Zhu et al.

Antimicrobial Resistance and Infection Control (2020) 9:91

https://doi.org/10.1186/s13756-020-00757-y

RESEARCH Open Access

Successful control of the first carbapenem-

resistant Klebsiella pneumoniae outbreak in
a Chinese hospital 2017–2019
Jiaying Zhu1,2†, Qi Li1†, Xiaoxia Li3†, Jianbang Kang3, Yan Song3, Junli Song3, Donghong Yin3 and Jinju Duan3*

Abstract
Background: Carbapenem-resistant Klebsiella pneumoniae (CRKP) is considered as a serious global threat. CRKPs
occurred only sporadically in the Second Hospital of Shanxi Medical University. Our study aimed to investigate and
control the first outbreak of CRKP in our hospital occurred between October 2017 and August 2019.
Methods: The antimicrobial stewardship (AMS) workers have been implemented control measures properly. Clinical
and epidemiological data were retrospectively collected from medical records. Carbapenemase genes were
detected by modified carbapenem inactivation method (mCIM) test and the EDTA-modified carbapenem
inactivation method (eCIM) test. Resistance genes were identified by polymerase chain reaction (PCR) and
sequencing. Genetic relatedness was studied by multilocus sequence typing (MLST).
Results: During the outbreak, 31 patients were infected with CRKP isolates. 20 (64.5%) patients were infected with
KPC-2 and/or NDM-1 producing K. pneumoniae. Mostly MLST-sequence types belonged to ST11 (21/31). The
outbreak was two major K. pneumoniae clusters present in epidemiologically linked patients.
Conclusions: Setting up AMS workers is potentially a highly efficient strategy for the successful control of the
outbreak. A multimodal and multidisciplinary infection control strategy proved to be crucial. The emergence of
CRKP in our hospital emphasizes the importance of continuous monitoring of these isolates, which helps to limit
the spread of CRKPs and improve the level of management.
Keywords: Carbapenem-resistant Klebsiella pneumoniae, Infection control, NDM, KPC, Phenotypic detection, Transmission

Introduction strains in different regions [2]. The problem of antimicro-

Klebsiella pneumoniae is one of the leading causes of bial resistance is highlighted by a recent increase of
hospital-acquired infections globally. Carbapenems are carbapenem-resistant K. pneumoniae (CRKP), which has
widely used for the treatment of serious infections caused largely been driven by the emergence and spread of
by multidrug resistant (MDR) Enterobacteriaceae such as mobile genetic elements carrying carbapenem resistance
AmpC β-lactamases and extended spectrum β-lactamases genes including either class B metallo-betalactamases
(ESBLs) [1]. However, in recent years, widespread use of (IMP, VIM, NDM) or classes A (KPC) and D (OXA-48)
carbapenems have accelerated the growth of resistant serine carbapenemases [3, 4]. KPC-producing strains, first
reported in 1996 [5], are considered as one of the most
* Correspondence: [email protected] common carbapenemases globally [3]. In China, KPC-
†
3
Jiaying Zhu, Qi Li and Xiaoxia Li contributed equally to this work. producing K. pneumoniae strains have been identified
Department of Pharmacy, Second Hospital of Shanxi Medical University, No
382, Wuyi Road, Xinghualing District, Taiyuan, Shanxi, People’s Republic of
since 2004 in Zhejiang Province [6] and have became
China endemic in many hospitals, with most of them harbouring
Full list of author information is available at the end of the article

