Background.Although the Netherlands is a country with a low endemic level, methicillin-resistant Staphylococcus aureus (MRSA) poses a significant health care problem. Therefore, high coverage... Show moreBackground.Although the Netherlands is a country with a low endemic level, methicillin-resistant Staphylococcus aureus (MRSA) poses a significant health care problem. Therefore, high coverage national MRSA surveillance has been in place since 1989. To monitor possible changes in the type-distribution and emergence of resistance and virulence, MRSA isolates are molecularly characterized.Methods.All 43,321 isolates from 36,520 persons, collected 2008-2019, were typed by multiple-locus variable number tandem repeats analysis (MLVA) with simultaneous PCR detection of the mecA, mecC and lukF-PV genes, indicative for PVL. Next-generation sequencing data of 4991 isolates from 4798 persons were used for whole genome multi-locus sequence typing (wgMLST) and identification of resistance and virulence genes.Results.We show temporal change in the molecular characteristics of the MRSA population with the proportion of PVL-positive isolates increasing from 15% in 2008-2010 to 25% in 2017-2019. In livestock-associated MRSA obtained from humans, PVL-positivity increases to 6% in 2017-2019 with isolates predominantly from regions with few pig farms. wgMLST reveals the presence of 35 genogroups with distinct resistance, virulence gene profiles and specimen origin. Typing shows prolonged persistent MRSA carriage with a mean carriage period of 407 days. There is a clear spatial and a weak temporal relationship between isolates that clustered in wgMLST, indicative for regional spread of MRSA strains.Conclusions.Using molecular characterization, this exceptionally large study shows genomic changes in the MRSA population at the national level. It reveals waxing and waning of types and genogroups and an increasing proportion of PVL-positive MRSA.A group of bacteria that cause difficult-to-treat infections in humans is methicillin-resistant Staphylococcus aureus (MRSA). The aim of this study was to monitor changes in the spread of MRSA, their disease causing potential and resistance to antibiotics used to treat MRSA infections. MRSA from patients and their contacts in the Netherlands were collected over a period of 12 years and characterized. This revealed new types of MRSA emerged and others disappeared. An increasing number of MRSA produces a protein called PVL toxin, enabling MRSA to cause more severe infections. Also, some people appear to carry MRSA without any disease for more than a year. These findings suggest an increasing disease potential of MRSA and possible unnoticed sources of infection. Consequently, it is important to maintain monitoring of these infections to minimize MRSA spread.Schouls et al. characterize 43,321 methicillin-resistant Staphylococcus aureus (MRSA) isolates obtained between 2008 and 2019 in the Netherlands. Genomic changes occur in the MRSA population, with increases in the proportion of PVL-positive MRSA. Show less
Debast, S.B.; Bauer, M.P.; Kuijper, E.J.; Comm 2014
Since a decade, Clostridium difficile infection (CDI) has increased progressively in incidence and severity of disease. Currently, CDI is considered the leading cause of nosocomial diarrhoea,... Show moreSince a decade, Clostridium difficile infection (CDI) has increased progressively in incidence and severity of disease. Currently, CDI is considered the leading cause of nosocomial diarrhoea, associated with an increased duration of hospitalization, healthcare expenses, morbidity and mortality. This thesis describes our findings with outbreak control, diagnosis, identification of specific risk factors and treatment of CDI after the discovery of the emergence of C. difficile PCR-ribotype 027 in the Netherlands. The studies illustrate the role of antibiotics in relation to persistence, severeness and spreading of CDI. Antibiotics are shown to be a primary risk factor for the development of (ribotype-specific) CDI and an essential part of the outbreak control measures (__bundle-approach__), namely antibiotic stewardship. The use of antibacterials is a risk for selection of novel endemic C. difficile strains in e.g. animals, which introduce an increasing risk of alternative zoonotic transmission routes. Except for very mild CDI, which is clearly induced by usage of specific antibiotics, antibacterial treatment is advised. This thesis reviews the comparative effectiveness of the currently available treatment modalities, thereby providing evidence-based recommendations for CDI remedies. Treatment options include: oral and non-oral antibiotics, toxin-binding resins and polymers, immunotherapy, probiotics, faecal or bacterial intestinal transplantation. Show less
