Additional File 1.
Table 1 - Characteristics of included studies reporting mortality outcomes
Adjusted
Author
Baseline
covariates for
Year
Infecting pathogen
Comorbidity
Appropriate IAT definition
Mortality N
Total N
Mortality
(Country)
(%)
Mean Score
outcome
Cordery
65% had
ESBL E.coli;
Antibiotic administration ≤24 h
Disease severity,
after blood cultures
ESBL infection
APACHE ≥20 or
2008
Klebsiella spp
55
25 (45)
None
85
21 (25)
None
63
41 (65)
SOFA ≥5
(UK)[12]
Subsequent identification of the
Du 2002
infecting pathogen’s in vitro
E.coli;
APACHE II 15.6
(China)[13]
K.pneumoniae
susceptibility to the IV antibiotic
(timeframe NR)
Antibiotic administration ≤72 h
Edis 2010
Acinetobacter spp
NR
appropriate to the antibiogram of
(Turkey)[15]
the identified pathogen
1
Adjusted
Author
Baseline
covariates for
Year
Infecting pathogen
Comorbidity
Appropriate IAT definition
Mortality N
Total N
Mortality
(Country)
(%)
Mean Score
outcome
Erbay 2009
APACHE II score
Antibiotic administration using
Age>65 years,
proper dosage and route ≤48 h after
septic shock,
A.baumannii
(Turkey)[16]
13.3
a blood culture, with at least one
mechanical
active antibiotic susceptible in vitro
ventilation
103
56 (54)
40
19 (48)
49
29 (59)
Antibiotic administration ≤72 h
Falagas 2006
APACHE II score
after a blood culture to which the
A.baumannii
(Greece)[17]
None
16.2
infecting pathogen was susceptible
in vitro
ICU Infection,
Ferraz de
Gouvea 2012 A.baumannii
Antibiotic administration ≤48 h
mechanical
after diagnosis
ventilation,
NR
(Brazil)[14]
resistance to
2
Adjusted
Author
Baseline
covariates for
Year
Infecting pathogen
Comorbidity
Appropriate IAT definition
Mortality N
Total N
Mortality
(Country)
(%)
Mean Score
outcome
carbapenem
GarnachoAdministered at least one effective
Age; chronic
antibiotic based on in vitro
cardiac
susceptibility (timeframe NR)
insufficiency
Montero
P.aeruginosa
APACHE II 19.1
183
77 (42)
240
92 (38)
2007
(Spain)[18]
APACHE II
Ecoli; Klebsiella
score>20; Total
APACHE II score
spp.; P.aeruginosa;
Gozel 2012
Administered antibiotic to which
parenteral
the infecting pathogens were
nutrition;
susceptible (timeframe NR)
Unconsciousness,
survivors 17.2;
Acinetobacter spp.;
(Turkey)[19]
Non-survivors
Enterobacter spp.;
21.4
S. maltophilia
Thrombocytopeni
a
3
Adjusted
Author
Baseline
covariates for
Year
Infecting pathogen
Comorbidity
Appropriate IAT definition
Mortality N
Total N
Mortality
(Country)
(%)
Mean Score
outcome
Antibiotic administration ≤72 h of
Huang 2012
APACHE II score
A.baumannii
(Taiwan)[20]
APACHE II
blood collection to which the
>20
226
56 (25)
198
61 (31)
116
44 (38)
286
95 (33)
score>20; shock
infecting pathogen was susceptible
Jamulitrat
2010
Administered antibiotic based on in
A.baumannii
SOFA: 5
(Thailand)[2
vitro susceptibility ≤72 h of blood
None
collection
1]
Administered antibiotic ≤24 h that
Joung 2010
(South
APACHE II
APACHE II 22.3
included at least one active
Charlson 2.5
antibiotic according to the
A.baumannii
score>=20;
Korea)[22]
MDR; PDR
sensitivity test
Kang 2005
E.coli;
APACHE II 11.2
Administered antibiotic ≤24 h of
Septic shock;
4
Adjusted
Author
Baseline
covariates for
Year
Infecting pathogen
Comorbidity
Appropriate IAT definition
Mortality N
Total N
Mortality
(Country)
(%)
Mean Score
outcome
(South
K.pneumonia;
culture samples via an appropriate
bacteremia;
Korea)[23]
Enterobacter spp;
route and dosage to which the
P.aeruginosa
P.aeruginosa
infecting pathogens were
infection;
susceptible in vitro
increasing
APACHE score
Carbapenem-
Antibiotic administration ≤24 h of
septic shock;
Kim 2012
resistant
APACHE II 12.4
blood culture via an appropriate
carbapenem-
Acinetobacter.