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Zhu et al. Antimicrobial Resistance and Infection Control (2020) 9:91 Page 2 of 9

blaKPC-2 allele [7]. In addition, blaNDM-1 is now consid- [12], and the results were interpreted according to CLSI
ered to be endemic in the Indian subcontinent [8] and categories and minimum inhibitory concentration (MIC)
reports of NDM-1-producing Klebsiella from hospital- breakpoints. The breakpoint of tigecycline for K. pneumoniae
and community-acquired infections elsewhere indicate was based on the US Food and Drug Administration stand-
global dispersion [9]. ard. Escherichia coli ATCC 25922 were used as quality
A total of 44 hospitals were included in the China Anti- control standards for antimicrobial susceptibility testing.
microbial Surveillance Network (CHINET, www.chinets.
com) in 2018. Most of the hospitals included are the largest Investigation of resistance mechanisms
tertiary-care teaching hospitals in each province or city To use the combined application of modified carbapenem
which represent 26 provinces or cities. These provinces or inactivation method (mCIM) test and the EDTA-modified
cities have a population of about nine hundred million. It carbapenem inactivation method (eCIM) test for discrimin-
has reported that Carbapenem resistance among K. pneu- ating between serine- and metal-dependent (such as
moniae, especially cultured from cerebrospinal fluid, in- metallo-β-lactamases (MBLs) carbapenemases) [12, 13]. For
creased significantly from 18.6 to 64.1% in 2018 [10]. From 31 CRKP strains, polymerase chain reaction (PCR) was used
2005 to 2018, the resistance rates of K. pneumoniae to imi- to detect genes encoding carbapenemases (blaKPC, blaNDM,
penem and meropenem were increased from 3.0 to 25%, blaGES, blaIMP, blaVIM, blaSIM, and blaOXA-48), ESBLs, and
2.9 to 26.3%, respectively [10]. Dissemination of the CRKP AmpC β-lactamases (blaCTX-M-1,3,10-12,15, blaCTX-M-2,4–
strains is facilitated by inadequate infection prevention and 7,Toho-1, blaCTX-M-9,13-14,16–19,Toho-2, blaACT, blaDHA, and
control practice in healthcare settings, uncontrolled or blaCMY), as previously described [5, 14–18]. The colistin
poorly controlled antimicrobial use, sewage water treat- resistance gene mcr-1 was also detected by PCR, as previ-
ment and general sanitation. The spread of such strains is ously described [19]. PCR products were purified with a
associated with high mortality rates, limited treatment QIAquick PCR Purification Kit (Qiagen, Valencia, CA,
options and rapid dissemination of successful bacterial USA) and sequenced by Sanger sequencing on an ABI
clones in the hospital setting. The occurrence of the above PRISM 3730XL system (Applied Biosystems, Foster City,
conditions can be effectively reduced by taking strict infec- CA, USA).
tion control measures [11]. In this report, we describe what
we believe to be the first outbreak of CRKP in our hospital, Multilocus sequence typing (MLST)
which occurred from October 2017 to August 2019. Our Multilocus sequence typing (MLST) was performed by
aims were to assess the antimicrobial resistance pheno- amplifying the internal fragments of seven K. pneumo-
types, the epidemiology, clinical features, outcomes and the niae housekeeping genes according to the MLST website
challenges faced in controlling CRKP during the 23 months (https://bigsdb.pasteur.fr/). A phylogeny was showed by
from October 2017 to August 2019 in a tertiary-care teach- using the seven concatenated MLST gene sequences of
ing hospital in Shanxi, China. all 31 strains. We constructed a refined maximum likeli-
hood phylogeny by MEGA7 to study these isolates in
Materials and methods greater detail.
Data collection
The Second Hospital of Shanxi Medical University is a Infection control program
2076-bed tertiary-care teaching hospital. A total of 31 In order to control the outbreak of infection, we have
non-duplicated CRKP strains were isolated and identi- set up a working group on the antimicrobial stewardship
fied from October 2017 to August 2019. All clinical and (AMS) in August 2018. The AMS workers consisted of
epidemiological data were retrospectively reviewed. All hospital administrators, health directors, physicians,
isolates in this study were defined as resistant to one of nurses, clinical pharmacists, a microbiologist, an envir-
meropenem, imipenem or ertapenem. A CRKP-positive onmental cleaning staff and staffs from the infection
case was defined as any patient infected or colonized management department, infectious diseases department
with CRKP. All isolates were identified by VITEK-2 and computer center department.
Compact system (BioMerieux Italia S.p.A) and matrix- During the outbreak, strict infection control procedures
assisted laser desorption ionization time-of-flight mass were put in place including a) Rapid communication
spectrometry (Bruker Daltonik, Bremen, Germany). between microbiological laboratories and AMS workers
was established to ensure early warning and timely sharing
Antimicrobial susceptibility testing of any pertinent epidemiological information, access to
Antimicrobial susceptibility was evaluated by the agar online results of microbiological testing was already rou-
dilution and microdilution methods at the Second tinely available; b) Infection control specialists and clinical
Hospital of Shanxi Medical University according to the pharmacists put forward suggestions on rational drugs use
Clinical and Laboratory Standards Institute (CLSI) guidelines in time and staffs underwent training courses. All CRKP
Zhu et al. Antimicrobial Resistance and Infection Control (2020) 9:91 Page 3 of 9

