Sepsis- ela ed
mo ali y
in
497
cases
wi h
blood
cul u e-posi i e
sepsis
in
an
eme gency
depa men
Juha
Rannikko
a,
*,
Jaana
Sy jänen
a
,
Tapio
Seiska i
b
,
Janne
Ai oniemi
b
,
Ree a
Hu unen
a
a
Depa men
o
In e nal
Medicine,
Tampe e
Uni e si y
Hospi al,
Box
2000,
FI-33521
Tampe e,
Finland
b
Depa men
o
Clinical
Mic obiology,
Fimlab
Labo a o ies,
Tampe e,
Finland
A
R
T
I
C
L
E
I
N
F
O
A icle
his o y:
Recei ed
14
Decembe
2016
Recei ed
in
e ised
o m
15
Feb ua y
2017
Accep ed
5
Ma ch
2017
Co esponding
Edi o :
Eskild
Pe e sen,
Aa hus,
Denma k
Keywo ds:
A ibu able
mo ali y
Blood
cul u e
In ec ious
disease
Rela ed
mo ali y
Sepsis
Su i al
qSOFA
S
U
M
M
A
R
Y
Objec i e:
Few
s udies
ha e
sough
o
es ablish
how
o en
dea h
a e
sepsis
is
ela ed
o
he
sepsis
and
how
o en
unde lying
diseases
ha e
a
majo
ole
in
case
a ali y.
Me hods:
In
his
e ospec i e
coho
s udy,
da a
we e
collec ed
on
497
cases
wi h
blood
cul u e-posi i e
sepsis
in
an
eme gency
depa men
(ED).
Resul s:
Sepsis
was
ca ego ized
as
se e e
in
31%
o
cases;
7%
had
sep ic
shock.
The
quick
Sepsis- ela ed
O gan
Failu e
Assessmen
sco e
was
posi i e
in
136
ou
o
473
cases
(29%).
Nine y-eigh
pa ien s
died
by
day
90;
in
16
o
hese
cases
(16%)
he
dea h
was
sepsis- ela ed
in
a
pa ien
wi hou
a
apidly
a al
unde lying
disease,
in
45
cases
(46%)
he
dea h
was
sepsis- ela ed
in
a
pa ien
wi h
a
apidly
a al
unde lying
disease,
and
in
37
cases
(38%)
he
dea h
was
un ela ed
o
sepsis.
Sepsis- ela ed
dea h
occu ed
in
58
ou
o
61
cases
(95%)
by
day
28.
Conclusions:
Unde lying
diseases
we e
ound
o
ha e
a
conside able
ole
in
he
dea h
o
pa ien s
su e ing
om
blood
cul u e-posi i e
sepsis
in
an
ED
o
a
de eloped
coun y,
as
only
16%
o
he
dea hs
by
day
90
occu ed
whe e
dea h
was
sepsis- ela ed
and
he
pa ien
had
a
li e-expec ancy
o
mo e
han
6
mon hs.
Imp o ing
he
ou come
o
sepsis
wi h
new
ea men s
is
hus
challenging.
I
is
possible
ha
day
7
+
day
28
mo ali y
is
a
mo e
app op ia e
endpoin
han
day
90
mo ali y
when
s udying
he
ou come
o
sepsis,
as
his
ime-span
includes
mos
o
he
pa ien s
whose
dea h
was
ela ed
o
sepsis.
©
2017
The
Au ho s.
Published
by
Else ie
L d
on
behal
o
In e na ional
Socie y
o
In ec ious
Diseases.
This
is
an
open
access
a icle
unde
he
CC
BY-NC-ND
license
(h p://c ea i ecommons.o g/licenses/by-
nc-nd/4.0/).
In oduc ion
Sepsis
is
one
o
he
leading
causes
o
dea h
wo ldwide.
I
has
been
anked
as
he
ele en h
mos
common
cause
o
dea h
in
he
USA.
1
Ad anced
age,
immunosupp ession,
diabe es,
and
cance
a e
majo
isk
ac o s
o
sepsis.
2–6
P ognos ic
ac o s
o
he
se e i y
and
ou come
o
sepsis
include
ad anced
age,
ype
o
in ec ion
(e.g.,
me hicillin- esis an
S aphylococcus
au eus
(MRSA),
polymic o-
bial),
numbe
o
o gan
dys unc ions,
and
adequacy
o
an imic obial
he apy.
7–9
S udies
ha e
been
pe o med
on
sepsis
pa ien s
in
eme gency
depa men s
(EDs)
and
in ensi e
ca e
uni s
(ICUs)
in
o de
o
de e mine
isk
ac o s
o
mo ali y
9–13
and
he
ae iology
o
illness.
