En e medades
In ecciosas
y
Mic obiología
Clínica
41
(2023)
162–168
www.else ie .es/eimc
O iginal
a icle
Use
o
hospi al
esou ces
in
ICU
inpa ien s
wi h
in ec ions
caused
by
ca bapenem- esis an
g am-nega i e
bac e ia:
A
eal
clinical
p ac ice-based
s udy
in
Spain
Rica d
Fe e a,
José
Ga nacho-Mon e ob,
Ped o
Rascadoc,
So ía
Con e asa,
Luisa
Can ón-Bulnesb,
Pa icia
Ba alc,
Inés
del
Ce od,
Xa ie
Badiad,∗
aIn ensi e
Ca e
Depa men ,
Vall
d’Heb on
Uni e si y
Hospi al,
Shock,
O gan
Dys unc ion
and
Resusci a ion
Resea ch
G oup
(SODIR),
VHIR,
Ba celona,
Spain
bIn ensi e
Ca e
Clinical
Uni ,
Vi gen
Maca ena
Uni e si y
Hospi al,
Se ille,
Spain
cIn ensi e
Ca e
Uni ,
Complejo
Hospi ala io
Uni e si a io
San iago
de
Compos ela,
San iago
de
Compos ela,
Spain
dOmakase
Consul ing
S.L.,
Ba celona,
Spain
a
i
c
l
e
i
n
o
A icle
his o y:
Recei ed
26
July
2021
Accep ed
3
Oc obe
2021
A ailable
online
5
Janua y
2023
Keywo ds:
Ca bapenem- esis ance
G am-nega i e
bac e ia
An ibio ic
esis ance
Real
wo d
e idence
Use
o
hospi al
esou ces
Cos s
a
b
s
a
c
In oduc ion:
Ca bapenem- esis an
G am-nega i e
bac e ia
(CRGN)
a e
an
u gen
public
heal h
h ea
because
o
he
limi ed
ea men
op ions,
i s
apid
sp eading
and
high
clinical
impac
and
mo ali y
a es.
Howe e ,
he
bu den
and
he
use
o
esou ces
o
hese
in ec ions
ha e
no
been
in es iga ed.
The
aim
o
he
cu en
s udy
is
o
unde s and
he
use
o
esou ces
associa ed
o
he
clinical
managemen
o
CRGN
in ec ions
in
eal
clinical
p ac ice
condi ions.
Me hods:
An
obse a ional
e ospec i e
cha
e iew
s udy
was
pe o med.
Da a
ega ding
pa ien
demog aphics,
clinical
managemen
and
use
o
esou ces
associa ed
o
hospi aliza ion
we e
e ie ed
om
clinical
cha s
o
ICU
inpa ien s
wi h
a
confi med
CRGN
in ec ion.
Th ee
e e ence
Spanish
hospi als
we e
selec ed
acco ding
o
hei
pa ien
olume
and
geog aphical
co e age.
Desc ip i e
analyses
o
he
clinical
managemen
and
he
use
o
esou ces
and
i s
cos
we e
pe o med
and
hen
o al
cos s
by
ype
o
esou ce
we e
calcula ed.
Resul s:
A
o al
o
130
pa ien s
we e
included
in
he
s udy.
The
highe
numbe
o
pa ien s
(n
=
43/33%)
we e
be ween
61
and
70
yea s
old.
Nine y- ou
(72%)
pa ien s
we e
male
and
115
(88%)
su e ed
om
como bidi ies.
The
mean
o al
cos
associa ed
o
he
esou ces
used
in
pa ien s
wi h
CRGN
in ec ions
hospi alized
in
ICU
was
96,878D
pe
pa ien .
These
o al
cos s
included
84,140D
o
o al
hospi al
s ay,
11,021D
o
ea men s
(558D
o
an ibio ics;
10,463D
o
o he
ea men s)
and
1717D
cos s
o
diagnos ic
es s.
Conclusions:
CRGN
in ec ion
causes
a
high
use
o
hospi al
esou ces,
being
he
leng h
o
s ay
ei he
in
hospi al
wa ds
o
ICU
he
d i e
o
he
o al
cos s.
Diagnos ic
es s
and
ea men s,
including
an ibio ics,
ep esen
he
lowes
pa
o
he
use
o
esou ces
and
cos s
(13%
o
o al
cos s).
©
2021
The
Au ho (s).
Published
by
Else ie
Espa˜
na,
S.L.U.
on
behal
o
Sociedad
Espa˜
nola
de
En e medades
In ecciosas
y
Mic obiolog´
ıa
Cl´
ınica.
This
is
an
open
access
a icle
unde
he
CC
BY
license
(h p://c ea i ecommons.o g/licenses/by/4.0/).
Uso
de
ecu sos
hospi ala ios
en
pacien es
hospi alizados
en
UCI
debido
a
in ecciones
causadas
po
bac e ias
g amnega i as
esis en es
a
ca bapenémicos:
un
es udio
basado
en
la
p ác ica
clínica
eal
en
Espa˜
na
Palab as
cla e:
Bac e ias
g amnega i as
esis en es
a
ca bapenémicos
Resis encia
a
an ibió icos
e
s
u
m
e
n
In oducción:
Las
bac e ias
g amnega i as
esis en es
a
ca bapenémicos
(CRGN)
son
una
amenaza
u gen e
de
salud
pública
po
las
limi adas
opciones
de
a amien o,
su
ápida
dispe sión
y
el
al o
impac o
clínico
y
asas
de
mo alidad.
Sin
emba go,
la
ca ga
y
el
uso
de
ecu sos
de
es as
in ecciones
no
han
sido
in es-
igadas.
El
obje i o
de
es e
es udio
es
comp ende
el
uso
de
ecu sos
asociado
al
manejo
clínico
de
las
in ecciones
po
CRGN
en
condiciones
de
p ác ica
clínica
eal.
∗Co esponding
au ho .
E-mail
add ess:
[email p o ec ed]
(X.
Badia).
h ps://doi.o g/10.1016/j.eimce.2021.10.009
2529-993X/©
2021
The
Au ho (s).
Published
by
Else ie
Espa˜
na,
S.L.U.
on
behal
o
Sociedad
Espa˜
nola
de
En e medades
In ecciosas
y
Mic obiolog´
ıa
Cl´
ınica.
This
is
an
open
access
a icle
unde
he
CC
BY
license
(h p://c ea i ecommons.o g/licenses/by/4.0/).
R.
Fe e ,
J.
Ga nacho-Mon e o,
P.
Rascado
e
al.
En e medades
In ecciosas
y
Mic obiología
Clínica
41
(2023)
162–168
E idencia
del
mundo
eal
Uso
de
ecu sos
hospi ala ios
Cos es
Mé odos:
Se
lle ó
a
cabo
un
es udio
obse acional
e ospec i o
de
e isión
de
his o ias
clínicas.
Se
ecogie on
da os
demog áficos,
del
manejo
clínico
y
del
uso
de
ecu sos
asociado
a
la
hospi alización
de
his o ias
clínicas
de
pacien es
hospi alizados
en
UCI
con
una
in ección
confi mada
po
CRGN.
Se
selecciona on
es
hospi ales
espa˜
noles
de
e e encia
po
su
cobe u a
geog áfica.
Se
ealiza on
análi-
sis
desc ip i os
del
manejo
clínico
y
el
uso
de
ecu sos
y
sus
cos es
en
episodios
de
in ecciones
po
CRGN,
y
se
calcula on
los
cos es
o ales
pa a
cada
ipo
de
ecu so.
