Background Methicillin-resistant Staphylococcus aureus (MRSA) is a major nosocomial pathogen subdivided into lineages termed sequence types (STs). Since the 1950s, successive waves of STs have appeared and replaced previously dominant lineages. One such event has been occurring in China since 2013, with community-associated (CA-MRSA) strains including ST59 largely replacing the previously dominant healthcare-associated (HA-MRSA) ST239. We previously showed that ST59 isolates tend to have a competitive advantage in growth experiments against ST239. However, the underlying genomic and phenotypic drivers of this replacement event are unclear. Methods Here, we investigated the replacement of ST239 using whole-genome sequencing data from 204 ST239 and ST59 isolates collected in Chinese hospitals between 1994 and 2016. We reconstructed the evolutionary history of each ST and considered two non-mutually exclusive hypotheses for ST59 replacing ST239: antimicrobial resistance (AMR) profile and/or ability to colonise and persist in the environment through biofilm formation. We also investigated the differences in cytolytic activity, linked to higher virulence, between STs. We performed an association study using the presence and absence of accessory virulence genes. Results ST59 isolates carried fewer AMR genes than ST239 and showed no evidence of evolving towards higher AMR. Biofilm production was marginally higher in ST59 overall, though this effect was not consistent across sub-lineages so is unlikely to be a sole driver of replacement. Consistent with previous observations of higher virulence in CA-MRSA STs, we observed that ST59 isolates exhibit significantly higher cytolytic activity than ST239 isolates, despite carrying on average fewer putative virulence genes. Our association study identified the chemotaxis inhibitory protein (chp) as a strong candidate for involvement in the increased virulence potential of ST59. We experimentally validated the role of chp in increasing the virulence potential of ST59 by creating Δchp knockout mutants, confirming that ST59 can carry chp without a measurable impact on fitness. Conclusions Our results suggest that the ongoing replacement of ST239 by ST59 in China is not associated to higher AMR carriage or biofilm production. However, the increase in ST59 prevalence is concerning since it is linked to a higher potential for virulence, aided by the carriage of the chp gene.

Cefiderocol, a new siderophore cephalosporin, has been approved in the United States and Europe but not in China. At present, there are almost no antimicrobial susceptibility evaluation data on cefiderocol in China.

Purpose Carbapenem-resistant Enterobacterales bloodstream infections (CRE BSIs) have a high mortality. However, an optimal antimicrobial treatment has not been determined. This study was conducted to evaluate the risk factors for mortality and provided potential therapeutic options for treatment of CRE infection. Patients and Methods We investigated patients with CRE BSIs from 18 hospitals across nine Chinese provinces from January to December 2019. Data were collected from the medical records according to a pre-established questionnaire. Antimicrobial susceptibility testing and DNA sequencing were performed to investigate the characteristics of isolates. Results A total of 208 patients enrolled; the overall 30-day mortality rate was 46.2%. The causative pathogen was carbapenem-resistant Klebsiella pneumoniae (CRKP) (85.6%). Patients infected by ST11-KL64 CRKP had a high sepsis/septic shock incidence rate (p < 0.05). Sepsis/septic shock, short duration of antimicrobial therapy and empirical using tigecycline were independent risk factors for mortality (p < 0.05 for each risks). Appropriate therapy had better survival benefit than inappropriate therapy (p = 0.003). No difference was identified between monotherapy and combination therapy (p = 0.105). Tigecycline as a frequently used antimicrobial had poor therapeutic effect on BSI patients (p < 0.001). Carbapenem-based treatment had a better therapeutic effect on patients infected by isolates with meropenem MIC ≤ 8 mg/L (p = 0.022). The patients who received short duration of antimicrobial therapy had poorer prognosis (p < 0.001) than the patients who received long duration of antimicrobial therapy. Conclusion Reducing the mortality of CRE BSIs need to comprehensively consider whether the antimicrobials were used appropriately, together with infection severity and CRE strains.

With the reduction in sequencing price and acceleration of sequencing speed, it is particularly important to directly link the genotype and phenotype of bacteria. Here, we firstly predicted the minimum inhibitory concentrations of ten antimicrobial agents for Staphylococcus aureus using 466 isolates by directly extracting k-mer from whole genome sequencing data combined with three machine learning algorithms: random forest, support vector machine, and XGBoost. Considering one two-fold dilution, the essential agreement and the category agreement could reach &gt;85% and &gt;90% for most antimicrobial agents. For clindamycin, cefoxitin and trimethoprim-sulfamethoxazole, the essential agreement and the category agreement could reach &gt;91% and &gt;93%, providing important information for clinical treatment. The successful prediction of cefoxitin resistance showed that the model could identify methicillin-resistant S. aureus. The results suggest that small datasets available in large hospitals could bypass the existing basic research and known antimicrobial resistance genes and accurately predict the bacterial phenotype.