndings in this year's report are a lower rate of increase for methicillin-resistant Staphylococcus aureus (MRSA) compared to the previous year, an increasing number of community-acquired cases of carbapenemase-producing Enterobacteriaceae (ESBLCARBA) in humans, and a continuing decrease in the occurrence of Clostridium diffcile infections. The increase in ESBLCARBA is considered worrying because it increases the risk of introducing ESBLCARBA among vulnerable patients, such as infants in neonatal units, which can have serious consequences. The increase in MRSA has not led to an increased spread of infection in hospitals, and future risk of such spread is considered small. In the veterinary sector, MRSA is rare in both farm and companion animals, and ESBLCARBA has not been reported.

Consumption of antibiotics

Antibiotic consumption in humans

The total consumption (including outpatient and hospital care) of antibiotics decreased by 1.6% in 2016 compared to 2015 (from 12.7 to 12.5 DDD per 1 000 inhabitants and day).

Outpatient care
In outpatient care (including prescription sales), antibiotic sales decreased by 1.6% from 323 prescriptions per 1 000 inhabitants in 2015 to 318 prescriptions in 2016. However, in the age groups 0–4 years and 5–14 years the sales increased by 4.4% and 2.1%, respectively. The increase was seen during the whole year, except from the frst quarter (January–March) when the sales slightly decreased. In the age groups 15–64 years and 65 years and older the sales continued to decrease as in previous years.

In 2016, there was a decrease in the number of antibiotic prescriptions in 13 out of Sweden’s 21 counties. There are still signifcant regional differences within Sweden, and the number of prescriptions per 1 000 inhabitants ranges from 345 in Stockholm County to 252 in Västerbotten County.

The decrease encompasses most antibiotic groups with the exception of pivmecillinam, beta-lactamase-sensitive penicillins, penicillins combined with beta-lactamase inhibitors, trimethoprim with sulfonamides, and nitrofurantoin.

Beta-lactamase-sensitive penicillins, along with tetracyclines, were the most commonly used antibiotics in outpatient care in 2016. Antibiotics commonly used to treat respiratory tract infections were the most frequently prescribed antibiotics. Among these substances, we have observed the greatest decrease in sales over the years. However, in 2016 the sales of these drugs increased by 1.3%.

Treatment of lower urinary tract infections (UTIs) in women appears to be following national treatment recommendations. In 2016, the total sale of antibiotics commonly used to treat UTIs in women aged 18–79 years decreased by 1.9% compared to 2015. There was increased use of the recommended drugs pivmecillinam and nitrofurantoin and reduced use of trimethoprim and fluoroquinolones.

Positive trends are also seen when it comes to UTI antibiotics to men. The total sales of antibiotics commonly used to treat UTIs in men 65 years and older decreased by 0.9% compared to 2015. In 2016, the sales of fluoroquinolones decreased by 3.1% compared to 2015, while the sales of pivmecillinam and nitrofurantoin increased by 8.3% and 3.6% (measured as prescriptions per 1 000 men and year), respectively.

Dentists account for approximately 6% of all antibiotics prescribed in outpatient care in Sweden. The sales of J01 and metronidazole (P01AB01) prescribed by dentists decreased by 3.0% in 2016 compared to 2015 – from 22.9 to 22.2 prescriptions per 1 000 inhabitants.

Hospital care
The total consumption of antibiotics in Swedish acute care hospitals was slightly lower in 2016 compared to 2015, measured as both DDD per 100 patient days and as DDD per 100 admissions. The use of penicillins with enzyme inhibitors and carbapenems has increased signifcantly in recent years. In 2016 the consumption of penicillins with enzyme inhibitors continued to increase by 12% when measured as DDD per 100 patient-days compared to 2015. Although, the consumption of carbapenems decreased for the frst time in many years in 2016 compared to 2015. These two agents have to a large extent replaced cephalosporins in many situations. The increase of these two substances is probably a result of an increased number of infections with ESBL-producing bacteria. When analysing the total antibiotic sales on requisition (consumption in all hospitals, including parts of nursing homes and other care units) from 2000 to 2016, a clear shift from high use of broad-spectrum antibiotics to narrow-spectrum antibiotics can be seen.

Sales of antibiotics for animals

In 2016, reported sales of antibiotics for animals were 10 543 kg, of which 57% were for benzylpenicillin. The corresponding fgures for 2007 were 17 106 kg and 44%, respectively.

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 2016, a total of 62.1 tonnes of antibiotics were sold for human use and 10.4 tonnes were sold for animal use. Measured as milligrams of active substance per kilogram biomass, the consumption was 93.8 and 13.4 milligrams per kilogram, respectively. Consumption by humans still dominates for all classes of antibiotics except for trimethoprim-sulphonamides and aminoglycosides.

In 2016, the consumption of antibiotics by humans in outpatient care was 362 packages per 1 000 individuals. The corresponding fgure for dogs was 263 packages per 1 000 individuals. The consumption pattern was also different. In outpatient care of humans, simple penicillins and penicillinase-stable penicillins dominated, while for dogs aminopenicillins with or without clavulanic acid were the most prescribed.