Resul ados:
Se
incluye on
en
el
es udio
un
o al
de
130
pacien es.
La
mayo ía
de
los
pacien es
(n
=
43;33%)
enían
en e
61-70
a˜
nos.
No en a
y
cua o
pacien es
(72%)
e an
homb es
y
115
(88%)
p esen a on
como -
bilidades.
El
cos e
medio
o al
asociado
a
los
ecu sos
usados
du an e
el
episodio
de
in ección
po
CRGN
po
pacien e
ue
de
96.878D
.
Es e
cos e
o al
incluye
84.140D
de
la
es ancia
en
el
hospi al,
11.021D
de
los
a amien os
(558D
de
an ibió icos
y
10.463D
de
o os
a amien os)
y
1.717D
del
cos e
de
es
diagnós icos.
Conclusiones:
El
episodio
de
in ección
po
CRGN
causa
un
al o
uso
de
ecu sos
hospi ala ios,
siendo
la
du ación
de
la
es ancia
an o
en
plan a
hospi ala ia
como
en
UCI
el
ac o
con
mayo
peso
de
los
cos es
o ales.
Los
es
diagnós icos
clínicos
y
los
a amien os,
incluyendo
los
an ibió icos,
ep esen an
la
pa e
más
peque˜
na
del
uso
de
ecu sos
y
sus
cos es
(13%
del
cos e
o al).
©
2021
El
Au o (s).
Publicado
po
Else ie
Espa˜
na,
S.L.U.
en
nomb e
de
Sociedad
Espa˜
nola
de
En e medades
In ecciosas
y
Mic obiolog´
ıa
Cl´
ınica.
Es e
es
un
a ´
ıculo
Open
Access
bajo
la
licencia
CC
BY
(h p://c ea i ecommons.o g/licenses/by/4.0/).
In oduc ion
Mul id ug- esis an
bac e ia
(MDR)
in ec ions
ha e
been
p i-
o i ized
as
a
global
and
u gen
challenge
o
public
heal h
by
he
Wo ld
Heal h
O ganiza ion
(WHO),
he
Eu opean
Commission
and
he
US
Depa men
o
Heal h,
amongs
o he
ins i u ions.1–3
The
esis ance
o
hese
bac e ia
o
a ailable
an ibio ics
has
di ec
and
indi ec
consequences
o
pa ien s
and
socie y,
such
as
longe
pa ien s’
illnesses
and
hospi al
s ays,
loss
o
p o ec ion
o
pa ien s
unde going
in asi e
p ocedu es,
losses
o
p oduc i i y,
inc eas-
ing
economic
cos s
o
d ama ic
a es
o
mo bidi y
and
mo ali y.1
Mo eo e ,
in ec ions
caused
by
MDR
equi e
s ic
isola ion
p e-
cau ions
o
limi
he
sp ead
o
hese
di ficul - o- ea
bac e ia.4
Isola ion
p ecau ions
a e
associa ed
wi h
clinical
ad e se
e ec s
which
may
esul
in
poo e
hospi al
ou comes.5Each
yea ,
he
incidence
o
MDR
in
he
Uni ed
S a es
is
es ima ed
in
2.8
million
in ec ion
wi h
mo e
han
35,000
dea hs
as
a
esul ,3meanwhile
in
Eu ope
he
es ima ed
numbe
o
dea hs
ise
un il
33,000.6Globally,
a ound
700,000
people
pe
annum
die
due
o
MDR
in ec ions,
bu
his
numbe
is
likely
o
be
unde es ima ed
because
o
poo
su eil-
lance
and
epo .7,8 Mo eo e ,
i
is
expec ed
ha
i
no
One
Heal h
ac ion
is
aken
agains
MDR
his
numbe
would
inc ease
un il
10
million
li es
by
2050,
eplacing
cance
as
he
fi s
cause
o
dea h.7
Amongs
he
di e en
ypes
o
pa hogenic
bac e ia,
ca bapenem- esis an
G am-nega i e
(CRGN)
a e
specially
complica ed
because
o
hei
de eloped
an ibio ic
esis ance,
hei
apid
sp eading
and
hei
agg essi e
clinical
impac .
By
using
di e en
biological
mechanisms
(e.g.,
ho izon al
gene
ans e )
G am-nega i e
bac e ia
become
esis an
o
ca bapenems
and
o he
an ibio ics,
limi ing
he
ea men
op ions.
As
a
esul ,
CRGN
in ec ions
cause
a
huge
numbe
o
se e e
medical
eme gencies,
se ious
complica ions
o
pa ien s,
long
hospi al
s ays
and
high
mo ali y
a es.8,9 In
addi ion,
i
has
been
demons a ed
ha
CRGN
bac e ia
con inuously
accumula e
mul id ug- esis ance
mechanisms,
making
hese
bac e ia
inc easingly
ha m ul.9Di -
e en
ac o s
a e
in ol ed
in
his
aising
o
de eloped
esis ance,
being
one
o
he
main
causes
he
abuse
o
an ibio ic
ea men
in
human
popula ion.
Spain
has
been
signaled
as
one
o
he
Eu opean
coun ies
wi h
a
highe
communi y
in ake
a e
o
an ibio ics,10 and
CRGN
bac e ia
ha e
been
de ec ed
as
he
fi s
sou ce
o
in ec ions
causing
a
high
numbe
o
medical
eme gencies,
mo bidi y
and
mo ali y.11 Na ional
and
egional
p og ams
ha e
been
es ablished
in
o de
o
con ain
his
public
heal h
issue.12
In
addi ion
o
he
pa ien
su e ing,
CRGN
in ec ions
also
lead
o
se ious
economic
consequences
and
only
in
he
Eu opean
Union
i
is
es ima ed
ha
MDR
in ec ions
suppose
D
1.5
billion
pe
yea
in
di ec
and
indi ec
cos s.2Despi e
he
abo e
men ioned
clinical
impac
and
he
economic
consequences,
he
bu den
and
he
use
o
esou ces
o
hospi al
CRGN
in ec ions
emain
unexplo ed
in
eal
clinical
p ac ice.
To
ou
knowledge,
ew
s udies
ha e
a emp ed
o
analyze
he
esou ces
consump ion
in
pa ien s
wi h
CRGN
in ec ion
wi h
public
a ailable
da a.6,13 Recen ly,
in
Spain
a
s udy
es ima ed
ha
CRGN
in ec ions
would
imply
a
o al
cos
o
D
472
million
pe
yea
o
he
Spanish
Na ional
Heal h
Sys em
(NHS).13
The
aim
o
he
s udy
was
o
desc ibe
he
use
o
hospi al
esou ces
associa ed
o
he
clinical
managemen
o
he
CRGN
in ec ion
in
c i -
ically
ill
pa ien s
wi h
a
labo a o y-confi med
in ec ion
caused
by
CRGN
bac e ia
in
condi ions
o
eal-li e
clinical
p ac ice.
Me hods
Pa icipan s
Th ee
p incipal
in es iga o s
om
e ia y
uni e si y
leading
Spanish
hospi als
we e
selec ed
o
pa icipa e
in
his
s udy.
