CTX-M ESBL-producing Enterobacteriaceae: estimated prevalence inadults in England in 2014
Cliodna A. M. McNulty1*, Donna M. Lecky1, Li Xu-McCrae2, Deborah Nakiboneka-Ssenabulya1, Keun-Taik Chung3,Tom Nichols4, Helen Lucy Thomas4, Mike Thomas5, Adela Alvarez-Buylla2, Kim Turner1, Sahida Shabir2,
Susan Manzoor2, Stephen Smith6, Linda Crocker1 and Peter M. Hawkey3
1Public Health England, Primary Care Unit, Microbiology Department, Gloucester Royal Hospital, Great Western Road, Gloucester GL13NN, UK; 2Public Health England, Heart of England NHS Foundation Trust, Public Health Laboratory, Bordesley Green E, Birmingham B9
5SS, UK; 3Institute of Microbiology and Infection, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK; 4Public HealthEngland, 61 Colindale Avenue, London NW9 5EQ, UK; 5University of Southampton, Aldermoor Health Centre, Aldermoor Close,
Southampton SO16 5ST, UK; 6University Hospitals of Coventry & Warwickshire NHS Trust, Midlands & NW Bowel Cancer Screening Hub,Hospital of St Cross, Barby Road, Rugby CV22 5PX, UK
*Corresponding author. Tel: !44-300-422-5066; E-mail: [email protected]
Received 2 June 2017; returned 3 September 2017; revised 14 December 2017; accepted 2 January 2018
Background: ESBL-producing Enterobacteriaceae (ESBLPE) are increasing in prevalence worldwide and are moredifficult to treat than non-ESBLPE. Their prevalence in the UK general population is unknown, as the only previousUK ESBLPE faecal colonization study involved patients with diarrhoea.
Objectives: To estimate the prevalence of CTX-M ESBLPE faecal colonization in the general adult population ofEngland in 2014, and investigate risk factors.
Methods: A stratified random sample of 58337 registered patients from 16 general practices within four areasof England were invited to participate by returning faeces specimens and self-completed questionnaires.Specimens were tested for ESBLPE and carbapenemase-producing Enterobacteriaceae (CPE).
Results: 2430 individuals participated (4% of those invited). The estimated prevalence of colonization withCTX-M ESBLPE in England was 7.3% (95% CI 5.6%–9.4%) (Shropshire 774 participants, 4.9% colonization;Southampton City 740 participants, 9.2%; Newham 612 participants, 12.7%; Heart of Birmingham 234 individ-uals, 16.0%) and was particularly high in: those born in Afghanistan (10 participants, 60.0% colonization, 95% CI29.7%–84.2%); those born on the Indian subcontinent (India, Pakistan, Bangladesh or Sri Lanka) (259 partici-pants, 25.0% colonization, 95% CI 18.5%–32.9%); travellers to South Asia (India, Pakistan, Bangladesh, Sri Lankaor Nepal) in the last year (140 participants, 38.5% colonization, 95% CI 27.8%–50.5%); and healthcare domestics(8 participants, unweighted 37.5% colonization, 95% CI 8.5%–75.5%). Risk factors identified included: beingborn in the Indian subcontinent (aOR 5.4, 95% CI 3.0–9.7); travel to South Asia (aOR 2.9, 95% CI 1.8–4.8) or toAfrica, China, South or Central America, South East or Pacific Asia or Afghanistan (aOR 2.6, 95% CI 1.7–4.1) in thelast year; and working as a healthcare domestic (aOR 6.2, 95% CI 1.3–31). None of the 48 participants who tookco-amoxiclav in the last year was colonized with CTX-M ESBLPE. blaCTX-M-15 accounted for 66% of CTX-M ESBLPEpositives. 0.1% (two participants) were colonized with CPE.
Conclusions: CTX-M ESBLPE are established in the general population in England and prevalence is particularly highin people from certain countries of birth or with recent travel. We recommend that these findings be taken into ac-count in guidance on the empirical management of patients presenting with a likely Enterobacteriaceae infection.
Introduction
Extensive overuse of antibiotics worldwide has led to increasingprevalence of antibiotic-resistant Gram-negative bacteria (mainly
Escherichia coli) that produce ESBLs; 85%–90% of these beingCTX-M genotypes.1–4 Carriage is particularly high in South Asia.4
Between 2010 and 2015 total E. coli bloodstream and urine
VC The Author(s) 2018. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy.This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecom-mons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the originalwork is properly cited. For commercial re-use, please contact [email protected]
1368
J Antimicrob Chemother 2018; 73: 1368–1388doi:10.1093/jac/dky007 Advance Access publication 5 March 2018
Downloaded from https://academic.oup.com/jac/article-abstract/73/5/1368/4885410by Southampton Oceanography Centre National Oceanographic Library useron 13 June 2018
infections in England have continued to rise and, moreover, resist-ance in E. coli to important hospital antibiotics such as co-amoxiclav and piperacillin/tazobactam rose significantly makingtreatment more difficult.5,6 ESBL-producing Enterobacteriaceae(ESBLPE) are opportunistic pathogens with large bowel coloniza-tion typically preceding an ESBLPE infection,7,8 so we believe thatunderstanding the prevalence of faecal colonization overall andfor certain sections of the general population will help inform em-pirical antibiotic guidance. Recent European studies indicate thattravellers to countries outside Europe have an up to 10-fold higherprevalence of ESBLPE faecal colonization than the local popula-tion.3,9,10 The prevalence of CTX-M ESBLPE in diagnostic faecalspecimens in a UK laboratory in 2010 was double in MiddleEastern/South Asian patients (22.8%) compared with Europeans(8.1%).11 Studies in returning European travellers have found thattravel to South Asia was the most important risk factor,12 whileantibiotic use10,12,13 and travellers’ diarrhoea were other possiblerisk factors for ESBLPE acquisition. Travel acquisition is importantas between 1% and 8% of returning travellers are hospitalized,14,15
equating to 3.1–24.8 million Europeans each year.16 Importantly,there are no studies of the colonization of ESBLPE in the UK generalpopulation.
This study aimed to estimate the prevalence of colonizationwith CTX-M ESBLPE across different sections of the adult generalpopulation of England in 2014, including different ethnic groups,and to investigate the potential risk factors for their carriage.
MethodsThe study was undertaken in four NHS Primary Care Trusts (PCTs) inEngland. PCTs were state-funded and commissioned primary medical carefrom general practices in England until 2015; this has now been taken overby Clinical Commissioning Groups. All the UK population are registered with,or have access to, a general medical practice whom they consult for pri-mary care. The four PCTs were purposively selected to capture the UK ethnicdiversity: Newham (London, highest ethnic diversity), Heart of Birmingham(predominantly Asian), Shropshire (rural, mostly white British) andSouthampton City (mixed ethnicity). Three to five willing Primary CareResearch Network practices from each PCT were non-randomly selected tobroadly represent each area with respect to ethnicity and deprivation.
Individuals aged �18 years in selected practices were stratified by re-cord of ethnicity (white, Asian, black, other/mixed or unknown), sex andage. Within each stratum individuals were randomly selected in 2013 and2014 to receive an invitation letter. Respondents were sent study informa-tion, a faeces sample collection kit (not rectal swab), £5 incentive offer anda questionnaire (Figure S1, available as Supplementary data at JAC Online)(including questions on age, ethnic group, country of birth, employment,household characteristics, hospitalization, antibiotic use, travel abroad inpast year and diet). Those not returning kits received a telephone reminder.Respondents were asked to collect scoops of faeces from both ends andthe middle of their faeces sample and place them in a sterile container,keep the container cool and return by first-class post within 24 h to a centrallaboratory. As sampling progressed, faeces returns were monitored and in-vitations to reach Asian, black and younger age group sample sizesincreased as necessary, including direct approach by general practice re-ceptionists to individuals in some ethnic groups. For some practices all indi-viduals within a given stratum were invited.
Laboratory analysisFaecal samples were screened for ESBLPE, using direct culture on selectivemedium (Brilliance
TM
ESBL agar, Oxoid Ltd) for 24 h. To increase sensitivity,
all samples were enriched as well as directly plated; 20 mg of each faecalsample was incubated for 24 h in 10 mL of brain heart infusion (BHI) brothcontaining 1 mg/L cefpodoxime17 and subcultured onto BrillianceTM agar asbefore.17,18 Oxidase-negative presumptive colonies of ESBLPE were definedas: !, 1–10 cfu; !!, 10–100 cfu; and !!!, �100 cfu. One colony fromeach different colony morphology, from each plate of Brilliance agar, wasidentified using MALDI-TOF MS (Bruker UK Ltd) and tested for the blaCTX-M
gene using multiplex PCR.19 Full-length gene amplification and sequencingidentified blaCTX-M genotypes (Table 1). A 10lg ertapenem disc was placedon all selective plates to detect potential carbapenemase-producingEnterobacteriaceae (CPE).20 Colonies growing in the zone of inhibition weretested by PCR for CPE genes.21
Data analysisTo estimate the prevalence of ESBLPE colonization for adults living inEngland in 2014 we used post-stratification weights based on the 2011 na-tional census and number of eligible individuals at selected practices. To es-timate the prevalence for each GP practice and PCT we used samplingweights based on the numbers of eligible individuals in each group at eachpractice. A new variable ‘region of origin’ was derived mainly from ethnicgroup and country of birth. Multivariable logistic regression models wereused to control for country of birth and region of origin (if born in the UK)(Table 2). Based on this preliminary analysis, factors that were associatedwith an increased risk of colonization were considered in further analysis.We also considered the strength of evidence and the number of missingvalues, and the evidence from other studies; we did not follow an auto-mated model selection process. The final multivariable model for coloniza-tion with CTX-M ESBLPE included country of birth and region of origin(if born in the UK) as a factor variable with eight categories, the base cat-egory of which was ‘born in some country not including the UK, India,Pakistan or Bangladesh (IPB), Sri Lanka, Afghanistan or the Middle East’(Table 3). From the final model we estimated the adjusted ORs (aORs) foreach risk factor, the percentage of carriers attributable to each risk factor(for example, travel to India) and, for groups of risk factors (for example,travel abroad in past year), the population attributable fraction (PAF). ThePAF is dependent on both the aOR and the probability of being exposed tothe factor.
Among participants colonized with CTX-M ESBLPE we calculated thepercentage colonized with a particular blaCTX-M genotype, and the percent-age belonging to particular ethnic groups among those who were carriersof a particular blaCTX-M genotype.
EthicsApproval for the study was obtained from the NRES Committee South West- Frenchay, Bristol, UK (13/SW/0017). The data we collected from GP prac-tices were anonymous.
Results
Of 76154 adult individuals registered in 16 GP practices, 58337 wereinvited to participate; 3389 (5.8%) expressed interest and were senta faeces kit, and 2331 (4.0%) returned a sample. A further 99 individ-uals invited by general practice receptionists participated, making atotal of 2430 participants. The number of stool specimens receivedfrom participants in each section of the adult population in England,the number of specimens positive for ESBLPE, and the unweightedand weighted percentage positive for ESBLPE are shown in Table 2.The estimated prevalence of colonization with CTX-M ESBLPEin adults living in England in 2014 was 7.3% (95% CI 5.6%–9.4%).Of the four PCTs, Heart of Birmingham teaching PCT (234 partici-pants) had the highest estimated prevalence at 16.0% (95% CI
CTX-M ESBL-producing Enterobacteriaceae prevalence JAC
1369Downloaded from https://academic.oup.com/jac/article-abstract/73/5/1368/4885410by Southampton Oceanography Centre National Oceanographic Library useron 13 June 2018
10.2%–24.2%) [Newham 612 participants, 12.7% (95% CI 9.1%–17.4%); Southampton City 740 participants, 9.2% (95% CI 6.1%–13.7%); and Shropshire County 774 participants, 4.9% (95% CI3.4%–7.0%)]. There was no evidence that estimated prevalence dif-fered by age or sex. There were high estimated prevalences for par-ticipants born in India (136 participants, 28.7% prevalence, 95% CI18.8%–41.2%), Pakistan (81 participants, 18.6% prevalence, 95% CI10.5%–30.8%), Bangladesh (34 participants, 23.5% prevalence, 95%CI 11.8%–41.3%), Sri Lanka (8 participants, 25.0% prevalence, 95%CI 7.2%–59.0%), Afghanistan (10 participants, 60.0% prevalence,95% CI 29.7%–84.2%) and the Middle East (18 participants, 15.5%prevalence, 95% CI 4.7%–40.5%) (Figure 1). The overall estimatedprevalence for those born in the Indian subcontinent (India,Pakistan, Bangladesh or Sri Lanka) combined (259 participants) was25.0%, (95% CI 18.5%–32.9%); differences between these fourcountries were non-significant (P"0.65). The estimated prevalencefor those born in the UK with an IPB region of origin was 15.7% (52participants), while for those born in the UK with a UK region of origin(1459 participants) it was 5.6% (95% CI 4.4%–7.1%, P"0.03).However there was a low estimated prevalence for those born inAfrica and of the IPB ethnic group (17 participants, 0% prevalence,95% CI 0%–19.5%).
Overall estimated prevalence of ESBLPE was the same in thosereporting taking any antibiotic in the last year (777 participants,6.8% prevalence 95% CI 5.1%–8.9%) or not (1427 participants,6.8% prevalence 95% CI 5.4%–8.6%). None of 48 participants whoreported having taken any co-amoxiclav in the past 12 monthscarried ESBLPE (0% prevalence, 95% CI 0%–7.4%, P"0.03).Estimated prevalence of ESBLPE in the 15 participants who hadtaken ciprofloxacin was 9.5%, (95% CI 2.5%–30.1%, P"0.61).
Two other groups with high estimated prevalence were thosewho had travelled to South Asia (India, Pakistan, Bangladesh, SriLanka or Nepal) in the last year (140 participants, 38.5% preva-lence, 95% CI 27.8%–50.5%) and those working as a domestic in ahealthcare setting [8 participants, unweighted prevalence 37.5%,95% CI 8.5%–75.5% (3/8; 1 black African, CTX-M-15, no travelabroad; 1 white British, CTX-M-15, travelled to India with partnerfor 12 days; 1 Asian Indian, CTX-M-27, travelled to India alone for42 days)]. If someone else in the participant’s household had beento India, Bangladesh, the Middle East, the Indian subcontinent orSouth East or Pacific Asia, this significantly increased the partici-pant’s risk for carrying blaCTX-M ESBL. Participants whose
housemates had travelled abroad in the last year to the Indiansubcontinent (India, Pakistan, Bangladesh or Sri Lanka) (120 par-ticipants, estimated prevalence 22.7%, 95% CI 14.2%–34.1%,P , 0.001), India (83 participants, estimated prevalence 24.9%95% CI 14.5%–39.2%, P , 0.001) and the Middle East (43 partici-pants, estimated prevalence 16.9%, 95% CI 7.5%–33.6%,P"0.02) had a higher prevalence. In 1071 of 1234 participants,both the housemate and the main participant had travelled to thesame country in the past 12 months.
