Original Article

Risk factors for carbapenem-resistant

Klebsiella pneumoniae infection/colonization
and predictors of mortality: a retrospective
study
Yang Jiao*1, Yanghua Qin*2, Jiajun Liu*3, Qiang Li1, Yuchao Dong1, Yan Shang1,
Yi Huang1, Rui Liu4
1

Department of Respiratory Medicine, Changhai Hospital, The Second Military Medical University, Shanghai,
China, 2Department of Clinical Laboratory, Changhai Hospital, The Second Military Medical University,
Shanghai, China, 3Shanghai Jiaotong University School of Medicine, Shanghai, China, 4Department of General
Surgery, Changhai Hospital, The Second Military Medical University, Shanghai, China
Objective: To identify risk factors associated with carbapenem-resistant Klebsiella pneumoniae (CRKP)
infection/colonization and death and to investigate the resistance and homology of CRKP.
Methods: A retrospective 1:1 casecontrol study was conducted at Changhai Hospital, China, from January
2010 to December 2011.The study population included 30 patients with CRKP infection/colonization and
30 matched patients with carbapenem-susceptible K. pneumoniae (CSKP) infection/colonization at the same
site. Homology analysis was conducted by multilocus sequence typing (MLST) and pulsed-field gel
electrophoresis (PFGE). Potential resistance genes were detected by PCR.
Results: Independent risk factors for CRKP infection/colonization were admission to exposure to glycopeptides
[Odds ratio (OR): 43.84, 95% confidence interval (CI): 1.731111.91, P50.020], cefoperazone plus sulbactam
(OR: 49.56, 95% CI: 1.421726.72, P50.030) and tracheostomy (OR: 677.82, 95% CI: 2.761667, P50.020).
Age (OR: 1.07, 95% CI: 1.001.14, P50.04), renal dysfunction (OR: 17.63, 95% CI: 2.34132.87, P50.005)
and exposure to cefoperazone plus sulbactam (OR: 8.87, 95% CI: 1.2961.07, P50.026) were independent
risk factors for the death of patients with K. pneumoniae infection/colonization. Older age (OR: 1.16, 95% CI:
1.011.39, P50.011) was an independent risk factor for the death of patients with CRKP infection/colonization.
Thirty CRKP strains were all KPC-2-producing resistant strains with genotype of ST-11.
Conclusion: Exposure to glycopeptides, cefoperazone plus sulbactam and tracheostomy were independent
risk factors for CRKP infection/colonization, and older age was an independent risk factor for CRKP infection/
colonization caused death.
Keywords: Carbapenem-resistant Klebsiella pneumoniae, Mortality, Risk factors, Antimicrobial resistance

Introduction
Klebsiella pneumoniae (K. pneumoniae) is one of the
pathogens responsible for hospital-acquired infections
including pneumonia, septicaemia, urinary tract and
lower biliary tract infections and hepatic abscess,
especially in immunocompromised people.13 Carbapenems are often used to treat infection/colonization
caused by K. pneumoniae producing extended-spectrum

* The first three authors contributed equally to this work.

Correspondence to: Yi Huang, Department of Respiratory Medicine,
Changhai Hospital, The Second Military Medical University, No. 168
Changhai Road, Shanghai 200433, China. Email: huangyihyer@163.com
or Rui Liu, Department of General Surgery, Changhai Hospital, The
Second Military Medical University, No. 168 Changhai Road, Shanghai
200433, China. Email: liuruilrer@163.com

W. S. Maney and Son Ltd 2015

DOI 10.1179/2047773215Y.0000000004

beta-lactamases (ESBLs).4 However, the increasing

prevalence of antibiotic-resistant bacteria, including
carbapenem-resistant K. pneumoniae (CRKP), has
become a potentially pathogenic and fatal factor.5
Mortality of the patients infected with CRKP seems
to be higher compared to the patients infected with
carbapenem-susceptible K. pneumoniae (CSKP).6
Carbapenem-resistant K. pneumoniae was first
reported in 1997 and very rare in the world at that
time.7 A novel carbapenem-hydrolyzing beta-lactamase
named KPC-1 was isolated from a carbapenem-resistant strain of K. pneumoniae in 2001.8 Currently, the
epidemic outbreaks of KPC-producing strains have
been reported in many countries and regions.911
K. pneumoniae is commonly present in intensive care

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Jiao et al.