These
hospi als
ha e
a
g ea
olume
o
CRGN
in ec ed
pa ien s
and
co e
di e en
geog aphical
egions
allowing
o
a
mo e
ep esen a i e
sample
o
he
coun y:
Vall
d’Heb on
Hospi al
(VdH;
Ba celona,
beds:
1315,
popula ion
co e ed:
430,000),
San iago
Uni e si y
Hospi al
(CHUS;
San iago
de
Compos ela,
beds:
1395,
popula ion
co e ed:
500,000)
and
Vi gen
de
la
Maca ena
Hospi al
(HUVM;
Se ille,
beds:
1279,
popula ion
co e ed:
558,000).
Inclusion
c i e ia
we e
defined
by
p esen ing
a
labo a o y
con-
fi med
CRGN
in ec ion
episode
(including
mixed
in ec ions
o
CRGN
bac e ia)
and
being
hospi alized
in
he
ICU
(in ensi e
ca e
uni )
be ween
Janua y,
1s
2015
and
Decembe ,
31s
2019.
Exclusion
c i e ia
included
being
unde
18
yea s
old
a
hospi aliza ion
ime,
pa icipa ion
o
he
subjec
in
andomized
clinical
ials,
ac i e
in ec ious
episodes
caused
by
bac e ia
o he
han
CRGN
o
CRGN
in ec ion
coexis ing
wi h
no
CR
bac e ia.
Sample
size
was
fixed
a
130
subjec s
o
achie e
he
pu poses
o
his
desc ip i e
s udy
and
o
be
illus a i e
o
he
use
o
esou ces
in
he
selec ed
cen e s.14 A
compe i i e
ec ui men
was
pe o med
be ween
cen e s
and
all
pa ien s
whose
cha s
ulfilled
he
s udy
inclusion
and
exclusion
c i e ia
we e
consecu i ely
included
un il
he
sample
size
was
eached.
The
p o ocol
o
he
s udy
was
app o ed
by
he
E hical
Boa ds
o
all
pa icipa ing
cen e s.
The
in es iga ion
ollowed
he
e hical
p inciples
o
he
Decla a ion
o
Helsinki15 and
he
equi emen s
o
he
Eu opean
Union
Gene al
Da a
P o ec ion
Regula ion
(GDPR).16
163
R.
Fe e ,
J.
Ga nacho-Mon e o,
P.
Rascado
e
al.
En e medades
In ecciosas
y
Mic obiología
Clínica
41
(2023)
162–168
P ocedu e
An
obse a ional
e ospec i e
cha
e iew
design
was
ol-
lowed
o
he
pu pose
o
his
s udy.
Re ospec i e
da a
om
clinical
cha s
ega ding
pa ien s’
demog aphics
and
he
use
o
esou ces
we e
collec ed
by
esea che s
ia
an
elec onic
Case
Repo
Fo m,
including
he
ollowing
in e es
a iables:
•Demog aphic
da a:
gende ,
age,
como bidi ies.
•Hospi aliza ion
ela ed
da a:
main
admission
diagnosis,
da es
o
hospi aliza ion
and
ICU
admission,
da e
o
CRGN
in ec ion
de ec-
ion,
discha ge
and
pa ien
isola ion.
•CRGN
iden ifica ion:
use
o
bioma ke s
(PCR,
p ocalci onin,
in e -
leukins),
mic obiological
(mul i- esis ance
an ibiog am,
acheal
aspi a e,
G am-nega i e
bacilli
an ibiog am,
specific
bac e ia
cul-
u e,
e c.)
and
imaging
es s,
da e
o
CRGN
iden ifica ion.
•Clinical
managemen
in
he
ICU:
main
adminis e ed
an ibi-
o ics,
de-escala ing
p ocess
ollowed,
eme gence
o
se ious
ad e se
e en s
(SAE:
dea h
o
li e- h ea ening)
and
i s
ea -
men
esou ces,
need
o
a
su ge y
associa ed
o
CRGN
in ec ion,
equi ed
en ila ion
and
dialysis,
and
he
da es
o
use
o
en ila-
ion
and
dialysis.
•Hospi aliza ion
da a
ou
o
he
ICU:
an ibio ic
ea men
ou
o
he
ICU,
achie emen
o
mic obiological
e adica ion
and
clinical
cu e
and
eadmission
o
he
hospi al
wi hin
30
days
ollowing
an
in ec ion
ecu ence.
A e
in o ma ion
collec ion,
all
da a
we e
checked
and
alida ed
by
expe imen ed
esea che s.
S a is ical
analyses
Use
o
esou ces
Desc ip i e
s a is ics
we e
pe o med
o
demog aphic
a i-
ables.
The
equencies
and
pe cen ages
o
hese
a iables
we e
ex ac ed.
Fo
he
da a
ega ding
he
hospi aliza ion,
CRGN
iden ifica ion,
clinical
managemen
o
CRGN
in ec ion
in
he
ICU
and
he
hospi-
aliza ion
ou
o
he
ICU,
he
equencies
and
pe cen ages
we e
ex ac ed
o
he
ca ego ical
a iables.
We
calcula ed
he
leng h
o
use
o
di e en
hospi al
esou ces
and
quan i a i e
con inu-
ous
a iables
we e
c ea ed:
o al
days
in
hospi al,
days
in
he
ICU,
days
in
isola ion,
days
on
an ibio ic
ea men ,
days
on
en ila-
ion,
days
on
dialysis,
and
days
om
hospi al
o
ICU
admission
o
CRGN
iden ifica ion.
Fo
hese
con inuous
a iables,
he
e-
quencies,
pe cen ages,
mean,
s anda d
de ia ion,
minimum
and
maximum
alues
we e
ex ac ed.
Di e en
g oups
we e
spli ,
based
in
p e iously
es ablished
isk
ac o s17:
age,
cen e
o
ec ui men ,
admission
diagnosis,
o
wa d
admission
(ICU/o he
wa d).
G oup
analyses
we e
pe o med
applying
independen -sample
- es
o
compa e
he
abo e
a i-
ables
be ween
hese
g oups.
Co ela ion
analyses
we e
also
pe o med
be ween
he
con in-
uous
a iables
o
he
leng h
o
use
o
di e en
hospi al
esou ces
desc ibed
abo e.
These
a iables
we e
fi s ly
es ed
o
no mal-
i y
h ough
he
Kolmogo o –Smi no
es .
Then,
non-pa ame ic
Spea man’s
co ela ions
we e
pe o med
in
o de
o
es
i
he
leng h
o
he
use
o
hese
esou ces
was
co ela ed
be ween
hem.
All
hese
s a is ical
analyses
we e
pe o med
by
using
SPSS
.23
(SPSS
Inc.,
Chicago,
IL).
Cos
o
esou ces
The
cos
o
use
o
esou ces
employed
in
pa ien s
wi h
CRGN
in ec ion
was
also
calcula ed.
Da a
o
he
cos s
o
he
Spanish
NHS
we e
ex ac ed
om
Bo
Plus
Spanish
da abase
(www.bo plusweb.
po al a ma.com/)
and
eSalud
(www.esalud.oblikue.com)
pla -
o m.
