Study risk factors and molecular characteristics of extensively drug-resistant and pandrug-resistant hypervirulent Enterobacteriaceae in Georgia
Project Status: 8 Project completed
Commencement Date: 01.02.2020
Duration in months: 33 months
Objective
Antimicrobial resistance (AMR) has been recognized as one of the most serious global threats to human health in the 21st century. The world faces a potential disaster. While few new classes of antibiotics are being developed, resistance to existing antibiotics continues to spread inexorably. AMR may end the antibiotic era in the next few years. Thus, extensively drug-resistant (XDR) or pandrug-resistant (PDR) infections may have few or no effective treatment options. Furthermore, their combinations with enhanced virulence have the potential to cause the next clinical crisis. Consequently, to reduce the spread and to develop new treatment options studying prevalence, the risk factors, and molecular characterization of XDR and PDR hypervirulent strains is an urgent priority. Enterobacteriaceae such as Klebsiella pneumoniae and Escherichia coli are responsible for a wide range of healthcare-associated infections. In 2017 from several hospitals in Tbilisi 46 cultures of K. pneumoniae were isolated among them 20 (43.5%) were resistant to carbapenems. In 5 of these cases the infections were severe and aggressive, indicating that they could be caused by hypervirulent strains. The study proposed in this application expands upon this preliminary study and will be the first systematic investigation of XDR and PDR hypervirulent Enterobacteriaceae in the Caucasus region. The project will develop an integrated analysis of virulence and resistance factors and will provide information about the relationship between these two factors. The study will contribute to the development of an evidence-based system of preventive measures and appropriate antimicrobial therapies against XDR and PDR hypervirulent Enterobacteriaceae infections. It will provide protocols for rapid detection of resistance mechanisms to allow for appropriate antimicrobial therapy and infection control measures, and foremost, preventing the spread of these resistance markers to other pathogens.
To identify risk factors for XDR and PDR hypervirulent Enterobacteriaceae infections, we will perform a case-control study. Statistical analysis will be carried out using SPSS 22.0. Odds ratios and their 95% CIs will be computed. In the risk factor analysis, multivariate logistic regression models will be used.
Antimicrobial susceptibility of Enterobacteriaceae isolates will be tested according to the EUCAST recommendations. XDR and PDR hypervirulent Enterobacteriaceae isolates will be screened for the presence of carbapenems and colistin resistance genes by multiplexed PCR. These strains will be screened for the presence of rmpA, rmpA2, magA and K genes by conventional PCR. The nucleotide sequence of plasmids to determine if they are carrying resistance and virulent genes will be determined by next generation sequencing (NGS). Relationship between the plasmids of different isolates will undergo bioinformatic analyses, and the epidemiology of resistance and virulent genes as well as their spread will be elucidated.
The project implementation will give us an opportunity to understand and control the important parameters of the influx of the AMR and virulence markers in Georgia and by extension to the region in a model system that has public health relevance.
Participating Institutions
COLLABORATOR
Lawrence Berkeley National Laboratory
COLLABORATOR
Université de Limoges
COLLABORATOR
Universiteit Antwerpen
COLLABORATOR
National Institute of Infectious Diseases
LEADING
National Center for Disease Control and Public Health (NCDC)
