Antibiotic and antimicrobial resistance

The Korean government established an antimicrobial resistance (AMR) surveillance system, compatible with the Global AMR Surveillance System (GLASS): Kor-GLASS. We describe results from the first year of operation of the Kor-GLASS from May 2016 to April 2017, comprising all non-duplicated clinical isolates of major pathogens from blood, urine, faeces and urethral and cervical swabs from six sentinel hospitals. Antimicrobial susceptibility tests were carried out by disk diffusion, Etest, broth microdilution and agar dilution methods. Among 67,803 blood cultures, 3,523 target pathogens were recovered. The predominant bacterial species were Escherichia coli (n = 1,536), Klebsiella pneumoniae (n = 597) and Staphylococcus aureus (n = 584). From 57,477 urine cultures, 6,394 E. coli and 1,097 K. pneumoniae were recovered. Bloodstream infections in inpatients per 10,000 patient-days (10TPD) were highest for cefotaxime-resistant E. coli with 2.1, followed by 1.6 for meticillin-resistant Sta. aureus, 1.1 for imipenem-resistant Acinetobacter baumannii, 0.8 for cefotaxime-resistant K. pneumoniae and 0.4 for vancomycin-resistant Enterococcus faecium. Urinary tract infections in inpatients were 7.7 and 2.1 per 10TPD for cefotaxime-resistant E. coli and K. pneumoniae, respectively. Kor-GLASS generated well-curated surveillance data devoid of collection bias or isolate duplication. A bacterial bank and a database for the collections are under development.

Defined daily doses (DDD) are the gold standard indicator for quantifying prescriptions. Since 2014, the European Centre for Disease Prevention and Control (ECDC) has also been using the number of packages per 1,000 inhabitants per day (ipd), as a surrogate for prescriptions, to report antibiotic consumption in the community and to perform comparisons between European Union (EU) countries participating in the European Surveillance of Antimicrobial Consumption Network (ESAC-Net). In 2015, consumption was reported to range across Europe from 1.0 to 4.7 packages per 1,000 ipd. Our analysis showed that consumption of antibiotics for systemic use per 1,000 ipd was on average 1.3 times greater in France than in Belgium when considering prescriptions in the numerator, 2.5 times greater when considering packages and 1.2 times greater when considering DDD. As long as the same metrics are used over time, antibiotic consumption data aggregated and disseminated by ECDC are useful for assessing temporal trends at the European level and within individual countries; these data may also be used for benchmarking across EU countries. While DDD - although imperfect - are the most widely accepted metric for this purpose, antibiotic packages do not appear suitable for comparisons between countries and may be misleading.

An important cornerstone in the control of antimicrobial resistance (AMR) is a well-designed quantitative system for the surveillance of spread and temporal trends in AMR. Since 2008, the Dutch national AMR surveillance system, based on routine data from medical microbiological laboratories (MMLs), has developed into a successful tool to support the control of AMR in the Netherlands. It provides background information for policy making in public health and healthcare services, supports development of empirical antibiotic therapy guidelines and facilitates in-depth research. In addition, participation of the MMLs in the national AMR surveillance network has contributed to sharing of knowledge and quality improvement. A future improvement will be the implementation of a new semantic standard together with standardised data transfer, which will reduce errors in data handling and enable a more real-time surveillance. Furthermore, the scientific impact and the possibility of detecting outbreaks may be amplified by merging the AMR surveillance database with databases from selected pathogen-based surveillance programmes containing patient data and genotypic typing data.

Currently, surveillance of livestock-associated meticillin-resistant Staphylococcus aureus (LA-MRSA) in humans in Europe is not systematic but mainly event-based. In September 2014, the European Centre for Disease Prevention and Control (ECDC) initiated a questionnaire to collect data on the number of LA-MRSA from human samples (one isolate per patient) from national/regional reference laboratories in European Union/European Economic Area (EU/EEA) countries in 2013. Identification of LA-MRSA as clonal complex (CC) 398 by multilocus sequence typing (MLST) was preferred, although surrogate methods such as spa-typing were also accepted. The questionnaire was returned by 28 laboratories in 27 EU/EEA countries. Overall, LA-MRSA represented 3.9% of 13,756 typed MRSA human isolates, but it represented ≥ 10% in five countries (Belgium, Denmark, Spain, the Netherlands and Slovenia). Seven of the reference laboratories did not type MRSA isolates in 2013. To monitor the dispersion of LA-MRSA and facilitate targeted control measures, we advocate periodic systematic surveys or integrated multi-sectorial surveillance.

