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

Autor: Fan YX; Institute of Antibiotics, Huashan Hospital, Fudan University, Shanghai, China.; Key Laboratory of Clinical Pharmacology of Antibiotics, National Population and Family Planning Commission, Shanghai, China.; National Clinical Research Center for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai, China., Chen MT; Institute of Antibiotics, Huashan Hospital, Fudan University, Shanghai, China.; Key Laboratory of Clinical Pharmacology of Antibiotics, National Population and Family Planning Commission, Shanghai, China.; National Clinical Research Center for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai, China., Li NY; Phase I Clinical Research Center, Huashan Hospital, Fudan University, Shanghai, China., Liu XF; Institute of Antibiotics, Huashan Hospital, Fudan University, Shanghai, China.; Key Laboratory of Clinical Pharmacology of Antibiotics, National Population and Family Planning Commission, Shanghai, China.; National Clinical Research Center for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai, China., Yang MJ; Institute of Antibiotics, Huashan Hospital, Fudan University, Shanghai, China.; Key Laboratory of Clinical Pharmacology of Antibiotics, National Population and Family Planning Commission, Shanghai, China.; National Clinical Research Center for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai, China., Chen YC; Phase I Clinical Research Center, Huashan Hospital, Fudan University, Shanghai, China., Liang XY; Institute of Antibiotics, Huashan Hospital, Fudan University, Shanghai, China.; Key Laboratory of Clinical Pharmacology of Antibiotics, National Population and Family Planning Commission, Shanghai, China.; National Clinical Research Center for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai, China., Wu JF; Institute of Antibiotics, Huashan Hospital, Fudan University, Shanghai, China.; Key Laboratory of Clinical Pharmacology of Antibiotics, National Population and Family Planning Commission, Shanghai, China.; National Clinical Research Center for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai, China.; Phase I Clinical Research Center, Huashan Hospital, Fudan University, Shanghai, China., Guo BN; Institute of Antibiotics, Huashan Hospital, Fudan University, Shanghai, China.; Key Laboratory of Clinical Pharmacology of Antibiotics, National Population and Family Planning Commission, Shanghai, China.; National Clinical Research Center for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai, China., Song SC; Shanghai-MOST Key Laboratory of Health and Disease Genomics, Chinese National Human, Genome Center at Shanghai, Shanghai, China.; Shanghai Institute for Biomedical and Pharmaceutical Technologies, Shanghai, China., Zhu YQ; Shanghai-MOST Key Laboratory of Health and Disease Genomics, Chinese National Human, Genome Center at Shanghai, Shanghai, China.; Shanghai Institute for Biomedical and Pharmaceutical Technologies, Shanghai, China., Zhang FY; Department of Pulmonary Medicine, Shanghai Putuo District People's Hospital, Shanghai, China., Hang JQ; Department of Pulmonary Medicine, Shanghai Putuo District People's Hospital, Shanghai, China., Wu SB; Department of Nephrology, Shanghai Ninth People's Hospital, Shanghai, China., Shen B; Department of Nephrology, Shanghai Ninth People's Hospital, Shanghai, China., Li HY; Department of Pulmonary Medicine, Zhongshan Hospital, Fudan University, Shanghai, China., Wang Q; Department of Pulmonary Medicine, Zhongshan Hospital, Fudan University, Shanghai, China., Luo XM; Department of Respiratory Medicine, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China., Chen QG; Department of Respiratory Medicine, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China., Zhang HF; Emergency & Critical Care Department, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China., Wang RL; Emergency & Critical Care Department, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China., Shen LH; Department of Critical Care, Fudan University Shanghai Cancer Center, Shanghai, China.; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China., Fu FM; Department of Critical Care, Fudan University Shanghai Cancer Center, Shanghai, China.; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China., Song XL; Department of Respiratory and Critical Care Medicine, Tenth People's Hospital of Tongji University, Shanghai, China., Zhang J; Institute of Antibiotics, Huashan Hospital, Fudan University, Shanghai, China.; Key Laboratory of Clinical Pharmacology of Antibiotics, National Population and Family Planning Commission, Shanghai, China.; National Clinical Research Center for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai, China.
Jazyk: angličtina
Zdroj: Microbiology spectrum [Microbiol Spectr] 2022 Oct 26; Vol. 10 (5), pp. e0134822. Date of Electronic Publication: 2022 Sep 12.
DOI: 10.1128/spectrum.01348-22
Abstrakt: 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 (AUC 0-24 ) 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 AUC 0-24 /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 .
Databáze: MEDLINE