National and regional changes in Methicillin-resistant Staphylococcus aureus type in bloodstream infections impact mortality

Objectives: A 2019 nationwide study in Japan revealed the predominant MRSA types in bloodstream infections (BSI) to be ST8-carrying SCCmec type IV (ST8-IV) and clonal complex 1-carrying SCCmec type IV (CC1-IV). However, the patient characteristics of the major MRSA types and how they change over time remain unknown. Methods: MRSA strains isolated from blood cultures at Nagasaki University during 2012-2019 were sequenced. The SCCmec types and patient characteristics identified from this and previous studies (conducted during 2003-2007 and 2008-2011) conducted at our hospital were compared. Additionally, patient and molecular characteristics among the major MRSA types were compared. Results: Between 2003-2007 and 2016-2019, SCCmec type II decreased from 79.2% to 15.5%, whereas type IV increased from 18.2% to 65.5%; severity and outcomes also changed, and SOFA score decreased from 5.8 ± 0.5 to 3.1 ± 0.5, whilst in-hospital mortality decreased from 39.8% to 15.5%. No changes in patient background such as age, sex, or underlying diseases were observed. The most common MRSA types detected between 2012 and 2019 were ST8-IV (37.6%), ST8-I (22.4%), ST5-II (18.8%), and CC1-IV (9.4%). In ST8-IV, MRSA/J and ST8-IV with spa type t5071 were identified, with MRSA/J being predominant. The detected MRSA/J, ST8-IV with t5071, and CC1-IV subtypes were similar in terms of drug resistance, molecular characteristics, and phylogenetic features to those detected in the nationwide surveillance. ST8-I was an MRSA-type circulating in the Kyushu region. Conclusions: The evolving nature of MRSA types in bloodstream infections, correlating with improved outcomes over time and influenced by changes in nationally and regionally circulating strains, is highlighted. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This work was supported by the Japanese Association for Infectious Diseases (The 1st Grant for Clinical Research Promotion, 2018) and the Japanese Antibiotics Research Association (The 23rd Encouragement Award, 2021). The funders had no role in the data analysis or the decision to publish. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: This study was approved by the Ethics Committee of the Nagasaki University Hospital (20072018). MRSA strains collected from blood cultures were anonymized and individually numbered. Patient information collected from the medical records was also anonymized and individually numbered when. The Ethics Committee of Nagasaki University Hospital waived the requirement for informed consent. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Raw data were generated at the Nagasaki University Hospital. The derived data supporting the findings of this study are presented in the paper and supplementary tables and figures. The WGS data reported in this study are available in the NCBI Sequence Read Archive (https://www.ncbi.nlm.nih.gov/sra) under the accession number PRJNA1065106. WGS data from the previous nationwide surveillance5 are available in the DDBJ Sequence Read Archive (https://www.ddbj.nig.ac.jp/dra/index-e.html) under the accession number DRA013058.