Yaxin Fan

Huashan Hospital

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Beining Guo

Fudan University

Jing Zhang

Shanghai Jiao Tong University

Yuancheng Chen

Huashan Hospital

Xiaofen Liu

Fudan University

Hailan Wu

Chinese University of Hong Kong, Shenzhen

Jicheng Yu

Beijing University of Chemical Technology

Yi Li

Fudan University

Jufang Wu

Huashan Hospital

Guoying Cao

Fudan University

Xiaojie Wu

Huashan Hospital

Cooperative Institutions

Ibero American University

Fudan University

Huashan Hospital

National Health and Family Planning Commission

Shanghai Jiao Tong University

Chinese Academy of Medical Sciences & Peking Union Medical College

Sun Yat-sen University

Chinese Academy of Sciences

Huazhong University of Science and Technology

Shanghai Public Health Clinical Center

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Degradation of vancomycin in external quality assessment samples is a factor to underestimate its concentration

Bioanalysis (2021)

Yaxin Fan Yu Wang Mengting Chen Yuancheng Chen Beining Guo

Aim: To compare the difference between the measured and target values in vancomycin external quality assessment (EQA) samples and to investigate the factors for underestimating its concentration. Materials & methods: A retrospective analysis of 195 international vancomycin EQA results was performed. Deviations of the concentrations determined by TDx fluorescence polarization immunoassay (FPIA), Axsym FPIA and Architect chemiluminescence microparticle immunoassay (CMIA) method were -2.43, -16.28 and -10.53%, respectively. Chromatographic peaks of the crystalling degradation products appeared in samples with large deviations. Vancomycin were degraded after long-term transporting and high temperature. Conclusion: Vancomycin concentrations measured by Axsym FPIA and Architect CMIA methods were likely to be underestimated. Long-term transporting resulted in low EQA results, suggesting that establishing a local EQA system for vancomycin is essential.

Fluorescence polarization immunoassay

Chemiluminescent immunoassay

10.4155/bio-2021-0163

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Proteomic Response Revealed Signaling Pathways Involving in the Mechanism of Polymyxin B-Induced Melanogenesis

Microbiology Spectrum (2022)

Chuhan Zhang Xiaofen Liu Hailan Wu Yu Wang Yaxin Fan

Polymyxin B is a last-line antibiotic for extensively resistant Gram-negative bacterial infection. Skin hyperpigmentation is a serious side effect induced by polymyxin B that severely compromises the psychological health and compliance of patients. The literature lacks mechanistic studies that explain how hyperpigmentation occurs, and this substantially hinders the development of intervention strategies and improved compliance. SK-MEL-2 cells were used for the polymyxin B-induced hyperpigmentation mechanism study. Melanin content and tyrosinase activity were measured after polymyxin B treatment. Tandem mass tag (TMT)-labeling quantitative proteomics was employed to investigate the response of SK-MEL-2 cells to polymyxin B treatment. Real-time quantitative PCR and Western blot were applied to validate the mRNA and protein levels of related genes and proteins. The melanin content and tyrosinase activity were significantly upregulated after polymyxin B treatment in SK-MEL-2 cells at 48 h and 72 h. Quantitative proteomics showed that 237 proteins were upregulated and 153 proteins were downregulated in the 48 h group, and 49 proteins were upregulated and 49 proteins were downregulated in the 72 h group. The differentially expressed proteins were involved in pathways such as lysosome, PI3K/Akt signaling pathway, and calcium signaling pathway. The upregulation of melanogenic enzymes and microphthalmia-associated transcription factor (MITF) was validated by qPCR and Western blot. Meanwhile, phosphorylation of PI3K, β-catenin, and cyclic-AMP response binding protein (CREB) in response to polymyxin B treatment was observed. The present study reveals the proteomic response of polymyxin B-induced melanogenesis in SK-MEL-2 cells for the first time. Signaling pathways, including melanin biosynthesis, PI3K/Akt, and calcium signaling pathways may be involved in the mechanism of melanogenesis. IMPORTANCE Polymyxin B-induced skin hyperpigmentation seriously affects the psychological health and compliance of patients. This study provides a proteomic clue to the mechanism at the cellular level for understanding polymyxin B-induced hyperpigmentation, contributing to a follow-up investigation of the corresponding PI3K/Akt signaling transduction pathway and calcium signaling pathway. The elucidation of its underlying mechanism is of great significance for patients' compliance improvement, intervention strategy, and new drug development.

