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SEWPROF ITN A new paradigm in drug use and human health risk assessment: Sewage profiling at the community level
Erika Castrignanò University of Bath, United Kingdom
Supervisor: Dr. Barbara Kasprzyk-Hordern
Meeting: WG 2 Meeting
Date and time: 27-28th October 2014
Location: Hal Luqa, Luqa, Malta
COST is supported by the
EU Framework Programme
Horizon 2020
ESF provides the COST
Office through an EC
contract
SEWPROF ITN A new paradigm in drug use and human health risk assessment: Sewage profiling at the community level
OUTLINE
• Antibiotics use and antimicrobial resistance
• Wastewater-based approach
• Methodologies
• Epidemiological studies
• Conclusions
SEWPROF ITN A new paradigm in drug use and human health risk assessment: Sewage profiling at the community level
ANTIBIOTIC USE IN EUROPE
ECDC-Annual epidemiological report -Reporting on 2010 surveillance
data and 2011 epidemic intelligence data 2012
2008
2009
2010
Trends in the consumption of antibacterials for systemic use (ATC group
J01) in the community (outside of hospitals), EU/EEA Countries, 2008-10
Consumption of antibacterials for systemic use (ATC group
J01) in the hospitals sector, EU/EEA Countries, 2010
Penicillins
Cephelosporins and other
beta lactams
Tetracyclines
Macrolides, lincosamides and
streptogramins
Quinolones
Sulfonamides and thrimetoprim
Other J01 classes
EE
LV
NL
LT
SE
SI
DE
AT
HU
NO
DK
CZ
BG
FI
UK
ES
IE
PL
MT
PT
IS
SK
IT
FR
BE
LU
CY
EL
RO
EE
LV
NL
LT
SE
SI
DE
AT
HU
NO
DK
CZ
BG
FI
UK
ES
IE
PL
MT
PT
IS
SK
IT
FR
BE
LU
CY
EL
SEWPROF ITN A new paradigm in drug use and human health risk assessment: Sewage profiling at the community level
ANTIMICROBIAL RESISTANCE
AMR
SEWPROF ITN A new paradigm in drug use and human health risk assessment: Sewage profiling at the community level
ANTIMICROBIAL RESISTANCE
SEWPROF ITN A new paradigm in drug use and human health risk assessment: Sewage profiling at the community level
ANTIMICROBIAL RESISTANCE
SEWPROF ITN A new paradigm in drug use and human health risk assessment: Sewage profiling at the community level
ANTIMICROBIAL RESISTANCE
SEWPROF ITN A new paradigm in drug use and human health risk assessment: Sewage profiling at the community level
ANTIMICROBIAL RESISTANCE SURVEILLANCE IN EUROPE 2012
Results presented in surveillance report from ECDC are based:
• on antimicrobial resistance data from invasive isolates reported to EARS-Net by
30 EU/EEA countries in 2013 (data referring to 2012),
• on trend analyses of EARSS/EARS-Net data reported by the participating
countries during the period 2009 to 2012
SEWPROF ITN A new paradigm in drug use and human health risk assessment: Sewage profiling at the community level
ANTIMICROBIAL RESISTANCE SURVEILLANCE IN EUROPE 2012
Escherichia coli
Third-generation cephalosporins
Fluoroquinolones Aminoglycosides
Combined resistance
SEWPROF ITN A new paradigm in drug use and human health risk assessment: Sewage profiling at the community level
ANTIMICROBIAL RESISTANCE SURVEILLANCE IN EUROPE 2012
Klebsiella pneumoniae
Third-generation cephalosporins
Fluoroquinolones Aminoglycosides
Combined resistance Carbapenems
SEWPROF ITN A new paradigm in drug use and human health risk assessment: Sewage profiling at the community level
ANTIMICROBIAL RESISTANCE SURVEILLANCE IN EUROPE 2012
• Carbapenem resistance and resistance to multiple antimicrobial groups
were also common in Pseudomonas aeruginosa and Acinetobacter spp.
isolates.
• Resistance trends in gram-positive bacteria showed a more diverse
pattern across Europe.
• The trends for Streptococcus pneumoniae and enterococci are generally
stable, but with large inter-country variations in the percentage of
resistant isolates.
• Meticillin-resistant Staphylococcus aureus (MRSA) remains a public
health priority as the percentage is still above 25% in seven of the 30
reporting countries, with a population-weighted EU/EEA mean of 17.8%.
