Extensively Drug-Resistant Causing Nosocomial Bloodstream Infections in China: Molecular Investigation of Antibiotic Resistance Determinants, Informing Therapy, and Clinical Outcomes.
Wenzi Bi, Haiyang Liu, Rhys A Dunstan, Bin Li, Von Vergel L Torres, Jianming Cao, Lijiang Chen, Jonathan J Wilksch, Richard A Strugnell, Trevor Lithgow, Tieli Zhou
Author Information
Wenzi Bi: Department of Clinical Laboratory, The First Affiliated Hospital of Wenzhou Medical UniversityWenzhou, China.
Haiyang Liu: Department of Clinical Laboratory, The First Affiliated Hospital of Wenzhou Medical UniversityWenzhou, China.
Rhys A Dunstan: Infection and Immunity Program, Biomedicine Discovery Institute and Department of Microbiology, Monash UniversityMelbourne, VIC, Australia.
Bin Li: Department of Clinical Laboratory, The First Affiliated Hospital of Wenzhou Medical UniversityWenzhou, China.
Von Vergel L Torres: Infection and Immunity Program, Biomedicine Discovery Institute and Department of Microbiology, Monash UniversityMelbourne, VIC, Australia.
Jianming Cao: School of Laboratory Medicine and Life Science, Wenzhou Medical UniversityWenzhou, China.
Lijiang Chen: Department of Clinical Laboratory, The First Affiliated Hospital of Wenzhou Medical UniversityWenzhou, China.
Jonathan J Wilksch: Infection and Immunity Program, Biomedicine Discovery Institute and Department of Microbiology, Monash UniversityMelbourne, VIC, Australia.
Richard A Strugnell: Department of Microbiology and Immunology, The Peter Doherty Institute, The University of MelbourneParkville, VIC, Australia.
Trevor Lithgow: Infection and Immunity Program, Biomedicine Discovery Institute and Department of Microbiology, Monash UniversityMelbourne, VIC, Australia.
Tieli Zhou: Department of Clinical Laboratory, The First Affiliated Hospital of Wenzhou Medical UniversityWenzhou, China.
The rise in diversity of antimicrobial resistance phenotypes seen in is becoming a serious antibiotic management problem. We sought to investigate the molecular characteristics and clinical implications of extensively drug-resistant (XDR) isolated from different nosocomial bloodstream infections (BSIs) patients from July 2013 to November 2015. Even in combination treatment, meropenem did not protect against mortality of BSIs patients ( = 0.015). In contrast, tigecycline in combination with other antimicrobial agents significantly protected against mortality ( = 0.016). Antimicrobial susceptibility tests, molecular detection of antibiotic resistance determinants, conjugation experiments, multilocus sequence typing (MLST), S1-PFGE, Southern blot, SDS-PAGE, immunoblot analysis, and pulsed-field gel electrophoresis (PFGE) were used to characterize these isolates. These XDR strains were resistant to conventional antimicrobials except tigecycline and polymyxin B and co-harbored diverse resistance determinants. as well as were located on a transferable plasmid of ~54.2 kb and the most predominant replicon type was IncF. 23 of the 35 isolates belonging the predominant clone were found to incorporate the globally-disseminated sequence type ST11, but others including a unique, previously undiscovered lineage ST2281 (allelic profile: 4-1-1-22-7-4-35) were also found and characterized. The porins OmpK35 and OmpK36 were deficient in two carbapenemase-negative carbapenem-resistant strains, suggesting decreased drug uptake as a mechanism for carbapenem resistance. This study highlights the importance of tracking hospital acquired infections, monitoring modes of antibiotic resistance to improve health outcomes of BSIs patients and to highlight the problems of XDR dissemination in healthcare settings.