Relative frequency of CTX-M genotypes (Figure 2)
Two hundred and eight participants were found to carry the CTX-Mgene; 184 (88%) by direct culture (25%!, 26%!!, 37%!!!)and a further 24 (12%) on enrichment; no single participant hadmore than one species of bacteria carrying CTX-M. Most isolates(199) were E. coli, 5 Klebsiella pneumoniae, 4 Enterobacter and 1Citrobacter. All isolates could be allocated a CTX-M grouping.Seventy-seven percent of participants with CTX-M ESBLPE (161/208) were colonized with CTX-M group 1; 25% (53/208) werecolonized with CTX-M group 9; 4% (9/208) were colonized withboth group 1 and group 9; and 1.4% (3/208) were colonized withCTX-M group 8, 25 or 26. Four isolates from group 1 and one isolatefrom group 9 could not be sequenced. The most common geno-type was blaCTX-M-15 (66%, 134/204) (Figure 2). Two other commongenotypes were blaCTX-M-14 (11%, 23/207) and blaCTX-M-27 (13%,27/207).
CTX-M genotypes and risk factors
Carriers of blaCTX-M-15 had a similar probability of being of whiteethnicity compared with carriers of other genotypes (62/134, 46%of blaCTX-M-15 were white; 46/134, 34% Asian IPB; and 26/134, 19%other ethnicity) and 84/129 (65%) had travelled abroad in the lastyear. A carrier of blaCTX-M-27 had a higher chance of being of theAsian-IPB ethnic group (16/27, 59% Asian IPB; 6/27, 22% white;5/27, 19% other ethnicity; 16/27, 59% travelled abroad) comparedwith carriers of other genotypes. A blaCTX-M-14 carrier had a higherchance of being of white ethnicity (19/23, 83% white; 2/23, 9%Asian IPB; 2/23, 9% other ethnicity; 14/23, 61% travelled abroad)compared with carriers of other genotypes. Carriers of the differentgenotypes CTX-M-15, -27 and -14 had a similar chance of having
Table 1. List of PCR and sequencing primers
CTX-M group Name Primer sequence Location
8 and 25/26 50CTXM26 TTG ATT AAC TAC AAC CCC AT CTX-M-26 (313–332)
30CTXM26 GAT ATC ATT CGT CGT ACC AT CTX-M-26 (747–728)
50CTXMF26-1 CTC TGC GCA ATC TGA CGT TG CTX-M-26 (575–594)
50CTXMF26-2 AAG GCG GGC GAT GTT AAT GA CTX-M-26 (18–37)
30CTXMR26-1 GCC AAT CGT ACG GGC AAA TG CTX-M-26 (477–458)
1 ISEcp1 AAA AAT GAT TGA AAG GTG GT ISEcp1 (#149 to #128)
30CTXM-1R ATA CAT CGC GAC GGC TTT CT CTX-M-1 (838–819)
50G1S1 ATG GTT AAA AAA TCA CTG CG CTX-M-15 (1–20)
9 50G9full GAA TAC TGA TGT AAC ACG GAT CTX-M-9 (#40 to #22)
30G9full AGT TAC AGC CCT TCG GCG AT CTX-M-9 (859–878)
McNulty et al.
1370Downloaded from https://academic.oup.com/jac/article-abstract/73/5/1368/4885410by Southampton Oceanography Centre National Oceanographic Library useron 13 June 2018
Tab
le2
.Pr
eva
len
ceo
fco
lon
iza
tio
nw
ith
bla
CT
X-M
ESB
LPE
ind
iffe
ren
tse
ctio
ns
of
the
ad
ult
po
pu
lati
on
of
Eng
lan
din
20
14
Fact
or
No
.of
spec
imen
s
No
.of
bla
CT
X-M
ESB
LPE-
po
siti
vesp
ecim
ens
bla
CT
X-M
ESB
LPE-
po
siti
ve(u
nw
eig
hte
d%
)
Prev
ale
nce
[95
%C
I](w
eig
hte
d%
)a
Test
for
ad
iffe
ren
cein
pre
vale
nce
be
twee
nth
eg
rou
ps
of
each
fact
or
(Pva
lue)
OR
ad
just
edfo
rb
(co
un
try
of
bir
tha
nd
reg
ion
of
ori
gin
ifb
orn
inth
eU
K)
(aO
R)
[95
%C
I]
Test
for
the
effe
cto
fea
chfa
cto
ra
fter
ad
just
men
tfo
rco
un
try
of
bir
tha
nd
reg
ion
of
ori
gin
ifb
orn
inth
eU
K(P
valu
e)
Ove
rall
24
27
20
88
.67
.3[5
.6,9
.4]
Pra
ctic
e/M
edic
alC
entr
e
Lath
om
Ro
ad
12
91
29
.31
1.1
[6.0
,19
.6]
0.0
21
0.7
4
Stra
tfo
rdV
illa
ge
23
01
87
.89
.0[4
.6,1
7.0
]1
.1[0
.5,2
.3]
StB
art
ho
lom
ew’s
22
42
91
2.9
15
.6[9
.3,2
4.9
]1
.6[0
.8,3
.3]
Gre
etM
edic
alP
ract
ice
47
11
23
.41
1.5
[5.6
,22
.1]
1.7
[0.6
,4.4
]
Hig
hTr
ees
89
13
14
.61
8.6
[6.4
,43
.5]
1.8
[0.7
,4.1
]
Kh
att
ak
Mem
ori
al
46
11
23
.91
8.9
[8.9
,35
.9]
1.2
[0.4
,3.6
]
Alm
a1
69
16
9.5
11
.7[6
.0,2
1.7
]1
.3[0
.6,2
.9]
Ald
erm
oo
r3
65
23
6.3
6.8
[4.4
,10
.5]
1.1
[0.5
,2.4
]
Ch
urc
hSt
rett
on
24
21
56
.26
.5[3
.8,1
0.8
]1
.2[0
.5,2
.8]
Pla
sFf
ynn
on
32
31
34
.03
.7[2
.2,6
.4]
0.7
[0.3
,1.7
]
The
Ca
xto
n2
09
94
.34
.8[2
.4,9
.1]
0.8
[0.3
,2.1
]
Mu
lber
ryH
ou
se1
85
17
9.2
9.5
[5.2
,16
.8]
1.7
[0.7
,3.9
]
Cit
yR
oa
d5
26
11
.51
5.5
[4.9
,39
.7]
1.0
[0.3
,2.7
]
Nic
ho
lsto
wn
70
71
0.0
24
.0[9
.7,4
8.3
]1
.0[0
.3,2
.7]
Ba
rkin
gR
oa
d2
96
20
.71
7.2
[6.2
,39
.6]
1.4
[0.4
,5.4
]
StD
en
y’s
21
29
.56
.7[1
.2,2
9.6
]1
.8[0
.4,8
.8]
PCT N
ew
ha
m6
12
65
10
.61
2.7
[9.1
,17
.4]
0.0
01
10
.33
Hea
rto
fB
irm
ing
ha
mte
ach
ing
23
44
11
7.5
16
.0[1
0.2
,24
.2]
1.1
[0.7
,1.8
]
Shro
psh
ire
Co
un
ty7
74
37
4.8
4.9
[3.4
,7.0
]0
.7[0
.4,1
.2]
Sou
tha
mp
ton
Cit
y7
40
58
7.8
9.2
[6.1
,13
.7]
1.0
[0.6
,1.5
]
Ag
eg
rou
p(y
ears
)
18
–39
56
25
39
.47
.6[5
.5,1
0.5
]0
.54
(tes
tfo
r
tren
d:P
"0
.30
)
10
.84
(tes
tfo
r
tren
d:P
"0
.77
)4
0–4
93
56
39
11
.05
.6[3
.5,8
.8]
1.1
[0.7
,1.8
]
50
–59
43
53
37
.66
.5[4
.3,9
.8]
0.9
[0.6
,1.5
]
60
–69
56
64
27
.47
.1[5
.2,9
.6]
1.1
[0.7
,1.7
]
70
–79
36
63
28
.77
.3[5
.0,1
0.5
]1
.3[0
.8,2
.1]
80
–10
01
42
96
.33
.7[1
.6,8
.4]
0.8
[0.4
,1.8
]
Gen
der
ma
le1
05
21
06
10
.17
.3[5
.5,9
.5]
0.4
01
.2[0
.9,1
.6]
0.2
6
fem
ale
13
78
10
27
.46
.3[5
.0,7
.8]
1
GP
reco
rdo
fw
het
her
an
tib
ioti
cu
sed
inth
eye
ar
bef
ore
no
16
41
13
28
.07
.0[5
.6,8
.6]
0.4
81
0.6
4
yes
78
67
69
.76
.1[4
.6,8
.1]
1.1
[0.8
,1.5
]
Co
nti
nu
ed
CTX-M ESBL-producing Enterobacteriaceae prevalence JAC
1371Downloaded from https://academic.oup.com/jac/article-abstract/73/5/1368/4885410by Southampton Oceanography Centre National Oceanographic Library useron 13 June 2018
Tab
le2
.C
on
tin
ued
Fact
or
No
.of
spec
ime
ns
No
.of
bla
CT
X-M
ESB
LPE-
po
siti
vesp
ecim
ens
bla
CT
X-M
ESB
LPE-
po
siti
ve(u
nw
eig
hte
d%
)
Prev
ale
nce
[95
%C
I](w
eig
hte
d%
)a
Test
for
ad
iffe
ren
cein
pre
vale
nce
be
twee
nth
eg
rou
ps
of
each
fact
or
(Pva
lue)
OR
ad
just
edfo
rb
(co
un
try
of
bir
tha
nd
reg
ion
of
ori
gin
ifb
orn
inth
eU
K)
(aO
R)
[95
%C
I]
Test
for
the
effe
cto
fea
chfa
cto
ra
fter
ad
just
men
tfo
rco
un
try
of
bir
tha
nd
reg
ion
of
ori
gin
ifb
orn
inth
eU
K(P
valu
e)
Bo
rnin
the
UK
?
UK
15
96
10
36
.55
.9[4
.6,7
.4]
,0
.00
1
oth
er7
60
98
12
.91
1.4
[8.9
,14
.4]
Co
un
try
of
bir
th
UK
15
96
10
36
.55
.9[4
.6,7
.4]
,0
.00
1
Irel
an
d2
41
4.2
4.2
[0.6
,24
.5]
Ind
ia1
36
33
24
.32
8.7
[18
.8,4
1.2
]
Paki
sta
n8
12
12
5.9
18
.6[1
0.5
,30
.8]
Ba
ng
lad
esh
34
82
3.5
23
.5[1
1.8
,41
.3]
SriL
an
ka8
22
5.0
25
.0[7
.2,5
9.0
]
Nep
al
40
00
[0,6
0.2
]
Afg
ha
nis
tan
10
66
0.0
60
.0[2
9.7
,84
.2]
Afr
ica
13
46
4.5
5.8
[2.2
,14
.5]
Au
stra
lasi
a7
11
4.3
9.5
[1.2
,48
.0]
Ca
rib
bea
n7
67
9.2
7.6
[3.7
,15
.1]
Ch
ina
17
00
0[0
,19
.5]
East
ern
Euro
pe
71
22
.83
.1[0
.6,1
5.1
]
Mid
dle
East
18
31
6.7
15
.5[4
.7,4
0.5
]
No
rth
Am
eric
a1
01
10
.08
.3[1
.0,4
4.6
]
Sou
tho
rC
entr
alA
mer
ica
13
00
0[0
,24
.7]
Sou
thEa
sto
rPa
cifi
cA
sia
31
39
.71
3.2
[4.0
,35
.6]
Wes
tern
Euro
pe
(exc
l.U
Ka
nd
Irel
an
d)
67
34
.55
.7[1
.5,1
9.5
]
Ma
uri
tiu
s1
00
00
[0,3
0.8
]
Co
un
try
of
bir
tha
mo
ng
the
Ind
ian
,Pa
kist
an
ior
Ba
ng
lad
esh
i(IP
B)
eth
nic
gro
up
Asi
an
-IPB
;bo
rnin
UK
46
81
7.4
18
.5[7
.5,3
9.1
],
0.0
01
Asi
an
-IPB
;bo
rnin
Ind
ia1
28
31
24
.22
9.5
[19
.2,4
2.4
]
Asi
an
-IPB
;bo
rnin
Paki
sta
n7
82
02
5.6
17
.8[9
.8,3
0.2
]
Asi
an
-IPB
;bo
rnin
Ba
ng
lad
esh
34
82
3.5
23
.5[1
1.8
,41
.3]
Asi
an
-IPB
;bo
rnin
Afr
ica
17
00
0[0
,19
.5]
Asi
an
-IPB
;bo
rnin
som
eo
ther
cou
ntr
y6
23
3.3
33
.1[6
.1,7
8.9
]
no
tA
sia
n-I
PB2
09
01
36
6.5
5.9
[4.8
,7.2
]
Eth
nic
gro
up
c
Wh
ite-
Bri
tish
15
32
92
6.0
5.7
[4.5
,7.2
],
0.0
01
Wh
ite-
Iris
h3
01
3.3
3.3
[0.5
,20
.2]
Wh
ite-
Gyp
syo
rIr
ish
Tra
velle
r2
00
0[0
,84
.2]
Wh
ite-
Oth
er1
69
95
.35
.1[2
.2,1
1.1
]
McNulty et al.