SEWPROF ITN A new paradigm in drug use and human health risk assessment: Sewage profiling at the community level
ANTIMICROBIAL RESISTANCE SURVEILLANCE IN EUROPE 2012
• For several antimicrobial agent–microorganism combinations, an
overall north-to-south and west-to-east gradient is evident in Europe.
• Differences in infection control practices
and antimicrobial use in the reporting
countries.
• Differences in effective prevention and
control efforts aimed at reducing the
selection and transmission of resistant
bacteria.
• The continuous loss of effective
antimicrobial therapy against gram
negative microorganisms.
• The need for comprehensive strategies
targeting all health sectors.
Countries contributing AMR data for 2012
to EARS-Net
Non participating Countries
Participating Countries
SEWPROF ITN A new paradigm in drug use and human health risk assessment: Sewage profiling at the community level
A real-time profiling of community-wide health and lifestyle is a
needed approach for the investigation of determinants of health-
related states.
World Health Organization (WHO)
Analysis of human
biomarkers statistics on health
themes
analytical studies
surveillance and descriptive studies (alert organism tracking, enhanced routine
surveillance, targeted surveys)
SEWPROF ITN A new paradigm in drug use and human health risk assessment: Sewage profiling at the community level
WASTEWATER ANALYSIS
How can we analyse a real-time profiling of a community?
CONSUMPTION
EXCRETION
MET
AB
OLI
SM
Multiplying with the flow rate of the wastewater stream (L/day)
Multiplying with CF (excretion pattern)
Dividing with amount of inhabitants present in the catchment area of the WWTP
SEWPROF ITN A new paradigm in drug use and human health risk assessment: Sewage profiling at the community level
WASTEWATER-BASED EPIDEMIOLOGY
Overview of the sewage
epidemiology approach
(modified from van Nuijs, A.L., et al.,
Sewage epidemiology-a real-time
approach to estimate the
consumption of illicit drugs in
Brussels, Belgium. Environ Int, 2011.
37(3): p. 612-21.)
Measured concentration of compounds
Multiplying with CF (degradation during transport of ww to WWTP)
Corrected concentration
Massloads of compounds (mg/day)
Amount of use illicit drug (mg/day)
Amount of use illicit drug (mg/day per 1000 inhabitants)
SEWPROF ITN A new paradigm in drug use and human health risk assessment: Sewage profiling at the community level
METHODOLOGIES
UHPLC-MS/MS (QqQ or QTOF)
has been used for target analysis
of chiral compounds
Sample
preparation:
filtration
Sample
preparation:
SPE
MS data interpretation
Sampling
Antibacterial drugs
WWTP influent Cilfynydd
WWTP effluent Cilfynydd
Trimethoprim 1879 ng/L 1004 ng/L
Sulfamethoxazole <LOQ 12 ng/L
Amoxicillin <LOQ <LOQ
Chloramphenicol <LOQ <LOQ
Erythromycin 404 ng/L 830 ng/L
Metronidazole 2608 ng/L 373 ng/L
SEWPROF ITN A new paradigm in drug use and human health risk assessment: Sewage profiling at the community level
METHODOLOGIES
B. Kasprzyk-Hordern et al. Anal Bioanal Chem (2008) 391:1293–1308
SEWPROF ITN A new paradigm in drug use and human health risk assessment: Sewage profiling at the community level
WASTEWATER-BASED EPIDEMIOLOGY
• Seasonal change in plant
A is caused by the
increased appearance of
epidemics during the
winter
L. Birošová et al. / Science of the Total Environment 490 (2014) 440–444
• In plant B, the same or
higher concentrations of
some antibiotics were
detected also in August.
hospitals and health
care facilities
• Misuse antibiotics Plant A (in 2010, 6th place in EU and
usage of antibiotics for prevention)
SEWPROF ITN A new paradigm in drug use and human health risk assessment: Sewage profiling at the community level
WASTEWATER-BASED EPIDEMIOLOGY
Temporal range: pandemic,
late- and inter-pandemic
Singer AC, Ja¨rhult JD, Grabic R, Khan GA, Lindberg RH, et al. (2014) Intra- and Inter-Pandemic
Variations of Antiviral, Antibiotics and Decongestants in Wastewater Treatment Plants and
Receiving Rivers. PLoS ONE 9(9): e108621.