Risk factor analysis for CRKP

unit (ICU) as a species of Enterobacteriaceae, which

is most prone to producing the enzyme associated
with carbapenem resistance.12 As treatment regimens
suitable for CRKP infection/colonization are limited,
epidemiological and microbiological studies on carbapenem-resistant Gramme-negative bacteria appear to
be particularly important.
Identifying risk factors for the development of
CRKP acquisition is important for treatment
options, and consequently, a number of risk factors
for CRKP infection/colonization have been revealed
in some retrospective clinical studies.4,1214 However,
the conclusions were not always consistent among
these studies. Antibiotic exposure was considered
an independent factor for CRKP infection/colonization in some studies,12 but not in all.6,13 Other independent factors were prior ICU stay, renal disease,
diabetes mellitus, solid tumour, tracheostomy, endoscopy, urinary catheter insertion and antipseudomonal penicillin use.4,6,1215
In order to improve empirical therapy efficacy, we
identified risk factors correlated with CRKP infection/
colonization and mortality caused by K. pneumoniae.
In addition, microbiological features of the strains
were also detected.

Methods
Subjects and study design
This retrospective study was performed at Shanghai
Changhai Hospital of China, a tertiary-care teaching
hospital with 2000 beds. Patients with hospitalacquired K. pneumoniae infection/colonization (positive K. pneumoniae culture 48 hours after admission)
from January 2010 to December 2011 were included
in this study.
Patients inclusion criteria were hospital stay
i7 days; age w18 years; no prior K. pneumoniae
infection/colonization before the current admission;
with the same site of infection/colonization for CRKP
and CSKP. Carbapenem-susceptible K. pneumoniae infected patients were with a difference in age of
+ 5 years and K. pneumoniae culture time of + 3 days
compared with CRKP-infected patients. If several
potential patients of the CSKP group met the qualification, only one was randomly selected.

Data collection
Data collection was performed by reviewing medical
and microbiological data and recording: clinical
departments where strains were isolated, patients
age, gender, comorbidities such as lung disease, cardiac insufficiency, renal insufficiency, diabetes mellitus and hypoalbuminaemia, treatments before
obtaining the positive culture such as mechanical
ventilation, invasive procedures (deep venous
catheterization, indwelling gastric tube, indwelling

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urethral catheter and tracheostomy), hospitalization

(length of ICU staying, APCHE II score), antibiotic
administration 3 months prior to the current hospitalization and during the current hospitalization
until the positive culture for K. pneumoniae was
obtained such as fluoroquinolones, first-generation
cephalosporins, second-generation cephalosporins,
third-generation cephalosporins, cefoperazone plus
sulbactam, carbapenems (imipenem or meropenem),
amikacin, glycopeptides (vancomycin, teicoplanin)
and the clinical outcomes. Among them, hypoproteinemia was defined as plasma albumin v30 g/l; lung
diseases included chronic obstructive pulmonary
disease, chronic bronchitis, and respiratory failure;
inclusion criteria for cardiac dysfunction were brain
natriuretic factor or peptide (BNP)w400 pg/ml or
previously conformed cardiac dysfunction. All antimicrobial agents included in the statistics were those
used for at least 48 hours before K. pneumoniae
infection/colonization.