Notifiable resistance

ESBL

A total of 10 659 human cases of extended spectrum betalactamase (ESBL)- producing Enterobacteriaceae were reported in 2016, an increase of 11% compared to 2015, and increases occurred in 15 of Sweden’s 21 counties. The most commonly reported species was Escherichia coli with 86% of all cases followed by Klebsiella pneumoniae with 9%. Most ESBL-producing bacteria were found in urine samples. Invasive infections with ESBL-producing bacteria increased from 578 cases in 2015 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 became notifable for both clinicians and laboratories in 2012. A total of 126 new cases were detected in 2016 compared to 115 cases 2015, and the two most common types of enzymes were OXA-48 and NDM. During the year, two clusters involving a total 12 cases of E. coli with NDM-5 were identifed using whole-genome typing. Several of these cases were domestically acquired, but for the majority of cases epidemiological data linking cases are missing. Because 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 2016, the occurrence of ESBL-producing E. coli in intestinal and meat samples from broilers and from intestinal samples from turkeys was investigated with screening methods. Such bacteria were isolated from 42% of the intestinal samples and 44% of the meat samples from broilers of Swedish origin. The occurrence in intestinal samples from broilers was comparable with 2015. Changes in the screening methodology prevent any direct comparisons with the fgures from previous years and for the occurrence in meat. For the frst time in Svarm, ESBL-producing E. coli was also detected in one (1%) of the intestinal samples from turkeys.

MRSA

The total number of reported human cases of MRSA was 4 402 in 2016, an increase of 13% compared to 2015. The rate of increase was lower than the previous year. The increase seen during 2015 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.

The majority of the MRSA infections were acquired abroad. Community-acquired infections dominated among domestic cases (76%) but were less frequent among imported cases (58%). Hospital-acquired infections were comparatively more common in imported cases (16%) than among domestic cases (4,6%). Forty-four invasive isolates of MRSA were reported in 2016.

The occurrence of MRSA in animals in Sweden is still low, which limits the spread from animals to humans. MRSA was found sporadically in dogs and cats in 2016, and MRSA with mecC was detected in samples from several goats and sheep in an outbreak at a zoo. 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.

MRSP

In 2016, the number of notifed cases of methicillin-resistant Staphylococcus pseudintermedius (MRSP) was on the same level as 2015. In total, 55 cases were notifed in 2016, which can be compared to 60 cases in 2015 and 39 cases in 2014. All cases except two were related to dogs. The picture of MRSP is becoming more diverse compared to earlier years, although the ST71-t02-SCCmecII-III lineage is still common. The emerging clone ST258 only constituted 9% of cases in 2016 compared to 33% of notifed cases in 2015. Furthermore, a new MLST variant, ST551, was identifed in 11% of cases in 2016. MRSP in humans is not notifable.

PNSP

Sixty-seven cases of pneumococci with reduced susceptibility to penicillin (PNSP, defned as MIC > 1 mg/L) were reported in humans in 2016, and in 2015 there were 59 reported cases. Two invasive cases were reported.

VRE

In 2016, a total of 165 new cases of vancomycin-resistant enterococci (VRE) were reported in humans compared to 157 cases in 2015. Enterococcus faecium carrying the resistance gene vanA (126 cases) was more common than those carrying vanB (24 cases). In 2016 there were no large hospital outbreaks reported. During years with large hospital outbreaks, vanB has been the most common resistance gene.

One invasive VRE infection was reported in 2016. 

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. Isolates from human invasive infections are markedly more resistant, which makes animals in Sweden an unlikely source for these infections.

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. In humans, only a small proportion of isolates are tested for susceptibility, and most of these are related to serious infections. See the "Comparative analysis” section of each bacterium.

Human clinical isolates

In this Swedres-Svarm report 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 15 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 will result in some differences in resistance levels, especially for species isolated less frequently and for unusual resistance types.

The following results are for invasive isolates from EARSNet. In general the level of resistance was lower for clinical isolates reported to ResNet. In E. coli and K. pneumoniae, the levels of resistance to third-generation cephalosporins has increased continually, and is now approximately 8% and 4%, respectively. MRSA isolates accounted for 2.3% of invasive S. aureus, which is low from a European perspective. For Enterococcus faecium the rate of vancomycin resistance was 0.4 %. The rate of non-susceptibility to penicillins in Streptococcus pneumoniae (referred to as PNSP) was 7% in 2016.

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

In 2016, 6 613 new CDI cases were reported corresponding to an incidence of 66 cases per 100 000 inhabitants, a continued reduction of 8% compared with 2015.

No isolates with a decreased susceptibility against metronidazole or vancomycin were found in 2016.

In 2016, 1 778 cases of gonorrhea were reported. Resistance to cefxime was 1%, 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 and E. coli.

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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