Microphthalmia-associated transcription factor

Polymyxin B

Skin hyperpigmentation

Polymyxin

10.1128/spectrum.02730-21

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Genotyping of RHD c.1227G>A allele by melting curve analysis

Transfusion and Apheresis Science (2021)

Ni Wang Yaxin Fan Shihang Zhou Lin‐Nan Shao Yuexin Xia

Melting curve analysis

High Resolution Melt

10.1016/j.transci.2021.103078

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Development and validation of a UHPLC–MS/MS assay for colistin methanesulphonate (CMS) and colistin in human plasma and urine using weak-cation exchange solid-phase extraction

Journal of Pharmaceutical and Biomedical Analysis (2016)

Miao Zhao Xiaojie Wu Yaxin Fan Beining Guo Jing Zhang

Colistin

Solid phase extraction

10.1016/j.jpba.2016.02.045

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Modeling Approach to Optimizing Dose Regimen of Vancomycin for Chinese Pediatric Patients with Gram-Positive Bacterial Infections

Frontiers in Pharmacology (2021)

Kai Shen Yaxin Fan Minjie Yang Yuancheng Chen Jinhao Tao

The aim of this study was to establish the population pharmacokinetics (PK) model of Vancomycin for Chinese pediatric patients which can extrapolate to whole age periods by bridging the published adult population PK model and the established pediatric population PK model. The final consolidated population PK model was used to explore the correlation of pharmacokinetics/pharmacodynamics (PK/PD) indices and efficacy of vancomycin and to provide evidence for the optimized regimen of vancomycin in Chinese pediatric patients with Gram-positive bacterial infection. 108 pediatric patients with Gram-positive infections from 2 pediatric hospitals in China in the first period of the prospective multi-center vancomycin clinical observational study were enrolled to establish the population PK model. A one-compartment population PK model was established and validated. The correlation between vancomycin PK/PD indices [trough concentration (C min ), peak concentration (C max ), 0–24 h area under the curve (AUC 0–24 ) and the area under the curve to minimum inhibitory concentration ratio (AUC 0–24 /MIC)] and the overall clinical outcomes (clinical efficacy and microbiological efficacy) in Chinese pediatric patients were evaluated. There is no significant correlation between PK/PD indices and clinical efficacy or microbiological efficacy. Considering the high clinical effective rate (>90%) and median AUC 0–24 /MIC values of 200–300, Chinese pediatric patients with Gram-positive bacterial infection may be suitable for lower AUC 0–24 /MIC target value compared to the target value of 400–600 recommended by IDSA guideline. Different optimal dose regimen of vancomycin for Chinese pediatric patients should be considered. Further evaluation in more prospective studies will be needed.

Pharmacodynamics

Regimen

Therapeutic Drug Monitoring

10.3389/fphar.2021.648668

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Correlation analysis of reject reaction and corneal endothelial cells after penetrating keratoplasty from donation after cardiac death

DOAJ (DOAJ: Directory of Open Access Journals) (2017)

Qian Cao Lan Li Yunchuan Li Yong Li Yuling Liang

10.3980/j.issn.1672-5123.2018.1.36

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Table of Contents

Clinical Therapeutics (2017)

Richard I. Shader Claire O ' Hanlon Anju Parthan Morgan Kruse Shannon Cartier

Table (database)

10.1016/s0149-2918(17)30741-5

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Comparative efficacy of vancomycin in treating ST5 and ST764 methicillin-resistant Staphylococcus aureus infections in adult patients

mSphere (2023)

Yaxin Fan Kaiting Zhang Mengting Chen Nanyang Li Xiaofen Liu

Methicillin-resistant Staphylococcus aureus (MRSA) is a bacterium that is resistant to multiple drugs and can cause serious infections. In recent years, one of the most widespread strains of MRSA worldwide has been the clonal complex 5 (CC5) type. Sequence type 5 (ST5) and ST764 are two prevalent CC5 strains. Although ST5 and ST764 are genotypically identical, ST764 is classified as a hybrid variant of ST5 with characteristics of community-associated MRSA (CA-MRSA). In contrast to ST5, ST764 lacks the tst and sec genes but carries the staphylococcal enterotoxin B (seb) gene. Vancomycin is commonly used as the first-line treatment for MRSA infections. However, it is currently unclear whether the genetic differences between the ST5 and ST764 strains have any impact on the efficacy of vancomycin in treating MRSA infections. We conducted a prospective observational study comparing the efficacy of vancomycin against ST5-MRSA and ST764-MRSA in five hospitals in China. There were significant differences in bacteriological efficacy between the two groups, with virulence genes, such as the tst gene, being a risk factor for bacterial persistence (adjusted odds ratio, 4.509; 95% confidence interval, 1.216 to 16.724; P = 0.024). In the future, it may be necessary to consider personalized vancomycin treatment strategies based on the genetic characteristics of MRSA isolates.