Statistical analysis
All statistical analyses were performed using statistical software SPSS 18.0 (SPSS Inc., Chicago, IL,
USA). All data were expressed as mean + standard
deviation for continuous variables or percent for categorical variables. In analysis of risk factors for
CRKP infection/colonization and mortality, univariate logistic regression analysis was performed.
To identify the independent risk factors, variables
with Pv0.05 in the univariate analysis were included
in multivariate logistic regression model and analyzed using backward stepwise regression. Odds
ratio (OR) and 95% confidence interval (CI) were
also calculated. For all statistical analyses, Pv0.05
indicated statistical significance.

Resistance mechanism and homology analysis of

CRKP
Imipenem susceptibility of the strains was determined
by metallo-beta-lactamases (MBLs) Etest.16 The
Hodge test was used when resistance to one of the
carbapenems was demonstrated.17 The minimum
inhibitory concentration (MIC)i16 mg/ml was used
as the standard of CRKP strains.18,19
The strain genotyping was performed using multilocus sequence typing (MLST) method. Seven housekeeping genes (rpoB, gapA, mdh, pgi, pho E, infB
and tonB) were, respectively, amplified. The products
were sequenced and aligned to obtain ST genotyping
of the strains at http://www.Pasteur.fr/cgi-bin/
genopole/PF8/mlstdbnet.pl?page5allseq&file5klebs_
profiles.xml. The potential resistance genes (NDM-1,
CTX and KPC) were obtained by PCR amplification.
The genomic DNA of the K. pneumoniae strains was
digested using XbaI restriction endonuclease.
The obtained fragments were separated using

Jiao et al.

Risk factor analysis for CRKP

departments and sites in CSKP group were in one-toone correspondence with those in CRKP group.

pulsed-field gel electrophoresis (PFGE). Pulsed-field

gel electrophoresis was performed with a contourclamped homogeneous electric field DRII apparatus
from Bio-Rad Laboratories (Richmond, CA, USA).
The chromosomal DNA was digested overnight
with Xba I (Takara, Dalian, China). DNA was electrophoresed in 1.2% agarose at 6 V/cm for
24 hours; the pulse time was increased from 5 to
40 seconds. The results were analyzed using the software of Bio-Rad Quantity one. The PFGE types
were analyzed according to the criteria defined by
Tenover et al.20

Risk factors for CRKP infection/colonization:

a clinical casecontrol study
Several factors were found to be associated with CRKP
infection/colonization, including prior exposure to cefoperazone plus sulbactam, carbapenems or glycopeptide,
deep venous catheterization, tracheostomy, indwelling
urethral catheter, indwelling gastric tube, higher
APCHE II score, ICU stay, and longer ICU length of
stay (Pv0.05) (Table 1). Among them, prior exposure
to glycopeptide (OR: 43.84, 95% CI: 1.731111.91,
P50.02) or cefoperazone plus sulbactam administration (OR: 49.56, 95% CI: 1.421726.72, P50.03),
deep venous catheterization (OR: 46.88, 95% CI: 0.52
4238.09, P50.09) and tracheotomy (OR: 677.82, 95%
CI: 2.761667, P50.020) were independent risk factors
for CRKP infection/colonization (Table 1).

Results
Thirty CRKP strains were separately derived from
emergency department (nine strains), department of
burn injury (six strains), osteology (three strains), neurology (one strain), neurosurgery (three strains), thoracic surgery (three strains), general surgery (three
strains), department of gastroenterology (one strain)
and pneumology (one strain). The specimens were collected from sputum (17 strains), wound secretions
(6 strains), urine (3 strains), blood (2 strains), and drainage fluid (2 strains). The specimen collection

Clinical cohort study on mortality: patients who

survived versus those died from K. pneumoniae
infection/colonization
Among the enrolled 60 patients with K. pneumoniae
infection or colonization, 15 (25%) patients died.
Univariate analysis indicated that older age, lung

Table 1 Analysis of risk factors for patients infected with CRKP

Variables
Risk factors

CRKP (n530) CSKP (n530)

Univariate analysis
OR (95% CI)