14
Less
a en ion
has
been
paid
o
he
ques ions
o
how
o en
hese
pa ien s
ac ually
die
o
sepsis,
how
o en
sepsis
is
a
con ibu o y
ac o
in
he
dea h
o
a
pa ien
wi h
an
ad anced
unde lying
disease,
and
how
o en
he
dea h
is
independen
o
sepsis.
In
his
e ospec i e
coho
s udy,
da a
we e
collec ed
on
497
adul
cases
o
blood
cul u e-posi i e
sepsis
in
he
ED
o
Tampe e
Uni e si y
Hospi al
(TAUH).
A
ca ego iza ion
o
causes
o
dea h
was
de eloped
in
o de
o
es ablish
how
o en
dea h
was
ela ed
o
sepsis
in
pa ien s
wi hou
a
apidly
a al
unde lying
disease
(g oup
1),
was
ela ed
o
sepsis
by
weakening
o
a
pa ien
wi h
a
apidly
a al
unde lying
disease
(g oup
2),
and
was
independen
o
sepsis
bu
caused
by
he
unde lying
disease
(g oup
3).
I
was
also
sough
o
de e mine
he
bes
cu -o
among
he
commonly
used
days
o
mo ali y
used
in
sepsis
esea ch,
i.e.
day
7,
day
28,
o
day
90,
o
mo ali y
ela ed
o
sepsis
(dea hs
in
g oups
1
and
2).
Ma e ials
and
me hods
TAUH
is
a
e ia y
hospi al
wi h
a
ca chmen
popula ion
o
app oxima ely
524
700
inhabi an s
in
Pi kanmaa
Coun y.
The
ED
o
* Co esponding
au ho .
Tel:
+358
3
31166747,
Fax:
+358
3
31164333.
E-mail
add ess:
[email p o ec ed]
(J.
Rannikko).
h p://dx.doi.o g/10.1016/j.ijid.2017.03.005
1201-9712/©
2017
The
Au ho s.
Published
by
Else ie
L d
on
behal
o
In e na ional
Socie y
o
In ec ious
Diseases.
This
is
an
open
access
a icle
unde
he
CC
BY-NC-ND
license
(h p://c ea i ecommons.o g/licenses/by-nc-nd/4.0/).
In e na ional
Jou nal
o
In ec ious
Diseases
58
(2017)
52–57
Con en s
lis s
a ailable
a
ScienceDi ec
In e na ional
Jou nal
o
In ec ious
Diseases
jou nal
homepage:
www.else ie .com/loca e/ijid
he
hospi al
handles
pa ien s
equi ing
bo h
basic
and
specialized
eme gency
ca e.
In
specialized
ca e,
he
majo i y
o
pa ien s
a e
in e nal
medicine
and
su gical
pa ien s.
Blood
cul u es
a e
aken
ou inely
om
pa ien s
wi h
signs
o
symp oms
o
sys emic
in ec ion.
The
popula ion
o
he
p esen
s udy
comp ised
497
adul
pa ien s
admi ed
o
he
ED
o
TAUH
and
ea ed
in
specialized
ca e,
who
had
blood
cul u e-posi i e
sepsis
du ing
he
pe iod
Ma ch
1,
2012
o
Feb ua y
28,
2014.
The
s udy
was
app o ed
by
he
E hics
Commi ee
o
Tampe e
Uni e si y
Hospi al.
The
need
o
in o med
consen
was
wai ed,
as
no
addi ional
blood
sampling
was
needed
and
ou ine
pa ien
ca e
was
no
modified.
TAUH
has
a
24-bed
ICU
which
includes
a
se en-bed
high
dependency
uni
(HDU).
In
his
a icle,
‘ICU’
e e s
o
bo h
o
hese.
The e
a e
ou
o he
HDUs
(ca diology,
pulmona y,
su gical,
and
in e nal
medicine),
all
aking
ca e
o
sepsis
pa ien s;
hese
a e
e e ed
o
as
‘HDUs’.
Blood
cul u es
we e
collec ed
in
BacT/Ale
Ae obic
(FA
Plus)
and
Anae obic
(FN
Plus)
blood
cul u e
bo les
and
placed
in
he
au oma ed
mic obial
de ec ion
sys em
BacT/Ale
3D
(bioMé ieux,
Ma cy
l’E oile,
F ance).
All
pa ien s
wi h
a
posi i e
blood
cul u e
ob ained
du ing
specialized
ca e
in
he
ED
we e
iden ified
in
he
mic obiology
labo a o y
se ing
TAUH
(Fimlab
Labo a o ies
plc).
Pa ien
de ails,
he
name
o
he
o ganism,
and
he
da e
o
blood
cul u e
we e
collec ed
by
clinical
mic obiologis s
(T.S.
and
J.A.).
Cul u es
posi i e
o
coagulase-nega i e
S aphylococcus,
P opio-
nibac e ium,
Mic ococcus,
Bacillus,
and
Co ynebac e ium,
wi h
de ec ion
in
a
single
blood
cul u e
bo le
and
wi hou
clinical
ele ance,
we e
conside ed
o
be
con aminan s
and
we e
excluded.