Charlson 2.7
route and dosage based on in vitro
resistance;
susceptibility
pneumonia
(South
95
30 (32)
76
19 (25)
Korea)[24]
baumannii
Antibiotic-resistant
APACHE II Non-
Gram-negative
survivors 23.5;
bacteria
Survivors 15.5
APACHE II
Kollef 2008
NR
score; Septic
(USA)[25]
shock
5
Adjusted
Author
Baseline
covariates for
Year
Infecting pathogen
Comorbidity
Appropriate IAT definition
Mortality N
Total N
Mortality
(Country)
(%)
Mean Score
outcome
Antibiotic IV administration using
APACHE II Nonproper dosage ≤48 h after a blood
Kuo 2012
A.nosocomialis
survivors 31;
None
266
25 (9)
298
100 (34)
culture with ≥ one active antibiotic
(Taiwan)[26]
Survivors 18
that is in vitro susceptible
imipenemresistant
Lee 2014
Charlson score: 3
Administration ≤48 hr of onset with
infection, higher
APACHE II: Non-
at least one antimicrobial agent,
Pitt bacteremia
survivors 24.5;
except aminoglycoside, susceptible
score, and
Survivors 18
in vitro
catheter-related
A. baumannii
(Taiwan)[27]
infection or
urinary tract
6
Adjusted
Author
Baseline
covariates for
Year
Infecting pathogen
Comorbidity
Appropriate IAT definition
Mortality N
Total N
Mortality
(Country)
(%)
Mean Score
outcome
infection
Intravenous administration with
appropriate dose ≤ 72 h of
Lin 2009
C.meningosepticum
NR
(Taiwan)[28]
Septic shock
32
13 (41)
None
189
48 (25)
100
31 (31)
diagnosis of antibiotic to which the
microorganism was susceptible
Administration of in vitro active
antibiotic after the index blood
Lin 2011
K.pneumonia
NR
culture and before availability of
(Taiwan)[29]
susceptibility results (timeframe
NR)
Lodise 2007
P.aeruginosa
(USA)[30]
Administration of at least one
APACHE-II
intravenous antibiotic to which the
score; ICU at
APACHE II 17.1
7
Adjusted
Author
Baseline
covariates for
Year
Infecting pathogen
Comorbidity
Appropriate IAT definition
Mortality N
Total N
Mortality
(Country)
(%)
Mean Score
outcome
pathogen was susceptible
onset; mechanical
(timeframe for analysis >52h)
ventilation at
onset; decubitus
ulcers
Male gender;
E.coli;
APACHE II*
surgical
Prescribed appropriate doses ≤24 h
K.pneumonia;
Nonsurvivors
Lye 2012
discipline; higher
that had in vitro activity against all
P.aeruginosa;
14,survivors 9;
A.baumannii;
Charlson*
Enterobacter spp;
Nonsurvivors 9,
Proteus
survivors 7
(Singapore)[
charlson
isolated organisms based on
31]
671
146 (22)
comorbidity
Sanford Guide to Antimicrobial
index; Higher
Therapy of antibiotics
APACHE II
score; Pneumonia
8
Adjusted
Author
Baseline
covariates for
Year
Infecting pathogen
Comorbidity
Appropriate IAT definition
Mortality N
Total N
Mortality
(Country)
(%)
Mean Score
outcome
or UTI; ICU stay
Age, diabetes,
end stage renal
disease,
ventilator
Administration of at least one
support, platelet
antibiotic within 24-48 h that was
count<1.5 lac, S.
