Comparative efficacy of vancomycin in treating ST5 and ST764 methicillin-resistant
Staphylococcus aureus
infections in adult patients
Authors: Fan Yaxin , Zhang Kaiting , Chen Mengting , Li Nanyang , Liu Xiaofen , Yang Minjie , Liang Xiaoyu , Wu Jufang , Guo Beining , Zheng Huajun , Zhu Yongqiang , Zhang Fengying , Hang Jingqing , Zhang Huifang , Wang Ruilan , Yuan Qing , Song Xiaolian , Wu Shengbin , Shen Bo , Zhang Jing 
Published: October 2023

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.