Pa ien s
whose
ou ine
blood
samples
aken
on
admission
we e
no
longe
a ailable
o
u he
s udies
we e
also
excluded.
This
could
be
due,
o
example,
o
he
ac
ha
he
blood
cul u e
became
posi i e
la e
han
72
h
a e
he
day
o
admission.
The
clinical
da a
o
he
pa ien s
included
in
he
s udy
we e
ga he ed
e ospec i ely
om
he
pa ien
eco ds
by
he
p incipal
in es iga o
(J.R.).
The
si e
o
in ec ion
was
decided
e ospec i ely
by
he
p incipal
in es iga o
based
on
clinical
judgemen .
Sepsis
was
deemed
o
be
heal hca e-associa ed
i
he
symp oms
had
s a ed
mo e
han
48
h
a e
admission
o
a
heal hca e
ins i u ion,
o
he
bac e aemia
was
ela ed
o
a
su gical
ope a ion
wi hin
he
p eceding
30
days
o
some
o he
in asi e
p ocedu e
wi hin
he
p e ious
10
days.
15
Da a
on
cause
o
dea h
we e
ga he ed
om
pa ien
eco ds
(and
au opsy
eco ds
when
applicable)
by
wo
clinicians
(J.R.
and
R.H.)
independen ly.
In
cases
o
disc epancy,
a
mee ing
was
held
oge he
wi h
a
hi d
clinician
(J.S.)
and
a
final
decision
was
made.
Cause
o
dea h
by
day
90
was
classified
in o
h ee
di e en
ca ego ies:
(1)
g oup
1
included
cases
o
sepsis- ela ed
mo ali y
in
pa ien s
wi hou
a
apidly
a al
unde lying
disease.
The
immedia e
cause
o
dea h
in
his
g oup
was
sepsis,
o
sepsis
was
a
ac o
in
a
chain
o
e en s
leading
o
dea h,
and
he
pa ien
had
a
li e-
expec ancy
o
mo e
han
6
mon hs.
(2)
G oup
2
included
cases
o
sepsis- ela ed
mo ali y
in
pa ien s
wi h
a
apidly
a al
unde lying
disease.
In
his
g oup,
he
pa ien
died
o
sepsis
(immedia e
cause
o
dea h,
o
sepsis
was
a
ac o
in
a
chain
o
e en s
leading
o
dea h)
by
weakening
o
a
pa ien
wi h
a
apidly
a al
(<6
mon hs)
unde lying
disease.
(3)
G oup
3
included
cases
o
mo ali y
ela ed
o
unde lying
disease.
In
his
g oup,
sepsis
was
no
an
immedia e
cause
o
dea h
o
a
ac o
in
a
chain
o
e en s
leading
o
dea h.
The
ca ego iza ion
was
based
on
clinical
decision
and
he
judgemen
was
based
on
he
se e i y
o
he
pa ien ’s
unde lying
disease,
he
pa ien ’s
p e-pe o mance,
se e i y
o
he
sepsis,
and
eco e y
a e
he
in ec ion.
The
main
unde lying
disease
associa ed
wi h
dea h
was
de e mined
e ospec i ely
by
he
p incipal
in es iga o .
Diagnoses
o
sepsis,
se e e
sepsis,
and
sep ic
shock
we e
made
acco ding
o
consensus
defini ions.
16
Fu he ,
he
quick
Sepsis-
ela ed
O gan
Failu e
Assessmen
sco e
(qSOFA)
was
calcula ed
pos -hoc
acco ding
o
ecen ly
published
defini ions.
17
The
qSOFA
sco e
was
posi i e
i
a
leas
wo
o
he
ollowing
h ee
c i e ia
we e
ulfilled
in
he
ED:
espi a o y
a e
22/min,
al e ed
men a ion,
and
sys olic
blood
p essu e
100
mmHg.
The
McCabe
classifica ion
was
de e mined
as
epo ed
by
McCabe
and
Jackson.
18
The
Pi
bac e aemia
sco e
was
calcula ed
as
p esen ed
by
Ko ick
e
al.
19
IBM
SPSS
e sion
22.0
so wa e
(IBM
Co p.,
A monk,
NY,
USA)
was
used
o
he
s a is ical
analyses.
Ca ego ical
da a
we e
analyzed
by
Chi-squa e
es ,
o
Fishe ’s
exac
es
when
app op ia e.
Odds
a ios
(OR)
wi h
95%
confidence
in e als
(95%
CI)
a e
also
p esen ed.
Resul s
The e
we e
800
consecu i e
posi i e
blood
cul u es
in
adul
pa ien s
du ing
he
s udy
pe iod.