60?6+ 17?2
0?86 (0?971?03)
Age (years)
59?8+ 17?5
Male, n (%)
25 (83?3)
5 (76?7)
0?66 (0?182?4)
Concomitant diseases, n (%)
Lung disease
15 (50?0)
10 (33?3)
2?0 (0?715?67)
Cardiac dysfunction
8 (26?7)
8 (26?7)
1?00 (0?323?14)
Renal dysfunction
12 (40?0)
7 (23?3)
2?19 (0?726?69)
Diabetes
5 (16?7)
4 (13?3)
1?30 (0?315?40)
Hypoalbuminaemia
18 (60)
13 (43?3)
1?96 (0?705?48)
Tumour
5 (16?7)
11 (36?7)
0?35 (0?101?16)
Antibiotics application before Klebsiella pneumoniae infection, n (%)
Fluoroquinolone
19 (63?3)
12 (40)
2?6 (0?917?30)
2nd generation cephalosporins 9 (30)
12 (40)
0?64 (0?221?87)
3rd generation cephalosporins
7 (23?3)
7 (23?3)
1?00 (0?303?30)
Amikacin
6 (20)
1 (3?3)
7?30 (0?8264?5)
Carbapenem
20 (66?7)
7 (23?3)
6?57 (2?1020?48)
Cefoperazone plus sulbactam 15 (50)
5 (16?7)
5?0 (1?5116?60)
Tazocin
4 (13?3)
5 (16?7)
0?77 (0?193?19)
Glycopeptides
17 (56?7)
4 (13?3)
8?5 (2?3730?46)
Invasive procedures, n (%)
Deep venous catheterization
27 (90)
17 (56?7)
6?88 (1?7127?8)
Tracheotomy
26 (86?7)
13 (43?3)
8?5 (2?3730?46)
Indwelling urethral catheter
26 (86?7)
19 (63?3)
3?76 (1?0413?64)
Indwelling gastric tube
25 (83?3)
16 (53?3)
4?37 (1?3214?50)
17?2+ 7?4
1?10 (1?02-1?18)
APCHE2 score
22?9+ 8?1
18?0+ 23?4
1?03 (1?001?06)
Hospital stay (days)
33?8+ 30?8
ICU stay (days)
25 (83?3)
18 (60)
3?33 (0?9911?14)
13?2+ 27?4
1?03 (1?011?06)
Hospital stay before
33?8+ 30?8
bacteraemia (days)
Outcomes
Death
10 (33?3)
5 (16?7)
Improvement
20 (66?7)
25 (83?3)

P-value

Multivariate analysis
OR (95% CI)

P-value

0?856
0?52
0?193
1
0?169
0?718
0?199
0?086
0?073
0?418
1
0?076
0?001
0?008
0?718
0?001
0?007
0?001
0?044
0?016
0?01
0?054
0?048
0?02

4?62 (0?2584?05)
0?3
49?56 (1?421726?72) 0?03
43?84 (1?731111?91) 0?02
46?88 (0?524238?09)
677?82 (2?761667)
0?11 (0?014?96)
0?05 (0?012?32)
1?01 (0?83-1?23)

0?09
0?02
0?26
0?13
0?92

0?54 (0?0214?66)
1?09 (0?981?2)

0?72
0?1

CRKP: carbapenem-resistant Klebsiella pneumonia; CSKP: carbapenem-sensitive Klebsiella; OR: odds ratio; CI: confidence
interval; ICU: intensive care unit.The variables screened in univariate analysis with Pv0?05 were included in the multivariate logistic
regression analysis after repeated verification of the fitted model.