1372Downloaded from https://academic.oup.com/jac/article-abstract/73/5/1368/4885410by Southampton Oceanography Centre National Oceanographic Library useron 13 June 2018
Mix
ed-W
hit
ea
nd
Bla
ckC
ari
bb
ean
60
00
[0,4
5.9
]
Mix
ed-W
hit
ea
nd
Bla
ckA
fric
an
60
00
[0,4
5.9
]
Mix
ed-W
hit
ea
nd
Asi
an
16
21
2.5
12
.5[3
.1,3
8.6
]
Mix
ed-O
ther
22
14
.54
.5[0
.6,2
6.2
]
Asi
an
-In
dia
n1
83
38
20
.82
6.1
[17
.6,3
6.8
]
Asi
an
-Pa
kist
an
i1
14
26
22
.81
7.4
[10
.2,2
8.0
]
Asi
an
-Ba
ng
lad
esh
i4
08
20
.02
0.0
[9.9
,36
.3]
Asi
an
-Ch
ines
e2
30
00
[0,1
4.8
]
Asi
an
-Oth
er6
81
42
0.6
20
.6[1
1.7
,33
.6]
Bla
ck-A
fric
an
10
05
5.0
5.0
[2.2
,11
.3]
Bla
ck-C
ari
bb
ean
96
10
10
.41
1.2
[6.2
,19
.4]
Bla
ck-O
ther
30
00
[0,7
0.8
]
Ara
b7
11
4.3
14
.3[2
.0,5
8.1
]
Oth
er1
01
10
.01
0.0
[1.4
,46
.8]
Reg
ion
of
ori
gin
d
UK
15
05
87
5.8
5.5
[4.3
,7.0
],
0.0
01
Irel
an
d3
82
5.3
4.8
[1.2
,17
.3]
Ind
ia1
92
39
20
.32
4.4
[16
.4,3
4.7
]
Paki
sta
n1
19
28
23
.51
8.6
[11
.4,2
8.9
]
Ba
ng
lad
esh
41
92
2.0
22
.6[1
1.8
,38
.9]
SriL
an
ka8
22
5.0
25
.0[7
.2,5
9.0
]
Nep
al
50
00
[0,5
2.2
]
Afg
ha
nis
tan
10
66
0.0
60
.0[2
9.7
,84
.2]
Afr
ica
11
86
5.1
6.6
[2.5
,16
.4]
Au
stra
lasi
a7
11
4.3
9.5
[1.2
,47
.8]
Ca
rib
bea
n1
18
11
9.3
8.2
[3.9
,16
.5]
Ch
ina
17
00
0[0
,19
.5]
East
ern
Euro
pe
77
22
.62
.8[0
.5,1
3.6
]
Mid
dle
East
16
21
2.5
12
.3[2
.8,4
1.2
]
No
rth
Am
eric
a9
11
1.1
11
.7[1
.4,5
5.7
]
Sou
tho
rC
entr
alA
mer
ica
71
14
.37
.1[1
.0,3
7.4
]
Sou
thEa
sto
rPa
cifi
cA
sia
31
39
.71
4.5
[4.7
,36
.7]
Wes
tern
Euro
pe
(exc
l.U
Ka
nd
Irel
an
d)
77
79
.11
0.8
[4.6
,23
.5]
Mix
ed1
20
00
[0,2
6.5
]
Ma
uri
tiu
s/Se
ych
elle
s8
00
0[0
,36
.9]
Co
mb
ina
tio
no
fre
gio
no
fo
rig
ind
an
dco
un
try
of
bir
thw
ith
11
gro
up
s
bo
rnin
UK
;UK
ori
gin
14
59
85
5.8
5.6
[4.4
,7.1
],
0.0
01
bo
rnin
UK
;Asi
a-I
PBo
rig
in5
28
15
.41
5.7
[6.3
,33
.9]
bo
rnin
UK
;Ca
rib
bea
no
rig
in3
24
12
.51
1.9
[3.3
,34
.8]
bo
rnin
UK
;Oth
er
ori
gin
45
51
1.1
8.1
[3.0
,20
.2]
bo
rnin
Ind
ia1
36
33
24
.32
8.5
[18
.7,4
1.0
]
bo
rnin
Paki
sta
n8
12
12
5.9
18
.6[1
0.5
,30
.7]
bo
rnin
Ba
ng
lad
esh
34
82
3.5
23
.5[1
1.8
,41
.3]
bo
rnin
SriL
an
ka8
22
5.0
25
.0[7
.2,5
9.0
]
Co
nti
nu
ed
CTX-M ESBL-producing Enterobacteriaceae prevalence JAC
1373Downloaded from https://academic.oup.com/jac/article-abstract/73/5/1368/4885410by Southampton Oceanography Centre National Oceanographic Library useron 13 June 2018
Tab
le2
.C
on
tin
ued
Fact
or
No
.of
spec
ime
ns
No
.of
bla
CT
X-M
ESB
LPE-
po
siti
vesp
ecim
ens
bla
CT
X-M
ESB
LPE-
po
siti
ve(u
nw
eig
hte
d%
)
Prev
ale
nce
[95
%C
I](w
eig
hte
d%
)a
Test
for
ad
iffe
ren
cein
pre
vale
nce
be
twee
nth
eg
rou
ps
of
each
fact
or
(Pva
lue)
OR
ad
just
edfo
rb
(co
un
try
of
bir
tha
nd
reg
ion
of
ori
gin
ifb
orn
inth
eU
K)
(aO
R)
[95
%C
I]
Test
for
the
effe
cto
fea
chfa
cto
ra
fter
ad
just
men
tfo
rco
un
try
of
bir
tha
nd
reg
ion
of
ori
gin
ifb
orn
inth
eU
K(P
valu
e)
bo
rnin
Afg
ha
nis
tan
10
66
0.0
60
.0[2
9.7
,84
.2]
bo
rnin
the
Mid
dle
East
18
31
6.7
15
.5[4
.7,4
0.5
]
bo
rnin
som
eo
ther
cou
ntr
y4
64
24
5.2
5.3
[3.3
,8.5
]
Co
mb
ina
tio
no
fre
gio
no
fo
rig
ind
an
dco
un
try
of
bir
thw
ith
8g
rou
ps
bo
rnin
UK
;UK
ori
gin
14
59
85
5.8
5.6
[4.4
,7.1
],
0.0
01
bo
rnin
UK
;Asi
a-I
PBo
rig
in5
28
15
.41
5.7
[6.3
,33
.9]
bo
rnin
UK
;Ca
rib
bea
no
rig
in3
24
12
.51
1.9
[3.3
,34
.8]
bo
rnin
UK
;Oth
er
ori
gin
45
51
1.1
8.1
[3.0
,20
.2]
bo
rnin
Ind
ia,P
aki
sta
n,B
an
gla
des
ho
rSr
iLa
nka
25
96
42
4.7
25
.0[1
8.5
,32
.9]
bo
rnin
Afg
ha
nis
tan
10
66
0.0
60
.0[2
9.7
,84
.2]
bo
rnin
the
Mid
dle
East
18
31
6.7
15
.5[4
.7,4
0.5
]
bo
rnin
som
eo
the
rco
un
try
46
42
45
.25
.3[3
.3,8
.5]
Do
you
wo
rkin
ah
ealt
hca
rese
ttin
g?
no
20
74
17
88
.66
.6[5
.5,8
.0]
0.6
01
0.8
9
yes
29
72
37
.77
.7[4
.6,1
2.6
]1
.0[0
.6,1
.7]
Typ
eo
fh
ea
lth
care
wo
rker
nu
rse
86
67
.05
.7[2
.1,1
4.5
]0
.39
0.8
[0.3
,2.1
]0
.25
care
ass
ista
nt
59
23
.48
.9[2
.2,2
9.9
]0
.4[0
.1,1
.9]
do
cto
r3
04
13
.31
8.0
[6.6
,40
.5]
1.6
[0.6
,4.6
]
do
mes
tic
83
37
.52
0.2
[3.9
,61
.1]
6.0
[1.1
,33
.3]
oth
erw
ork
inh
ealt
hca
re(i
ncl
.un
sp.)
11
48
7.0
5.6
[2.3
,13
.1]
1.1
[0.5
,2.3
]
no
tw
ork
ing
inh
ealt
hca
re2
07
41
78
8.6
6.6
[5.5
,8.0
]1
Typ
eo
fh
ea
lth
care
wo
rker
ha
nd
s-o
nh
ealt
hca
rew
ork
er1
75
12
6.9
8.7
[4.4
,16
.5]
0.1
40
.8[0
.4,1
.6]
0.5
3
ha
nd
s-o
ffh
ealt
hca
rew
ork
er(i
ncl
.un
sp.)
12
21
19
.06
.3[2
.9,1
3.2
]1
.4[0
.7,2
.6]
no
tw
ork
ing
inh
ealt
hca
re2
07
41
78
8.6
6.6
[5.5
,8.0
]1
Do
esyo
ur
wo
rkin
volv
eco
nta
ctw
ith
an
ima
ls?
no
22
19
19
28
.76
.8[5
.6,8
.1]
0.9
31
0.7
5
yes
85
67
.16
.5[2
.8,1
4.4
]1
.2[0
.5,2
.7]
Typ
eo
fw
ork
invo
lvin
gco
nta
ctw
ith
an
ima
ls
farm
wo
rk(i
ncl
.mea
tp
rep
.)4
85
10
.49
.7[3
.9,2
2.6
]0
.76
1.8
[0.7
,4.5
]0
.33
vete
rin
ary
wo
rk1
30
00
[0,2
4.7
]0
oth
erw
ork
wit
ha
nim
als
(in
cl.u
nsp
.)2
41
4.2
2.8
[0.4
,17
.8]
0.7
[0.1
,5.4
]
no
tw
ork
ing
wit
ha
nim
als
22
19
19
28
.76
.8[5
.6,8
.1]
1
McNulty et al.
1374Downloaded from https://academic.oup.com/jac/article-abstract/73/5/1368/4885410by Southampton Oceanography Centre National Oceanographic Library useron 13 June 2018
Ha
veyo
ub
een
ho
spit
aliz
edin
the
pa
st1
2m
on
ths?
no
21
26
17
48
.26
.6[5
.4,8
.0]
0.6
31
0.7
3
yes
24
02
41
0.0
7.6
[4.4
,12
.9]
1.1
[0.7
,1.7
]
Ha
veyo
uta
ken
an
ya
nti
bio
tics
inth
ep
ast
12
mo
nth
s?
no
14
27
11
17
.86
.8[5
.4,8
.6]
0.9
61
0.8
8
yes
77
77
39
.46
.8[5
.1,8
.9]
1.0
[0.7
,1.4
]
Ha
veyo
uta
ken
an
ya
mo
xici
llin
inth
ep
ast
12
mo
nth
s?
no
18
35
14
78
.06
.8[5
.5,8
.4]
0.9
01
0.5
9
yes
36
93
71
0.0
6.6
[4.5
,9.7
]0
.9[0
.6,1
.3]
Ha
veyo
uta
ken
an
ytr
imet
ho
pri
min
the
pa
st1
2m
on
ths?
no
21
58
18
18
.46
.8[5
.7,8
.2]
0.6
41
0.8
2
yes
46
36
.55
.3[1
.7,1
5.0
]0
.9[0
.3,2
.8]
Ha
veyo
uta
ken
an
yer
yth
rom
ycin
inth
ep
ast
12
mo
nth
s?
no
21
57
17
98
.36
.7[5
.6,8
.1]
0.4
31
0.5
7
yes
47
51
0.6
10
.3[3
.6,2
6.1
]1
.3[0
.5,3
.5]
Ha
veyo
uta
ken
an
ycl
ari
thro
myc
inin
the
pa
st1
2m
on
ths?
no
21
78
18
18
.36
.8[5
.7,8
.2]
0.8
31
0.6
7
yes
26
31
1.5
5.9
[1.6
,19
.3]
1.3
[0.4
,5.0
]
Ha
veyo
uta
ken
an
yco
-am
oxi
cla
vin
the
pa
st1
2m
on
ths?
no
21
56
18
48
.57
.0[5
.8,8
.4]
0.0
31
0.0
04
yes
48
00
0[0
,7.4
]0
Ha
veyo
uta
ken
an
yci
pro
flo
xaci
nin
the
pa
st1
2m
on
ths?
no
21
89
18
08
.26
.8[5
.6,8
.1]
0.6
11
0.0
3
yes
15
42
6.7
9.5
[2.5
,30
.1]
3.0
[1.1
,8.1
]
Ha
veyo
uta
ken
an
yce
fale
xin
inth
ep
ast
12
mo
nth
s?
no
21
77
18
08
.36
.8[5
.6,8
.1]
0.3
41
0.3
1
yes
27
41
4.8
11
.4[3
.8,2
9.3
]1
.8[0
.6,5
.8]
Ha
veyo
uta
ken
an
yo
ther
an
tib
ioti
csin
the
pa
st1
2m
on
ths?
no
20
82
17
78
.56
.8[5
.6,8
.2]
0.9
71
0.2
6
yes
12
27
5.7
6.7
[2.5
,16
.7]
0.6
[0.3
,1.4
]
Ha
veyo
uta
ken
co-a
mo
xicl
av,
cip
rofl
oxa
cin
or
cefa
lexi
nin
the
pa
st1
2m
on
ths?
no
21
19
17
78
.46
.9[5
.7,8
.3]
0.2
21
0.7
6
yes
85
78
.24
.1[1
.7,9
.4]
0.9
[0.4
,1.9
]
Do
you
curr
entl
yh
ave
au
rin
ary
cath
eter
?
no
22
75
19
28
.46
.8[5
.7,8
.2]
0.2
71
0.6
2
yes
15
21
3.3
15
.5[3
.3,4
9.3
]1
.4[0
.4,5
.5]
Do
you
reg
ula
rly
eat
bee
f?
no
84
19
21
0.9
7.5
[5.8
,9.7
]0
.39
10
.87
yes
15
17
10
56
.96
.5[5
.1,8
.2]
1.0
[0.7
,1.4
]
Do
you
reg
ula
rly
eat
po
rk/h
am
/ba
con
?
no
55
87
61
3.6
11
.4[8
.5,1
5.1
],
0.0
01
10
.36
yes
16
81
10
36
.15
.8[4
.6,7
.3]
0.8
[0.6
,1.2
]
Do
you
reg
ula
rly
eat
lam
b?
no
94
06
67
.06
.5[4
.8,8
.7]
0.6
81
0.3
1
yes
12
91
12
19
.47
.1[5
.6,8
.9]
1.2
[0.9
,1.7
]
Co
nti
nu
ed
CTX-M ESBL-producing Enterobacteriaceae prevalence JAC
1375Downloaded from https://academic.oup.com/jac/article-abstract/73/5/1368/4885410by Southampton Oceanography Centre National Oceanographic Library useron 13 June 2018
Tab
le2
.C
on
tin
ued
Fact
or
No
.of
spec
ime
ns
No
.of
bla
CT
X-M
ESB
LPE-
po
siti
vesp
ecim
ens
bla
CT
X-M
ESB
LPE-
po
siti
ve(u
nw
eig
hte
d%
)
Prev
ale
nce
[95
%C
I](w
eig
hte
d%
)a
Test
for
ad
iffe
ren
cein
pre
vale
nce
be
twee
nth
eg
rou
ps
of
each
fact
or
(Pva
lue)
OR
ad
just
edfo
rb
(co
un
try
of
bir
tha
nd
reg
ion
of
ori
gin
ifb
orn
inth
eU
K)
(aO
R)
[95
%C
I]
Test
for
the
effe
cto
fea
chfa
cto
ra
fter
ad
just
men
tfo
rco
un
try
of
bir
tha
nd
reg
ion
of
ori
gin
ifb
orn
inth
eU
K(P
valu
e)
Do
you
reg
ula
rly
eat
chic
ken
?
