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.

Phenotypic and genotypic characterisation of thymine auxotrophy in Escherichia coli isolated from a patient with recurrent bloodstream infection.

INTRODUCTION: Thymine auxotrophic in vitro mutants of Escherichia coli were first reported in the mid-20th century. Later, thymine-dependent clinical strains of E. coli as well as other Enterobacterales, Enterococcus faecalis and Staphylococcus aureus have been recognized as the cause of persistent and recurrent infections. OBJECTIVES: The aim of this study was to characterize the phenotype and investigate the molecular basis of thymine auxotrophy in ten E. coli isolates obtained at different time points from a patient with recurrent bloodstream infection (BSI) due to a chronic aortic graft infection treated with Trimethoprim/sulfamethoxazole (TMP-SMX). METHODS: Clinical data was obtained from hospital records. Growth characterization and antimicrobial susceptibility testing to TMP-SMX was performed on M9 agar and in MH broth with different thymine concentrations (0.5, 2, 5, 10 and 20 µg/mL), on Mueller-Hinton (MH) and blood agar. Whole genome sequencing (WGS) was performed on all E. coli isolates. RESULTS: E. coli were isolated from ten consecutive BSI episodes from a patient with chronic aortic graft infection. Six of these isolates were resistant to TMP-SMX when assayed on blood agar. Growth experiments with added thymine confirmed that these isolates were thymine-dependent (thy-), and revealed growth defects (slower growth rate and smaller colony size) in these isolates relative to thy+ isolates (n = 4). WGS indicated that all isolates were of the same clonal lineage of sequence type 7358. Genomic analysis revealed a G172C substitution in thyA in all TMP-SMX resistant isolates, while mutations affecting genes involved in the deoxyribose salvage pathway (deoB and deoC) were identified in eight isolates. CONCLUSION: This case highlights the risk of resistance development to TMP-SMX, especially for long-term treatment, and the possible pitfalls in detection of growth-deficient subpopulations from chronic infections, which could lead to treatment failure.

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.