CHU UCL Namur site Godinne
Laboratory of microbiology
National Reference Center of Gram Negative Bacilli Antibiotic Resistant
Avenue Gaston Therasse 1,
5530 Yvoir _Belgium
Tel: 081/42.32.06 _ Fax: 081/42.32.04
Since 1998 the University Hospital of Mont Godinne-UCL and Erasme-ULB have served as “non official” National Reference Center (NRC) for the analysis of Gram negative bacteria.Over the last two decades, both laboratories have been intensively involved in epidemiological surveys of antimicrobial resistance in Gram negative isolates in Belgium. In 2010, the two laboratories were officially recognized as associated NRC for ESBL and carbapenemases in Enterobacterales and for multi-drug resistant Pseudomonas and Acinetobacter spp. Since January 2020, the laboratory of CHU UCL Namur (Godinne) is officially recognized as the NRC laboratory for ESBL and carbapenemases in Enterobacterales and for multi-drug resistant Pseudomonas and Acinetobacter spp.
Team presentation
|
Members of NRC |
Email adress |
|
|
Head of NRC |
Pr. Dr. Huang Te-Din Daniel |
|
|
Ir.PhD Bogaerts Pierre |
||
|
Technical team NRC BGN/ NRC H. pylori |
Sc. Evrard Stéphanie |
|
|
Ms Berhin Catherine |
||
| Ms Bouchahrouf Warda | ||
| Mr Hoebeke Martin | ||
|
Ms Wallemme Isaline |
||
| Mr Gilliard Nicolas | ||
|
Secretariat |
Ms De Bonhome Tamara |
|
Missions of the NRC
Detection and characterization of emerging mechanisms of resistance in Enterobacterales, Pseudomonas and Acinetobacter spp.
Evaluation of new methods to improve the detection of resistance mechanisms in Gram negative isolates.
Establishment of collaborations with national surveillance networks concerning antibiotic resistance.
Elaboration and formulation of national guidelines and recommendations for the control of transmission of multidrug resistant Gram negative organisms in health care facilities.
Diffusion of data collected by NRC.
Background of Multidrug-resistant Enterobacterales in Belgium
Extended-spectrum beta-lactamases (ESBLs) in Enterobacterales have emerged in early 80's in Europe and have spread worldwide. Initially, the first ESBLs were derived from narrow-spectrum beta-lactamases of the TEM and SHV families by point mutations resulting in an extended spectrum of hydrolysis to 3rd and 4th generation cephalosporins and monobactams. Since 2000's the epidemiology has changed drastically with the emergence of the CTX-M ESBL families which subsequently become dominant globally, in Escherichia coli but also in other Enterobacterales. The large intra- and inter-species transmission of ESBLs is due to the mobilization of resistance genes through various mobile genetic elements. Further, some clones of E. coli (ST131 clone) can spread easily and disseminated worlwide. These different factors altogether account for the increase in the hospitals, but also in the community, of infections caused by often multidrug-resistant (MDR) ESBL-producers, which usually require the use of carbapenems that were the only antibiotics retaining activity against ESBLs and considered as the last-line treatment. Carbapenemase-producing Gram negative bacteria (Enterobacteriales as well as Pseudomonas and Acinetobacter spp.) were first reported in the early nineties. In Belgium, the first cases of infection or colonization with CPE were mainly associated with imported cases from endemic regions. Since 2011, there has been a dramatic increase in the number of CPE strains referred to our national reference center and large-scale nosocomial outbreaks have been reported in many hospitals over the last years (2011-2020 period). Between 2012 and 2015, an active epidemiological and microbiological surveillance programme has been launched jointly by the national reference center in collaboration with the Scientific Institute of Public Health (Sciensano). Currently, the majority of CPE strains detected are no longer related to travel abroad suggesting their rapid autochthonous spread in Belgium.