sensitive in vitro
creatinine 1.5,
Mehta 2012
Acinetobacter spp
NR
81
36 (44)
(India)[32]
Prothrombin
time>15 sec,
Blood urea
>40mg/dL,
9
Adjusted
Author
Baseline
covariates for
Year
Infecting pathogen
Comorbidity
Appropriate IAT definition
Mortality N
Total N
Mortality
(Country)
(%)
Mean Score
outcome
Carbapenem
resistance
Antibiotics active in vitro (except
None
ceftriaxone, cefotaxime and
Metan 2005
ESBL E.coli
NR
ceftazidime) administered with
53
14 (26)
100
63 (63)
154
30 (20)
(Turkey)[33]
appropriate dosage and route
(timeframe NR)
Administration ≤24 h of blood
Metan 2009
None
culture via appropriate dosage and
Acinetobacter spp
NR
(Turkey)[34]
route of one or more agents active
against infecting pathogen
Metan 2013
E.coli Klebsielle
NR
Administration with proper dosage
None
10
Adjusted
Author
Baseline
covariates for
Year
Infecting pathogen
Comorbidity
Appropriate IAT definition
Mortality N
Total N
Mortality
(Country)
(%)
Mean Score
outcome
(Turkey)[35]
spp.; P.aeruginosa;
and route of administration ≤24 h
Acinetobacter spp;
after blood sample collection that
S. maltophilia
was active in vitro (except
ceftriaxone, cefotaxime and
ceftazidime)
Race; infection
A positive blood culture result that
source; acute
SAP Survivors
was effectively treated with
renal failure;
10.9 Nonsurvivors
antibiotic at the time the pathogen
patient location;
13.8
and its susceptibility were known
respiratory
(timeframe NR)
failure;
Micek 2005
P.aeruginosa
305
64 (21)
(USA)[36]
circulatory shock;
11
Adjusted
Author
Baseline
covariates for
Year
Infecting pathogen
Comorbidity
Appropriate IAT definition
Mortality N
Total N
Mortality
(Country)
(%)
Mean Score
outcome
and SAP score
OXA-48-
Navarro-San
carbapenemase-
Administration of at least one
Francisco
producing
Charlson* 5
active agent against the isolate that
None
40
20 (50)
None
180
49 (27)
191
22 (12)
2012
K.pneumonia;
is susceptible (timeframe NR)
(Spain)[37]
E.coli
Administration ≤48 h of at least one
Park 2013
(South
Acinetobacter spp
APACHE II: 18
Korea)[39]
Pena 2008
was susceptible (timeframe NR)
Administration ≤48 h of at least one
Source of
antibiotic active in vitro against the
infection; type of
infecting microorganism
ESBL pathogen
ESBL and nonNR
(Spain)[40]
antibiotic to which the pathogen
ESBL E.coli
12
Adjusted
Author
Baseline
covariates for
Year
Infecting pathogen
Comorbidity
Appropriate IAT definition
Mortality N
Total N
Mortality
(Country)
(%)
Mean Score
outcome
Charlson: Non-
Administration ≤24 h of
survivor 2.6
antimicrobial therapy to which P.
Survivor 2.2
aeruginosa isolate was susceptible.
Pena 2013
P.aeruginosa
None
91
47 (52)
None
96
29 (30)
78
51 (65)
109
28 (26)
(Spain)[41]
Administration ≤24 h after blood
Rodriguezsample for culture was draw of
Bano 2010
ESBL E.coli
Charlson>2: 42%
active antibiotic at the
(Spain)[42]
recommended dosages
Antibiotic agents with correct
Su 2013
P.aeruginosa
dosage used ≤72 h and proved to be
Pittsburgh
effective in vitro against the
bacteremia score
Pittsburg 5.0
(Taiwan)[43]
infecting pathogen.