no
23
22
29
.57
.5[4
.6,1
2.1
]0
.67
10
.68
yes
21
05
17
68
.46
.7[5
.5,8
.1]
1.1
[0.7
,1.9
]
Do
you
reg
ula
rly
eat
fish
/sea
foo
d?
no
29
53
31
1.2
9.4
[6.0
,14
.3]
0.1
01
0.5
9
yes
20
01
15
77
.86
.3[5
.1,7
.6]
0.9
[0.6
,1.4
]
Do
you
reg
ula
rly
eat
sala
dp
rod
uct
s?
no
12
11
61
3.2
9.1
[5.2
,15
.4]
0.3
01
0.1
1
yes
22
07
17
98
.16
.7[5
.5,8
.1]
0.6
[0.4
,1.1
]
No
tre
gu
larl
yea
tin
gm
eat
no
21
72
17
88
.26
.6[5
.4,8
.0]
0.2
41
0.8
9
yes
17
62
01
1.4
9.2
[5.5
,15
.1]
1.0
[0.6
,1.8
]
No
tre
gu
larl
yea
tin
gm
eat,
fish
or
sea
foo
d(v
eget
ari
an
)
no
22
51
18
68
.36
.6[5
.5,8
.0]
0.2
51
0.5
5
yes
10
51
21
1.4
10
.0[5
.0,1
8.8
]0
.8[0
.4,1
.6]
Inth
ep
ast
yea
r,h
ave
you
spen
tti
me
ina
ny
cou
ntr
yo
uts
ide
the
UK
?
no
11
42
75
6.6
4.6
[3.3
,6.3
],
0.0
01
1,
0.0
01
yes
12
34
12
71
0.3
8.8
[7.1
,10
.8]
2.0
[1.5
,2.8
]
Ha
veyo
ub
een
ho
spit
aliz
ed
ab
roa
din
the
last
yea
r?
no
23
64
19
98
.46
.6[5
.5,8
.0]
,0
.00
11
0.0
4
yes
12
32
5.0
37
.7[1
3.1
,70
.8]
3.6
[1.1
,12
.2]
Ha
veyo
uh
ad
dia
rrh
oea
ab
roa
din
the
last
yea
r?
no
22
39
18
68
.36
.5[5
.4,7
.8]
0.0
91
0.0
3
yes
13
71
61
1.7
11
.2[6
.1,1
9.7
]1
.8[1
.0,3
.2]
Ha
veyo
ub
een
ab
roa
dto
Ind
iain
the
last
yea
r?
no
22
79
17
47
.66
.2[5
.1,7
.5]
,0
.00
11
0.0
01
yes
97
28
28
.93
3.7
[22
.6,4
7.0
]3
.2[1
.7,6
.2]
Ha
veyo
ub
een
ab
roa
dto
Paki
sta
nin
the
last
yea
r?
no
23
52
19
18
.16
.6[5
.5,7
.8]
,0
.00
11
0.0
07
yes
24
11
45
.84
8.6
[24
.8,7
3.1
]3
.6[1
.4,9
.1]
Ha
veyo
ub
een
ab
roa
dto
Ba
ng
lad
esh
inth
ela
stye
ar?
no
23
65
20
08
.56
.7[5
.6,8
.1]
0.1
61
0.9
3
yes
11
21
8.2
17
.4[4
.2,5
0.1
]0
.9[0
.2,4
.9]
Ha
veyo
ub
een
ab
roa
dto
SriL
an
kain
the
last
yea
r?
no
23
67
19
98
.46
.7[5
.6,8
.0]
,0
.00
11
0.0
2
yes
93
33
.33
9.8
[12
.4,7
5.6
]6
.4[1
.3,3
1.4
]
McNulty et al.
1376Downloaded from https://academic.oup.com/jac/article-abstract/73/5/1368/4885410by Southampton Oceanography Centre National Oceanographic Library useron 13 June 2018
Ha
veyo
ub
een
ab
roa
dto
Nep
ali
nth
ela
stye
ar?
no
23
73
20
18
.56
.6[5
.5,7
.9]
,0
.00
11
0.1
1
yes
31
33
.37
6.8
[17
.9,9
8.0
]8
.9[0
.6,1
33
]
Ha
veyo
ub
een
ab
roa
dto
Sou
thA
sia
(In
dia
,Pa
kist
an
,Ba
ng
lad
esh
,Sri
Lan
kao
rN
epa
l)in
the
last
yea
r?
no
22
36
15
87
.15
.8[4
.7,7
.1]
,0
.00
11
,0
.00
1
yes
14
04
43
1.4
38
.5[2
7.8
,50
.5]
3.3
[2.0
,5.6
]
Ha
veyo
ub
een
ab
roa
dto
Afg
ha
nis
tan
inth
ela
stye
ar?
no
23
74
20
18
.56
.7[5
.6,8
.1]
0.4
31
0.2
2
yes
21
50
.01
7.1
[1.3
,76
.1]
3.5
[0.5
,25
.2]
Ha
veyo
ub
een
ab
roa
dto
Afr
ica
inth
ela
stye
ar?
no
22
35
18
48
.26
.2[5
.1,7
.5]
,0
.00
11
0.0
06
yes
14
11
81
2.8
16
.4[9
.4,2
7.0
]2
.2[1
.2,3
.7]
Ha
veyo
ub
een
ab
roa
dto
Au
stra
lasi
ain
the
last
yea
r?
no
23
41
20
08
.56
.7[5
.6,8
.1]
0.7
51
0.9
4
yes
35
25
.78
.6[1
.9,3
1.5
]0
.9[0
.2,4
.0]
Ha
veyo
ub
een
ab
roa
dto
the
Ca
rib
bea
nin
the
last
yea
r?
no
23
19
19
78
.56
.7[5
.6,8
.0]
0.4
91
0.5
0
yes
57
58
.89
.8[3
.3,2
5.5
]1
.4[0
.5,3
.9]
Ha
veyo
ub
een
ab
roa
dto
Ch
ina
inth
ela
stye
ar?
no
23
52
19
88
.46
.6[5
.5,7
.9]
0.0
31
0.0
6
yes
24
41
6.7
22
.9[7
.1,5
3.5
]2
.9[0
.9,9
.1]
Ha
veyo
ub
een
ab
roa
dto
East
ern
Euro
pe
inth
ela
stye
ar?
no
21
27
18
78
.86
.9[5
.7,8
.3]
0.5
11
0.7
7
yes
24
91
56
.05
.7[3
.3,9
.7]
0.9
[0.5
,1.6
]
Ha
veyo
ub
een
ab
roa
dto
the
Mid
dle
East
inth
ela
stye
ar?
no
23
29
19
58
.46
.7[5
.6,8
.0]
0.2
91
0.2
2
yes
47
71
4.9
10
.6[4
.5,2
3.0
]1
.7[0
.7,3
.8]
Ha
veyo
ub
een
ab
roa
dto
No
rth
Am
eric
ain
the
last
yea
r?
no
22
18
18
68
.46
.4[5
.3,7
.7]
0.0
71
0.0
6
yes
15
81
61
0.1
11
.3[6
.2,1
9.8
]1
.7[1
.0,3
.0]
Ha
veyo
ub
een
ab
roa
dto
Sou
tho
rC
entr
alA
mer
ica
inth
ela
stye
ar?
no
23
47
19
78
.46
.6[5
.5,7
.9]
0.0
51
0.0
4
yes
29
51
7.2
19
.4[6
.3,4
6.4
]3
.1[1
.1,9
.2]
Ha
veyo
ub
een
ab
roa
dto
Sou
thEa
sto
rPa
cifi
cA
sia
inth
ela
stye
ar?
no
23
09
19
18
.36
.4[5
.3,7
.7]
0.0
03
10
.00
1
yes
67
11
16
.41
7.4
[9.0
,31
.1]
3.3
[1.6
,6.5
]
Ha
veyo
ub
een
ab
roa
dto
aco
un
try
inW
este
rnEu
rop
e(n
ot
incl
.UK
an
dIr
ela
nd
)in
the
last
yea
r?
no
16
07
14
49
.06
.4[5
.1,7
.9]
0.4
11
0.1
9
yes
76
95
87
.57
.4[5
.5,1
0.0
]1
.3[0
.9,1
.8]
Ha
veyo
ub
een
ab
roa
dto
Ma
ldiv
es,M
au
riti
us
or
Seyc
he
lles
inth
ela
stye
ar?
no
23
58
20
28
.66
.8[5
.7,8
.1]
0.3
91
0.1
4
yes
18
00
0[0
,18
.5]
0
Ha
veyo
ub
een
ab
roa
dto
:Au
stra
lia,t
he
Ca
rib
bea
n,E
ast
ern
Euro
pe,
the
Mid
dle
East
,No
rth
Am
eric
a,W
este
rnEu
rop
e(n
ot
incl
.UK
an
dIr
ela
nd
),M
ald
ives
,
Ma
uri
tiu
so
rSe
ych
elle
sin
the
last
yea
r?
no
13
35
11
98
.96
.0[4
.7,7
.7]
0.2
01
0.0
3
yes
10
41
83
8.0
7.6
[5.9
,9.8
]1
.4[1
.0,2
.0]
Co
nti
nu
ed
CTX-M ESBL-producing Enterobacteriaceae prevalence JAC
1377Downloaded from https://academic.oup.com/jac/article-abstract/73/5/1368/4885410by Southampton Oceanography Centre National Oceanographic Library useron 13 June 2018
Tab
le2
.C
on
tin
ued
Fact
or
No
.of
spec
ime
ns
No
.of
bla
CT
X-M
ESB
LPE-
po
siti
vesp
ecim
ens
bla
CT
X-M
ESB
LPE-
po
siti
ve(u
nw
eig
hte
d%
)
Prev
ale
nce
[95
%C
I](w
eig
hte
d%
)a
Test
for
ad
iffe
ren
cein
pre
vale
nce
be
twee
nth
eg
rou
ps
of
each
fact
or
(Pva
lue)
OR
ad
just
edfo
rb
(co
un
try
of
bir
tha
nd
reg
ion
of
ori
gin
ifb
orn
inth
eU
K)
(aO
R)
[95
%C
I]
Test
for
the
effe
cto
fea
chfa
cto
ra
fter
ad
just
men
tfo
rco
un
try
of
bir
tha
nd
reg
ion
of
ori
gin
ifb
orn
inth
eU
K(P
valu
e)
Ha
veyo
ub
een
ab
roa
dto
:Afr
ica
,Ch
ina
,So
uth
or
Ce
ntr
alA
mer
ica
,So
uth
East
or
Paci
fic
Asi
ao
rA
fgh
an
ista
nin
the
last
yea
r?
no
21
25
16
67
.85
.6[4
.6,6
.8]
,0
.00
11
,0
.00
1
yes
25
13
61
4.3
16
.6[1
1.3
,23
.7]
2.8
[1.8
,4.3
]
Nu
mb
ero
fa
du
lts
livin
gin
resp
on
den
t’s
ho
use
ho
ld(i
ncl
.res
po
nd
ent)
14
13
29
7.0
6.1
[3.8
,9.5
]0
.02
(tes
tfo
r
tren
d:P
"0
.06
)
10
.65
(tes
tfo
r
tren
d:P
"0
.96
)2
11
77
87
7.4
5.9
[4.6
,7.5
]1
.0[0
.6,1
.6]
34
06
39
9.6
8.3
[5.3
,13
.0]
1.1
[0.6
,1.8
]
42
08
19
9.1
6.1
[3.5
,10
.6]
0.8
[0.4
,1.6
]
58
61
51
7.4
18
.8[9
.8,3
2.9
]1
.7[0
.8,3
.5]
6!
67
10
14
.97
.6[3
.0,1
7.9
]0
.9[0
.3,2
.1]
Nu
mb
ero
fch
ildre
na
ged
5–1
7ye
ars
livin
gin
resp
on
den
t’s
ho
use
ho
ld
01
88
81
52
8.1
6.9
[5.6
,8.4
]0
.18
(tes
tfo
r
tren
d:P
"0
.77
)
10
.24
(tes
tfo
r
tren
d:P
"0
.47
)1
24
51
56
.13
.6[1
.8,7
.0]
0.6
[0.3
,1.0
]
21
56
20
12
.89
.5[5
.1,1
7.1
]1
.1[0
.6,1
.9]
3!
68
12
17
.68
.1[3
.4,1
7.9
]0
.8[0
.4,1
.6]
Nu
mb
ero
fch
ildre
na
ged
0–4
yea
rsliv
ing
inre
spo
nd
ent’
sh
ou
seh
old
02
07
81
65
7.9
6.4
[5.2
,7.8
]0
.12
(tes
tfo
r
tren
d:P
"0
.28
)
10
.85
(tes
tfo
r
tren
d:P
"0
.24
)1
21
02
51
1.9
9.9
[6.1
,15
.6]
1.0
[0.6
,1.7
]
2!
69
91
3.0
4.6
[1.9
,10
.4]
1.2
[0.6
,2.3
]
Nu
mb
ero
fch
ildre
na
ged
0–1
7ye
ars
livin
gin
resp
on
den
t’s
ho
use
ho
ld
01
71
91
32
7.7
6.5
[5.2
,8.1
]0
.96
(tes
tfo
r
tren
d:P
"0
.44
)
10
.78
(tes
tfo
r
tren
d:P
"0
.96
)1
29
12
37
.97
.0[4
.2,1
1.6
]0
.8[0
.5,1
.3]
22
46
27
11
.07
.1[4
.1,1
2.0
]1
.0[0
.6,1
.6]
3!
10
11
71
6.8
7.9
[3.9
,15
.1]
0.9
[0.5
,1.6
]
Nu
mb
ero
fp
eop
leliv
ing
inre
spo
nd
ent’
sh
ou
seh
old
13
77
27
7.2
5.8
[3.6
,9.4
]0
.07
(tes
tfo
r
tren
d:P
"0
.06
)
10
.71
(tes
tfo
r
tren
d:P
"1
.00
)2
90
16
47
.16
.2[4
.8,8
.1]
1.0
[0.6
,1.7
]
33
93
30
7.6
7.2
[4.3
,11
.8]
0.9
[0.5
,1.6
]
43
17
21
6.6
4.6
[2.5
,8.2
]0
.7[0
.4,1
.4]
51
83
25
13
.79
.6[6
.0,1
5.1
]1
.2[0
.7,2
.3]
69
11
41
5.4
13
.2[6
.1,2
6.4
]1
.0[0
.4,2
.2]
74
61
02
1.7
19
.0[8
.0,3
8.7
]1
.5[0
.6,3
.8]
8!