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diseases, cardiac dysfunction, renal dysfunction,

exposure to cefoperazone plus sulbactam and longer
ICU length of stay were associated with the death of
the
K.
pneumoniae-infected/colonized
patients
(Pv0.05) (Table 2). Multivariate analysis showed that
older age (OR: 1.07, 95% CI: 1.001.14, P50.04),
renal dysfunction (OR: 17.63, 95% CI: 2.34132.87,
P50.005) and exposure to cefoperazone plus sulbactam
(OR: 8.87, 95% CI: 1.2961.07, P50.026) were independent risk factors associated with K. pneumonia infection/
colonization induced death (Table 2).

Clinical cohort study on mortality: patients who

survived versus those died from CRKP infection/
colonization
Ten of the 30 patients with CRKP infection/colonization died. Univariate analysis indicated that the factors
such as older age, renal dysfunction and exposure to
cefoperazone plus sulbactam were associated with
death (Pv0.05) (Table 3). Among them, only older
age (OR: 1.16, 95% CI: 1.011.39, P50.011) was the
independent risk factor for death of patients with
CRKP infection/colonization (Table 3).

Resistance mechanism and homology analysis of

CRKP
All of the 30 imipenem-resistant CRKP strains
(MICi16 mg/ml) were multiresistant (susceptibility

to polymyxin was not measured). The main resistance mechanism of the 30 CRKP strains was attributed to KPC production. The genotypes of all
strains were ST-11 (Fig. 1).

Discussion
Since the reports on CRKP, treating K. pneumoniae
infection/colonization using carbapenems has been
challenged. To improve empirical therapy efficacy, we
studied the risk factors for CRKP infection/colonization. Our investigation indicates that CRKP infection/
colonization was associated with various factors such
as ICU stay, prior antibiotic use and invasive procedures. Exposure to glycopeptides or cefoperazone
plus sulbactam as well as tracheotomy were independent risk factors for CRKP infection/colonization;
age, renal insufficiency and cefoperazone plus sulbactam administration were independent risk factors for
death of K. pneumoniae-infected patients; older age
was an independent risk factor for death of patients
with CRKP infection/colonization. These findings
suggested that the clinicians should place emphasis on
the appropriate antibiotic use and aseptic invasive
procedures.
Our study suggested that ICU staying and longer
length of ICU stay before K. pneumoniae infection/
colonization were associated with CRKP infection/

Table 2 Analysis of risk factors associated with Klebsiella pneumoniae infection/colonization induced death
Variables
Risk factors

Univariate analysis

Death (n515) Survival (n545)

56?5+ 16?8
Age (years)
71?3+ 13?8
Male, n (%)
11 (73?3)
37 (82?2)
Concomitant diseases, n (%)
Lung disease
10 (66?7)
15 (33?3)
Cardiac dysfunction
7 (46?7)
9 (20)
Renal dysfunction
10 (66?7)
9 (20)
Liver dysfunction
1 (6?7)
1 (2?2)
Diabetes
2 (13?3)
7 (15?6)
Hypoalbuminaemia
9 (60)
22 (48?9)
Tumour
4 (26?7)
12 (26?7)
Antibiotics application before K. pneumoniae infection, n (%)
Fluoroquinolone
11 (73?3)
20 (44?4)
2nd generation cephalosporins 4 (26?7)
17 (37?8)
3rd generation cephalosporins
6 (40)
8 (17?8)
Amikacin
2 (13?3)
5 (11?1)
Carbapenem
9 (60)
18 (40)
Cefoperazone plus sulbactam
9 (60)
11 (24?4)
Tazocin
3 (20)
6 (13?3)
Glycopeptides
5 (33?3)
16 (35?6)
Invasive procedures, n (%)
Deep venous catheterization
13 (86?7)
31 (68?9)
Tracheotomy
12 (80)
27 (60)
Indwelling urethral catheter
12 (80)
33 (73?3)
Indwelling gastric tube
12 (80)
29 (64?4)
Surgery
4 (26?7)
24 (53?3)
16?5+ 5?7
APCHE2 score
30?7+ 4?3
ICU stay (days)
13 (86?7)
30 (66?7)
18+ 24?5
Hospital stay before
41+ 41?2
bacteraemia, days