These organisms represent a major public threat worldwide in all human healthcare settings (acute and chronic care sectors), nowadays also including the community. Carbapenemase production in bacterial pathogens jeopardizes the successful treatment of severe infections, often implicating multidrug resistant strains such as extended-spectrum beta-lactamase producing Enterobacterales (ESBLE). Since carbapenemase resistance determinants are located on mobile genetic elements (plasmids, transposons) often in association with resistance to several other classes of antimicrobials, very few drugs (including scarce newly released antibacterials) remain active against these isolates and this may lead to therapeutic dead-ends for the treatment of systemic infections. The occurrence of severe systemic infections (i.e.: bacteremia) caused by carbapenemase-producing organisms has been associated on the average with a three- to four-fold increase of mortality rate in hospitalized patients in comparison to the rate associated with susceptible isolates belonging to the same species and with a delay of appropriate antibiotic therapy leading to major complications and an increase in length of stay of several days. Carbapenemase encoding genes can be easily transferable through plasmids from one bacteria to another and thus explains the rapid diffusion of these resistance mechanisms amongst the intestinal microbiota. Therefore, early identification of patients colonized or infected with carbapenemase-(or ESBL) producing organisms is crucial for the appropriate antimicrobial treatment and for the containment of their dissemination in healthcare settings and in the community.
Detection of carbapenemases in the microbiology laboratory is challenging because of the diversity of the enzymes and their variable level of expression. Despite major development of rapid diagnostic tests which greatly improved the performance of carbapenemase detection, characterization of the precise type of carbapenemase involved still requires molecular methods including whole genome sequencing. One of the missions of the NRC is to help clinical laboratories for the detection and the confirmation of carbapenemases-producing organisms and also to evaluate the analytical performance of new diagnostic tests.
Background for Acinetobacter and Pseudomonas spp in Belgium
Acinetobacter and Pseudomonas spp are common pathogens in hospitals and particularly in intensive care units (ICU). These organisms have been responsible for numerous hospital outbreaks due to their ability to upregulate and/or acquire resistance determinants and thanks their capacity to survive for prolonged periods throughout the hospital environment. In contrast to Enterobacterales, these organisms may survive for several weeks up to months in diverse environmental conditions. Especially for A. baumannii several studies have demonstrated the presence of these strains in various environmental locations (on inanimate surfaces, soil or surface water, …).
Difficulties in the identification in Acinetobacter species by conventional biochemistry methods are commonly described. MALDITOF mass spectrometry has greatly improved identification performance, although genome sequencing is sometimes still needed to achieve exact species identification, considering the difference in natural intrinsic resistance determinants and clinical significance of different species. A. baumannii is recognized as the most clinically relevant species, largely implicated in severe nosocomial infections and associated with high mortality rates. A. baumannii is usually more resistant than others species from this genus and multidrug-resistant A. baumannii are frequently involved in outbreaks in the ICU as well and have become a major nosocomial pathogen in the recent years. Resistance to carbapenems in Acinetobacter spp. can result from different mechanisms: the “non-enzymatic mechanisms” such as permeability defects or overexpression of efflux pumps, but also through “enzymatic mechanisms “ including ESBL (VEB, PER, …) or carbapenemase productions (mainly OXA-23, OXA-24 and OXA-58 class D oxacillinases and at lesser extent class B metallo-beta-lactamases). The majority of carbapenemase genes identified in Acinetobacter baumannii are located on mobile genetic elements facilitating their spread in other clinical relevant species, suggesting their rapid dissemination and the potential reservoir. The rapid detection and identification of carbapenemase-resistant A. baumannii is essential to limit the dissemination of carbapenemase genes within the Acinetobacter genus but also to Enterobacterales. Although more phenotypic techniques have been proposed, the identification of carbapenemase in Acinetobacter spp. remains difficult (lack of sensitivity or specificity) and requires molecular confirmation.
P. aeruginosa carries intrinsic resistance mechanisms to β-lactams (e.g. production of chromosomal cephalosporinase) and additional resistance mechanisms such as overexpression of efflux pumps, decreased porin expression, acquisition of ESBL and/or Ambler class B carbapenemase genes (VIM, IMP,…) can be easily acquired leading to the emergence of multidrug-resistant P. aeruginosa. In the last decade, the emergence and diffusion of several multi-drug resistant P. aeruginosa clones have become a serious issue in many countries. The dissemination of carbapenem-resistant and carbapenemase-producing strains emphasizes the need to develop rapid and accurate detection methods for the choice of optimal treatments and for the implementation of infection control measures.
The aim of National Reference Center is to help the diagnostic laboratories in the identification and characterization of the precise transferable resistance mechanisms (i.e: ESBL and/or carbapenemase expressed among Pseudomonas and Acinetobacter spp through phenotypic and molecular tests.
Rue Docteur Gaston Therasse 1, 5530 Yvoir (Belgique)