Genomic epidemiology and characterisation of penicillin-sensitive Staphylococcus aureus isolates from invasive bloodstream infections in China: an increasing prevalence and higher diversity in genetic typing be revealed

Many countries have reported increasing rates of penicillin-susceptible methicillin-sensitive Staphylococcus aureus (MSSA-PEN(S)). To date, there is relatively little known about the current situation and molecular characteristics of MSSA-PEN(S) in China. In this study, we carried out a laboratory-based multi-region retrospective study to investigate the genomic epidemiology and characterisation of MSSA-PEN(S) isolated from invasive bloodstream infections (BSIs) across 17 provinces. The prevalence of MSSA-PEN(S) isolates increased significantly over the 6-year period, with the proportion increasing from 3.51% in 2014–8.80% in 2019, an average relative increase of 22.14% per year (95% confidence interval 9.67%-34.61%, P for trend <0.001), suggesting that China is experiencing a resurgence of MSSA-PEN(S). Phylogenetic analysis showed a higher strain diversity occurred; the most frequent clonal complexes (CCs) identified were CC188 (17.14%), CC398 (15.71%) and CC5 (15.71%). Over half of MSSA-PEN(S) strains were pan-susceptible, with erythromycin the most frequent resistance observed. Moreover, 25 isolates were identified as immune evasion cluster negative, including CC15, CC188 and CC1, and 6 strains encoded the Panton-Valentine leucocidin gene. Importantly, virulence assays showed that MSSA-PEN(S) exhibited a level of virulence comparable to that of penicillin-resistant MSSA (MSSA-PEN(R)), indicating that more-sensitive strains should not be mistaken for lacking aggressiveness in vivo. Furthermore, 11 of these isolates were confirmed as blaZ positive but phenotype sensitive, with different amino acid changes in blaZ. Our data support the recommendation to clinicians regarding the usage of penicillin in invasive BSIs caused by MSSA-PEN(S), which might create a novel opportunity for better antimicrobial stewardship in the future.