One
hund ed
and
hi y-six
o
hese
we e
conside ed
o
be
con aminan s
and
167
we e
excluded
o
o he
easons.
A
o al
497
cases
o
posi i e
blood
cul u e
among
484
pa ien s
we e
hus
included.
All
497
cases
had
sepsis.
Du ing
he
s udy
pe iod,
11
pa ien s
had
sepsis
wice
on
di e en
admissions
and
one
pa ien
had
sepsis
h ee
imes.
O
he
o al
s udy
popula ion,
262
(53%)
we e
male
and
235
(47%)
we e
emale;
hey
anged
in
age
om
16
o
95
yea s
(median
68
yea s).
Table
1
p o ides
he
demog aphic
da a,
da a
on
he
causa i e
o ganisms,
and
da a
on
he
unde lying
diseases
s a ified
in o
six
di e en
ca ego ies:
g oups
1,
2,
and
3
(as
no ed
in
he
Ma e ials
and
me hods
sec ion),
all
pa ien s
who
died,
all
pa ien s
who
su i ed,
and
all
cases.
Fo
16
ou
o
98
pa ien s
(16%)
who
died
by
day
90,
dea h
was
ela ed
o
sepsis
and
he
pa ien
did
no
ha e
a
apidly
a al
unde lying
disease
(g oup
1),
i.e.
3%
o
all
497
sepsis
cases.
Fo
45
pa ien s
(46%
o
all
dea hs
by
day
90),
dea h
was
ela ed
o
sepsis
in
ha
i
weakened
he
pa ien
leading
o
he
dea h,
which
was
in
any
case
expec ed
as
he
pa ien
had
a
apidly
a al
unde lying
disease
(g oup
2).
Fo
37
pa ien s
(38%),
dea h
by
day
90
was
un ela ed
o
sepsis
and
was
caused
by
an
unde lying
disease(s)
in
he
pa ien
(g oup
3).
O
he
g oup
1
pa ien s,
ou
(25%)
had
alcohol
abuse
as
an
unde lying
disease
(Table
1).
One
was
wi hou
any
unde lying
disease.
Fou
o
he
pa ien s
in
g oup
1
we e
o e
80
yea s
o
age
(25%).
Th ee
g oup
1
pa ien s
(19%)
we e
ound
lying
a
home
wi h
a
low
le el
o
consciousness
and
we e
ans e ed
o
hospi al.
In
g oup
2
pa ien s,
he
apidly
a al
unde lying
disease
was
a
solid
umou
wi h
me as asis
in
eigh
cases
(18%)
and
a
haema ological
malignancy
in
nine
(20%).
In
g oup
3
pa ien s,
he
cause
o
dea h
was
a
solid
umou
wi h
me as asis
in
19
pa ien s
(51%)
and
a
haema ological
malignancy
in
wo
(5%).
Thus,
malignancies
we e
associa ed
wi h
dea h
in
46%
o
pa ien s
in
g oups
2
and
3
combined.
O he
common
apidly
a al
unde lying
diseases
associa ed
wi h
dea h
among
he
pa ien s
in
g oups
2
and
3
we e
li e
disease
(11%),
hea
disease
(11%),
and
neu ological/neu o-
su gical
disease
(10%).
The
case
a ali y
a e
by
day
7,
day
28,
and
day
90
was
9%,
14%,
and
20%,
espec i ely.
Dea h
occu ed
by
day
7
in
94%
o
g oup
1
pa ien s,
in
56%
o
g oup
2
pa ien s,
and
in
11%
o
g oup
3
pa ien s
(Figu e
1).
All
excep
wo
cases
in
g oup
2
died
be o e
day
28.
The
dea hs
in
g oup
3
occu ed
mos
o en
be ween
day
29
and
day
90
(68%).
Nine y-fi e
pe
cen
o
all
sepsis- ela ed
dea hs
occu ed
wi hin
28
days
a e
sepsis.
Table
2
gi es
da a
on
he
se e i y
o
sepsis
s a ified
in o
he
same
ca ego ies
as
used
in
Table
1.
The
qSOFA
was
posi i e
in
136
ou
o
473
cases
(29%).
G oup
1
had
he
highes
Pi
bac e aemia
sco es.
Fo y-eigh
(10%)
cases
we e
ans e ed
om
he
ED
o
he
ICU
and
52
(11%)
o
HDUs.
Thus,
he
majo i y
o
sepsis
pa ien s
and
he
majo i y
o
qSOFA-posi i e
cases
we e
aken
ca e
o
in
gene al
wa ds.
Ou
o
449
cases
who
we e
ea ed
ou side
he
ICU,
104
J.
Rannikko
e
al.
/
In e na ional
Jou nal
o
In ec ious
Diseases
58
(2017)
52–57
53
(23%)
had
se e e
sepsis
and
nine
(2%)
had
sep ic
shock.
