Insights from a decade of surveillance: Molecular epidemiology of methicillin-resistant Staphylococcus aureus in Norway from 2008 to 2017.

AIM: Norway has a low prevalence of methicillin-resistant Staphylococcus aureus (MRSA) and reporting of all MRSA cases has been mandatory, including infections and carriage, since 1995 and 2005 accordingly. This provides a unique window to study the spread of MRSA in Norway over time. The aim of this study was to analyze the nationwide trends in the molecular epidemiology of MRSA in Norway over a period of 10 years. METHODS: Clinical and epidemiological data as well as bacterial genotype (spa-type and PVL) were analyzed for all reported MRSA cases in Norway in the period 2008-2017. RESULTS: During the study period, there were 15,200 MRSA cases reported in Norway, from 14,386 patients. The notification rate per 100,000 population increased by 15% annually, rising from 14.2 in 2007 to 48.6 in 2017. This increase was primarily driven by MRSA carriage and community-associated MRSA cases. The incidence of invasive infections remained stable and low, at less than 0.5. The incidence of healthcare-associated MRSA showed an increasing trend, while the number of outbreak-related cases, particularly those associated with nursing homes, decreased. Overall, there were significantly more MRSA infections in males than females. Interestingly, there was a significantly higher prevalence of MRSA infections in female young adolescents compared to males. spa-typing revealed a very heterogeneous MRSA population (D = 0.97), predominantly impacted by international travel and migration patterns, and less by domestic spread in the community. CONCLUSIONS: This study highlights that Norway, while still classified as a low-prevalence country, has experienced a significant increase in the incidence of MRSA between 2008 and 2017, which can predominantly be attributed to CA-MRSA and MRSA carriage.

MRSA surveillance programmes worldwide: moving towards a harmonised international approach.

Multinational surveillance programmes for methicillin-resistant Staphylococcus aureus (MRSA) are dependent on national structures for data collection. This study aimed to capture the diversity of national MRSA surveillance programmes and to propose a framework for harmonisation of MRSA surveillance. The International Society of Antimicrobial Chemotherapy (ISAC) MRSA Working Group conducted a structured survey on MRSA surveillance programmes and organised a webinar to discuss the programmes' strengths and challenges as well as guidelines for harmonisation. Completed surveys represented 24 MRSA surveillance programmes in 16 countries. Several countries reported separate epidemiological and microbiological surveillance. Informing clinicians and national policy-makers were the most common purposes of surveillance. Surveillance of bloodstream infections (BSIs) was present in all programmes. Other invasive infections were often included. Three countries reported active surveillance of MRSA carriage. Methodology and reporting of antimicrobial susceptibility, virulence factors, molecular genotyping and epidemiological metadata varied greatly. Current MRSA surveillance programmes rely upon heterogeneous data collection systems, which hampers international epidemiological monitoring and research. To harmonise MRSA surveillance, we suggest improving the integration of microbiological and epidemiological data, implementation of central biobanks for MRSA isolate collection, and inclusion of a representative sample of skin and soft-tissue infection cases in addition to all BSI cases.

A tale of two STs: molecular and clinical epidemiology of MRSA t304 in Norway 2008-2016.

The purpose of this study was to investigate the epidemiological, molecular, and clinical characteristics of MRSA t304/ST8 and t304/ST6 in Norway from 2008 to 2016. Clinical and epidemiological data were collected for each case included in the study. Strains were characterized by PCR, spa typing, antimicrobial susceptibility testing, and whole genome sequencing. The overall number of cases of MRSA t304 increased from 27 in 2008 to 203 in 2016. Most MRSA t304/ST8 cases were defined as HA-MRSA (89.9%) and diagnosed in persons with Norwegian background, many of them living in nursing homes (62.3%). The number of t304/ST8 cases declined throughout the study period and it has not been reported in Norway since 2014. The increasing MRSA t304/ST6 genotype has mainly been introduced to Norway by immigration from the Middle East, but also from other parts of the world. The t304/ST6 clone is mostly classified as CA-MRSA (75.1%), does not seem to cause serious infections, is not multi-resistant, and has not yet caused outbreaks in Norway. This study provides an example of two MRSA clones with the same spa type found in different epidemiological settings. This is very unusual, but still a reminder that spa typing in some cases may have insufficient discriminatory power for surveillance of MRSA. Our results highlight the importance of active surveillance and characterization of emerging MRSA clones with high potential for spread in the community, which may potentially cause outbreaks in healthcare facilities.

Increasing Incidences and Clonal Diversity of Methicillin-Resistant Staphylococcus aureus in the Nordic Countries - Results From the Nordic MRSA Surveillance.

