Insertion sequences – the driving force behind Klebsiella pneumoniae colistin resistance in Vietnam
To Nguyen 1,2,3, Francesca Short 1,2, Duy Pham Thanh 3,4
1 Infection Program, Monash Biomedicine Discovery Institute, Department of Microbiology, Monash University, Clayton, VIC, Australia
2 Centre to Impact AMR, Monash University, Clayton, Victoria, Australia
3 Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam
4 Centre for Tropical Medicine and Global Health, University of Oxford, Oxford, UK
Antimicrobial resistance is increasingly an urgent threat to public health. The wide spread of multidrug-resistance (MDR) of Gram-negative bacteria is among the most concerning problems. The MDR Klebsiella pneumoniae has increasingly attracted more attention due to limited options of antimicrobials for treatment. Furthermore, drug-resistant K. pneumoniae is considered as the most common cause of nosocomial outbreaks worldwide, with high mortality rates caused by resistance to the last-line antimicrobials such as carbapenems and colistin. While carbapenem resistance mainly involves the production of carbapenemasesencoded by acquired genes (blaKPC, blaNDM, blaOXA-48, …), the primary mechanisms of colistin resistance involve modifications of the bacterial lipopolysaccharide through mutations in two-component systems (TCSs) (e.g. pmrA/B, phoQ/P and crrA/B), or mutations/disruptions in the mgrB gene (a TCS regulator). In Vietnam, K. pneumoniae has been reported as the most common pathogens of hospital-acquired infections (HAIs) and there is an increasing prevalence of carbapenem-resistant K. pneumoniae. From October 2019 to January 2020, there were two concurrent nosocomial outbreaks in a referral hospital in Ho Chi Minh City, with a high mortality rate (6/8 patients died; 75%). Two distinct lineages of the K. pneumoniae ST16 that were extensively drug resistant, including resistance to carbapenem and colistin, were identified as causes of the outbreaks. Notably, colistin resistance was found to be caused by disruption of the mgrB gene by an ISL3- like element, and carbapenem resistance was mediated by a transferable IncF/blaOXA-181 plasmid also carrying an ISL3-like element. There were two environmental isolates collected from a hospital bed and blood pressure cuff phylogenetically linked to outbreak cluster. This study not only revealed the roles of insertion elements in antimicrobial resistance but also highlighted the importance of coordinated efforts between clinical and molecular biologists and infection control teams toidentify and rapidly respond to nosocomial outbreaks.