Profile in Pan European Networks Science & Technology – Issue 14

PROFILE
INFECTIOUS DISEASES
A NEED FOR GLOBAL ACTIONS
Alongside appropriate antibiotic usage, rapid diagnosis of multidrug-resistant
bacteria may limit their spread and save lives, explains Youri Glupczynski,
professor of clinical microbiology at the Université catholique de Louvain
ntibiotics are one of the most important therapeutic
discoveries in medical history. They have revolutionised
the treatment of patients with bacterial infections and
have contributed to reducing the mortality and morbidity of
bacterial diseases. Unfortunately, antibiotics have been liable to
misuse, and they are often unnecessarily prescribed for viral
infections against which they have no effect. Similarly, when
diagnoses are not accurately made, which too often still occurs in
current medical practice, broad-spectrum antibiotics (i.e.
antibiotics that kill a large proportion of various bacteria and not
only the bacteria responsible for the disease) are prescribed
because the causative micro-organism is not known. Misuse of
antibiotics leads to the emergence and selection of resistant
bacteria. It has become the reality that doctors in Europe and
worldwide sometimes now face situations where infected patients
cannot be treated adequately because the bacterium responsible
is totally resistant to available antibiotics.
A
Youri Glupczynski, professor of clinical microbiology at the
Université catholique de Louvain, heads the National Reference
Centre in Belgium for the surveillance of multi-resistant Gramnegative organisms (Enterobacteriaceae, Pseudomonas and
Acinetobacter spp). In the following, he outlines the aims of his
current research into tackling multidrug-resistant bacteria (MDRB)
and his hopes for the future.
Focus of interests
The main field of our laboratory research focuses on the
development and validation of novel diagnostic tools for the rapid
diagnosis of MDRB, mostly carbapenemase-producing
Enterobacteriaceae (CPE). The Enterobacteriaceae compose part
of the commensal human gut flora and are often the cause of
community and healthcare-associated infections. Klebsiella
pneumoniae and Escherichia coli are two bacteria that belong to
the Enterobacteriaceae family. Klebsiella pneumoniae is a
common cause of Gram-negative urinary, respiratory tract and
bloodstream infections. Escherichia coli is the most frequent
cause of bloodstream, community and hospital-acquired urinary
tract infections reported worldwide and one of the most common
global food-borne pathogens. Treatment of infections due to CPE
has become more challenging since a large percentage of these
bacteria have become resistant to many and sometimes all
antibiotics to which they were once susceptible. CPE have
increasingly spread in Europe over recent years. In 2013, only a
minority of countries in the EU reported no cases of CPE, and
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Pan European Networks: Science & Technology 14
Youri Glupczynski
several others that had only reported sporadic occurrences of CPE
in 2010 were witnessing regional or inter-regional spread, or even
an endemic situation.
Classically, the detection of MDRB from clinical or screening
specimens from patients may take up to three to four days by
conventional microbiological methods, which may be too long to
wait before providing appropriate treatment to patients with
severe infection and which may also lead to secondary crosstransmission of these bacteria to other persons (mostly through
healthcare personnel during nursing activities because of
inadequate hand hygiene practice).
The second main focus of research is to provide novel
understanding of the epidemiology (i.e. the reservoirs and modes
of transmissions of MDRB) and to gain insights into the patient’s
individual risk factors and the dynamic of diffusion of these
organisms in different human health sectors (hospitals, long term
facility care and the primary care level in the community). The
implementation of an integrated surveillance laboratory network
(including both hospital and private laboratories) coupled with the
development of early warning systems aims to implement welladapted strategies (barrier precautions, good hand hygiene
practice) for prevention of cross-transmission of CPE within and
between the different human healthcare sectors.