Mean,
maximum
and
minimum
cos s
we e
calcula ed
o
he
esou ces
employed
in
ICU
inpa ien s
wi h
CRGN
in ec ion:
diag-
nos ic
es s
(bioma ke s,
mic obiological
and
adiological
es s),
s ay
in
wa d
and
ICU,
and
ea men s
(including
an ibio ics,
ex a-
co po eal
echniques
( en ila ion,
dialysis
and
su ge y)
and
SAE),
as
ollows:
•Mean
cos
o
esou ce
pe
pa ien
=
Uni a y
cos
o
esou ce
×
Mean
uni s
o
days
o
use
du ing
he
hospi aliza ion
×
Numbe
o
pa ien s
using
he
esou ce
•Maximum
cos
o
esou ce
pe
pa ien
=
Uni a y
cos
o
esou ce
×
Maximum
alue
o
use
o
he
esou ce
×
Numbe
o
pa ien s
using
he
esou ce
•Minimum
cos
o
esou ce
pe
pa ien
=
Uni a y
cos
o
esou ce
×
Minimum
alue
o
use
o
he
esou ce
×
Numbe
o
pa ien s
using
he
esou ce
The
calcula ed
cos s
o
he
use
o
esou ces
we e
agg ega ed
in
di e en
sec ions:
cos s
o
diagnos ic
es s,
cos s
o
hospi al
s ay
and
cos s
o
ea men s.
The
o al
di ec
medical
cos s
(mean,
max-
imum
and
minimum)
we e
finally
calcula ed
by
he
addi ion
o
he
o al
cos s
o
each
o
hese
sec ions.
Resul s
A
o al
o
134
pa ien s
we e
included
in
he
s udy:
VdH,
n
=
53;
CHUS,
n
=
50;
HUVM,
n
=
31.
All
o
hem
accomplished
inclusion
and
exclusion
c i e ia.
Fou
subjec s
(3,
VdH;
1,
HUVM)
we e
excluded
om
he
s udy
sample
because
he
in o ma ion
o
he
cha
needed
o
ulfill
he
s udy
was
incomple e.
Demog aphic
cha ac e is ics
o
he
s udy
sample
(gende ,
age
and
como bidi ies)
a e
p esen ed
in
Table
1.
Table
1
Sociodemog aphic
esul s
and
diagnoses
a
admission
o
pa ien s
wi h
CRGN
in ec ion.
n
%
Gende ,
male
94
72%
Age
<50
yea s
13
10%
50–60
yea s
28
22%
61–70
yea s
43
33%
71–80
yea s
32
25%
>80
yea s
14
11%
Como bidi ies
115
88%
n
%
Main
hospi al
admission
diagnos ic
Sep ic
shock
28
21.5%
Pos ope a i e
18
13.8%
Respi a o y
in ec ion
13
10.0%
Bipulmona
ansplan
pos ope a i e
9
6.9%
Consciousness
al e a ion
5
3.8%
Ce eb al
haemo hage
4
3.1%
Suba achnoid
haemo hage
3
2.3%
Ischemic
shock 2
1.5%
Unipulmona
ansplan
pos ope a i e
2
1.5%
Ca dio espi a o y
a es
2
1.5%
Hepa ic
ansplan
pos ope a i e
1
0.8%
Haemo hagic
shock
1
0.8%
O he a42
32.3%
aA
lis
o
o he
hospi al
admission
diagnoses
can
be
consul
in
he
Table
S1
in
he
Supplemen a y
Ma e ial.
164
R.
Fe e ,
J.
Ga nacho-Mon e o,
P.
Rascado
e
al.
En e medades
In ecciosas
y
Mic obiología
Clínica
41
(2023)
162–168
Table
2
Clinical
diagnos ic
es s
pe o med
in
CRGN
in ec ed
pa ien s.
n
%
Mean
SD
Min
Max
Bioma ke s
PCR
124
95.4% 10.0
15.8
1
159
P ocalci onin
62
47.7%
5.0
4.4
1
17
None
6
4.6%
1
0
1
1
In e leukins
4
3.1%
4.0
2.4
1
6
O he
bioma ke a1
0.8%
2
0
2
2
Mic obiological
analyses
Blood
cul u e 105
80.8% 3.2 3.2 1
26
U ine
cul u e 77
59.2%
2.7
2.2
1
10
Mul i- esis ance
an ibiog am
51
39.2%
2.7
2.1
1
11
T acheal
aspi a e
44
33.8%
4.2
3.4
1
15
Con en ional
cul u e
36
27.7%
2.9
3.4
1
19
B onchial
aspi a e
cul u e
26
20.0%
2.8
2.9
1
15
Semiquan i a i e
cul u e
(maki
echnique) 21
16.2% 2.1 2.1 1
11
G am-nega i e
bacilli
an ibiog am
10
7.7%
2.0
1.3
1
4
S ool
cul u e
7
5.4%
4.1
3.7
1
12
B onchoal eola
la age 6
4.6% 1.0 0.0 1
1
Spu um
6
4.6%
1.8
0.8
1
3
De ec ion
by
PCR
( i us) 5
3.8%
1.8
1.8
1
5
Asci es
5
3.8%
1.2
0.4
1
2
CSF
5
3.8%
2.0
1.0
1
3
Specific
bac e ia
cul u e
(Clos idium)
4
3.1%
1.8
1.0
1
3
Specific
bac e ia
cul u e
(S aphylococcus)
3
2.3%
1.7
1.2
1
3
Pleu al
fluid
cul u e 2
1.5% 2.5
0.7
2
3
Specific
bac e ia
cul u e
(Pseudomonas)
2
1.5%
1.0
0.0
1
1
O he
mic obiological
analysesb2
1.5%
1.0
0.0
1
1
Mycobac e ia
cul u e
1
0.8%
1.0
0
1
1
Specific
bac e ia
cul u e
in
u ine
(Legionella)
1
0.8%
1.0
0
1
1
G am-posi i e
bacilli
an ibiog am
1
0.8%
1.0
0
1
1
Radiological
es s
X- ay
123
94.6%
14.1
15.1
1
98
CAT
76
58.5%
2.6
2.2
1
12
Ul asound
27
20.8%
1.4
1.1
1
6
Magne ic
esonance
imaging
7
5.4%
1.2
0.4
1
2
O he
adiological
es c3
2.3%
1.0
0.0
1
1
CAT
=
compu e ized
axial
omog aphy;
CSF
=
ce eb ospinal
fluid;
PCR
=
polyme ase
chain
eac ion;
SD
=
s anda d
de ia ion.
aO he
bioma ke s:
1
c ea inine
kinase,
1
oponin.
bO he
mic obiological
analyses:
1
li e
biopsy,
1
pa asi es
es .
cO he
adiological
es s:
1
angio omog aphy,
2
a e iog aphy.
n
=
numbe
o
pa ien s
who
unde wen
he
clinical
diagnos ic
es ;
%
=
pe cen age
o
pa ien s
who
unde wen
he
es ;
mean
=
mean
o
es s
pe
pa ien ;
SD
=
s anda d
de ia ion
o
he
mean;
min
=
minimum
alue
o
es s
pe o med
in
he
pa ien s
wi h
he
es ;
max
=
maximum
alue
o
es s
pe o med
in
he
pa ien s
wi h
he
es .
Use
o
esou ces
Pa ien s
we e
admi ed
in
he
hospi al
and
ICU
wi h
di e en
p ima y
diagnoses,
being
sep ic
shock
and
pos ope a i e
com-
plica ions
he
mos
common
admission
diagnoses
(Table
1
and
Table
S1
in
he
Supplemen a y
Ma e ial).
Thi y- wo
pe cen
o
pa ien s
we e
di ec ly
admi ed
o
he
ICU
due
o
hei
se e e
con-
di ion,
and
he
es
o
hem
we e
p e iously
admi ed
o
ano he
wa d.
The
use
o
bioma ke s,
mic obiological
analyses
and
adiological
es s
a e
shown
in
Table
2.