49
81
6.3
6.6
[2.9
,14
.0]
0.7
[0.3
,1.7
]
Do
you
ha
vea
ny
cats
livin
gin
you
rh
ou
seo
rfl
at?
no
19
39
16
98
.76
.9[5
.7,8
.4]
0.7
01
0.7
4
yes
42
23
27
.66
.3[4
.1,9
.7]
1.1
[0.7
,1.6
]
Do
you
ha
vea
ny
do
gs
livin
gin
you
rh
ou
seo
rfl
at?
no
19
89
17
88
.97
.1[5
.9,8
.6]
0.2
01
0.8
8
yes
36
22
26
.15
.0[3
.0,8
.3]
1.0
[0.6
,1.7
]
McNulty et al.
1378Downloaded from https://academic.oup.com/jac/article-abstract/73/5/1368/4885410by Southampton Oceanography Centre National Oceanographic Library useron 13 June 2018
Do
you
ha
vea
ny
rab
bit
sliv
ing
inyo
ur
ho
use
or
fla
t?
no
21
21
18
38
.66
.5[5
.4,7
.8]
0.9
41
0.7
9
yes
45
36
.76
.8[1
.9,2
1.6
]0
.8[0
.2,3
.0]
Do
you
ha
vea
ny
gu
ine
ap
igs
livin
gin
you
rh
ou
seo
rfl
at?
no
20
91
18
28
.76
.6[5
.5,7
.9]
0.2
31
0.2
1
yes
36
12
.80
.9[0
.1,6
.4]
0.3
[0.0
4,2
.0]
Do
you
ha
vea
ny
ha
mst
ers
livin
gin
you
rh
ou
seo
rfl
at?
no
20
92
18
38
.76
.7[5
.5,8
.1]
0.2
31
0.4
3
yes
30
13
.32
.2[0
.3,1
4.1
]0
.5[0
.08
.3.0
]
Do
you
live
ina
nu
rsin
gh
om
e,ca
reh
om
eo
rre
sid
enti
alh
om
e?
no
23
48
20
08
.56
.8[5
.7,8
.1]
1.0
01
0.1
4
yes
90
00
[0,3
3.6
]0
Isth
ere
an
yon
ein
you
rh
ou
seh
old
wh
ow
ork
sin
ah
ealt
hca
rese
ttin
g?
no
20
45
17
38
.56
.7[5
.5,8
.1]
0.9
71
0.8
1
yes
28
72
38
.06
.8[4
.0,1
1.3
]0
.9[0
.6,1
.5]
Isth
ere
an
yon
ein
you
rh
ou
seh
old
wh
ose
wo
rkin
volv
esco
nta
ctw
ith
an
ima
ls?
no
22
25
18
98
.56
.9[5
.7,8
.3]
0.3
91
0.7
6
yes
91
66
.64
.7[2
.0,1
0.9
]1
.1[0
.5,2
.7]
Isth
ere
an
yon
ein
you
rh
ou
seh
old
wh
oh
as
bee
nh
osp
ita
lized
inth
ep
ast
yea
r?
no
20
96
17
88
.56
.9[5
.7,8
.3]
0.6
11
0.4
0
yes
25
02
18
.45
.9[3
.2,1
0.5
]0
.8[0
.5,1
.4]
Isth
ere
an
yon
ein
you
rh
ou
seh
old
wh
oh
as
take
na
nti
bio
tics
inth
ep
ast
yea
r?
no
15
46
11
47
.46
.4[5
.1,8
.1]
0.9
11
0.5
7
yes
73
77
39
.96
.6[4
.9,8
.9]
1.1
[0.8
,1.5
]
Isth
ere
an
yon
ein
you
rh
ou
seh
old
wh
oh
as
spen
tti
me
ab
roa
din
the
last
yea
r?
no
13
18
96
7.3
5.6
[4.3
,7.3
]0
.03
1,
0.0
01
yes
10
17
10
31
0.1
8.3
[6.5
,10
.5]
1.8
[1.3
,2.4
]
Ho
use
ma
teb
een
toIn
dia
inth
ela
stye
ar
no
22
51
17
87
.96
.5[5
.4,7
.8]
,0
.00
11
0.0
1
yes
83
21
25
.32
4.9
[14
.5,3
9.2
]2
.4[1
.3,4
.6]
Ho
use
ma
teb
een
toPa
kist
an
inth
ela
stye
ar
no
23
14
19
58
.46
.8[5
.7,8
.1]
0.2
11
0.8
5
yes
20
42
0.0
15
.6[3
.9,4
5.5
]1
.1[0
.3,3
.6]
Ho
use
ma
teb
een
toB
an
gla
des
hin
the
last
yea
r
no
23
24
19
98
.66
.8[5
.7,8
.2]
1.0
01
0.0
2
yes
10
00
0[0
,30
.8]
0
Ho
use
ma
teb
een
toSr
iLa
nka
inth
ela
stye
ar
no
23
26
19
78
.56
.8[5
.6,8
.1]
0.0
61
0.1
3
yes
82
25
.02
6.6
[5.5
,69
.5]
3.7
[0.7
,19
.6]
Ho
use
ma
teb
een
toth
eIn
dia
nsu
bco
nti
nen
t(I
nd
ia,P
aki
sta
n,B
an
gla
des
ho
rSr
iLa
nka
)in
the
last
yea
r
no
22
14
17
27
.86
.4[5
.3,7
.7]
,0
.00
11
0.0
5
yes
12
02
72
2.5
22
.7[1
4.2
,34
.1]
1.7
[1.0
,3.0
]
Ho
use
ma
teb
een
toA
fgh
an
ista
nin
the
last
yea
r
no
23
32
19
98
.56
.8[5
.7,8
.2]
1.0
01
0.3
9
yes
20
00
[0,8
4.2
]0
Ho
use
ma
teb
een
toA
fric
ain
the
last
yea
r
no
22
39
19
08
.56
.6[5
.5,8
.0]
0.2
01
0.2
7
yes
95
99
.51
1.5
[5.0
,24
.3]
1.5
[0.7
,3.0
]
Co
nti
nu
ed
CTX-M ESBL-producing Enterobacteriaceae prevalence JAC
1379Downloaded from https://academic.oup.com/jac/article-abstract/73/5/1368/4885410by Southampton Oceanography Centre National Oceanographic Library useron 13 June 2018
Tab
le2
.C
on
tin
ued
Fact
or
No
.of
spec
ime
ns
No
.of
bla
CT
X-M
ESB
LPE-
po
siti
vesp
ecim
ens
bla
CT
X-M
ESB
LPE-
po
siti
ve(u
nw
eig
hte
d%
)
Prev
ale
nce
[95
%C
I](w
eig
hte
d%
)a
Test
for
ad
iffe
ren
cein
pre
vale
nce
be
twee
nth
eg
rou
ps
of
each
fact
or
(Pva
lue)
OR
ad
just
edfo
rb
(co
un
try
of
bir
tha
nd
reg
ion
of
ori
gin
ifb
orn
inth
eU
K)
(aO
R)
[95
%C
I]
Test
for
the
effe
cto
fea
chfa
cto
ra
fter
ad
just
men
tfo
rco
un
try
of
bir
tha
nd
reg
ion
of
ori
gin
ifb
orn
inth
eU
K(P
valu
e)
Ho
use
ma
teb
een
toA
ust
rala
sia
inth
ela
stye
ar
no
23
04
19
78
.66
.7[5
.6,8
.0]
0.4
31
0.8
6
yes
30
26
.71
2.5
[2.5
,44
.0]
1.1
[0.3
,4.9
]
Ho
use
ma
teb
een
toth
eC
ari
bb
ean
inth
ela
stye
ar
no
22
88
19
68
.66
.8[5
.7,8
.1]
0.6
61
0.8
5
yes
46
36
.58
.9[2
.6,2
6.9
]1
.1[0
.3,3
.8]
Ho
use
ma
teb
een
toC
hin
ain
the
last
yea
r
no
23
13
19
68
.56
.7[5
.6,8
.0]
0.0
71
0.1
6
yes
21
31
4.3
20
.1[5
.6,5
1.4
]2
.6[0
.7,9
.9]
Ho
use
ma
teb
een
toEa
ster
nEu
rop
ein
the
last
yea
r
no
21
26
18
58
.76
.9[5
.7,8
.2]
0.8
61
0.7
9
yes
20
81
46
.76
.5[3
.4,1
2.1
]1
.1[0
.6,1
.9]
Ho
use
ma
teb
een
toth
eM
idd
leEa
stin
the
last
yea
r
no
22
91
18
98
.26
.7[5
.6,8
.0]
0.0
21
0.0
3
yes
43
10
23
.31
6.9
[7.5
,33
.6]
2.5
[1.1
,5.6
]
Ho
use
ma
teb
een
toN
ort
hA
mer
ica
inth
ela
stye
ar
no
21
92
18
58
.46
.8[5
.6,8
.1]
0.7
01
0.1
5
yes
14
21
49
.97
.6[4
.2,1
3.4
]1
.6[0
.9,2
.8]
Ho
use
ma
teb
een
toSo
uth
or
Cen
tra
lAm
eric
ain
the
last
yea
r
no
23
09
19
68
.56
.8[5
.7,8
.1]
0.7
71
0.1
6
yes
25
31
2.0
8.1
[2.5
,23
.4]
2.4
[0.7
,8.2
]
Ho
use
ma
teb
een
toSo
uth
East
or
Paci
fic
Asi
ain
the
last
yea
r
no
22
85
19
18
.46
.5[5
.4,7
.8]
0.0
11
0.0
06
yes
49
81
6.3
17
.9[8
.4,3
4.1
]3
.1[1
.4,7
.1]
Ho
use
ma
teb
een
toW
este
rnEu
rop
e(n
ot
incl
.UK
an
dIr
ela
nd
)in
the
last
yea
r
no
17
08
14
98
.76
.8[5
.5,8
.3]
0.9
11
0.1
1
yes
62
65
08
.06
.9[4
.9,9
.7]
1.4
[0.9
,1.9
]
Ho
use
ma
teb
een
toa
no
ther
reg
ion
of
the
wo
rld
inth
ela
stye
ar
no
23
17
19
88
.56
.8[5
.7,8
.1]
0.9
21
0.8
1
yes
17
15
.97
.5[1
.1,3
7.7
]0
.8[0
.1,5
.5]
Als
osh
ow
na
reth
eO
Rs
for
po
ten
tia
lris
kfa
cto
rsfo
rco
lon
iza
tio
na
fter
ad
just
men
tfo
rth
ep
erso
n’s
cou
ntr
yo
fb
irth
an
dth
ep
erso
n’s
reg
ion
of
ori
gin
ifb
orn
inth
eU
K.
aTo
esti
ma
teth
ep
reva
len
ceo
fES
BLP
Eco
lon
iza
tio
nfo
ra
du
lts
livin
gin
Eng
lan
din
20
14
we
use
dw
eig
hts
ba
sed
on
the
20
11
na
tio
na
lcen
sus
an
dth
en
um
ber
of
elig
ible
ind
ivid
ua
lsa
tth
ese
lect
edp
ract
ices
.Wei
gh
tsfo
ret
hn
icg
rou
p,a
ge
gro
up
an
dse
xw
ere
calc
ula
ted
for
all
ind
ivid
ua
lsb
ase
do
nth
ece
nsu
sd
ata
alo
ne.
Toes
tim
ate
the
pre
vale
nce
for
each
GP
pra
ctic
ea
nd
PCT
we
use
dw
eig
hts
ba
sed
on
the
nu
mb
ers
of
elig
ible
ind
ivid
ua
lsin
each
gro
up
at
each
pra
ctic
e.bC
ate
go
ries
of
this
fact
or
vari
ab
lere
ferr
edto
inth
ista
ble
incl
ud
e:B
orn
inth
eU
K:U
Ko
rig
in;B
orn
inth
eU
K:I
nd
ia,P
aki
sta
no
rB
an
gla
des
ho
rig
in;B
orn
inth
eU
K:C
ari
bb
ean
ori
gin
;Bo
rnin
the
UK
:oth
er
ori
gin
;Bo
rnin
Ind
ia;B
orn
inPa
kist
an
;Bo
rnin
Ba
ng
lad
esh
;Bo
rnin
SriL
an
ka;B
orn
inA
fgh
an
ista
n;B
orn
inth
eM
idd
leEa
st;a
nd
Bo
rnin
som
eo
ther
cou
ntr
y.c Et
hn
icg
rou
pw
as
self
-dec
lare
db
yea
chp
art
icip
an
tw
hen
com
ple
tin
gth
ere
sea
rch
qu
esti
on
na
ire.
dR
egio
no
fo
rig
in/o
rig
inis
der
ived
fro
mth
ese
lf-d
ecla
red
eth
nic
gro
up
an
dco
un
try
of
bir
th.
McNulty et al.