Methicillin-resistant Staphylococcus aureus (MRSA) is notifiable in Denmark, Finland, Iceland, Norway and Sweden. The prevalence of MRSA in this region has been low for many years, but all five countries experience increasing numbers of new cases. The aim of the study was to describe the molecular epidemiology in the Nordic countries 2009-2016. Numbers of new cases of MRSA from 1997 to 2016 were compared, and a database containing information on spa-type and place of residence or acquisition, for all new MRSA isolates from 2009 to 2016 was established. A website was developed to visualize the geographic distribution of the spa-types. The incidence of new MRSA cases increased in all Nordic countries with Denmark having 61.8 new cases per 100,000 inhabitants in 2016 as the highest. The number of new cases 2009 to 2016 was 60,984. spa-typing revealed a high genetic diversity, with a total of 2,344 different spa-types identified. The majority of these spa-types (N = 2,017) were found in 1-10 cases. The most common spa-types t127/CC1, t223/CC22, and t304/CC6:8 increased significantly in all Nordic countries during the study period, except for Iceland, while spa-type t002/CC5 decreased in the same four countries. The trends of other common spa-types were different in each of the Nordic countries. The Nordic countries were shown to share similar trends but also to have country-specific characteristics in their MRSA populations. A continued increasing numbers of MRSA will challenge the surveillance economically. A more selected molecular surveillance will probably have to be employed in the future.

Livestock-Associated MRSA CC1 in Norway; Introduction to Pig Farms, Zoonotic Transmission, and Eradication.

Farm animals have been identified as an emerging reservoir for transmission of livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA) to humans. The low incidence of MRSA in humans and farm animals in Norway has led to the implementation of a national strategy of surveillance and control of LA-MRSA aiming to prevent livestock becoming a domestic source of MRSA to humans. In 2015, MRSA clonal complex 1 spa-type t177 was identified in nine Norwegian pig herds in two neighboring counties. An outbreak investigation was undertaken, and measures of control through eradication were imposed. We performed a register-based cohort study including pig herds and MRSA-positive persons in Norway between 2008 and 2016 to investigate the livestock-association of MRSA CC1, the transmission of the outbreak strain to humans before and after control measures, and the effect of control measures imposed. Data from the Norwegian Surveillance System of Communicable Diseases were merged with data collected through outbreak investigations for LA-MRSA, the National Registry and the Norwegian Register for Health Personnel. Whole-genome sequencing was performed on isolates from livestock and humans identified through contact tracing, in addition to t177 and t127 isolates diagnosed in persons in the same counties. It is likely that a farm worker introduced MRSA CC1 to a sow farm, and further transmission to eight fattening pig farms through trade of live pigs confirmed the potential for livestock association of this MRSA type. The outbreak strain formed a distinct phylogenetic cluster which in addition to the pig farms included one sheep herd and five exposed persons. None of the investigated isolates from possible cases without direct contact to the MRSA positive farms were phylogenetically related to the outbreak strain. Moreover, isolates of t177 or t127 from healthcare and community-acquired cases were not closely related to the outbreak cluster. Eradication measures imposed were effective in eliminating MRSA t177 from the positive pig holdings, and the outbreak strain was not detected in the national pig population or in persons from these counties after control measures.

The fight to keep resistance at bay, epidemiology of carbapenemase producing organisms (CPOs), vancomycin resistant enterococci (VRE) and methicillin resistant Staphylococcus aureus (MRSA) in Norway, 2006 - 2017.

INTRODUCTION: Scandinavian countries have traditionally had a low prevalence of resistant organisms, but have in recent years experienced a change in their epidemiology. We aim to describe the epidemiology of carbapenemase-producing organisms (CPOs), vancomycin-resistant enterococci (VRE) and methicillin-resistant S. aureus (MRSA) in Norway, measure the importance of infections contracted abroad, and assess the morbidity and mortality associated with these resistant bacteria in Norway. METHODS AND MATERIALS: We used data from the Norwegian surveillance system for communicable diseases covering all findings of the selected resistant bacteria including both infections and colonisation, in the period 2006-2017. Annual trends were assessed using negative binomial regression. For MRSA, we were able to calculate the Morisita-Horn index and transmission numbers following importation in order to assess the effect this had on further domestic transmission. RESULTS: The incidence rates (per 100,000 personyears) of the three groups of resistant bacteria have increased during the period. In 2017 the incidence rates were 0.82 for CPOs, 7.09 for VRE and 43.8 for MRSA. 81% of CPO cases were diagnosed in hospitals, but 73% were infected abroad. Most VRE cases were infected in Norwegian hospitals, 85% were associated with hospitals outbreaks. MRSA was predominantly diagnosed in the community, only 21% were diagnosed in hospitals. Of all MRSA cases, 35% were infected in other countries. Most MRSA spa-types were not identified again after introduction, resulting in a transmission of MRSA equivalent to a mean of 0.30 persons infected from each spa-type identified (range: 0-22). The proportion of infections among all notified cases within each diagnose was 44% for MRSA, 9% for VRE and 45% for CPOs. Among persons notified with bacteraemia, the 30 days all-cause mortality were 20%, 16% and 50% for MRSA, VRE and CPOs respectively. DISCUSSION: The incidence rates of CPOs, VRE and MRSA in Norway are low, but increasing. The continuing increase of notified resistant bacteria highlights the need for a revision of existing infection prevention and control guidelines.