Main
an ibio ics
used
o
in ec ion
man-
agemen
a
he
ICU
a e
ully
p esen ed
in
Table
3,
being
colis in,
igecycline
and
me openem
he
mos
equen ly
adminis e ed.
A
single-an ibio ic
he apy
was
employed
in
54%
o
pa ien s,
and
he
es
o
pa ien s
ecei ed
a
combined
he apy
o
2-4
di e en
an ibi-
o ics
(Table
S2
in
he
Supplemen a y
Ma e ial).
The
delay
o
he
an ibio ic
ea men
was
also
calcula ed
wi h
he
da es
o
CRGN
iden ifica ion
and
he
beginning
o
he
an ibio ic
ea men ,
and
anges
be ween
−10
days
(iden ifica ion
be o e
an ibio ic)
and
19
days
(an ibio ic
be o e
ea men ,
empi ical
diagnosis).
An
an ibi-
o ic
de-escala ing
p ocess
was
pe o med
in
only
15%
o
pa ien s.
SAEs
ela ed
o
an ibio ic
ea men
we e
obse ed
in
only
4
sub-
jec s
o
he
sample
(being
kidney
ailu e,
ca dio espi a o y
a es ,
a ial
fib illa ion
and
dea h
due
o
espi a o y
insu ficiency).
Eigh y- wo
pe cen
o
pa ien s
equi ed
isola ion
du ing
hei
s ay
in
he
hospi al.
Su gical
p ocedu es
we e
ollowed
in
11%
Table
3
Main
an ibio ic
ea men
adminis e ed
o
pa ien s
wi h
CRGN
in ec ion.
n
%
Colis in
66
51.6%
Tigecycline
31
24.2%
Me openem
29
22.7%
Pipe acillin/ azobac am
12
9.4%
Co imoxazole
11
8.6%
Le ofloxacin
10
7.8%
Ce azidime
10
7.8%
Amikacin
6
4.7%
Cip ofloxacin
6
4.7%
Ce olozane/ azobac am
5
3.9%
Ce azidime/a ibac am
4
3.1%
Tob amycin
3
2.3%
Ce o axime
3
2.3%
Fos omycin
3
2.3%
Az eonam
2
1.6%
Amoxicillin
cla ulanic
1
0.8%
Azi h omycin
1
0.8%
o
pa ien s
and
20%
ecei ed
dialysis.
Mo eo e ,
85%
o
subjec s
ecei ed
en ila ion
o
17
days
on
a e age
be o e
he
CRGN
iden-
ifica ion.
Nine y-one
pe cen
o
his
en ila ion
was
in asi e.
To al
hospi al
s ay,
leng h
o
s ay
(LOS)
in
he
ICU,
days
in
isola ion,
an ibio ic
ea men ,
en ila ion,
dialysis
and
days
om
hospi al
o
ICU
admission
o
CRGN
iden ifica ion
a e
p esen ed
in
Table
4.
Wi h
excep ion
o
he
leng h
o
dialysis,
he
o he
quan i a i e
con in-
165
R.
Fe e ,
J.
Ga nacho-Mon e o,
P.
Rascado
e
al.
En e medades
In ecciosas
y
Mic obiología
Clínica
41
(2023)
162–168
Table
4
Leng h
o
use
o
di e en
hospi al
esou ces
by
he
pa ien s
wi h
CRGN
in ec ion
episode.
Mean
SD
Minimum
alueaMaximum
alue
To al
hospi aliza ion
days
60
36.5
5
173
Days
in
ICU 33
28.8 1
155
Days
in
isola ion
32
30.3
1
122
Days
in
an ibio ic
ea men
12
12.4
1
85
Days
in
en ila ion
31
26.5
1
155
Days
in
dialysis
15
19.0
1
81
Days
om
hospi al
admission
o
CRGN
iden ifica ion
27
20.0
0
93
Days
om
ICU
admission
o
CRGN
iden ifica ion
17
18.0
-10
78
aNega i e
alues
in
Minimum
alue
column
indica e
ha
he
iden ifica ion
o
CRGN
bac e ia
was
pe o med
be o e
he
ICU
admission
Fig.
1.
Co ela ion
ma ix
o
he
a iables
o
leng h
o
use
o
di e en
hospi al
esou ces
in
pa ien s
wi h
episodes
o
CRGN
in ec ion.
uous
a iables
showed
s ong
posi i e
associa ions
be ween
hem
(see
Fig.
1).
A e
he
ICU
discha ge,
40%
o
pa ien s
con inued
wi h
an ibi-
o ic
ea men .
The
clinical
cu e
and
he
mic obiological
e adica ion
we e
ob ained
in
61%
and
46%
o
he
pa ien s,
espec i ely.
Only
12%
o
pa ien s
we e
e-admi ed
o
he
hospi al
30
days
a e
discha ge.
No
di e ences
we e
ound
be ween
g oups
spli
by
gende
o
age.
Di e ences
ound
be ween
si es,
admission
diagnos ic
and
wa d
admission
g oups
we e
obse ed
mainly
in
he
LOS
in
hos-
pi al
and
ICU.
A
de ailed
desc ip ion
o
hese
esul s
can
be
ound
in
he
Supplemen a y
Ma e ial,
Tables
S3–S5.
Cos
o
esou ces
The
mean,
maximum
and
minimum
cos s
o
he
used
esou ces
in
pa ien s
wi h
CRGN
in ec ion
a e
p esen ed
in
Table
5.
The
mean
o al
cos
in
pa ien s
wi h
CRGN
in ec ion
hospi alized
in
ICU,
pe
pa ien ,
was
96,978D
.
The
highe
cos s
in
he
CRGN
in ec ion
episode
we e
hose
ela ed
o
he
LOS
in
hospi al
and
ICU
wi h
84,140D
,
since
he
cos
o
an ibio ic
ea men
was
558D
ha
ep-
esen ed
less
han
he
1%
o
he
o al
cos s
o
he
CRGN
in ec ion
episode
and
5%
o
he
o al
cos
o
he
o he
ea men s
in ol ed
in
in ec ion
managemen
du ing
he
comple e
hospi al
s ay.
Discussion
This
s udy
demons a ed
ha
episodes
o
CRGN
in ec ions
in
condi ions
o
eal
clinical
p ac ice
imply
a
high
u iliza ion
o
hos-
pi al
esou ces
in
hospi alized
pa ien s
in
ICU.
The
managemen
o
hese
in ec ions
equi es
an
in ensi e
use
o
hospi al
esou ces,
such
as
s ic
isola ion
measu es,
ea men s,
o
diagnos ic
es s.
To
ou
knowledge,
his
is
he
fi s
wo k
s udying
he
use
o
esou ces
in
he
p ocess
o
CRGN
in ec ion
managemen
in
pa ien s
ha
a e
admi ed
o
he
ICU
wi h
eal
clinical
p ac ice
da a
in
Spain.
We
ound
ha
he
majo i y
o
pa ien s
in ec ed
by
a
CRGN
p esen ed
p e iously
isk
ac o s,
as
ad anced
age
o
166

R.
Fe e ,
J.
Ga nacho-Mon e o,
P.
Rascado
e
al.
En e medades
In ecciosas
y
Mic obiología
Clínica
41
(2023)
162–168
Table
5
Cos s
o
he
esou ces
used
in
pa ien s
wi h
an
episode
o
CRGN
in ec ion.