1380Downloaded from https://academic.oup.com/jac/article-abstract/73/5/1368/4885410by Southampton Oceanography Centre National Oceanographic Library useron 13 June 2018
Tab
le3
.Fi
na
lmu
ltiv
ari
ate
mo
del
for
colo
niz
ati
on
wit
hC
TX-M
ESB
LPE
Ris
kfa
cto
rC
ate
go
ries
Nu
mb
ero
fp
eop
leex
po
sed
toth
eri
skfa
cto
rin
the
mo
del
(n"
23
19
)a
OR
[95
%C
I];
Pva
lue
Perc
enta
ge
PAF
[95
%C
I]Pe
rcen
tag
ePA
F[9
5%
CI]
Co
un
try
of
bir
tha
nd
reg
ion
of
ori
gin
aif
bo
rnin
the
UK
Bo
rnin
the
Ind
ian
sub
con
tin
ent
(In
dia
,Pa
kist
an
,Ba
ng
lad
esh
or
SriL
an
ka)
25
65
.4[3
.0,9
.7];
,0
.00
12
3.8
[15
.9,3
0.9
]2
7.7
[19
.5,3
5.1
]
Bo
rnin
Afg
ha
nis
tan
94
6.0
[9.6
,21
8];
,0
.00
12
.8[1
.3,4
.3]
Bo
rnin
the
Mid
dle
East
18
4.7
[1.3
,17
.0];
0.0
21
.1[#
0.4
,2.6
]
Bo
rnin
the
UK
an
do
fU
Ko
rig
in1
45
11
.3[0
.8,2
.1];
0.2
49
.9[#
7.1
,24
.1]
15
.3[#
3.5
,30
.6]
Bo
rnin
the
UK
an
do
fIP
Bo
rig
in5
23
.8[1
.5,9
.2];
0.0
04
2.8
[0.1
,5.4
]
Bo
rnin
the
UK
an
do
fC
ari
bb
ean
ori
gin
32
3.4
[1.0
,10
.9];
0.0
41
.4[#
0.6
,3.3
]
Bo
rnin
the
UK
an
do
fso
me
oth
ero
rig
ino
ro
fm
ixed
ori
gin
45
2.2
[0.7
,6.5
];0
.17
1.3
[#1
.0,3
.5]
Co
mp
are
dw
ith
(Ref
eren
ceca
teg
ory
):B
orn
inso
me
cou
ntr
yo
ther
tha
nU
K,I
PB,S
riLa
nka
,Afg
ha
nis
tan
or
the
Mid
dle
East
46
4Re
fere
nce
Refe
ren
ceRe
fere
nce
Tra
vela
bro
ad
inth
ep
ast
yea
rS
ou
thA
sia
13
32
.9[1
.8,4
.8];
,0
.00
11
2.1
[5.9
,7.8
]2
7.9
[16
.0,3
8.1
]
•In
dia
�Sr
iLa
nka
•Pa
kist
an
�N
epa
l
•B
an
gla
des
h
Co
mp
are
dw
ith
(Ref
eren
ceca
teg
ory
):
No
tra
velt
oSo
uth
Asi
a
21
86
Ref
eren
ceRe
fere
nce
Co
un
trie
so
uts
ide
Asi
aw
ith
hig
her
risk
24
62
.6[1
.7,4
.1];
,0
.00
19
.9[4
.3,1
5.1
]
•A
fric
a�
Sou
thEa
sto
rPa
cifi
cA
sia
•C
hin
a�
Afg
ha
nis
tan
•So
uth
or
Cen
tra
lAm
eric
a
Co
mp
are
dw
ith
(Ref
eren
ceca
teg
ory
):
No
tra
velt
oco
un
trie
so
uts
ide
Asi
aw
ith
hig
her
risk
20
73
Ref
eren
ceRe
fere
nce
Oth
er
cou
ntr
ies
10
21
1.3
[0.9
,1.8
];0
.15
7.9
[#3
.5,1
8.1
]
•A
ust
rala
sia
�M
au
riti
us
•Th
eC
ari
bb
ean
�Se
ych
elle
s
•Th
eM
idd
leEa
st�
Ma
ldiv
es
•N
ort
hA
mer
ica
�Eu
rop
e(e
xcl.
UK
&Ir
ela
nd
)
Co
mp
are
dw
ith
(Ref
eren
ceca
teg
ory
):
No
tra
velt
oO
ther
cou
ntr
ies
12
98
Ref
eren
ceRe
fere
nce
Do
mes
tic
wo
rkin
ah
ealt
hca
rese
ttin
gYe
s8
6.2
[1.3
,31
];0
.03
1.1
[#0
.2,2
.3]
Co
mp
are
dw
ith
(Ref
eren
ceca
teg
ory
):N
o2
31
1R
efer
ence
Refe
ren
ce
aR
egio
no
fo
rig
in/o
rig
inis
de
rive
dfr
om
the
self
-dec
lare
det
hn
icg
rou
pa
nd
cou
ntr
yo
fb
irth
.
CTX-M ESBL-producing Enterobacteriaceae prevalence JAC
1381Downloaded from https://academic.oup.com/jac/article-abstract/73/5/1368/4885410by Southampton Oceanography Centre National Oceanographic Library useron 13 June 2018
travelled abroad in the last year. Of the 199 E. coli, 87% (173/199)were ST131. ST131 was not significantly more common in CTX-Mcarriers who had spent time anywhere abroad in the last year, or inthe Indian subcontinent (India, Pakistan, Bangladesh or Sri Lanka),compared with those who had not (spent time anywhere abroad87% ST131 versus not spent time abroad 79%, P"0.17; spenttime abroad in the Indian subcontinent 91% ST131 versus notspent time in the Indian subcontinent 82%, P"0.17).
Risk factors for colonization with CTX-M ESBLPE
After adjusting for country of birth and region of origin (if born inthe UK) we found no evidence for an independent association be-tween CTX-M ESBLPE colonization and GP practice, age group, sex,overall antibiotic use in the past year or hospitalization in the pastyear (Table 2). Factors that remained significant after adjusting forcountry of birth and region of origin (if born in the UK) and weretherefore considered for inclusion in the final model included: par-ticipant’s travel abroad, or diarrhoea or hospitalization abroad inthe last year; use of ciprofloxacin or co-amoxiclav; being a domes-tic healthcare worker; and housemates’ travel abroad (overall andby country) in the last year. When added to the final multivariablemodel, there was no strong evidence that colonization was inde-pendently associated with either taking antibiotics in the last year(aOR 0.99, 95% CI 0.7–1.4, P"0.95), hospitalization abroad in thelast year (aOR 2.7, 95% CI 0.8–9.1, P"0.11, 3/12 colonized), diar-rhoea while abroad in the last year (aOR 1.1, 95% CI 0.6–1.9,P" 0.84, 16/137 colonized) or travel abroad by a participant’shousemate in the past year (aOR 1.4, P"0.11, 103/1071 colon-ized). Use of ciprofloxacin remained a significant risk factor for
ESBLPE-CTX-M in the final model (4/15 ESBLPE positive, aOR 3.2,P"0.03), whereas co-amoxiclav was protective for presence ofESBLPE-CTX-M (0/48 ESBLPE positive, aOR 0, P"0.006).
Being born in the Indian subcontinent (India, Pakistan,Bangladesh or Sri Lanka) was the most important identified riskfactor for faecal colonization (aOR 5.4, 95% CI 3.0–9.7), and we es-timate it accounted for 23.8% (95% CI 15.9%–30.9%) of peoplecolonized in England in 2014 (Table 3). Being born in Afghanistan(aOR 46.0, 95% CI 9.6–218) or the Middle East (aOR 4.7, 95% CI1.3–17.0) were factors strongly associated with colonization, butbeing relatively rare we estimate them to have accounted for rela-tively few people colonized [2.8% (95% CI 1.3%–4.3%) and 1.1%(95% CI#0.4% to 2.6%), respectively]. We found no evidencewhen tested in the final model that birth in or travel to other coun-tries including Eastern Europe increased risk of colonization (travelto Eastern Europe aOR 0.8, P"0.42; born in Eastern Europe aOR0.5, P"0.38). There was no evidence that being born in the UKwith a UK region of origin was a risk factor for colonization(aOR 1.3, 95% CI 0.8–2.1, P"0.24); but as there were so many par-ticipants in this group, we estimate it accounted for 9.9%(95% CI#7.1% to 24.1%) of people colonized. Being born in the UKwith an IPB region of origin was strongly associated with coloniza-tion (aOR 3.8, 95% CI 1.5–9.2), and we estimate it accounted for2.8% (95% CI 0.1%–5.4%) of people colonized. Being born in theUK with a Caribbean region of origin was almost as strongly associ-ated with colonization as being born in the UK with an IPB region oforigin (aOR 3.4, 95% CI 1.0–10.9), and we estimate it accountedfor 1.4% (95% CI#0.6% to 3.3%) of people colonized.
Travel to South Asia (India, Pakistan, Bangladesh, Sri Lanka orNepal) in the last year was strongly associated with colonization
*IPB = India, Pakistan or Bangladesh
0 10 20 30 40 50 60 70 80 90% Prevalence of colonization with CTX-M ESBLPE
Born UK : UK origin
Born UK : Asia-IPB* origin
Born UK : Caribbean origin
Born UK : Other origin
Born India
Born Afghanistan
Born Middle East
Born some other country (incl.Caribbean)
Born IPB or Sri Lanka
Born Sri Lanka
Born Bangladesh
Born Pakistan
England Overall
Region of origin/origin is derived from the self-declared ethnic group and country of birth
Figure 1. Prevalence of colonization with CTX-M ESBLPE by country of birth and region of origin if born in the UK (with 95% CI). Adults from thegeneral population of England in 2014. Dotted line is the estimated 2014 prevalence in England.
McNulty et al.
1382Downloaded from https://academic.oup.com/jac/article-abstract/73/5/1368/4885410by Southampton Oceanography Centre National Oceanographic Library useron 13 June 2018
(aOR 2.9, 95% CI 1.8–4.8), and we estimate it accounted for 12.1%(95% CI 5.9%–17.8%) of people colonized. Travel to Africa, China,South or Central America, South East or Pacific Asia or Afghanistanin the last year also increased the risk of colonization (aOR 2.6,95% CI 1.7–4.1), and we estimate it accounted for 9.9% (95% CI4.3%–15.1%) of people colonized. Travel to other countries in thelast year put participants at a small increased chance of coloniza-tion (aOR 1.3, 95% CI 0.9–1.8; P"0.15) and, being relatively com-mon, we estimate it accounted for 7.9% (95% CI #3.5% to 18.1%)of people colonized. Working as a domestic in the healthcare set-ting was strongly associated with colonization (aOR 6.2, 95% CI1.3–31.0), but, being relatively rare, we estimate it to have ac-counted for just 1.1% (95% CI#0.2% to 2.3%) of people colonized.Collectively all risk factors in the final multivariable model ex-plained 60.4% (95% CI 40.0%–73.8%) of cases.
Only 0.1% of participants (2/2430) were colonized with CPE; nei-ther was born in the UK, and both had a history of travel to India inthe past year.
Discussion
The 7.3% estimate for the prevalence of faecal colonization withCTX-M ESBLPE in adults living in England in 2014, and the high esti-mated prevalence in those born in South Asia (India, Pakistan,Bangladesh or Sri Lanka) and in those travelling to certain areasincluding South Asia, is of concern and has implications for empir-ical antimicrobial prescribing for suspected infections caused byEnterobacteriaceae and infection prevention and controlwithin healthcare in England and beyond. The significantly higher
estimated prevalence (15.7%) in the 52 participants born in the UKwith an IPB region of origin, compared with those born in theUK with a UK region of origin (1459 participants, estimated preva-lence 5.6%), is interesting; the higher estimated prevalence maybe due to acquisition during repeated travel to their country of ori-gin, or from visits by family and friends to or from their country oforigin, during the last year or more than 1 year ago, or acquisitionfrom relatives in the home.22
Previous studies in the UK
The only previous faecal colonization study of ESBLPE in the UK(in 2010) showed that Middle Eastern or South Asian (India,Pakistan, Bangladesh, Sri Lanka or Nepal) patients being investi-gated for gastrointestinal infections had a significantly higherprevalence than Europeans.11 Although UK studies estimatingESBLPE infection rates in hospitalized patients or patients withurine infections (UTIs) have suggested (similar to this presentstudy) that rates of ESBLPE infection vary widely between differentareas of the UK23,24 they have not investigated other risk factors.
Previous studies of a general population in NorthernEurope
A 2011 postal study in urban Amsterdam estimated that the over-all prevalence of ESBLPE faecal colonization was 8.6% and travelto Asia or Africa (aOR 2.1–2.2) in the last year increased the risk.Unlike the present or other studies, they found antibiotic use inthe last year and travel to North America (aOR 2.7) were also
Group 1161, 77%
Group 8*3, 1.4%
CTX-M-15
CTX-M-1
CTX-M-55
CTX-M-3
CTX-M-32
New?
Not Typed
134 (66%)
9 (4.4%)
2 (1%)
1 (0.5%)
4 (2%)
3 (1.5%)
8 (3.9%)
CTX-M-14:19/23, 83% White2/23, 9% Asian IPB
2/23, 9% Other ethnicity14/23, 61% Travel abroad
CTX-M-27
CTX-M-14
27 (13%)
23 (11%)
CTX-M-9
New?
Not Typed 1 (0.5%)
1 (0.5%)
1 (0.5%)
CTX-M-15:62/134, 46% White
46/134, 34% Asian IPB26/134, 19% Other ethnicity84/129, 65% Travel abroad
CTX-M-27:6/27, 22% White
16/27, 59% Asian IPB5/27, 19% Other ethnicity16/27, 59% Travel abroad
Group 953, 24%
As each isolate could have more than one genotype, the relative frequencies for the different genotypes sum to more than 100% of individuals as nine individual isolates carried both CTX-M group 1 and group 9 genes
*The three isolates in group 8 were not sequenced
Figure 2. Relative frequency of the blaCTX-M genotypes from 208 individuals, characterizations of these genotypes and risk factors for them.
CTX-M ESBL-producing Enterobacteriaceae prevalence JAC
1383Downloaded from https://academic.oup.com/jac/article-abstract/73/5/1368/4885410by Southampton Oceanography Centre National Oceanographic Library useron 13 June 2018
risk factors.3 The Amsterdam study found, as in the present study,that country of origin was important, as having a mother born inAsia was a risk factor independent of foreign travel (aOR 2.4). Inthe present and Amsterdam studies, hospitalization abroad in thepast year led to significantly higher faecal colonization and risk inthe univariable analysis, but neither found hospitalization abroadsignificant on multivariable analysis.3 The Amsterdam study didnot investigate travellers’ diarrhoea as a risk factor.3
A 2014/15 general population study in the rural SouthernNetherlands estimated the prevalence of faecal colonization withESBL/AmpC Enterobacteriaceae to be 4.5%. This is similar to our esti-mate for adults living in Shropshire in 2014, which is also rural with al-most the entire population born in the UK and of UK origin. This study,like ours, found travel to Africa, Asia and Latin America (aOR 2.9), wasa risk factor for carriage.25 Participants living in close proximity tomink farms (but not other farms) and keeping cows for a hobby in thelast 5 years (aOR 3.56) had increased risk.25 Despite other studiesshowing that contact with broiler farms increased risk in theNetherlands,26 neither contact with animals, pets or eating meat(including chicken) increased the risk of ESBLPE colonization in ourstudy. The risk factor associated with animals may only be evidentwhen you closely examine particular livestock, which we did not do.