O
hose
wi h
sep ic
shock,
h ee
died
in
he
ED
and
he
emainde
had
unde lying
diseases
ha
had
p og essed
oo
a
o
hem
o
benefi
om
ea men
in
he
ICU.
By
si e
o
in ec ion,
he
mos
common
in ec ion
was
u ina y
ac
in ec ion
(131
cases,
26%),
ollowed
by
in a-abdominal
in ec ion
(84
cases,
17%),
in ec ion
o
he
skin,
so
issues,
and
bones
(72
cases,
15%),
and
lowe
espi a o y
ac
in ec ion
(54
cases,
11%).
The
si e
o
in ec ion
was
unknown
in
118
cases
Table
1
Cha ac e is ics
unde lying
diseases,
and
causa i e
o ganisms
in
ela ion
o
he
ou come.
Sepsis- ela ed
mo ali y
in
pa ien s
wi hou
a
apidly
a al
unde lying
disease
(G oup
1)
(n
=
16)
Sepsis- ela ed
mo ali y
in
pa ien s
wi h
a
apidly
a al
unde lying
disease
(G oup
2)
(n
=
45)
Mo ali y
ela ed
o
unde lying
disease
(G oup
3)
(n
=
37)
All
pa ien s
who
died
(n
=
98)
Pa ien s
who
su i ed
(n
=
399)
All
cases
(N
=
497)
n
(%)
n
(%)
n
(%)
n
(%)
n
(%)
n
(%)
Median
age,
yea s
( ange)
77
(51–94)
78
(42–93)
70
(44–91)
74
(42–94)
68
(16–95)
68
(16–95)
Male
sex
8
(50)
24
(53)
25
(68)
57
(58)
205
(51)
262
(53)
Unde lying
diseases
Hea
disease
8
(50)
23
(51)
10
(27)
41
(42)
135
(34)
176
(35)
Diabe es
melli us,
any
ype
6
(38)
15
(33)
13
(35)
34
(34)
105
(26)
139
(28)
Neu ological
5
(31)
14
(31)
9
(24)
28
(29)
84
(21)
112
(23)
Solid
umou
wi h
me as asis
a
1
(6)
10
(22)
17
(46)
28
(29)
29
(7)
57
(12)
Alcohol
abuse
b
4
(25)
5
(11)
8
(22)
17
(17)
35
(9)
52
(11)
Li e
disease
3
(19)
8
(18)
6
(16)
17
(17)
32
(8)
49
(10)
Haema ological
malignancy
0
(0)
11
(24)
4
(11)
15
(15)
30
(8)
45
(9)
No
unde lying
diseases
1
(6)
0
(0)
0
(0)
1(6)
70
(14)
71
(14)
Causa i e
o ganism
c
G am-posi i e
5
(31)
18
(40)
13
(35)
36
(37)
189
(47)
225
(45)
G am-nega i e
9
(56)
19
(42)
14
(38)
42
(43)
181
(45)
223
(45)
Esche ichia
coli
u osepsis
3
(19)
6
(13)
3
(8)
12
(12)
85
(21)
97
(20)
Polymic obial
and
anae obes
2
(13)
8
(18)
10
(27)
20
(20)
28
(7)
48
(10)
a
The
mos
common
solid
umou
wi h
me as asis
was
cance
o
he
gas oin es inal
ac
(36
cases).
b
Social
o
medical
p oblems
o
alcohol
abuse
in
he
pas
12
mon hs.
c
Excluding
ungi
(n
=
1).
N=15
94%
N=0
0%
N=1
6%
N=25
56%
N=18
40%
N=2
4%
N=4
11%
N=8
22%
N=25
68%
0
5
10
15
20
25
30
Days 0-7
Days 8-
28
Days 29
-90
Sepsis- ela ed
mo al
i y
in
pa ie
n s wi hou a
api
dly
a al un
de lyi
ng diseas
e (G oup 1)
Sepsis- ela ed
mo al
i y
in
pa ie
n s wi h a api
dly
a al un
de lyi
ng diseas
e (G oup 2)
Unde
lyin
g disease
– ela
ed
mo ali y (G oup 3)
Figu e
1.
Numbe
o
cases
in
g oups
1,
2,
and
3
in
ela ion
o
day
o
case
a ali y
in
a
o al
o
98
pa ien s
who
died
wi hin
90
days
a e
sepsis.
The
pe cen age
is
pe
ca ego y
o
cause
o
dea h.
54
J.
Rannikko
e
al.
/
In e na ional
Jou nal
o
In ec ious
Diseases
58
(2017)
52–57
(24%).
Sepsis
was
heal hca e-associa ed
in
81
pa ien s
(16%).
The
p e ious
use
o
immunosupp essi e
medica ions
was
common:
94
(19%)
pa ien s
we e
aking
co icos e oids
(any
dose)
and
56
(11%)
we e
on
cance
chemo he apy.