As antibiotic consumption rates between hospitals can vary depending on the characteristics of the patients treated, risk-adjustment that compensates for the patient-based variation is required to assess the impact of any stewardship measures. The aim of this study was to investigate the usefulness of patient-based administrative data variables for adjusting aggregate hospital antibiotic consumption rates. Data on total inpatient antibiotics and six broad subclasses were sourced from 34 acute hospitals from 2006 to 2014. Aggregate annual patient administration data were divided into explanatory variables, including major diagnostic categories, for each hospital. Multivariable regression models were used to identify factors affecting antibiotic consumption. Coefficient of variation of the root mean squared errors (CV-RMSE) for the total antibiotic usage model was very good (11%), however, the value for two of the models was poor (> 30%). The overall inpatient antibiotic consumption increased from 82.5 defined daily doses (DDD)/100 bed-days used in 2006 to 89.2 DDD/100 bed-days used in 2014; the increase was not significant after risk-adjustment. During the same period, consumption of carbapenems increased significantly, while usage of fluoroquinolones decreased. In conclusion, patient-based administrative data variables are useful for adjusting hospital antibiotic consumption rates, although additional variables should also be employed.

This study sought to analyse antimicrobial pressure, indications for treatment, and compliance with treatment recommendations and to identify possible problem areas where inappropriate use could be improved through interventions by the network of the local Swedish Strategic Programme Against Antibiotic Resistance (Strama) groups. Five point-prevalence surveys were performed in between 49 and 72 participating hospitals from 2003 to 2010. Treatments were recorded for 19 predefined diagnosis groups and whether they were for community-acquired infection, hospital-acquired infection, or prophylaxis. Approximately one-third of inpatients were treated with antimicrobials. Compliance with guidelines for treatment of community-acquired pneumonia with narrow-spectrum penicillin was 17.0% during baseline 2003–2004, and significantly improved to 24.2% in 2010. Corresponding figures for quinolone use in uncomplicated cystitis in women were 28.5% in 2003–2004, and significantly improved, decreasing to 15.3% in 2010. The length of surgical prophylaxis improved significantly when data for a single dose and 1 day were combined, from 56.3% in 2003–2004 to 66.6% in 2010. Improved compliance was possibly the effect of active local feedback, repeated surveys, and increasing awareness of antimicrobial resistance. Strama groups are important for successful local implementation of antimicrobial stewardship programs in Sweden.

Following the European Union (EU) Council Recommendation on prudent use of antimicrobial agents in human medicine in 2001, and the success of national campaigns, i.e. Belgium and France, the European Centre for Disease Prevention and Control (ECDC) decided to establish the European Antibiotic Awareness Day (EAAD) on 18 November as platform to support national campaigns across Europe. This article provides an overview of EAAD tools, materials, and activities developed during the first five years. It shows that EAAD has been successful due to good cooperation between ECDC and national institutions, strong political and stakeholder support and evidence-based development of campaign materials. EAAD has provided a platform for pre-existing national campaigns and encouraged similar campaigns to develop where neither political support had been secured, nor financial support had been available. As a result, participating countries have continuously expressed strong support for ECDC to continue its work on EAAD. This has been endorsed by a steadily increasing number of countries participating and the growing interest of varied professional and stakeholder organisations. We conclude that EAAD should continue to act as catalyst for discussion and as mechanism to raise awareness of the public and prescribers about prudent use of antibiotics.

Based on data collected by the European Antimicrobial Resistance Surveillance Network (EARS-Net) and the former EARSS, the present study describes the trends in antimicrobial susceptibility patterns and occurrence of invasive infections caused by Escherichia coli and Staphylococcus aureus in the period from 2002 to 2009. Antimicrobial susceptibility results from 198 laboratories in 22 European countries reporting continuously on these two microorganisms during the entire study period were included in the analysis. The number of bloodstream infections caused by E. coli increased remarkably by 71% during the study period, while bloodstream infections caused by S. aureus increased by 34%. At the same time, an alarming increase of antimicrobial resistance in E. coli was observed, whereas for S. aureus the proportion of meticillin resistant isolates decreased. The observed trend suggests an increasing burden of disease caused by E. coli. The reduction in the proportion of meticillin-resistant S. aureus and the lesser increase in S. aureus infections, compared with E. coli, may reflect the success of infection control measures at hospital level in several European countries.

The emergence and global spread of carbapenemase-producing Enterobacteriaceae is of great concern to health services worldwide. These bacteria are often resistant to all beta-lactam antibiotics and frequently co-resistant to most other antibiotics, leaving very few treatment options. The epidemiology is compounded by the diversity of carbapenem-hydrolysing enzymes and the ability of their genes to spread between different bacterial species. Difficulties are also encountered by laboratories when trying to detect carbapenemase production during routine diagnostic procedures due to an often heterogeneous expression of resistance. Some of the resistance genes are associated with successful clonal lineages which have a selective advantage in those hospitals where antimicrobial use is high and opportunities for transmission exist; others are more often associated with transmissible plasmids. A genetically distinct strain of Klebsiella pneumoniae sequence type (ST) 258 harbouring the K. pneumoniae carbapenemases (KPC) has been causing epidemics of national and international proportions. It follows the pathways of patient referrals, causing hospital outbreaks along the way. Simultaneously, diverse strains harbouring New Delhi metallo-beta-lactamase (NDM-1) are repeatedly being imported into Europe, commonly via patients with prior medical exposure in the Indian subcontinent. Since the nature and scale of carbapenem-non-susceptible Entrobacteriaceae as a threat to hospital patients in Europe remains unclear, a consultation of experts from 31 countries set out to identify the gaps in diagnostic and response capacity, to index the magnitude of carbapenem-non-susceptibility across Europe using a novel five-level staging system, and to provide elements of a strategy to combat this public health issue in a concerted manner.