Most important advances
In close collaboration with the Public Health Institute, the
laboratory has been able to organise a structured active
surveillance of MDRB in Belgium since 2010. Since antimicrobial
resistance is a global issue, our current programme focuses on
the situation not only in hospitals but also in nursing homes. My
laboratory co-ordinated a multicentric survey carried out in 2011
(to be repeated in May 2015) to assess the prevalence and the
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PROFILE
INFECTIOUS DISEASES
laboratories. In collaboration with an industrial partner (CorisBio
Concept), the group developed an immunochromatographic test
(lateral-flow assay) for rapid identification of OXA-48 and KPC
carbapenemase-producing organisms using monoclonal
antibodies targeting specific regions of the carbapenemase
proteins (OXA-48 and KPC K-SeT). In combination with the BYG
electrochemical sense screening, this immunochromatographic
assay will render possible the precise identification of CPE isolates
from culture colonies in less than one hour. Clinical validation of
these two assays is currently on-going in the setting of a
multicentric survey with reference laboratories in several countries
(France, UK, Germany, Spain and Greece).
Rapid diagnosis of infection caused by MDRB may improve patient
management and save lives
risk factors of asymptomatic carriage of MDRB in 3,000 residents
from 60 nursing homes in Belgium. This study showed that low
functional status of residents (i.e. lack of independency for
practising common activities of daily life) and exposure to
antibiotics (within the last three months) were strong predictors
for colonisation by MDRB (especially Enterobacteriaceae).
Microbiological characterisation also showed close relatedness
between MDRB found in nursing home residents and in
hospitalised patients, suggesting cross-transmission and hence
emphasising the need for global co-ordination of the surveillance
of MDRB within and between nursing homes and hospitals.
The implementation of a large network including more than 100
laboratories (out of a total of 140) also allowed for improvement
of diagnostic practices through education activities (organisation
of external quality assessments, education workshops, and onsite training sessions). A collaborative network could also
successfully be implemented with healthcare providers on the
field, and this has proved very useful to standardising practices at
the local and regional level.
Our group’s final ambition is to create and develop simple
diagnostic tests that may speed up the identification of MDRB. We
believe that early accurate laboratory diagnoses may prove useful
for better patient management (in improving antibiotic usage) and
may ultimately save lives.
Hope for the future
The global expansion of MDRB is a multifaceted problem which
will require vast and versatile solutions. Tackling the burden of
antimicrobial resistance will require comprehensive interventions
involving a wide range of sectors of society: policy makers,
healthcare, education, industry, environmental agencies,
veterinary medicine, research and other areas. While the new EU
framework programme has placed emphasis on supporting
research and innovation in health, the area of prevention is not at
the top of the agenda in most countries where it remains
insufficiently funded. A co-ordinated effort should be made in
order to reduce inequalities between healthcare systems in
Europe, and alongside innovative laboratory diagnostic tests and
the development of antibiotics with new mechanisms of action,
emphasis should be put more on surveillance system design and
guidance on infection prevention and control measures for
MDRB – research areas that are clearly underfunded.
Current developments
Our research group is currently involved in the development of
several new diagnostic tools aiming at the rapid and specific
detection of CPE using innovative approaches. One such assay
(BYG test) uses electrochemical sense technology
(electrochemical portable USB station and activated disposable
miniature electrodes counting eight electrochemical cells). This
assay allows for the detection of carbapenem hydrolysis and is
able to detect all different types of CPE isolates from culture
colonies within 30 minutes. This simple technology is prone to
multiplexing, hence potentially allowing the development of a novel
rapid antimicrobial susceptibility method in the laboratory (in vitro
assessment of susceptibility to antibiotics by conventional
methods takes 18-24 hours). The identification of the exact type of
carbapenemases (which may be needed for epidemiology
purposes) is mostly based on molecular techniques targeting
specific DNA sequences present in the bacteria (carbapenemaseencoding genes). These tests are expensive and necessitate skilled
personnel ,hence limiting their use to only a small number of
Youri Glupczynski, MD, PhD
Professor of Clinical Microbiology,
Université Catholique de Louvain
Head of National Reference Laboratory
for Antimicrobial Resistance
CHU Dinant Godinne UCL
tel: +32 81423245
[email protected]
[email protected]
http://www.uclouvain.be/
https://nrchm.wiv-isp.be/fr/default.aspx
http://www.nsih.be/surv_carba/carbapenemase_fr.asp
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