Mean
cos
(pe
pa ien )
Minimum
cos
(pe
pa ien )
Maximum
cos
(pe
pa ien )
To al
cos s
o
diagnos ic
es s
To al
bioma ke s 1166
D136
D16,367
D
To al
mic obiological
analyses
183
D
66
D
993
D
To al
adiological
s udies
368
D
122
D
1,867
D
To al
cos s
o
hospi al
s ay
(including
wa d
and
ICU)
84,140
D
11,260
D
164,651
D
To al
cos s
o
ea men s
To al
cos s
o
an ibio ics
558
D
156
D
2,478
D
To al
cos s
o
o he
ea men s
(including
SAE) 10,463
D360
D51,452
D
To al
di ec
medical
cos s 96,878
D
12,100
D
237,808
D
como bidi ies.18–20 The
iden ifica ion
o
he
CRGN
bac e ia
was
confi med
on
a e age
17
days
a e
he
admission
o
he
ICU,
in
acco dance
wi h
p e ious
esea ch
epo ing
simila
anges
o
CRGN
iden ifica ion21 and
suppo ing
he
e idence
ega ding
he
isk
o
CRGN
in ec ion
acquisi ion
in
hospi alized
pa ien s.22,23
Mechanical
en ila ion
has
been
also
iden ified
as
a
isk
ac o
o
hospi al
bac e ial
in ec ion
and
has
been
associa ed
wi h
an
inc eased
mo ali y
in
CRGN
in ec ion
pa ien s.18,24,25
In
ou
sample,
a
e y
high
pe cen age
o
pa ien s
ecei ed
in asi e
en ila ion
be o e
he
CRGN
pa hogen
iden ifica ion,
and
we
also
ound
a
posi i e
co ela ion
be ween
diagnosis
o
CRGN
in ec ion
wi h
LOS
and
numbe
o
en ila ion
days.
In asi e
en-
ila ion
has
been
p e iously
poin ed
ou
as
a
isk
ac o
o
CRGN
in ec ion,19 bu
ou
da a
do
no
allow
o
confi m
ha
in
he
pa ien s
o
ou
s udy
a
causal
ela ion
exis s.
In
ou
s udy,
he
LOS
in
hospi-
al
and
ICU
we e
long
and
co ela ed
posi i ely
wi h
he
du a ion
o
an ibio ic
ea men
(
=
0.19,
p
=
0.03;
=
0.15,
p
=
0.09,
espec-
i ely),
en ila ion
(
=
0.54,
p
=
0.01;
=
0.82,
p
=
0.01,
espec i ely)
and
isola ion
(
=
0.61,
p
=
0.01;
=
0.41,
p
=
0.01,
espec i ely).
P e i-
ously,
he
LOS
in
hospi al
has
been
di ec ly
associa ed
wi h
highe
an ibio ic
esis ance
and
wi h
posi i e
cul u es
o
P.
ae uginosa,
one
o
he
CRGN
pa hogens
causing
he
highes
mo ali y
a es.13,26
The
mos
used
an ibio ics
o
he
ea men
o
he
in ec ious
episodes
in
ou
sample
we e
colis in,
igecycline
and
me openem,
in
line
wi h
CRGN
ea men s
ollowed
in
p e ious
publica ions
despi e
he
p e ious
e idence
abou
hei
high
oxici y.25,27 Clini-
cal
cu e
and
he
mic obiological
e adica ion
we e
no
achie ed
in
a
high
pe cen age
o
ou
pa ien s,
signaling
he
need
o
de eloping
and
access
o
new
e ec i e
d ugs
ha
allows
a
as
in e en ion
in
o de
o
educe
he
ime
o
hospi al
s ay
and
i s
associa ed
isks.28 Di e ences
be ween
he
spli
g oups
we e
no
significan
and
should
be
deeply
s udied
in
he
u u e
wi h
mo e
specific
da a.
The
high
use
o
hospi al
esou ces
leads
o
a
high
economic
impac .
In
Spain,
i
has
been
es ima ed
ha
CRGN
o al
economic
cos s
suppose
D
472
million
pe
yea
o
he
Spanish
NHS.13 Based
in
eal-li e
da a,
we
calcula ed
ha
he
o al
mean
economic
impac
o
CRGN
in ec ions
in
ICU
pa ien s
is
abou
96,878D
.
Impo an ly,
we
obse ed
ha
he
cos
o
hospi al
s ay,
wi h
84,140D
pe
CRGN
in ec ed
pa ien ,
was
he
esou ce
wi h
he
bigges
weigh
in
he
o al
medical
cos s
o
hese
pa ien s.
We
also
obse ed
ha
he
cos
o
an ibio ics
was
almos
insignifican
(only
558D
)
in
compa ison
wi h
all
he
o he
esou ces
used,
ep esen ing
only
1%
o
hem.
These
esul s
poin
o
he
ac
ha
e en
i
he
cos s
o
he
CRGN
in ec ion
episodes
a e
ele a ed,
he
weigh
o
an ibio ics
in
he
whole
episode
is
no
significan .
The e o e,
he
po en ial
impac
o
employing
mo e
expensi e
bu
e ec i e
d ugs
ha
may
po en ially
educe
he
use
o
o he
esou ces
(e.g.,
he
leng h
o
hospi al
and
ICU
s ay)
should
be
in es iga ed
and
should
be
e en ually
conside ed
in
clinical
p ac ice.
The e
a e
some
limi a ions
in
ou
s udy
ha
should
be
acknowl-
edged.
Some
da a
as
he
ype
o
bac e ia
o
he
si e
o
in ec ion
ha e
no
been
collec ed,
since
he
objec i e
o
he
s udy
was
o
ge
a
gene al
pic u e
o
he
use
o
hospi al
esou ces
dedica ed
o
ea
and
manage
he
CRGN
in ec ion
episodes,
bu
no
o
speci -
ically
compa e
be ween
he
di e en
pa hogens
o
he
sys ems
a ec ed
by
he
in ec ion.
Howe e ,
he
s udy
o
he
associa ed
use
o
esou ces
o
each
pa hogen
would
be
use ul
o
he
de elopmen
o
mo e
a ge ed
in e en ions
in
he
u u e.6Eigh een
pe cen
o
pa ien s
we e
no
isola ed.
Usually,
all
pa ien s
wi h
CRGN
in ec-
ions
a e
isola ed
due
o
he
pa hogens
sp eading.29 In
ou
sample,
exi us
o
he
pa ien
o
missing
da a
can
explain
his
esul
and
his
esul
should
be
cau iously
in e p e ed.
Da a
ega ding
he
mo ali y
we e
no
collec ed.
Gi en
he
high
mo ali y
and
mo -
bidi y
associa ed
o
CRGN
in ec ion,
including
da a
ela ed
o
hese
a iables
would
be
in e es ing
in
u u e
s udies
o
calcula e
he
mo ali y,
he
yea s
o
li e
los
o
he
yea s
o
p oduc i e
li e
los
due
o
CRGN
in ec ions.6,7,9 Since
possible
neph o oxic
e ec
o
an ibi-
o ics
(e.g.,
colis in)
a e
co e ed
in
his
s udy
by
dialysis
and
he
numbe
o
days
o
dialysis,
o he
ad e se
e en s
(AEs)
we e
no
ga he ed.
Only
SAEs
we e
collec ed
because
hei
high
impac
in
he
o al
cos
o
CRGN
in ec ions
and
because
AEs
a e
defined
as
any
un owa d
e ec
a e
he
adminis a ion
o
a
p oduc
ha
is
no
necessa ily
ela ed
wi h
he
ea men .30 I
would
be
he e o e
di ficul
o
dis inguish
i
AEs
we e
caused
by
an ibio ics
and
he
es ima ion
o
he
use
o
esou ces
could
be
con amina ed
by
AEs
no
ela ed
wi h
CRGN
in ec ion.”