A total of 2,662 samples, collected from March to September 2009 in Switzerland, were tested for the presence of meticillin-resistant Staphylococcus aureus (MRSA). The collection comprised nasal swabs from 148 pig farmers, 133 veterinarians, 179 slaughterhouse employees, 800 pigs, 300 calves, 400 cattle, 100 pooled neck skin swabs from chicken carcasses, and 460 food samples of animal origin. Moreover, 142 S. aureus strains, isolated from bovine mastitis milk, were included in the study. Twenty samples (<1%; four veterinarians, 10 pigs, three calves, one young bull, and two mastitis milk samples) tested positive for MRSA. Genotyping of the MRSA strains was performed by multilocus sequence typing, spa- and SCCmec-typing, and revealed ST398 (n=18), ST8 (n=1), ST 1 (n=1), spa types t011 (n=7), t034 (n=11), t064 (n=1), t127 (n=1), and SCCmec types IV (n=4) and V (n=16). The 20 MRSA strains were subjected to antibiotic susceptibility testing and pulsed-field gel electrophoresis using the restriction enzyme EagI. Supplementary PCR reactions were performed to investigate the presence of Panton-Valentine leukocidin and staphylococcal enterotoxins A to D.

Antibiotic resistance and nosocomial infections have recently been recognised as a growing threat in Latvian hospitals. We used a modified point prevalence study design to gain accurate information on the antibiotic prescription pattern and the prevalence of nosocomial infections in different hospital departments. A given department was observed on a given day in a given month (May) five years in a row. All antibiotic treatments, dose and route of administration were recorded, in addition to demographic data. The most commonly used antibiotic groups were first generation cephalosporins (35.6-38.9%), broad-spectrum penicillins (17.5-23.0%), fluoroquinolones (8.4-14.5%) and aminoglycosides (7.7-12.6%). Cefazolin was the most commonly used antibiotic. Antibiotics were predominantly used intravenously. The proportion of oral administration varied from 15.1% to 21.8%. A large proportion (13.3%) of the antibiotics was administered without clear reason. The crude prevalence rate of infection treated with antibiotics was 19.3%. The average prevalence of nosocomial infections was found to be 3.6%. These prevalence studies provided an opportunity to compare hospitals and outline variations and problem areas. They indicated the main problems in antibiotic prescription: large interhospital variations in the choice of an antibiotic for the most common infections, frequent antibiotic use without clear reason, and predominant intravenous administration.

A Belgian Antibiotic Policy Coordination Committee (BAPCOC) was officially established in 1999 by Royal Decree. The overall objective of BAPCOC is to promote judicious use of antibiotics in humans and animals and to promote infection control and hospital hygiene, with the overall aim to reduce antibiotic resistance. BAPCOC fostered strong and interdisciplinary public health, scientific and political leadership, which led to many evidence-based interventions such as multimedia campaigns to promote the prudent use of antibiotics in the community, national campaigns to promote hand hygiene in hospitals, publication of clinical practice guidelines, staffing and technical support for establishment of antibiotic management teams in all Belgian hospitals, surveillance programmes on antibiotic use and resistance in humans and animals and the promotion of research. These activities and interventions resulted in a measurable decrease in antibiotic use and resistance in the community and hospitals.

The overall aim of Strama (The Swedish Strategic Programme Against Antibiotic Resistance) is to preserve the effectiveness of antibiotics in humans and animals. Strama is organised at two levels: a network of independent local multidisciplinary groups in each county that provide prescribers with feedback on antibiotic use and resistance and implement guidelines; and a national executive working group funded by the government. To gain an insight into antibiotic use, Strama has conducted several large diagnosis-prescribing surveys in primary care, in the hospital settings and in nursing homes. National antibiotic susceptibility data for Sweden and mandatory notification show that in recent years the proportion of Streptococcus pneumoniae with decreased sensitivity to penicillin V has stabilised (around 6 %), but the number of notified cases of meticillin-resistant Staphylococcus aureus (MRSA) has increased and ESBL-producing Enterobacteraceae have turned into an endemic situation. Still, Sweden is among the countries with the lowest rates of MRSA (<1 %), S. pneumoniae can still be treated with penicillin V and the rate of Escherichia coli-producing ESBLs is below 5 %. Strama´s activities have contributed to a steady decrease in antibiotic use from the mid 1990s until 2004 (when total use slowly started to increase again) without measurable negative consequences. Regular collaboration with national and regional news media has been one of the key strategies.

For the past seven years (1999 to 2006), the European Antimicrobial Resistance Surveillance System (EARSS) has collected antimicrobial susceptibility test results of invasive isolates in humans of seven bacterial species that serve as indicators for the development of antimicrobial resistance in Europe.