An ibio ics
we e
s a ed
on
he
day
o
admission
in
93%
o
pa ien s.
The
mos
common
an ibio ic
was
ce u oxime
(57%),
ollowed
by
ce iaxone
(18%)
and
fluo oquinolone
(11%).
An
an ibio ic
combina ion
was
s a ed
in
16%
o
pa ien s.
The
median
ime
om
admission
o
he
s a
o
an ibio ics
was
174
min
( ange
0–1269
min).
O
all
cases,
426
(86%)
had
one
o
mo e
unde lying
diseases.
As
shown
in
Table
1,
he e
we e
significan ly
mo e
alcohol
abuse s
in
g oup
1
as
compa ed
o
hose
who
su i ed
o
mo e
han
90
days
(4/16
s.
35/399;
OR
3.8,
95%
CI
1.2–12.4,
p
=
0.04).
The e
we e
also
significan ly
mo e
pa ien s
wi h
a
solid
umou
wi h
me as asis
and
pa ien s
wi h
haema ological
malignancies
among
hose
who
died
by
day
90
han
among
su i o s
(28/98
s.
29/399,
OR
5.1,
95%
CI
2.9–9.1,
p
<
0.01
and
15/98
s.
30/399,
OR
2.2,
95%
CI
1.1–4.3,
p
=
0.02,
espec i ely).
The
causa i e
o ganisms
a e
lis ed
in
Table
3.
G am-posi i e
and
G am-nega i e
o ganisms
we e
equally
common.
The e
we e
ew
cases
wi h
MRSA
and
ex ended-spec um
be a-lac amase-p oduc-
ing
En e obac e iaceae
and
no
cases
wi h
ancomycin- esis an
en e ococci
o
ca bapenemase-p oducing
En e obac e iaceae.
Discussion
In
his
s udy,
he
case
a ali y
a e
by
day
7,
day
28,
and
day
90
was
9%,
14%,
and
20%,
espec i ely,
in
497
cases
wi h
blood
cul u e-posi i e
sepsis
ea ed
in
an
ED.
The
day
7
and
day
28
case
a ali y
a es
in
his
s udy
a e
simila
o
hose
epo ed
in
a
s udy
by
Lin
e
al.,
who
also
s udied
bac e aemic
pa ien s
in
he
ED.
9
In
wo
o he
s udies
in es iga ing
he
day
28
case
a ali y
a e
in
bac e aemic
pa ien s
in
he
ED,
Lee
e
al.
epo ed
a
a e
o
9%
and
Kao
e
al.
epo ed
a
a e
o
19%.
12,20
Only
16%
o
all
dea hs
by
day
90
in
he
p esen
s udy
we e
ela ed
o
sepsis
in
pa ien s
wi h
a
li e-expec ancy
o
mo e
han
6
mon hs
(g oup
1).
Fo y-six
pe cen
o
dea hs
occu ed
in
pa ien s
wi h
a
apidly
a al
unde lying
disease
al hough
dea h
was
sepsis-
ela ed
(g oup
2),
and
38%
o
dea hs
we e
ela ed
o
he
unde lying
disease
(g oup
3).
I
is
known
ha
unde lying
diseases
ha e
a
ole
in
he
dea hs
o
sepsis
pa ien s,
2–4,9
bu
he
ca ego iza ion
o
he
p esen
s udy
gi es
a
pic u e
o
he
significance
o
he
unde lying
diseases
in
hese
dea hs.
E en
pa ien s
in
g oup
1
had
many
ac o s
con ibu ing
o
dea h,
o
example
alcoholism
o
e y
old
age.
The e
was
only
one
pa ien
in
his
g oup
wi hou
any
unde lying
disease.
I
is
possible
ha
he e
we e
pa ien s
in
g oup
1
who
sough
ea men
oo
la e,
as
h ee
pa ien s
in
his
g oup
we e
ound
lying
a
home
wi h
a
low
le el
o
consciousness.
The e
we e
also
significan ly
mo e
alcohol
abuse s
as
compa ed
o
hose
who
su i ed
mo e
han
90
days.
Al oge he ,
in
his
coho
consis ing
mos ly
o
communi y-
acqui ed
cases
seen
in
a
uni e si y
hospi al
ED
in
a
de eloped
coun y,
he e
we e
ew
non-su i o s
who
would
ha e
had
a
li e-
expec ancy
o
mo e
han
6
mon hs
and
who
migh
ha e
benefi ed
om
a
no el
d ug
di ec ed
agains
sepsis
o
sep ic
shock.
This
may
also
explain
why
so
many
clinical
ials
in
he
field
o
sepsis
ha e
ailed.
21
Day
90
mo ali y
has
been
used
as
he
endpoin
in
many
sepsis
s udies.
