7-4-2014
3rd Euregional Maastricht Symposium
on Immune Compromised Traveller
24 March 2014, Maastricht, The Netherlands
Acquisition of ESBL‐ and
carbapenemase‐producing Enterobacteriaceae
during travel:
The Carriage of Multiresistant
Bacteria After Travel (COMBAT) Study
John Penders
Dept. of Medical Microbiology
j.penders@maastrichtuniversity.nl
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Disclosure belangen spreker
John Penders
(potentiële)
Geen
belangenverstrengeling
voor bijeenkomst mogelijk
Geen
relevante
relaties met bedrijven
• sponsoring of
Geen
onderzoeksgeld
• honorarium of andere
(financiële) vergoeding
• aandeelhouder
• andere relatie
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Why clinically relevant? (1)
Extended-spectrum beta-lactamases
• ESBLs: Resistant against most beta-lactam anitibiotics except
Study
•
carbapenems
• Often on plasmids together with additional genes providing co-
Reddy,
2007
HR patients
ESBL-E
infection
rate Inthan
ESBL-E
Higher
colonization rates in
high-risk
patients
in
colonized vs. uncolonized patients
healthy individuals (Kader 2007,
Ko 2013)
ICU/solid-organ transplant/
hematology/oncology
BSI: 8.5% vs. 0.1%
resistance (a.o. quinolones, aminoglycosides)
Liss,•
2012
• Resistence less extreme than carbapenemases, yet
“problematic”:
Bert,
2012
• Acquisition and spread in open population
hematology/oncology
BSI:shown
6.6% vs.to0.5%
ESBL-E
colonization has been
increase the risk of a
subsequent ESBL-E infection in high-risk patients
- Impaired mucosal barrier in HR patients
Liver transplant
BSI/UTI/RTI/intra-abdominal/skin/soft
tissue infections: 44.8% vs. 3.8%
• Increased use of carbapenems
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Why clinically relevant? (2)
• ESBL-E often not susceptible to antimicrobial spectrum of
empirical regimens
• Negative impact of delayed initiation of adequate treatment in
high-risk setting more pronounced than in immunocompetent
patients
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Risk factors
• Besides nosocomial acquisition community serves as
an important source of ESBL-E colonization (Arnan 2011;
Calatayud 2008; Thiebaut 2012)
• Risk factors: prior exposure to antibiotics (3GC), prior
health care contact (abroad)
• Recently foreign travel identified as a risk (Paltansing 2013,
Identification of major risk factors for acquisition ESBL-E:
Östholm-Balkhed 2013, Tangden 2010)
- Recommendations to prevent colonization
- Narrowing down the target population for potential
infectious control measures (screening, contact precautions, decolonization)
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COMBAT Study
Carriage Of Multiresistant Bacteria After Travel
Tropenpoli AMC
Havenziekenhuis
EASE Travel Clinic
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Baseline data
• Inclusion Nov. 2012-Nov. 2013
• 2001 travelers, 215 household members
• Response rate: T1 97.8%, T2 96.6%
2,000 Travelers
&
400 household members
Pre-travel
Objectives:
• Incidence of colonization ESBL- and
• Age: 50.4 (18.1-81.7), M/F: 45.9/54.1
Pre-travel colonization
Q + swab
Travel
carbapenemase-producing
Post-travel
• 124 (6.2%) Travellers
Q + swab
Enterobacteriaceae
1 month
Q + swab
• 14 (6.4%) HH members
3 months
Q + (swab)
• 1884 Travellers “at risk”
6 months
Q + (swab)
12 months
Q + (swab)
• Persistence of colonization
• Transmission to household members
• (Travel-associated) risic factors
• Examining the resistome
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Main organisms and co-resistance
ESBL-E acquisition according to UN subregions
Escherichia coli
Klebsiella pneumoniae
Enterobacter cloacae
Proteus vulgaris
Citrobacter freundii
Citrobacter braakii
Proportion of resistant strains
Proteus mirabilis
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Carbapenemase-producing Enterobacteriaceae
• 4/2000 “at risk” travelers acquired CP-E
– Incidence rate 0.2% (95%CI 0.075-0.5%)
Pretravel
Posttravel
1
OXA-48
E. coli
2/Turkey & Greece
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E. coli
Klebsiella
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Conclusions and discussion
• 1 Traveler CP-E positive pre-travel (OXA-48 E. coli)
1 month
3 months
6 months
OXA-48
E. coli
OXA-48
E. coli
NEG
…….
…….
NEG
OXA-48
Klebsiella
NEG
NEG
…….
……..
3/Indonesia
NEG
OXA-48
E. coli
OXA-48
E. coli
OXA-48
E. coli
OXA-48
E. coli
……..
4/Indonesia
NEG
NEG
NEG
OXA-48
E. coli
NEG
……..
5/Myanmar
NEG
NDM-1
E. coli
NDM-1
E. coli
NEG
……
……
6/SE Asia
NEG
NDM-1
E. coli
NEG
NEG
……
…….
Subject/destinatio
n
1
0,9
0,8
0,7
0,6
0,5
0,4
0,3
0,2
0,1
0
1 year
• Very high ESBL-E acquisition rates in travelers to Asia & Northern
Africa
• Within subregions large variations between countries
• Acquisition (and transmission?) of CP-E in travelers without
health care contact
• Travel- and traveler-associated risk factor analysis will provide
further insight into (modifiable) risk factors
• Infection control measures: prevention, screening, contact
precautions?
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Thank you!
Erasmus MC - Rotterdam
Dr. Damian Melles
Prof. dr. Henri Verbrugh
Drs. Maris Arcilla
ESBL-E colonization over time
MUMC – Maastricht
Dr. J. Penders
Dr. Ellen Stobberingh
0,4
0,35
Colonization rate (%)
COMBAT-study Team
AMC - Amsterdam
Prof. dr. Menno de Jong
Dr. Constance Schultsz
Dr. Bram Goorhuis
Drs. Jarne van Hattem
14
UMC Utrecht
Dr. Martin Bootsma
Havenziekenhuis Rotterdam
Dr. Perry van Genderen
0,3
0,25
Travelers
0,2
Household members
0,15
0,1
0,05
0
Pre-travel
Post-travel
1 month post-travel
..and all employees of the Travel Clinics (Havenziekenhuis,
Tropenpoli AMC, EASE Travel & Health Support)!
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Chronic diseases
Disease/condition
Prevalence (%)
Diabetes
2.7%
Respiratory
4.3%
CVD
4.4%
GI
2.7%
Hepatic/renal
0.4%
Malignancy
0.9%
Autoimmune disease
1.5%
Immunosuppressive drug use
1.2%
3