Understand the differential
pharmaceutical use patterns
during the pandemic
Examine the suitability of
employing a wastewater
epidemiology approach for
the estimation of drug users
SEWPROF ITN A new paradigm in drug use and human health risk assessment: Sewage profiling at the community level
WASTEWATER-BASED EPIDEMIOLOGY
WW epidemiology approach will need to address:
1. Heterogeneity in the temporal distribution of prescriptions over time
2. Heterogeneity in the spatial distribution of prescriptions (across the UK) over time
3. Heterogeneity in in vivo and environmental stability of the antibiotic, including sewage
pipes prior to reaching the WWTP inlet
4. Variability in compliance rate, sample size and sampling method
5. Variability in environmental temperatures and precipitation
Singer AC, Ja¨rhult JD, Grabic R, Khan GA, Lindberg RH, et al. (2014) Intra- and Inter-
Pandemic Variations of Antiviral, Antibiotics and Decongestants in Wastewater Treatment
Plants and Receiving Rivers. PLoS ONE 9(9): e108621.
SEWPROF ITN A new paradigm in drug use and human health risk assessment: Sewage profiling at the community level
WASTEWATER-BASED EPIDEMIOLOGY
Y. Xiao et al. / J. Chromatogr. A 1214 (2008) 100–108
• Different consumption
style in China
SEWPROF ITN A new paradigm in drug use and human health risk assessment: Sewage profiling at the community level
WASTEWATER-BASED EPIDEMIOLOGY
• ~ 107–1010 CFU per day per inhabitant equivalent can be discharged by the final
effluent of UWTP and could have any kind of acquired antibiotic resistance.
• Only 1% of the total of the culturable fraction of the bacterial population is being
considered.
L. Rizzo et al. / Science of the Total Environment 447 (2013) 345–360
• 140 clinically relevant genes, encoding resistance to the
different classes of antibiotics, were detected
(Szczepanowski et al., 2009).
• Occurrence of antimicrobial residues, selecting
resistance phenotypes, may also disturb the indigenous
bacterial communities (Novo et al., in press).
• Current knowledge about the relationship between
antibiotics and the spread of ARG in microbial
communities: the result of retrospective evidences.
SEWPROF ITN A new paradigm in drug use and human health risk assessment: Sewage profiling at the community level
WASTEWATER-BASED EPIDEMIOLOGY
L. Rizzo et
al. /
Science of
the Total
Environme
nt 447
(2013)
345–360
In an attempt to establish a relationship between the most severe cases reported in
clinical settings and environment, the search for the last generation antibiotic
resistant determinants is also reported in UWTP studies (Araújo et al., 2010;
Czekalski et al., 2012; Figueira et al., 2011a,b; Gajan et al., 2008; Parsley et al.,
2010; Szczepanowski et al., 2009).
SEWPROF ITN A new paradigm in drug use and human health risk assessment: Sewage profiling at the community level
WASTEWATER-BASED EPIDEMIOLOGY
L. Rizzo et
al.
Science of
the Total
Environm
ent 447
(2013)
345–360
Ciprofloxacin resistant E. coli : significantly higher prevalence in the final
effluent than in the raw inflow of an UWTP. Ferreira da Silva et al., 2007
Acinetobacters: resistance to amoxicillin/clavulanic acid, chloramphenicol,
rifampin, and multi-drug significantly increased from the raw influent samples to
the final effluent samples, and was significantly higher in the downstream samples
than in the upstream samples. Y. Zhang et al. (2009)
Carbapenem resistance: Not been reported in recent studies concerning
wastewaters (Figueira et al., 2011a; Łuczkiewicz et al., 2010).
… it will be a matter of time
L.
Birošová
et al.
Science of
the Total
Environme
nt 490
(2014)
440–444
Most coliforms are resistant to
ampicillin:
it is in accordance with the
frequent prescription of β-lactams
in Slovakia
SEWPROF ITN A new paradigm in drug use and human health risk assessment: Sewage profiling at the community level
Prof. Ed Feil Professor of Microbial Evolution
University of Bath
United Kingdom
Supervisors:
• Exploring antibiotics profiling and microbial resistance at community level via
wastewater-based epidemiology
• Understanding the origin of a drug residue, recognizing the direct consumption
from its disposal
• Monitoring of changing patterns of antibacterial drugs use
Dr. Barbara Kasprzyk-Hordern Dept. Chemistry, University of Bath
United Kingdom
Dr. Sara Castiglioni Istituto di Ricerche Farmacologiche Mario
Negri
Italy
Dr. Anneke Lubben Mass Spectrometrist ,University of Bath
United Kingdom
SEWPROF ITN A new paradigm in drug use and human health risk assessment: Sewage profiling at the community level
CONCLUSIONS
Wastewater-based epidemiology:
Evidence-based and real time estimates of a
community antibacterial usage
• Spatial and temporal differences among Countries
• Changes in consumption trends
• Monitoring of AMR
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