22–24
Howe e ,
he
p esen
s udy
showed
ha
mos
(95%)
o
he
pa ien s
whose
dea h
was
sepsis- ela ed
died
wi hin
28
days
a e
sepsis,
while
he
majo i y
o
dea hs
occu ing
be ween
day
28
Table
2
Se e i y
o
he
sepsis
in
ela ion
o
he
ou come.
Sepsis- ela ed
mo ali y
in
pa ien s
wi hou
a
apidly
a al
unde lying
disease
(G oup
1)
(n
=
16)
Sepsis- ela ed
mo ali y
in
pa ien s
wi h
a
apidly
a al
unde lying
disease
(G oup
2)
(n
=
45)
Mo ali y
ela ed
o
unde lying
disease
(G oup
3)
(n
=
37)
All
pa ien s
who
died
(n
=
98)
Pa ien s
who
su i ed
(n
=
399)
All
cases
(N
=
497)
n
(%)
n
(%)
n
(%)
n
(%)
n
(%)
n
(%)
Se e e
sepsis
16
(100)
30
(67)
13
(35)
59
(60)
93
(23)
152
(31)
Sep ic
shock
9
(56)
9
(20)
4
(11)
22
(22)
15
(4)
37
(7)
qSOFA-posi i e
a
13
(81)
26
(59)
16
(46)
55
(58)
81
(21)
136
(29)
Admi ed
om
ED
o
ICU
11
(69)
7
(16)
3
(8)
21
(21)
27
(7)
48
(10)
Pi
bac e aemia
sco e
b
0–1
1
(6)
16
(36)
20
(57)
37
(39)
269
(68)
306
(62)
2–3
3
(19)
17
(39)
10
(29)
30
(32)
93
(24)
123
(25)
4
12
(75)
11
(25)
5
(14)
28
(29)
33
(8)
61
(12)
ED,
eme gency
depa men ;
ICU,
in ensi e
ca e
uni ;
qSOFA,
quick
sepsis- ela ed
o gan
ailu e
assessmen .
a
Da a
a ailable
o
473
cases
(95
who
died
and
378
who
su i ed).
b
Da a
a ailable
o
490
cases.
Table
3
Causa i e
o ganisms.
O ganisms
n
(%)
G am-posi i e
225
(45.3)
S aphylococcus
au eus
74
(14.9)
MRSA
3
(0.6)
Coagulase-nega i e
S aphylococcus
11
(2.2)
S ep ococcus
pneumoniae
52
(10.5)
b
-haemoly ic
s ep ococci
45
(9.1)
Vi idans
s ep ococci
21
(4.2)
En e ococci
17
(3.4)
O he
G am-posi i e
5
(1.0)
G am-nega i e
223
(44.9)
Esche ichia
coli
159
(32.0)
ESBL-E.
coli
9
(1.8)
Klebsiella
sp
21
(4.2)
ESBL-Klebsiella
sp
0
(0.0)
Pseudomonas
ae uginosa
18
(3.6)
O he
G am-nega i e
25
(5.0)
O he s
49
(9.9)
Anae obes
15
(3.0)
Fungi
1
(0.2)
Polymic obial
33
(6.6)
All
497
(100)
MRSA,
me hicillin- esis an
S aphylococcus
au eus;
ESBL,
ex ended-
spec um
be a-lac amase.
J.
Rannikko
e
al.
/
In e na ional
Jou nal
o
In ec ious
Diseases
58
(2017)
52–57
55
and
day
90
we e
independen
o
sepsis.
This
makes
day
28
a
mo e
app op ia e
ime-poin
o
in es iga e
sepsis- ela ed
mo ali y,
as
egula o y
agencies
ha e
indeed
conside ed.
21
None heless,
only
34%
o
dea hs
occu ing
be ween
day
0
and
day
7
we e
sepsis-
ela ed
in
pa ien s
wi h
a
li e-expec ancy
o
mo e
han
6
mon hs.
Thus,
e en
when
day
7
and
day
28
a e
used
as
endpoin s
o
sepsis
mo ali y,
dea hs
independen
o
sepsis
a e
no
uled
ou .
This
s udy
has
some
limi a ions.
By
eason
o
he
s udy
design,
i
was
no
possible
o
include
all
blood
cul u e-posi i e
cases
admi ed
o
he
ED
du ing
he
s udy
pe iod.
The
po en ial
ep esen a i eness
o
he
ma e ial
was
assessed
by
e iewing
he
blood
cul u e
findings
o
hose
cases
ha
we e
no
included
in
he
s udy.
Al oge he
he e
we e
167
such
cases
(con aminan s
excluded).
The
pe cen ages
o
he
mos
common
blood
cul u e
findings,
S.
au eus
and
Esche ichia
coli,
did
no
di e
be ween
he
s udy
popula ion
and
he
cases
ha
we e
no
included.
I
is
hus
unlikely
ha
missed
cases
would
ha e
had
a
majo
impac
on
he
esul s.