A systematic review of faecal colonization27 with Ambler class AESBLPE in healthy individuals between 1992 and 2014 found thatESBLPE colonization had increased over time and was presentworldwide in 2014. The pooled estimated prevalence was highestin the West Pacific (46%), followed by South East Asia and Africa(22%), the Eastern Mediterranean (15%) and Northern Europe(4%). Factors associated with a higher risk of colonization wereinternational travel (RR 4.06) and antibiotic use in the previous year(RR 1.58), but this was a univariate analysis.27 The significant effectof antibiotic use in that review may not have remained on multi-variable analysis or may be caused by relatively greater use ofbroader spectrum antibiotics (especially quinolones) in countriesoutside Northern Europe and in travellers. Interestingly, althoughoverall antibiotic use was not a significant risk factor in our study,participants reporting ciprofloxacin use in the past year did havesignificantly increased estimated prevalence and this risk re-mained in the final multivariable model (aOR 3.2, P" 0.03).However, all four cases who reported taking ciprofloxacin and wereCTX-M ESBLPE positive had other risk factors (all four participantswere of Asian ethnicity, three were hospitalized in the past yearand one travelled to Pakistan). In contrast, reported co-amoxiclavuse in the last year appeared to be protective, as none of these48 participants was positive for CTX-M ESBLPE (0%, P"0.03). This isan important and interesting finding that needs further investiga-tion. Although co-amoxiclav has limited clinical activity againstCTX-M ESBLPE it is possible that there are high enough concentra-tions in the gut to eliminate faecal carriage. In contrast, ciprofloxa-cin would be expected to encourage colonization as almost all UKCTX-M ESBLPE are resistant.28 Only one of the previously publishedstudies of ESBLPE colonization in the general population reportedestimated prevalence by region of origin, and found birth in Africa,or parents born in Africa or Asia, to be an important risk factor.3
Previous studies of travellers
Like this study, studies of travellers from other European countrieshave identified travel outside Europe, and especially to the Middle
East, Africa and South Asia, to be a risk for ESBLPE faecal coloniza-tion and acquisition;10,27,29–31 with travel to Southern India beingthe greatest risk.10 In several studies, travellers’ diarrhoea and theuse of antimicrobials were independent risk factors for acquiringESBLPE, which is not consistent with our own findings.10,27,29–31
However, another 2012 study of travellers from a Swiss travel clinicto South Asia found length of stay, visiting friends and relativesand eating ice-cream were risk factors for acquisition of ESBLPE E.coli; whereas travellers’ diarrhoea was not a risk factor.13 Visitingfriends or relatives is probably a marker of being born in South Asia,which was a risk factor for colonization in our present study. Instudies like this and ours, which included a larger proportion oftravellers visiting relatives, travellers’ diarrhoea may not be suchan important marker for faecal colonization, as these travellers’gut microbiome may have already adapted to the South Asian dietand environmental flora. Although travel abroad by a housematewas associated with significantly higher carriage, this did not re-main significant in the final model. Travel abroad by a housematewas closely correlated with spending time abroad by the partici-pant themselves (1071/1234); so it is therefore not possible to dis-tinguish between the effect of this variable and the effect of travelabroad by the person themselves.
Two longitudinal studies of travellers who were ESBLPE carrierson return from abroad report the prevalence of carriage 12 monthsafter returning to be 11.3% and 2.2%, respectively, confirming thattravel abroad more than 1 year ago could be an important factorto investigate in future studies.10,32 Our questions about travelabroad were limited to the last year; this omission could be import-ant for travellers who travel repeatedly to areas with higher preva-lence of CTX-M ESBLPE and poor hygiene or sanitation, for exampleparticipants born in the UK of IPB or Caribbean origin who may bemore likely to repeatedly visit family and friends. This would helpto explain the higher carriage and risk conferred by being UK-bornbut of IPB or Caribbean origin.
Unlike the 2016 systematic review we did not find that esti-mated prevalence of CTX-M ESBLPE was significantly higher inthose born in or travelling to Eastern Europe (15/249 participantsCTX-M ESBLPE positive, aOR 0.9, 95% CI 0.5–1.6, P"0.77).27 Thismay be because sanitation facilities in these countries are betterthan on the Indian subcontinent (India, Pakistan, Bangladesh or SriLanka) so that acquisition in these countries is less common.
In our study the estimated prevalence of CTX-M ESBLPE amongthose working as domestics in healthcare was 37.5% (3/8 partici-pants, 95% CI 8.5%–75.5%). The risk factor was found to be inde-pendently associated with an increased risk of colonization; andthese eight participants were not similarly exposed to any otherparticular risk factor. Domestics in healthcare settings may be putat increased risk through their work cleaning toilet facilities; cer-tainly studies suggest that environmental acquisition may be re-sponsible for the spread of ESBLPE.13 Transmission of ESBLPEoccurs between patients in healthcare settings and staff do not al-ways adhere to infection control guidelines.33
As in other studies3,11,24,34 the dominant CTX-M ESBLPE geno-type was blaCTX-M-15, making up 66% of carriers of CTX-M ESBLPE.Interestingly we saw very few carriers of blaCTX-M-1, typically associ-ated with European farm animals,35,36 suggesting little acquisitionfrom these sources. This is supported by our lack of evidence thateither having a meat diet or working with animal livestock were riskfactors for CTX-M ESBLPE colonization. A quarter of carriers in our
McNulty et al.
1384Downloaded from https://academic.oup.com/jac/article-abstract/73/5/1368/4885410by Southampton Oceanography Centre National Oceanographic Library useron 13 June 2018
study carried a genotype belonging to CTX-M group 9, similar to theprevious UK study of diagnostic faeces samples in Birmingham.11
blaCTX-M-27 made up half of the group 9 CTX-Ms in our study, butwas not found in the Birmingham study; in contrast, we found onlyone blaCTX-M-9, whereas this constituted 74% of group 9 in theBirmingham study.11 blaCTX-M-27, which is part of group 9, is a vari-ant of blaCTX-M-14 that has been reported both from the Far Eastand from Europe, and in the UK has been reported at a low fre-quency from food animals, notably dairy cattle.37 In our study, car-riers of blaCTX-M-27 were mainly from the Asian-IPB ethnic group(59%), whereas carriers of blaCTX-M-14 were mainly from the whiteethnic group (83%); this variation by ethnicity warrants further in-vestigation. In a Spanish study38, CTX-M-14-producing E. coli weremainly isolated from community UTIs; this was also found in aWelsh study, where 83% of the CTX-M-14 genotype were commu-nity acquired39 and they were more common in rural areas.40 CTX-M-14 E. coli may be indigenous in the UK community, possiblyacquired from cattle.41 Consistent with other work, we found nogroup 2 isolates.1
The present study shows that the ST131 clone was the mostprevalent among the isolated E. coli demonstrating that the spreadof CTX-M-15 in the UK may be due to this clone. Our results indicatethat being born in or travel to the Indian subcontinent (India,Pakistan, Bangladesh or Sri Lanka) was the biggest overall risk fac-tor, but in the IPB countries the ST131 clone is uncommon.42,43 Thismay help us to further explore CTX-M ESBLPE originating in the UK.
As no data exist on the frequency of community colonization ofCPE in the UK, we used our study to gain some insight into theirprevalence. Our culture methods, whilst potentially missing someOXA-type carbapenemases, are recognized reference laboratorymethods.20 Like other European studies, we found a low incidence ofCPE (0.1%) in England in 2014;44,45 the two positive participants (oneAsian woman with E. coli OXA-48 with CTX-M group 9, and one UKman with E. coli NDM-1 with CTX-M-15) had both travelled to SouthAsia (India, Pakistan, Bangladesh, Sri Lanka or Nepal). This representsa potential route for the introduction and future spread of CPE.
Strengths
This is the first study to estimate the prevalence of colonizationwith CTX-M ESBLPE in the UK general population. We invited a strati-fied random sample of individuals from the general populationfrom GP patient lists rather than selecting patients who had givendiagnostic faecal samples or returning travellers who are unrepre-sentative of the general population. An added value of this study isthe specific focus on ethnicity and the oversampling to retrieve suf-ficient data in ethnic minority groups, which enabled us to achievesufficient power to identify some ethnicities and some countries ofbirth as risk factors. The questionnaires that were returned werewell completed and allowed us to investigate a broad range of po-tential independent risk factors for CTX-M ESBLPE colonization.Rather than use swabs, we used faecal samples that increase sensi-tivity of detection of ESBLPE by 10%17,46 and enrichment, whichincreased our sensitivity of isolating CTX-M ESBLPE by 12%.17
Limitations
We only sought CTX-M ESBLPE (and not ESBLPE carrying the otherb-lactamase genes blaTEM, blaOXA and blaSHV) as CTX-Ms still
constitute more than 90% of ESBLPE genotypes and cause moreESBLPE infections than any other type of ESBLPE worldwide.3,47,48
We have not examined the genetic context of blaCTX-M, whichwould have given an insight into its linkage to IS elements.However, this would be unlikely to impact on the control of ESBLPEtransmission. For those exposed to a relatively rare risk factor, thesample size was small and the CI was wide.
We did not ask about the characteristics of the housemate whotravelled or their relationship to the participant, and housematetravel did not remain a significant risk in the final multivariablemodel (P"0.11). However, it was not our intention to study trans-mission. In future studies it would be interesting to confirmwhether housemates usually travelled to the same countries withthe participant or at a different time. Many cases of CTX-M faecalcolonization may be unexplainable by any risk factor we could con-ceivably have collected data on; so, it is possible we have investi-gated all the important risk factors. However, it is also possible thatsome cases could be explained by a risk factor that we did nothave sufficient power to detect or we did not ask about. Questionsabout travel abroad and about antibiotic use were limited to thelast year, so this study was not able to investigate whether travelabroad more than a year earlier or antibiotic use more than a yearearlier are risk factors for colonization. Furthermore we did not col-lect data on the use of proton-pump inhibitors, found to be a riskfactor for faecal carriage in the Amsterdam 2011 communitystudy (aOR 1.9)3 and the rural study.25 Since CTX-M ESBLPE arenow widely established in the English general population we werenot surprised to find that many cases were not directly attributableto travel abroad in the last year.
Most of our prevalence estimates come from a weighted ana-lysis that weighted participants by ethnic group, age group andsex. Should our participants be unrepresentative in respect of anyother variable then prevalence estimates for the general popula-tion could be biased. The risk of such a bias is compounded by thelow response rate (4%) and variation in response rate in the differ-ent groups.
Implications
Faecal colonization with ESBLPE usually precedes an ESBLPE infec-tion when it occurs7,8 so we believe that this study, showing CTX-MESBLPE to be established in the general population of England andthe prevalence of colonization to be considerably higher amongsome sections of the general population, has implications forempirical prescribing for all infections typically caused byEnterobacteriaceae, and that antimicrobial guidance should re-flect our findings.49 The population that is most relevant to anyconclusions about empirical antibiotic prescribing is the populationof those who have infections likely caused by Enterobacteriaceaeand are seen by clinicians. We haven’t studied this population butwe believe that a high prevalence estimate for a section of thegeneral population can be used to inform on the likely prevalenceof those from the same section of the general population whoseek treatment for infections likely caused by Enterobacteriaceae.When selecting empirical treatment for uncomplicated UTIwe suggest that clinicians should consider the risk of ESBLPE,noting recent travel, country of birth and region of origin,especially South Asia (India, Pakistan, Bangladesh, Sri Lanka orNepal). Nitrofurantoin, which has greater activity against ESBLPE,
CTX-M ESBL-producing Enterobacteriaceae prevalence JAC
1385Downloaded from https://academic.oup.com/jac/article-abstract/73/5/1368/4885410by Southampton Oceanography Centre National Oceanographic Library useron 13 June 2018
is preferable to trimethoprim as an empirical agent in most casesof acute uncomplicated UTI.49 Although nitrofurantoin will still beappropriate for most patients with acute uncomplicated UTI, in pa-tients belonging to a section of the population that has a particu-larly high risk of ESBLPE carriage it may be preferable to obtainmicrobiology specimens before starting antibiotics. This might in-clude those born in South Asia and in patients who have travelledto South Asia in the last year. Empirical antimicrobials prescribedfor ‘sepsis’50 should always include an antimicrobial agent thattreats ESBLPE.51
Previous studies of the length of faecal colonization withESBLPE have been in patients who have attended a travel clinicand have acquired colonization abroad. There is wide variation inthe estimates of the percentage still colonized, from 4.8%52 to14.3%10 of travellers with faecal ESBLPE colonization at 6 months,and from 2.2%52 to 11.3%10 at 12 months. We need to understandthe length of carriage and transmission in the general population,which may be different; this would be best investigated in a longi-tudinal study in a typical population. Prospective or case–controlstudies designed to look at the risk of UTI or future infections inthose with ESBLPE faecal colonization are needed. To improve ourunderstanding of evolving risk groups for ESBLPE infections, wesuggest enhanced or periodic antimicrobial resistance surveillanceshould be extended to patients with uncomplicated infections(to reduce spectrum bias),6 and data collection should include eth-nic group, age and sex of the patient. If feasible to do so, we alsosuggest collecting: country of birth, recent travel history, ethnicorigins, occupation and use of antibiotics and antacids in thelast year.
A study of healthcare domestics’ colonization with ESBLPE com-pared with other healthcare workers, and possibly patients, isneeded as their numbers in our study were small, and there arelarge numbers of domestics working in healthcare with the poten-tial to transfer ESBLPE. Additionally, domestics receive less trainingabout infection prevention and control than other healthcareworkers, as they have no direct role in hands-on patient care.
According to our results the prevalence of CPE in the generalpopulation is still very low, and therefore efforts to reduce UKhealthcare transmission of CPE are worthwhile and could help todelay the inevitable expansion of these genes into the generalpopulation.
AcknowledgementsWe thank all the individuals who returned stool samples and question-naires; without you we could not have done this study. We wish to thank:Andre Charlett for all his help with the statistical interpretation and ad-vice on the paper; Rahim Shabbir for building the Access database;Katherine Butler and Eileen Hamilton for administrative support; the GPpractice staff; Primary Research network staff; ethics committees;Research Support Unit in Gloucester, especially Mark Walker; ElizabethCoates, Head of research governance at PHE; communications teams atPHE and radio stations who advertised the project; and Mike Nelson.
FundingThe report is based on independent research commissioned and fundedby the NIHR Policy Research Programme (Ref.041/0038S).
Transparency declarationsNone to declare.
