Molecular characterization of MRSA collected during national surveillance between 2008 and 2019 in the Netherlands

Leo M Schouls; Sandra Witteveen; Marga van Santen-Verheuvel; Angela de Haan; Fabian Landman; Han van der Heide; Ed J Kuijper; Daan W Notermans; Thijs Bosch; Antoni P A Hendrickx; Dutch MRSA surveillance study group

doi:10.1038/s43856-023-00348-z

Molecular characterization of MRSA collected during national surveillance between 2008 and 2019 in the Netherlands

Commun Med (Lond). 2023 Sep 12;3(1):123. doi: 10.1038/s43856-023-00348-z.

Collaborators

Dutch MRSA surveillance study group:
A L E van Arkel, M A Leversteijn-van Hall, W van den Bijllaardt, R van Mansfeld, K van Dijk, B Zwart, B M W Diederen, H Berkhout, D W Notermans, A Ott, K Waar, W Ang, J da Silva, A L M Vlek, A G M Buiting, L G M Bode, A Jansz, S Paltansing, A J van Griethuysen, J R Lo Ten Foe, M J C A van Trijp, M Wong, A E Muller, M P M van der Linden, M van Rijn, S B Debast, E Kolwijck, N Al Naiemi, T Schulin, S Dinant, S P van Mens, D C Melles, J W T Cohen Stuart, P Gruteke, A van Dam, I Maat, B Maraha, J C Sinnige, E van der Vorm, M P A van Meer, N van Maarseveen, E de Jong, S J Vainio, E Heikens, M den Reijer, J W Dorigo-Zetsma, A Troelstra, E Bathoorn, J de Vries, D W van Dam, E I G B de Brauwer, R Steingrover

Affiliations

¹ Centre for Infectious Disease Control. National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands. leo.schouls@rivm.nl.
² Centre for Infectious Disease Control. National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands.
³ Department of Medical Microbiology and Experimental Bacteriology, Leiden University Medical Center, Leiden, The Netherlands.

Abstract

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 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.

Plain language summary

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.