carriers were isolated in a single room with strict month later, the patient gradually tests positive from
contact precautions and flagged in the hospital infor- both sputum and blood again. That patient was defined
mation system (HIS); c) The AMS workers enhanced as patient 01 (Fig. 1). After that in January 2018 the two
chlorhexidine disinfection of the patients’ room at least index patients in the intensive care unit (ICU) were
three times a day and implemented surveillance detected, whom defined as patient 02 and 03, neither
cultures of the hand and environment. The AMS team had a history of hospitalization nor travel in a foreign
held meetings regularly for update the outbreak situ- country. Then three other patients were test positive for
ation, the implemented measures and proposed future CRKP in 2 days and all of them were in the ICU, with
actions; d) All contact patients are systematically sub- no signs of infection or colonization on admission. They
jected to rectal and pharyngeal screening once a week; were in individual beds in the same room but had over-
e) After CRKP-positive cases were discharged, the sur- lapping nurses, physicians, and respiratory technicians,
roundings were cleaned in depth using a 500-ppm they also shared thermometers (disinfection of alcohol
chlorine solution. High-touch surfaces such as door cotton swabs) and stethoscopes before isolation precau-
handles, bedside lockers and chairs and bed rails were tions were ordered. At the affected wards new CRKP
emphasized by the hospital hygiene nurse manager for strains were isolated, five in January and three in Febru-
cleaning to reduce cross-transmission. Infection control ary (Table 1). Some of them were in direct contact with
staffs followed up the measures; f) When the affected patient 02 or 03 in the ICU, while others who came into
patients transfer to other hospitals, these hospitals should contact with ICU of patient 02 or 03 were subsequently
be forewarned. transferred to regular wards (Fig. 2). Some of the
patients transferred to the regular wards were in the
Results same room. In a few new CRKP-positive cases there was
Epidemiological investigation of the outbreak no direct contact with infected patients, however, they
Until 2018, CRKPs occurred only sporadically. During were in adjacent rooms and were cared for by the same
October 2017, CRKP was detected from one patient in doctor, nurse or environmental cleaning staff (Fig. 2).
Hematology ward, who was hospitalized because of PH- From the October 2017 to August 2018, a total of 26
positive acute lymphoblastic leukemia with lack of gran- patients with KPC-2 and/or NDM-1 CRKP were found
ulocytes. The patient did test positive for CRKP from in ten different wards (including ICU), all with an
fecal culture which was turn out to be colonization. Two epidemiological connection to the outbreak. As this was