Tam
P.aeruginosa
APACHE II:
Administration with appropriate
Multidrug
13
Adjusted
Author
Baseline
covariates for
Year
Infecting pathogen
Comorbidity
Appropriate IAT definition
Mortality N
Total N
Mortality
(Country)
(%)
Mean Score
outcome
2010[44]
MDR 14.9; MDS
dosage ≤24 h of sample culture was
resistance;
12.2
obtained to which the isolate was
APACHE II
found to be susceptible on the final
score; renal
susceptibility report
condition;
immunosuppressi
on; source of
bacteremia
Modified APS at
Administration between 8-24 h
first time point;
Thom 2008
E.coli; Klebsiella
Acute physiology
with antimicrobials to which the
change in
(USA)[45]
spp.; P.aeruginosa
score 19.2
328
96 (29)
specific isolate displayed in vitro
severity-ofsusceptibility
illness scores
14
Adjusted
Author
Baseline
covariates for
Year
Infecting pathogen
Comorbidity
Appropriate IAT definition
Mortality N
Total N
Mortality
(Country)
(%)
Mean Score
outcome
Charlson*
Nonsurvivors 2;
Administration of at least one drug
septic shock at
survivors 2
displaying in vitro activity against
BSI onset, high
Tumbarello
KPC producing
2012
K.pneumoniae
APACHE
the infecting pathogen (timeframe
APACHE III
Nonsurvivors 40;
NR)
scores
125
52 (42)
99
39 (39)
104
48 (46)
(Italy)[47]
survivors 24
SOFA at
Administration of at least one agent
Tumbarello
pneumonia onset:
Diabetes, higher
displaying in vitro activity against
2013
P.aeruginosa
7; SAPS II on
SAPS II, and
the isolated pathogen (timeframe
(Italy)[48]
admission: 43
older age
NR)
43
Tuon 2011
ESBL K.
NR
Administration ≤48 h of diagnosis
None
15
Adjusted
Author
Baseline
covariates for
Year
Infecting pathogen
Comorbidity
Appropriate IAT definition
Mortality N
Total N
Mortality
(Country)
(%)
Mean Score
outcome
(Brazil)[49]
pneumoniae
of antibiotic to which the isolated
pathogen was susceptible
Infecting pathogen was susceptible
Tuon 2012
P.aeruginoas
NR
to the antibiotic used/started in ≤24
None
77
38 (49)
None
80
47 (59)
None
135
64 (47)
(Brazil)[50]
h after blood collection
Vitkauskiene
Administration of antibiotic to
2010
P.aeruginoas
NR
which the pathogen was found to be
(Lithuania)[5
susceptible (timeframe NR)
1]
Antibiotic administration with an
Yang 2013
Acinetobacter spp.
APACHE II: 26
approved route and dosage, ≥48 h
(Taiwan)[52]
after the onset of bacteremia, to
16
Adjusted
Author
Baseline
covariates for
Year
Infecting pathogen
Comorbidity
Appropriate IAT definition
Mortality N
Total N
Mortality
(Country)
(%)
Mean Score
outcome
which the causative pathogen was
susceptible
Administration ≤24 h of infection
Zarkotou
KPC producing
2011
onset of in vitro active
APACHE II 21
K.pneumonia
None
53
18 (34)
antimicrobials against the study
(Greece)[53]
isolates
Abbreviations: A.baumannii, Acinetobacter baumannii; APACHE, acute physiology and chronic health evaluations; ESBL, Extended spectrum
beta-lactamase; ICU, Intensive care unit; IAT, Inappropriate initial antibiotic therapy; IRAB, Imipenem-Resistant Acinetobacter Baumannii; KPC,
Klebsiella pneumoniae carbapenemases; MDR, Multi-drug Resistant; MDS, Multi-drug susceptible; NR, Not Reported; SD, Standard deviation;
S.maltophilia, Stenotrophomonas maltophilia; SAP, simplified acute physiology, SOFA, Sequential Organ Failure Assessment score
17