Among
cases
no
included
in
he
ma e ial
as
compa ed
o
hose
included,
he
pe cen age
o
anae obes
and
o he
G am-
nega i e
o ganisms
(see
Table
3)
was
somewha
highe
(9.0%
s.
3.0%
and
10.2%
s.
5.0%,
espec i ely)
and
he
pe cen age
o
S ep ococcus
pneumoniae
was
lowe
(4.2%
s.
10.5%).
This
may
be
due
o
he
long
incuba ion
pe iod
o
anae obes
and
o he
G am-
nega i e
o ganisms
and
he
sho
incuba ion
pe iod
o
S.
pneumo-
niae.
Again,
assuming
ha
case
a ali y
among
missed
cases
wi h
anae obes
o
o he
G am-nega i es
would
be
app oxima ely
he
same
as
among
hose
included
in
he
s udy,
he
numbe s
would
be
oo
low
o
al e
he
majo
findings
o
he
s udy.
Only
blood
cul u e-posi i e
cases
we e
included,
which
would
exclude
o
example
hose
wi h
alse-nega i e
blood
cul u es.
This
migh
also
ha e
led
o
a
lowe
numbe
o
sep ic
pa ien s
wi h
espi a o y
in ec ion.
Howe e ,
i
is
also
a
s eng h
ha
cul u e-
nega i e
sepsis
cases,
which
a e
di ficul
o
define,
we e
no
included.
Hence
he
ma e ial
consis s
mo e
o
ue
in ec ions
han
pa ien s
who
we e
o
example
only
posi i e
o
sys emic
inflamma o y
esponse
synd ome
(SIRS).
The
ma e ial
was
ga he ed
in
a
e ia y
le el
hospi al
o
a
de eloped
coun y
wi h
a
low
incidence
o
mul i- esis an
bac e ia.
These
ypes
o
esul s
canno ,
he e o e,
be
gene alized
o
low-income
coun ies,
as
has
been
poin ed
ou
by
Rello
and
Leblebicioglu.
25
I
is
possible
ha
he
ole
o
he
unde lying
diseases
would
also
ha e
been
di e en
i
he
s udy
pa ien s
had
been
only
om
ICUs.
The
me hod
used
o
ca ego ize
he
cause
o
dea h
was
de eloped
by
he
au ho s.
I
encompasses
he
classifica ion
used
on
he
dea h
ce ifica e
(immedia e
cause
and
unde lying
cause)
and
combines
i
wi h
he
McCabe
classifica ion
o
apidly
a al
disease.
This
has
limi a ions,
since
in
some
cases
i
was
no
easy
o
decide
whe he
he
pa ien
would
ha e
li ed
o
mo e
han
6
mon hs
wi hou
he
sepsis
o
no .
E en
g oup
1
pa ien s
we e
elde ly
and
had
many
unde lying
diseases.
Howe e ,
he
au ho s
belie e
ha
he
ca ego iza ion
used
is
illus a i e
o
he
cou se
o
e en s
among
hese
pa ien s,
and
he
use
o
wo
o
h ee
clinicians
o
p o ide
a
judgemen
gi es
i
su ficien
alidi y.
In
conclusion,
his
s udy
showed
ha
pa ien s
wi h
sepsis
who
die
wi hin
90
days
a e
sepsis
in
a
de eloped
coun y,
die
mos ly
ei he
o
sepsis
by
weakening
o
he
pa ien
wi h
a
apidly
a al
(<6
mon hs)
unde lying
disease,
o
o
he
unde lying
disease
i sel .
This
does
no
mean
ha
sepsis
pa ien s
do
no
need
high-quali y
ca e.
Indeed,
he
low
numbe
o
cases
o
sepsis- ela ed
mo ali y
among
pa ien s
wi h
a
li e-expec ancy
o
mo e
han
6
mon hs
may
be
a ibu ed
o
he
good
quali y
o
he
ca e
hese
pa ien s
ecei ed.
When
in es iga ing
sepsis- ela ed
mo ali y,
day
28
should
be
used
as
he
endpoin
o
iden i y
mos
o
he
sepsis- ela ed
mo ali y,
while
a
la ge
pa
o
sepsis-independen
mo ali y
is
uled
ou .
Funding
This
wo k
was
suppo ed
by
he
Compe i i e
Resea ch
Financing
o
Tampe e
Uni e si y
Hospi al
(g an
9N075
o
J.R.
and
X50060
o
J.A.).
The
au ho s’
wo k
was
independen
o
he
unde
( he
unding
sou ce
had
no
in ol emen ).
E hical
app o al
The
s udy
was
app o ed
by
he
E hics
Commi ee
o
Tampe e
Uni e si y
Hospi al.
Conflic
o
in e es
JR,
JS,
TS,
JA,
and
RH
epo
no
conflic
o
in e es .
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