Next-Generation Sequencing Confirms Presumed Nosocomial Transmission of Livestock-Associated Methicillin-Resistant Staphylococcus aureus in the Netherlands

Abstract

ABSTRACT Livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA) was detected in 2003 and rapidly became the predominant MRSA clade in the Netherlands. Studies have shown that transmissions are difficult to identify, since this MRSA variant represents a genetically homogenous clade when current typing techniques are used. Here, next-generation sequencing was performed on 206 LA-MRSA isolates to assess the capability of LA-MRSA to be transmitted between humans. The usefulness of single nucleotide variants (SNVs), the composition of the SCC mec region, and the presence of plasmids to identify transmission of LA-MRSA were assessed. In total, 30 presumed putative nosocomial transmission events and 2 LA-MRSA outbreaks were studied; in most cases, SNV analysis revealed that the isolates of the index patient and the contact(s) clustered closely together. In three presumed events, the isolates did not cluster together, indicating that transmission was unlikely. The composition of the SCC mec region corroborated these findings. However, plasmid identification did not support our SNV analysis, since different plasmids were present in several cases where SNV and SCC mec analysis suggested that transmission was likely. Next-generation sequencing shows that transmission of LA-MRSA does occur in Dutch health care settings. Transmission was identified based on SNV analysis combined with epidemiological data and in the context of epidemiologically related and unrelated isolates. Analysis of the SCC mec region provided limited, albeit useful, information to corroborate conclusions on transmissions, but plasmid identification did not. IMPORTANCE In 2003, a variant of methicillin-resistant Staphylococcus aureus (MRSA) isolated from pigs was also found in pig farmers in France and the Netherlands. Soon thereafter, this livestock-associated MRSA (LA-MRSA) was identified in many other countries. Transmission of LA-MRSA between humans, particularly in the health care setting, is regarded to occur sporadically. Moreover, studies that describe LA-MRSA transmission used molecular characterization of isolates with limited discriminatory power, making the validity of the conclusion that transmission occurred questionable. In our study, we sequenced the complete genomes of 206 LA-MRSA isolates, obtained from more than 30 presumed LA-MRSA transmission events. Analysis of the data showed that transmission of LA-MRSA between humans had indeed occurred in more than 90% of these events. We conclude that transmission of LA-MRSA between humans does occur in Dutch health care settings; therefore, a decision to discontinue the search and destroy policy for LA-MRSA should be taken with caution.