Abstract
KPC-producing Klebsiella pneumoniae isolates have emerged as important pathogens of nosocomial infections, and tigecycline is one of the antibiotics recommended for severe infections caused by KPC-producing K. pneumoniae. To identify the susceptibility profile of KPC-producing K. pneumoniae to tigecycline and investigate the role of efflux pumps in tigecycline resistance, a total of 215 KPC-producing K. pneumoniae isolates were collected. The minimum inhibitory concentration (MIC) of tigecycline was determined by standard broth microdilution tests. Isolates showing resistance to tigecycline underwent susceptibility test with efflux pump inhibitors. Expression levels of efflux pump genes (acrB and oqxB) and their regulators (ramA, marA, soxS and rarA) were examined by real-time PCR, and the correlation between tigecycline MICs and gene expression levels were analysed. Our results show that the tigecycline resistance rate in these isolates was 11.2%. Exposure of the tigecycline-resistant isolates to the efflux pump inhibitor NMP resulted in an obvious decrease in MICs and restored susceptibility to tigecycline in 91.7% of the isolates. A statistically significant association between acrB expression and tigecycline MICs was observed, and overexpression of ramA was found in three tigecycline-resistant isolates, further analysis confirmed ramR mutations existed in these isolates. Transformation of one mutant with wild-type ramR restored susceptibility to tigecycline and repressed overexpression of ramA and acrB. These data indicate that efflux pump AcrAB, which can be up-regulated by ramR mutations and subsequent ramA activation, contributed to tigecycline resistance in K. pneumoniae clinical isolates.
Highlights
Klebsiella pneumoniae has emerged worldwide as an important pathogen of nosocomial infections that causes a variety of infections, including pneumonia, liver abscesses, urinary-tract infections and bacteraemia
A total of 215 Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae isolates were collected between Jan. 2010 and Dec. 2013 from the following centres in China: First Affiliated Hospital, School of Medicine, Zhejiang University (ZJF); Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University (ZJS); The First Affiliated Hospital of Kunming Medical University (KM); The First Affiliated Hospital of Zhengzhou University (ZZ)
KPC-producing K. pneumoniae isolates have emerged as important pathogens of nosocomial infections
Summary
Klebsiella pneumoniae has emerged worldwide as an important pathogen of nosocomial infections that causes a variety of infections, including pneumonia, liver abscesses, urinary-tract infections and bacteraemia. Carbapenems are often the last resort for treating infections due to the emergence. Tigecycline Resistance Mechanism in KPC-Producing K. pneumoniae of multidrug-resistant K. pneumoniae [1]. The acquisition of carbapenemase has contributed to resistance to all β-lactams including carbapenem antibiotics. Carbapenem-hydrolysing Klebsiella pneumoniae carbapenemase (KPC)-type enzymes have been identified mostly in K. pneumoniae. Most KPC carbapenemase-producing K. pneumoniae show resistance to almost all antibiotics except colistin and tigecycline
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