Author contributionsC. A. M. M. (Principal Investigator) led the writing of the grant applicationand protocol, was involved in the literature review, contributed to the de-sign of the questionnaire, led the project steering group and led the writ-ing of the manuscript. D. M. L. (Project Manager Mar–Jul 2014 and fromApr 2015) was involved in practice and patient recruitment, data collec-tion and data management, was a steering group member and helpedwrite the manuscript. L. X.-M. (Clinical Scientist) was a grant co-applicantand was involved in study design and laboratory supervision, supportedlaboratory data management, was a steering group member and con-tributed to the writing of the manuscript. D. N.-S. (Research Assistant)was involved in ethics application, practice and participant recruitmentand data collection and entry, was a steering group member and com-mented on and agreed the final manuscript. K.-T. C. (Research Scientist)was involved in laboratory work, recording and data entry and agreedthe final manuscript. T. N. (Statistician) was a grant co-applicant, wasinvolved in study design, practice and participant selection, data man-agement and data analysis, was a steering group member and contrib-uted to the writing of and agreed the final manuscript. H. L. T.(Epidemiologist) was a grant co-applicant, was involved in study andquestionnaire design and data interpretation, was a steering group mem-ber and commented on and agreed the final manuscript. M. T. was a grantco-applicant, was involved in study and questionnaire design, was a steer-ing group member, was primary care lead, was involved in practice selec-tion and commented on and agreed the final manuscript. A. A.-B.(Research Scientist) was involved in laboratory work and data cleaning andagreed the final manuscript. K. T. (Unit Administrator) was involved in par-ticipant recruitment and liaison and data collection and entry and agreedthe final manuscript. S. Sh. (Research Scientist) was involved in laboratorywork and data collection and agreed the final manuscript. S. M. (ResearchScientist) was involved in laboratory work and data collection and agreedthe final manuscript. S. Sm. was a grant co-applicant and was involved instudy design, was a steering group member and commented on andagreed the final manuscript. L. C. (Project Manager Oct 2014–Mar 2015)was involved in organizing distribution of sample kits and data manage-ment and agreed the final manuscript. P. M. H. was a grant co-applicantand was involved in literature review, study design, questionnaire design,laboratory supervision and data interpretation, was a steering group mem-ber and contributed to the writing of and agreed the final manuscript.
DisclaimerThe views expressed in the publication are those of the authors and notnecessarily those of the NHS, the NIHR, the Department of Health, ‘arms’length bodies or other government departments.
Supplementary dataThe questionnaire is available as Figure S1 at JAC Online.
References1 Hawkey P, Jones A. The changing epidemiology of resistance. J AntimicrobChemother 2009; 64 Suppl 1: i3–10.
2 Horner C, Fawley W, Morris K et al. Escherichia coli bacteraemia: 2 yearsof prospective regional surveillance (2010-12). J Antimicrob Chemother2014; 69: 91–100.
McNulty et al.
1386Downloaded from https://academic.oup.com/jac/article-abstract/73/5/1368/4885410by Southampton Oceanography Centre National Oceanographic Library useron 13 June 2018
3 Reuland EA, Al Naiemi N, Kaiser AM et al. Prevalence and risk factors forcarriage of ESBL-producing Enterobacteriaceae in Amsterdam. J AntimicrobChemother 2016; 71: 1076–82.
4 Woerther PL, Burdet C, Chachaty E et al. Trends in human fecal carriage ofextended-spectrum b-lactamases in the community: toward the globaliza-tion of CTX-M. Clin Microbiol Rev 2013; 26: 744–58.
5 Ironmonger D, Edeghere O, Bains A et al. Surveillance of antibiotic suscepti-bility of urinary tract pathogens for a population of 5.6 million over 4 years.J Antimicrob Chemother 2015; 70: 1744–50.
6 PHE. English Surveillance Programme for Antimicrobial Utilisation andResistance (ESPAUR) Report. 2016. https://www.gov.uk/government/uploads/system/uploads/attachment_data/file/575626/ESPAUR_Report_2016.pdf.
7 Harris AD, Perencevich EN, Johnson JK et al. Patient-to-patient transmis-sion is important in extended-spectrum b-lactamase–producing Klebsiellapneumoniae acquisition. Clin Infect Dis 2007; 45: 1347–50.
8 Asir J, Nair S, Devi S et al. Simultaneous gut colonisation and infection byESBL-producing Escherichia coli in hospitalised patients. Australas Med J2015; 8: 200–7.
9 Epelboin L, Robert J, Tsyrina-Kouyoumdjian E et al. High rate of multidrug-resistant Gram-negative bacilli carriage and infection in hospitalized return-ing travelers: a cross-sectional cohort study. J Travel Med 2015; 22: 292–9.
10 Arcilla MS, van Hattem JM, Haverkate MR et al. Import and spread ofextended-spectrum b-lactamase-producing Enterobacteriaceae by interna-tional travellers (COMBAT study): a prospective, multicentre cohort study.Lancet Infect Dis 2017; 17: 78–85.
11 Wickramasinghe NH, Xu L, Eustace A et al. High community faecal car-riage rates of CTX-M ESBL-producing Escherichia coli in a specific populationgroup in Birmingham, UK. J Antimicrob Chemother 2012; 67: 1108–13.
12 von Wintersdorff CJH, Penders J, Stobberingh EE et al. High rates of anti-microbial drug resistance gene acquisition after international travel, TheNetherlands. Emerg Infect Dis 2014; 20: 649–57.
13 Kuenzli E, Jaeger VK, Frei R et al. High colonization rates of extended-spectrum b-lactamase (ESBL)-producing Escherichia coli in Swiss travellers toSouth Asia- a prospective observational multicentre cohort study looking atepidemiology, microbiology and risk factors. BMC Infect Dis 2014; 14: 528.
14 Freedman DO, Weld LH, Kozarsky PE et al. Spectrum of disease andrelation to place of exposure among ill returned travelers. N Engl J Med2006; 354: 119–30.
15 Steffen R, Ba~nos A. Travel epidemiology—a global perspective. Int JAntimicrob Agents 2003; 21: 89–95.
16 Eurostat. Tourism Statistics. http://ec.europa.eu/eurostat/statistics-explained/index.php/Tourism_statistics.
17 Jazmati N, Hein R, Hamprecht A. Use of an enrichment broth improvesdetection of extended-spectrum-b-lactamase-producing Enterobacteria-ceae in clinical stool samples. J Clin Microbiol 2016; 54: 467–70.
18 Willems E, Cartuyvels R, Magerman K et al. Evaluation of 3 different agarmedia for rapid detection of extended-spectrum b-lactamase-producingEnterobacteriaceae from surveillance samples. Diagn Microbiol Infect Dis2013; 76: 16–9.
19 Xu L, Ensor V, Gossain S et al. Rapid and simple detection of blaCTX-M genesby multiplex PCR assay. J Med Microbiol 2005; 54: 1183–7.
20 Lolans K, Calvert K, Won S et al. Direct ertapenem disk screening methodfor identification of KPC-producing Klebsiella pneumoniae and Escherichia coliin surveillance swab specimens. J Clin Microbiol 2010; 48: 836–41.
21 Findlay J, Hopkins KL, Alvarez-Buylla A et al. Characterization ofcarbapenemase-producing Enterobacteriaceae in the West Midlands regionof England: 2007-14. J Antimicrob Chemother 2017; 72: 1054–62.
22 Rodriguez-Bano J, Lopez-Cerero L, Navarro MD et al. Faecal carriage ofextended-spectrum b-lactamase-producing Escherichia coli: prevalence, risk
factors and molecular epidemiology. J Antimicrob Chemother 2008; 62:1142–9.
23 Moore LS, Freeman R, Gilchrist MJ et al. Homogeneity of antimicrobialpolicy, yet heterogeneity of antimicrobial resistance: antimicrobial non-susceptibility among 108717 clinical isolates from primary, secondaryand tertiary care patients in London. J Antimicrob Chemother 2014; 69:3409–22.
24 Horner CS, Abberley N, Denton M et al. Surveillance of antibiotic suscepti-bility of Enterobacteriaceae isolated from urine samples collected from com-munity patients in a large metropolitan area, 2010-2012. Epidemiol Infect2014; 142: 399–403.
25 Wielders CC, van Hoek AH, Hengeveld PD et al. Extended-spectrum b-lac-tamase- and pAmpC-producing Enterobacteriaceae among the generalpopulation in a livestock-dense area. Clin Microbiol Infect 2017; 23: 120.e1–8.
26 Huijbers PM, Graat EA, Haenen AP et al. Extended-spectrum and AmpCb-lactamase-producing Escherichia coli in broilers and people living and/orworking on broiler farms: prevalence, risk factors and molecular characteris-tics. J Antimicrob Chemother 2014; 69: 2669–75.
27 Karanika S, Karantanos T, Arvanitis M et al. Fecal colonization withextended-spectrum b-lactamase-producing Enterobacteriaceae and risk fac-tors among healthy individuals: a systematic review and metaanalysis. ClinInfect Dis 2016; 63: 310–8.
28 Xu L, Shabir S, Bodah T et al. Regional survey of CTX-M-type extended-spectrum b-lactamases among Enterobacteriaceae reveals marked het-erogeneity in the distribution of the ST131 clone. J Antimicrob Chemother2011; 66: 505–11.
29 Barreto Miranda I, Ignatius R, Pfuller R et al. High carriage rate of ESBL-producing Enterobacteriaceae at presentation and follow-up among travel-lers with gastrointestinal complaints returning from India and SoutheastAsia. J Travel Med 2016; 23: tav024.
30 Cummins C, Winter H, Cheng KK et al. An assessment of the NamPehchan computer program for the identification of names of south Asianethnic origin. J Public Health Med 1999; 21: 401–6.
31 Kantele A, Laaveri T, Mero S et al. Antimicrobials increase travelers’ risk ofcolonization by extended-spectrum b-lactamase-producing Enterobacteria-ceae. Clin Infect Dis 2015; 60: 837–46.
32 Ruppe E, Armand-Lefevre L, Estellat C et al. Long-term persistence ofmultidrug-resistant Enterobacteriaceae after travel to the tropics: reply. ClinInfect Dis 2015; 61: 1767.
33 Andersson H, Lindholm C, Iversen A et al. Prevalence of antibiotic-resistant bacteria in residents of nursing homes in a Swedish municipality:healthcare staff knowledge of and adherence to principles of basic infectionprevention. Scand J Infect Dis 2012; 44: 641.
34 Ensor VM, Shahid M, Evans JT et al. Occurrence, prevalence and geneticenvironment of CTX-M b-lactamases in Enterobacteriaceae from Indian hos-pitals. J Antimicrob Chemother 2006; 58: 1260–3.
35 Petternel C, Galler H, Zarfel G et al. Isolation and characterization ofmultidrug-resistant bacteria from minced meat in Austria. Food Microbiol2014; 44: 41–6.
36 Michael GB, Kaspar H, Siqueira AK et al. Extended-spectrum b-lactamase(ESBL)-producing Escherichia coli isolates collected from diseased food-producing animals in the GERM-Vet monitoring program 2008-2014. VetMicrobiol 2017; 200: 142–50.
37 Snow LC, Warner RG, Cheney T et al. Risk factors associated withextended spectrum b-lactamase Escherichia coli (CTX-M) on dairy farms inNorth West England and North Wales. Prev Vet Med 2012; 106: 225–34.
38 Valverde A, Canton R, Garcillan-Barcia MP et al. Spread of blaCTX-M-14
is driven mainly by IncK plasmids disseminated among Escherichia coliphylogroups A, B1, and D in Spain. Antimicrob Agents Chemother 2009; 53:5204.
CTX-M ESBL-producing Enterobacteriaceae prevalence JAC
1387Downloaded from https://academic.oup.com/jac/article-abstract/73/5/1368/4885410by Southampton Oceanography Centre National Oceanographic Library useron 13 June 2018
39 Tyrrell JM, Wootton M, Toleman MA et al. Genetic & virulence profiling ofESBL-positive E. coli from nosocomial & veterinary sources. Vet Microbiol2016; 186: 37–43.
40 Wootton M, Tyrrell JM, Walsh TR et al. Prevalence of CTX-M-14 type inWelsh hospitals. In: Abstracts of the Fiftieth Interscience Conference onAntimicrobial Agents and Chemotherapy, Boston, MA, USA, 2010. Abstract C2-676. American Society for Microbiology, Washington, DC, USA.
41 Stokes MO, Cottell JL, Piddock LJ et al. Detection and characterization ofpCT-like plasmid vectors for blaCTX-M-14 in Escherichia coli isolates fromhumans, turkeys and cattle in England and Wales. J Antimicrob Chemother2012; 67: 1639–44.
42 Hussain A, Ranjan A, Nandanwar N et al. Genotypic and phenotypic pro-files of Escherichia coli isolates belonging to clinical sequence type 131(ST131), clinical non-ST131, and fecal non-ST131 lineages from India.Antimicrob Agents Chemother 2014; 58: 7240–9.
43 Bevan ER, Jones AM, Hawkey PM. Global epidemiology of CTX-M b-lacta-mases: temporal and geographical shifts in genotype. J AntimicrobChemother 2017; 72: 2145–55.
44 Gijon D, Curiao T, Baquero F et al. Fecal carriage of carbapenemase-producing Enterobacteriaceae: a hidden reservoir in hospitalized and nonho-spitalized patients. J Clin Microbiol 2012; 50: 1558–63.
45 van Hattem JM, Arcilla MS, Bootsma MC et al. Prolonged carriage and po-tential onward transmission of carbapenemase-producing Enterobacteria-ceae in Dutch travelers. Future Microbiol 2016; 11: 857–64.
46 Lautenbach E, Harris AD, Perencevich EN et al. Test characteristics of peri-rectal and rectal swab compared to stool sample for detection offluoroquinolone-resistant Escherichia coli in the gastrointestinal tract.Antimicrob Agents Chemother 2005; 49: 798–800.
47 Hawkey PM. Multidrug-resistant Gram-negative bacteria: a product ofglobalization. J Hosp Infect 2015; 89: 241–7.
48 Canton R, Gonzalez-Alba JM, Galan JC. CTX-M enzymes: origin and diffu-sion. Front Microbiol 2012; 3: 110.
49 PHE. Managing Common Infections: Guidance for Primary Care. 2017.https://www.gov.uk/government/publications/managing-common-infections-guidance-for-primary-care.
50 National Institute for Health and Care Excellence. Sepsis: Recognition,Diagnosis and Early Management. 2016. https://www.nice.org.uk/guidance/ng51/resources/sepsis-recognition-diagnosis-and-early-management-pdf-1837508256709.
51 Hawkey PM, Warren RE, Livermore DM et al. Treatment of infectionscaused by multidrug-resistant Gram-negative bacteria: report of the BritishSociety for Antimicrobial Chemotherapy/Healthcare Infection Society/BritishInfection Association Joint Working Party. J Antimicrob Chemother 2018; inpress.
52 Ruppe E, Armand-Lefevre L, Estellat C et al. High rate of acquisition butshort duration of carriage of multidrug-resistant Enterobacteriaceae aftertravel to the tropics. Clin Infect Dis 2015; 61: 593–600.
McNulty et al.
1388Downloaded from https://academic.oup.com/jac/article-abstract/73/5/1368/4885410by Southampton Oceanography Centre National Oceanographic Library useron 13 June 2018