OR (95% CI)

P-value

1?07 (1?021?12)
0?59 (0?152?35)

0?007
0?459

4
(1?1613?82)
3?5 (112?22)
8
(2?1829?31)
3?14 (0?1853?59)
0?84 (0?154?54)
1?57 (0?485?14)
1
(0?273?75)

0?028
0?049
0?002
0?429
0?835
0?458
1

3?44 (0?9512?45)
0?6 (0?162?18)
3?08 (0?8511?14)
1?23 (0?217?12)
2?25 (0?687?42)
4?64 (1?3515?97)
1?62 (0?357?5)
0?91 (0?263?12)

0?06
0?437
0?086
0?817
0?183
0?015
0?534
0?876

2?94 (0?5814?79)
2?67 (0?6610?8)
1?45 (0?356?06)
2?21 (0?548?99)
0?32 (0?091?15)
10?67 (0?87130?64)
3?25 (0?6516?3)
1?02 (1?001?04)

0?192
0?69
0?607
0?269
0?081
0?064
0?152
0?031

Multivariate analysis
OR (95% CI)
1?07 (1?001?14)

P-value
0?04

1?05 (0?166?7)
0?96
17?63 (2?34132?87) 0?005

8?87 (1?2961?07)

0?026

1?01 (0?981?03)

0?48

OR: odds ratio; CI: confidence interval; ICU: intensive care unit.The variables screened in univariate analysis with Pv0?05 were
included in the multivariate logistic regression analysis after repeated verification of the fitted model.

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Table 3 Analysis of risk factors associated with CRKP infection/colonization induced death
Variables
Risk factors

Death (n510)

Survival (n520)

Univariate analysis
OR (95% CI)

52?9+ 16?0
1?11 (1?031?20)
Age (years)
73?6+ 11?1
Male, n (%)
7 (70)
18 (90)
0?26 (0?041?9)
Concomitant diseases, n (%)
Renal dysfunction
7 (70)
5 (25)
7
(1?2937?91)
Antibiotics application before K. pneumoniae infection, n (%)
Cefoperazone plus
8 (80)
7 (35)
7?43 (1?2345?01)
sulbactam

P-value
0?009
0?18

Multivariate analysis
OR (95% CI)
1?16 (1?011?39)

P-value
0?011

0?024

185?69 (0?9137 797?14)

0?054

0?029

319?05 (0?68149 157?23)

0?07

CRKP: carbapenem-resistant Klebsiella pneumonia; OR: odds ratio; CI: confidence interval; ICU: intensive care unit.The variables
screened in univariate analysis with Pv0?05 were included in the multivariate logistic regression analysis after repeated verification
of the fitted model.

Figure 1 Pulsed-field gel electrophoresis (PFGE) patterns

of carbapenem-resistant Klebsiella pneumoniae (CRKP).
The fourth lane indicated ESBL 1 CSKP (ATCC 700603), and
the others indicated CRKP strains.

colonization, which was consistent with the studies

conducted by Gregory et al.21 and Schwaber et al.22
Most patients admitted to the ICU have relatively
serious complications. Furthermore, the airborne
and contact transmission of resistant bacteria in the
ICU environment may lead to nosocomial infection/colonization. The patients with prolonged ICU
stay may undergo more invasive procedures and
may be treated with a longer duration of antibiotics
use or with broad spectrum antibiotics. All the
above factors can lead to the emergence of carbapenems-resistant bacteria.
Carbapenems administration has been proven to
be an independent risk factor for carbapenem-resistant Pseudomonas aeruginosa and Acinetobacter baumannii
infection/colonization.23,24
Our
study
suggested that carbapenems administration prior to
K. pneumoniae infection was also associated with
CRKP infection, which was consistent with many
previous retrospective clinical studies.22,2529 The
fluoroquinolones or quinolones utilization was also
an independent risk factor for CRKP infection/