Ano he
limi a ion
o
he
p esen
s udy
is
he
di ficul y
o
es ab-
lish
a
pe iod
o
ac i e
in ec ion.
The
leng h
o
s ay
in
hospi al
was
hen
calcula ed
using
he
o al
days
o
s ay
a
hospi al.
Di e en
easons
made
di ficul
o
define
cu -o
poin s
o
ac i e
in ec ion:
he
sample
p esen s
he e ogenous
diagnoses
(sepsis
o
in ec ion
a
he
admission
o
o he
diagnoses),
we
did
no
collec
he
in o ma-
ion
ega ding
como bidi ies
o
pa ien ’s
in ec ion
as
a
seconda y
diagnose
a
admission,
he
days
o
an ibio ic
a e
ICU
was
nei-
he
ga he ed,
so
a
ollow-up
o
he
ea men
was
no
possible
o
be
pe o med.
A
p ospec i e
me hodology
would
be
mo e
app o-
p ia e
o
con ol
hese
a iables
and
o
define
an
accu a e
ac i e
in ec ion
pe iod,
and
he
esul s
o
he
p esen
s udy
should
be
cau iously
in e p e ed
as
me ely
desc ip i e.
The
sample
size
o
he
s udy
is
ep esen a i e
o
he
cen e s
included
bu
i
canno
be
ex apola ed
o
all
Spanish
popula ion,
especially
o
low-le el
hospi als.
Ne e heless,
he
di e ences
in
he
esou ces
used
o
he
managemen
o
CRGN
in ec ions
a e
la ge
and
we
would
no
expec
o
obse e
many
changes
in
his
dis ibu ion
wi h
bigge
samples.
Mo e
s udies
ocused
on
he
use
o
esou ces
o
CRGN
in ec ion
episodes
in
his
and
o he
popula ions
(e.g.,
pedia ic,
immuno-
supp essed
pa ien s,
o he
ype
o
Spanish
hospi als
like
low-le el
hospi als
o
om
o he
geog aphical
a eas)
should
be
conduc ed
o
gain
a
deepe
knowledge
o
he
clinical
impac
o
hese
sp eading
pa hogens
and
i s
impac
o
he
NHS.
Also,
in e na ional
mul i-
cen ic
s udies
would
be
use ul
o
c ea e
awa eness
abou
his
global
p oblem.
I
an ibio ics
ha
could
imp o e
o
cu e
he
CRGN
episodes
we e
a ailable,
i
would
be
expec ed
ha
he
use
o
167
R.
Fe e ,
J.
Ga nacho-Mon e o,
P.
Rascado
e
al.
En e medades
In ecciosas
y
Mic obiología
Clínica
41
(2023)
162–168
esou ces
and
he
hospi al
and
ICU
s ays
associa ed
cos s,
which
a e
he
mos
impo an
cos ,
would
dec ease.
In
conclusion,
in
ou
sam-
ple
CRGN
in ec ions
lead
o
a
high
use
o
hospi al
esou ces,
being
he
leng h
o
s ay
in
ICU
and
o he
wa ds
he
d i e
o
he
o al
cos s.
The
lowes
pa
o
he
esou ce
consump ion
in
hese
hospi als
(13%)
was
ep esen ed
by
diagnos ic
es s
and
ea men s,
includ-
ing
an ibio ics.
Fu he
s udies
would
be
necessa y
o
eplica e
his
s udy
in
o he
Spanish
hospi als,
o
ge
a
mo e
ep esen a i e
pic-
u e
o
he
bu den
o
CRGN
in ec ion
and
i ’s
cos
o
he
Na ional
Heal h
Sys em.
Funding
This
s udy
has
been
financed
by
Shionogi
Inc.
Conflic
o
in e es s
RF
has
ecei ed
ees
o
ad iso y
boa ds
and
con e ences
om
Shionogi,
MSD,
Pfize ,
Gilead,
GSK
and
Mena ini.
JG-M
has
pa ic-
ipa ed
in
educa ional
ac i i ies
o
Shionogi
and
Pfize .
PR
epo s
g an s
om
Shionogi,
g an s
and
pe sonal
ees
om
Pfize ,
and
pe -
sonal
ees
om
Shionogi,
MSD,
and
Mena ini.
LB-C
has
ecei ed
ees
o
con e ences
om
Shionogi.
IdC
and
XB
ecei ed
unding
o
he
design
and
analysis
o
he
da a
o
he
s udy
om
Shionogi
Inc.
Appendix
A.
Supplemen a y
da a
Supplemen a y
da a
associa ed
wi h
his
a icle
can
be
ound,
in
he
online
e sion,
a
doi:10.1016/j.eimc.2021.10.007.
Re e ences
1.
Wo ld
Heal h
O ganiza ion.
Global
ac ion
plan
on
an imic obial
esis ance
[In e ne ];
2015.
A ailable
om:
h p://www.who.in /
an imic obial- esis ance/publica ions/global-ac ion-plan/en/
[ci ed
6.5.21].
2.
Eu opean
Commission.
A
Eu opean
One
Heal h
Ac ion
Plan
agains
An imi-
c obial
Resis ance
(AMR)
[In e ne ];
2017.
A ailable
om:
h p://www.
who.in /en i y/d ug esis ance/documen s/su eillance epo /en/index.h ml
[ci ed
6.5.21].
3.
Cen e
o
Con ol
and
P e en ion.
An ibio ic
esis ance
h ea s
in
he
Uni ed
S a es;
2019.
4.
Abella
Ál a ez
A,
Janei o
Lumb e as
D,
Lobo
Valbuena
B,
Naha o
Abellán
A,
To ejón
Pé ez
I,
Enciso
Calde ón
V,
e
al.
Analysis
o
he
p edic i e
alue
o
p e en i e
isola ion
c i e ia
in
he
in ensi e
ca e
uni .
Med
In ensi a.
2021;45:205–10.
5.
Abad
C,
Fea day
A,
Sa da
N.
Ad e se
e ec s
o
isola ion
in
hospi alised
pa ien s:
a
sys ema ic
e iew.
J
Hosp
In ec .
2010;76:97–102.
6.
Cassini
A,
Högbe g
LD,
Plachou as
D,
Qua occhi
A,
Hoxha
A,
Simonsen
GS,
e
al.
A ibu able
dea hs
and
disabili y-adjus ed
li e-yea s
caused
by
in ec-
ions
wi h
an ibio ic- esis an
bac e ia
in
he
EU
and
he
Eu opean
Economic
A ea
in
2015:
a
popula ion-le el
modelling
analysis.
Lance
In ec
Dis.
2019;19:
56–66.
7.
O’Neill
J.
Tackling
d ug- esis an
in ec ions
globally:
final
epo
and
ec-
ommenda ions
[In e ne ];
2016.
A ailable
om:
h ps://am - e iew.o g/
si es/de aul /files/160525
Finalpape
wi hco e .pd
[ci ed
6.5.21].
8.
De
Oli ei a
DMP,
Fo de
BM,
Kidd
TJ,
Ha is
PNA,
Schemb i
MA,
Bea son
SA,
e
al.
An imic obial
esis ance
in
ESKAPE
pa hogens.
Clin
Mic obiol
Re .
2020;33:e00181–219.
9.
Mele is
G.
