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

Fan, Yaxin; Chen, Min‐Te; Li, Nan-Yang; Liu, Xiaofen; Yang, Mei; Chen, Yuancheng; Liang, Xiaoyu; Wu, Jiang; Guo, Beining; Song, Sichao; Zhu, Yongqiang; Zhang, Fengying; Hang, Jingqing; Wu, Shuang; Shen, Bo; Li, Huayin; Wang, Qin; Luo, Xuming; Chen, Qing-Ge; Zhang, Huifang; Wang, Ruilan; Shen, Lihua; Fu, Fengming; Song, Xiaolian; Zhang, Jing

doi:10.1128/spectrum.01348-22

Cited by 4 publications

(6 citation statements)

References 31 publications

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“…As previously described, we used a modified population analysis area under the curve method (PAP-AUC) to screen for hVISA ( 31 , 32 ). For classification, strains with ratios greater than 1.3 were categorized as VISA, ratios between 0.9 and 1.3 were classified as hVISA, and strains with ratios less than 0.9 were considered as vancomycin-susceptible S. aureus (VSSA).…”

Section: Methodsmentioning

confidence: 99%

“…Biofilm formation was determined by a crystalline violet method ( 32 ) and controlled against the ATCC29213 standard strain. Fresh overnight bacteria were selected, adjusted for turbidity to 0.5 McFarland, and shaken overnight at 37°C 180 rpm.…”

Section: Methodsmentioning

confidence: 99%

“…Patient demographics, ICU admissions, underlying diseases, curative treatment, clinical laboratory tests, bacteriological tests, and vancomycin doses were collected. In this study, we included underlying diseases such as cardiovascular diseases, diabetes, and strokes, as they have the potential to impact the efficacy of anti-infection therapy ( 32 , 33 ).…”

Section: Methodsmentioning

confidence: 99%

“…A previously published method ( 32 ) was used to simulate the concentration-time profile of patients and calculate the PK/PD indices of patients after vancomycin dosing. C min , C max , and AUC 0-24 values were calculated as weighted means using the dose and interval of administration, respectively.…”

Section: Methodsmentioning

confidence: 99%

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

Fan,

Zhang,

Chen

et al. 2023

mSphere

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This study compared the impact of sequence type 5 (ST5) and ST764, on the efficacy of vancomycin treatment in methicillin-resistant Staphylococcus aureus (MRSA) infections. From July 2012 to June 2020, a prospective observational study was conducted in five hospitals in China, enrolling 90 patients with MRSA infections, including 44 patients with ST5-MRSA and 46 patients with ST764-MRSA infections. All strains were subjected to minimal inhibitory concentration (MIC) determination, biofilm expression, heterogeneous vancomycin-intermediate S. aureus (hVISA) screening, and whole-genome sequencing. Vancomycin therapeutic drug monitoring was conducted, and the 24-hour area under the curve (AUC 0-24 ) and AUC 0-24 /MIC values were calculated. ST5-MRSA shows elevated hVISA/VISA presence, increased biofilm formation, and higher presence of virulence genes like tst , sec , and sel . ST764-MRSA expresses seb , aiding infection in elderly patients in the community. Additionally, patients with ST764 infections exhibit higher vancomycin AUC 0-24 /MIC values, and fewer tracheotomies compared to ST5. Clinical signs and symptoms improvement were observed in 27 (61.4%) and 33 (71.7%) patients in the ST5 and ST764 groups, respectively ( P = 0.372). On the other hand, 28 (63.6%) and 39 (84.8%) patients had laboratory-confirmed bacterial eradication in two groups, respectively ( P = 0.029). Multivariate analysis showed that the virulence genes, such as the tst gene, were a risk factor for bacterial persistence (adjusted odds ratio, 4.509; 95% confidence interval, 1.216 to 16.724; P = 0.024). Our study showed that vancomycin was less effective in treating ST5-MRSA infection compared to ST764-MRSA infection, in part because ST5-MRSA is healthcare-associated MRSA while ST764-MRSA carries genetic characteristics of community-associated MRSA. IMPORTANCE 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.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