10.1128/msphere.00457-23

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Risk factors for readmission within one year after acute exacerbations of bronchiectasis in a Chinese tertiary hospital: a retrospective cohort study

BMC Pulmonary Medicine (2024)

Yaxin Fan Yu‐Jih Su Huiyong Zhang Xiaoyu Yang Zhengyi Zhang

Frequent exacerbations of bronchiectasis lead to poor quality of life, impaired lung function, and higher mortality rates. This study aims to evaluate the risk factors associated with readmission within one year due to acute exacerbation of bronchiectasis (AEB). A retrospective cohort study was performed on 260 patients with bronchiectasis who were hospitalized in the respiratory and critical care department of a tertiary hospital in China. Univariate and multivariate Cox analyses were used to evaluate the risk factors for readmission within one year. Readmission within one year was found in 44.6% of 260 patients hospitalized with acute exacerbation of bronchiectasis. The risk factors associated with readmission included age over 65 years (HR = 3.66; 95% CI: 2.30 to 5.85), BMI < 18.5 kg/m2 (HR = 1.71; 95% CI: 1.16 to 2.51), respiratory intensive care unit (RICU) stay during admission (HR = 2.06, 95% CI: 1.16–3.67), involvement of 3 or more lobes on chest high-resolution computed tomography (HRCT) (HR = 1.85; 95% CI, 1.22 to 2.80), chronic Pseudomonas aeruginosa (PA) colonization (HR = 2.29; 95% CI: 1.54 to 3.38), and positive sputum culture results within 24 h after admission (HR = 1.93; 95% CI: 1.27 to 2.94). Long-term oral antibiotics use after discharge was associated with decreased hazard of readmission (HR = 0.34; 95% CI: 0.20 to 0.59). Patients with bronchiectasis have a high rate of readmission, which is linked to varieties of risk factors, and identifying these risk factors is importance for effectively managing patients with bronchiectasis.

Sputum culture

10.1186/s12890-024-03402-1

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Sequence Type 5 (ST5) as a Possible Predictor of Bacterial Persistence in Adult Patients with Methicillin-Resistant Staphylococcus aureus Pneumonia Treated with Vancomycin

Microbiology Spectrum (2022)

Yaxin Fan Min‐Te Chen Nan-Yang Li Xiaofen Liu Minjie Yang

Vancomycin remains the mainstay of treatment for methicillin-resistant Staphylococcus aureus (MRSA) pneumonia. This study assessed risk factors for vancomycin failure in 63 patients with MRSA pneumonia through detailed clinical, microbiological, pharmacokinetic/pharmacodynamic, and genetic analyses of prospective multicenter studies conducted from February 2012 to July 2018. Therapeutic drug monitoring was performed during vancomycin treatment, and the 24-h area under the curve (AUC0-24) was calculated. All baseline strains were collected for MIC determination, heterogeneous vancomycin-intermediate S. aureus (hVISA) screening, and biofilm determination. Whole-genome sequencing was performed on the isolates to analyze their molecular typing and virulence and adhesion genes. Clinical signs and symptoms improved in 44 patients (44/63, 69.8%), with vancomycin daily dose (P = 0.045), peak concentration (P = 0.020), and sdrC (P = 0.047) being significant factors. Isolates were eradicated in 51 patients (51/63, 81.0%), with vancomycin daily dose (P = 0.009), cardiovascular disease (P = 0.043), sequence type 5 (ST5; P = 0.017), tst (P = 0.050), and sec gene (P = 0.044) associated with bacteriological failure. Although the AUC0-24/MIC was higher in the groups with bacterial eradication, the difference was not statistically significant (P = 0.108). Multivariate analysis showed that no variables were associated with clinical efficacy; ST5 was a risk factor for bacterial persistence (adjusted odds ratio, 4.449; 95% confidence interval, 1.103 to 17.943; P = 0.036). ST5 strains had higher frequencies of the hVISA phenotype, biofilm expression, and presence of some adhesion and virulence genes such as fnbB, tst, and sec than non-ST5 strains. Our study suggests that ST5 is a possible predictor of bacterial persistence in MRSA pneumonia treated with vancomycin. IMPORTANCE Few studies have simultaneously examined the influence of clinical characteristics of patients with pneumonia, the vancomycin pharmacokinetic/pharmacodynamic (PK/PD) index, and the phenotypic and genetic characteristics of methicillin-resistant Staphylococcus aureus (MRSA) strains. We assessed risk factors for vancomycin failure in patients with MRSA pneumonia by analyzing these influences in a prospective multicenter study. Sequence type 5 (ST5) was a possible predictor of bacterial persistence in adult patients with MRSA pneumonia (adjusted odds ratio, 4.449). We found that this may be related to ST5 strains having higher levels of vancomycin heterogeneous resistance, biofilms, and the presence of adhesion and virulence genes such as fnbB, tst, and sec.

Persistence (discontinuity)

10.1128/spectrum.01348-22

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Citations (4)