Ca bapenem
esis ance:
o e iew
o
he
p oblem
and
u u e
pe spec-
i es.
The
Ad
In ec
Dis.
2016;3:15–21.
10.
Eu opean
Cen e
o
Disease
P e en ion
and
Con ol.
An imic obial
consump ion
in
he
EU
and
EEA:
Annual
Epidemiological
Repo
[In e ne ];
2019.
A ailable
om:
h ps://www.ecdc.eu opa.eu/si es/
de aul /files/documen s/An imic obial-consump ion-in- he-EU-
Annual-Epidemiological-Repo -2019.pd
[ci ed
6.5.21].
11.
Sociedad
Espa˜
nola
de
En e medades
In ecciosas
y
Mic obiología
Clínica
(SEIMC).
Regis o
hospi ala io
de
pacien es
a ec ados
po
las
esis encias
bac e ianas
[In e ne ];
2018.
A ailable
om:
h ps://seimc.
o g/con enidos/no icias/2018/seimc-Regis o
de
Pacien es
BMR.pd
[ci ed
6.5.21].
12.
Minis e io
de
Sanidad
Consumo
y
Bienes a
Social.
Plan
nacional
en e
a
la
esis encia
a
los
an ibió icos
2019–2021
[In e ne ];
2019.
A ailable
om:
h ps:// esis enciaan ibio icos.es/
[ci ed
6.5.21].
13.
Can ón
R,
Hua e
R,
Mo a a
L,
T illo-Ma a
JL,
Mu˜
noz
R,
González
J,
e
al.
De e mining
he
bu den
o
in ec ious
diseases
caused
by
ca bapenem- esis an
G am-nega i e
bac e ia
in
Spain.
En e m
In ecc
Mic obiol
Clin.
2021;39:179–83.
14.
Beck
RW.
Sample
size
o
a
clinical
ial:
why
do
some
ials
need
only
100
pa ien s
and
o he s
1000
pa ien s
o
mo e?
Oph halmology.
2006;113:721–2.
15.
Wo ld
Medical
Associa ion.
Wo ld
Medical
Associa ion
decla a ion
o
Helsinki:
E hical
p inciples
o
medical
esea ch
in ol ing
human
subjec s.
JAMA.
2013;310:2191–4.
16.
The
Eu opean
Pa liamen
and
he
Council
o
he
Eu opean
Union.
Regula ion
(EU)
2016/679
o
he
Eu opean
Pa liamen
and
o
he
Council
o
he
Eu opean
Union
[In e ne ];
2016.
A ailable
om:
h ps://eu -lex.eu opa.eu/legal-con en /EN/TXT/PDF/?u i=CELEX:32016R0679
[ci ed
21.5.21].
17.
Sociedad
Espa˜
nola
de
Medicina
P e en i a
Salud
Pública
e
Higiene.
P e alencia
de
in ecciones
( elacionadas
con
la
asis encia
sani a ia
y
comuni a ias)
y
uso
de
an imic obianos
en
hospi ales
de
agudos.
2019.
18.
B i
NS,
Ri chie
DJ,
Kolle
MH,
Bu nham
CAD,
Du kin
MJ,
Hamp on
NB,
e
al.
Clinical
epidemiology
o
ca bapenem- esis an
G am-nega i e
sepsis
among
hospi alized
pa ien s:
Shi ing
bu den
o
disease?
Am
J
In ec
Con ol.
2018;46:1092–6.
19.
Fe e
R,
So iano
A,
Can ón
R,
Del
Pozo
JL,
Ga cía-Vidal
C,
Ga nacho-Mon e o
J,
e
al.
A
sys ema ic
e iew
and
expe ’s
analysis
o
isk
ac o s
o
in ec ions
in
adul s
due
o
ca bapenem- esis an
Pseudomonas
ae uginosa
o
Acine obac e
baumannii
in
Spain.
Re
Espa˜
nola
Quimio e .
2021;34:298–307.
20.
Li
J,
Li
Y,
Song
N,
Chen
Y.
Risk
ac o s
o
ca bapenem- esis an
Klebsiella
pneu-
moniae
In ec ion:
a
me a-analysis.
J
Glob
An imic ob
Resis .
2020;21:306–13.
21.
Mal ezou
HC,
Kon opidou
F,
Ka e elos
P,
Daikos
G,
Roilides
E,
Theodo idou
M.
In ec ions
caused
by
ca bapenem- esis an
G am-nega i e
pa hogens
in
hospi-
alized
F
child en.
Pedia
In ec
Dis
J.
2013;32:e151–4.
22.
Vincen
JL.
Nosocomial
in ec ions
in
adul
in ensi e-ca e
uni s.
Lance .
2003;361:2068–77.
23.
Sociedad
Espa˜
nola
de
Medicina
In ensi a
C í ica
y
Unidades
Co ona ias
(SEMI-
CYUC),
G upo
de
abajo
de
En e medades
In ecciosas
y
Sepsis.
ENVIN
HELICS
–
Es udio
nacional
de
igilancia
de
in ección
nosocomial
en
se icios
de
Medicina
In ensi a;
2020.
24.
Zhu
WM,
Yuan
Z,
Zhou
HY.
Risk
ac o s
o
ca bapenem- esis an
Klebsiella
pneumoniae
in ec ion
ela i e
o
wo
ypes
o
con ol
pa ien s:
a
sys ema ic
e iew
and
me a-analysis.
An imic ob
Resis
In ec
Con ol.
2020;9:23.
25.
Codjoe
F,
Donko
E.
Ca bapenem
esis ance:
a
e iew.
Med
Sci
(Basel).
2017;6:1,
h p://dx.doi.o g/10.3390/medsci6010001.
26.
Wanis
M,
Walke
SAN,
Daneman
N,
Elligsen
M,
Palmay
L,
Simo
A,
e
al.
Impac
o
hospi al
leng h
o
s ay
on
he
dis ibu ion
o
G am-nega i e
bac e ia
and
likelihood
o
isola ing
a
esis an
o ganism
in
a
Canadian
bu n
cen e .
Bu ns.
2016;42:104–11.
27.
Giske
CG,
Monne
DL,
Ca s
O,
Ca meli
Y.
Clinical
and
economic
impac
o
com-
mon
mul id ug- esis an
G am-nega i e
bacilli.
An imic ob
Agen s
Chemo he .
2008;52:813–21.
28.
Basse i
M,
Echols
R,
Ma sunaga
Y,
A iyasu
M,
Doi
Y,
Fe e
R,
e
al.
E ficacy
and
sa e y
o
cefide ocol
o
bes
a ailable
he apy
o
he
ea men
o
se ious
in ec-
ions
caused
by
ca bapenem- esis an
G am-nega i e
bac e ia
(CREDIBLE-CR):
a
andomised,
open-label,
mul icen e,
pa hogen- ocused,
desc ip i e,
phase
3
ial.
Lance
In ec
Dis.
2021;21:226–40.
29.
Gasink
L,
B ennan
P.
Isola ion
p ecau ions
o
an ibio ic- esis an
bac e ia
in
heal hca e
se ings.
Cu
Opin
In ec
Dis.
2009;22:339–44.
30.
Eu opean
Medicines
Agency.
ICH
Topic
E
2
A
Clinical
Sa e y
Da a
Managemen :
Defini ions
and
S anda ds
o
Expedi ed
Repo ing
[In e ne ];
1995.
A ailable
om:
h p://www.emea.eu.in
[ci ed
9.9.21].
168