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

Fan,

Zhang,

Chen

et al. 2023

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“…Recently, ST5 has been reported as a possible predictor of bacterial persistence in adult patients with MRSA pneumonia, which may be related to ST5 strains having higher levels of vancomycin heterogeneous resistance, biofilm formation, and the presence of adhesion and virulence genes, such as fnbB , tst , and sec ( 10 ). In addition to high-level vancomycin heterogeneous resistance, ST5-MRSA clones have acquired multiple resistance phenotypes ( 11 , 12 ), including fosfomycin resistance ( 10 , 13 ). Chinese ST5 methicillin-susceptible S. aureus (MSSA) is recognized as a hypervirulent ST5 subtype that poses a serious clinical threat ( 14 ).…”

Section: Introductionmentioning

confidence: 99%

Global genetic diversity and Asian clades evolution: a phylogeographic study of Staphylococcus aureus sequence type 5

Chen,

Yin,

Chen

et al. 2024

Antimicrob Agents Chemother

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Staphylococcus aureus sequence type (ST) 5 has spread worldwide; however, phylogeographic studies on the evolution of global phylogenetic and Asian clades of ST5 are lacking. This study included 368 ST5 genome sequences, including 111 newly generated sequences. Primary phylogenetic analysis suggested that there are five clades, and geographical clustering of ST5 methicillin-resistant S. aureus (MRSA) was linked to the acquisition of S. aureus pathogenicity islands (SaPIs; enterotoxin gene island) and integration of the prophage φSa3. The most recent common ancestor of global S. aureus ST5 dates back to the mid-1940s, coinciding with the clinical introduction of penicillin. Bayesian phylogeographic inference allowed to ancestrally trace the Asian ST5 MRSA clade to Japan, which may have spread to major cities in China and Korea in the 1990s. Based on a pan-genome-wide association study, the emergence of Asian ST5 clades was attributed to the gain of prophages, SaPIs, and plasmids, as well as the coevolution of resistance genes. Clade IV displayed greater genomic diversity than the Asian MRSA clades. Collectively, our study provides in-depth insights into the global evolution of S. aureus ST5 mainly in China and the United States and reveals that different S. aureus ST5 clades have arisen independently in different parts of the world, with limited geographic dispersal across continents.

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Age-Related Differences in Vancomycin-Associated Nephrotoxicity and Efficacy in Methicillin-Resistant Staphylococcus aureus Infection: A Comparative Study between Elderly and Adult Patients

Xi,

Li,

Chen

et al. 2024

Antibiotics

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Elderly patients (age ≥ 65 years) are susceptible to methicillin-resistant Staphylococcus aureus (MRSA) infections, with potential for more adverse treatment outcomes or complications compared to younger adults (18–64 years). This study compared vancomycin-associated nephrotoxicity and efficacy in elderly and adult patients and investigated the correlation between vancomycin pharmacokinetic/pharmacodynamic (PK/PD) indices and clinical outcomes. A prospective study was conducted in 10 hospitals in Shanghai from October 2012 to November 2019. A total of 164 patients with MRSA infections were enrolled, including 83 elderly and 81 adult patients. Vancomycin therapeutic drug monitoring (TDM) was performed in all patients, indicating significantly higher vancomycin trough concentrations (Ctrough), 24-h area under the curve (AUC24) values, and AUC24/minimum inhibitory concentration (AUC24/MIC) values in elderly patients compared to adult patients. The incidence of vancomycin-associated nephrotoxicity was nearly three times higher in elderly patients (18.1% vs. 6.2%, p = 0.020), despite similar clinical and microbiological efficacy. Of particular importance, a Ctrough > 20 mg/L was found as an independent factor of nephrotoxicity in elderly patients. Further analysis of patients with an estimated glomerular filtration rate (eGFR) > 60 mL/min/1.73 m2 also revealed that elderly patients had significantly higher vancomycin-related PK/PD indices and more nephrotoxicity than adult patients. In conclusion, elderly patients receiving vancomycin therapy face a higher risk of nephrotoxicity, which requires close vancomycin TDM, especially when the Ctrough exceeds 20 mg/L.

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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

Cited by 4 publications

References 31 publications

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

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

Global genetic diversity and Asian clades evolution: a phylogeographic study of Staphylococcus aureus sequence type 5

Age-Related Differences in Vancomycin-Associated Nephrotoxicity and Efficacy in Methicillin-Resistant Staphylococcus aureus Infection: A Comparative Study between Elderly and Adult Patients

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