colonization29 and death.26,30 Laboratory evidences

indicated that plasmid-encoded quinolone resistance
determinant gene causing low-level fluoroquinolone
resistance was located on K. pneumoniae plasmids
encoding KPC gene (especially blaKPC-2 and
qnrB4). However, the present study as well as the
studies conducted by Gregory et al.,21 Kwalk
et al.25 and Wu et al.31 failed to prove the correlation
between fluoroquinolones use and CRKP infection/
colonization. This might be due to the fact that quinolones abuse in some regions had resulted in nonsignificant difference in the clinical studies.
We also found that glycopeptide or cefoperazone
plus sulbactam administration were risk factors for
CRKP infection/colonization, which was consistent
with the previous finding.31 Long-term application
of glycopeptides would significantly inhibit the
growth of Gramme-positive bacteria and thus lead
to more frequent mutations and drug resistance of
Gramme-negative bacteria. However, cefoperazone
plus sulbactam administration could not be
explained by this possible mechanism. Further microbiological researches remain to be performed.
Our studies suggested that tracheotomy was an
independent risk factor associated with CRKP infection/colonization. Frequent invasive operations and
tube indwelling may cause respiratory tract or gastrointestinal mucosal injury easily. The mucosal barrier injury will cause further decline in the body
resistance and increase in probabilities of bacterial
colonization or infection/colonization.
Besides, this study concluded that older age, concomitant disease (renal insufficiency) and application
of cefoperazone plus sulbactam were independent
risk factors for death caused by K. pneumoniae infection/colonization. Advanced age, severe underlining
diseases and inadequate antibiotic treatment would
reduce the immunity, which increased the risk of
infection/colonization and even death.
Most of the present clinical studies focus on the
risk factors for acquisition of CRKP, but few reports

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Risk factor analysis for CRKP

combined the mechanisms of resistance. The risk

factors and sensitivity of antibiotic agent of CRKP
may not differ with different mechanisms of resistance, so microbiological detection of K. pneumoniae
was particularly included in our study. Analysis on
the genotypes and homogeneity of the strains
suggested that KPC-2 was the main factor causing
antibiotic resistance in CRKP strains. Some researchers also indicated that the resistance mechanisms of
53% CRKP strains were due to KPC-2 producing.24,3234 In addition to producing KPC enzyme,
the CRKP resistance mechanisms also included the
loss of outer membrane proteins and production of
beta-lactam-hydrolyzing enzymes.35
Our study also has some limitations. First, we should
acknowledge that the sample size was not large enough,
which might lead to errors in statistical analysis and the
omission of some other risk factors. Second, there was
not an established criterion for differentiating infection
from colonization of K. pneumoniae in the study.
In addition, this study was only conducted in one
tertiary-care teaching hospital. Prospective, multicenter
clinical trials are expected to be performed.

Conclusion
This retrospective study indicated that exposure to glycopeptides or cefoperazone plus sulbactam, as well as
tracheostomy, were independent risk factors for severe
infection/colonization caused by CRKP. These findings
may provide some recommendation for the diagnosis
and treatment of patients infected with KPC-producing
CRKP strains in Shanghai, China.

Disclaimer Statements
Contributors
Funding. This study was supported by research grants
from the Important National Science and Technology Specific Projects (NO.2013ZX10003009).
Conflicts of interest .We declare that we have no conflicts of interest.
Ethics approval. This retrospective study was performed in Shanghai Changhai Hospital of China.

References
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LH. Development of a new trend conjugate vaccine for the
prevention of Klebsiella pneumoniae. Infect Dis Rep. 2012;4:e33.
3 Neuhauser MM, Weinstein RA, Rydman R, Danziger LH,
Karam G, Quinn JP. Antibiotic resistance among gram-negative bacilli in us intensive care units: implications for fluoroquinolone use. JAMA. 2003;289:8858.

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