Fig. 1 Timeline of events during the outbreak of carbapenemase-resistant K. pneumoniae. Dates are given as month. LOS1: Length of stay until
first detection; LOS2: Length of stay after first detection; K: KPC; N: NDM; K&N: KPC and NDM; −: no-KPC and no-NDM
Table 1 Epidemiological and clinical data of the 31 patients infected with CRKP during the outbreak
Carbapenemase
ID Sex Age(y) APACHE II Department when Clinic samples Outcome CIM eCIM MLST KPC NDM Other ESBL AmpC mcr-1
infection
P01 F 56 14 Hematology Blood Death I – ST147 – – – + – –
P02 M 62 32 ICU Respiratory secretions Discharge + + ST1 – NDM-1 – – – –
P03 F 78 12 ICU Respiratory secretions Death + + ST11 KPC-2 NDM-1 – – – –
P04 M 88 20 ICU Respiratory secretions Death + + ST11 – – – – – –
P05 M 52 26 Respiratory Respiratory secretions Discharge + + ST11 – NDM-1 – – – –
P06 M 48 20 ICU Respiratory secretions Death + + ST11 – – – – – –
P07 M 40 26 ICU Respiratory secretions Death + + ST11 – NDM-1 – – – –
P08 M 54 20 Respiratory Respiratory secretions Death + + ST11 – NDM-1 – – – –
P09 M 54 26 ICU Respiratory secretions Death + + ST11 – – – – – –
P10 F 85 14 Gastroenterology Secretions Discharge + + ST11 – NDM-1 – – – –
Zhu et al. Antimicrobial Resistance and Infection Control

P11 M 56 25 ICU Respiratory secretions Discharge + – ST11 KPC-2 – – + + –

P12 M 76 24 Neurosurgery Cerebrospinal Death + + ST11 – NDM-1 – – – –
fluid
P13 M 44 5 General Surgery Pus Discharge + + ST11 – – – – – –
P14 M 30 6 Hematology Respiratory secretions Death – – ST15 – – – – – –
(2020) 9:91

P15 M 90 15 Cardiothoracic Surgery Blood Discharge + + ST11 – – – – – –

P16 M 62 10 Hematology Respiratory secretions Discharge + + ST3744 – NDM-1 – – – –
P17 M 66 13 Nephrology Respiratory secretions Discharge + + ST11 – NDM-1 – – – –
P18 M 62 8 Rheumatology Blood Discharge + + ST11 – – – – – –
P19 F 71 7 Respiratory Respiratory secretions Discharge + + ST11 – NDM-1 – – – –
P20 M 42 7 ICU Blood Discharge + + ST11 – NDM-1 – – – –
P21 M 57 9 Hematology Respiratory secretions Discharge + + * – NDM-1 – + – –
P22 M 70 29 Neurosurgery Respiratory secretions Death + – ST11 KPC-2 – – + – –
P23 F 44 18 Hematology Blood Discharge + + ST690 – NDM-1 – – – –
P24 F 76 11 Neurosurgery Cerebrospinal Discharge + – ST11 KPC-2 – – + – –
fluid
P25 M 45 10 ICU Blood Discharge + + ST11 – NDM-1 – – – –
P26 F 38 5 Orthopedics Respiratory secretions Discharge + + ST11 – NDM-1 – – – –
P27 M 95 16 Respiratory Respiratory secretions Discharge + + ST784 – – – – – –
P28 F 68 18 Hematology Blood Discharge – – ST7 – – – – – –
P29 F 85 7 ICU Secretions Death + + ST524 – – – – – –
P30 M 67 22 Neurosurgery Cerebrospinal fluid Discharge + – ST307 KPC-2 – – – – –
P31 M 76 3 Neurosurgery Cerebrospinal fluid Discharge + – ST11 KPC-2 – – + – –
APACHE II Acute Physiology and Chronic Health Evaluation II, ST sequence type, ICU intensive care unit, mCIM modified carbapenem inactivation method, eCIM EDTA-modified carbapenem inactivation method, MLST
Page 4 of 9

multilocus sequence typing, ESBLs extended spectrum β-lactamases; *: data not publish; —: negative
Zhu et al. Antimicrobial Resistance and Infection Control (2020) 9:91 Page 5 of 9

Fig. 2 Epidemiological links between CRKP patients (n = 31 cases). Nodes represent cases (1–31) and color represent department when infection.
Arrows indicate epidemiological link between cases, directly (patients in the same ward) or indirectly (share common room, environmental source
or via undetected intermediate patient)

now considered as an outbreak, hospital infection man- including treatment in the 90 days before the strains iso-
agement department were notified. The AMS workers lated. Among all the patients in this study, 11 (33.3%)
ensuring that these measures mentioned in the methods died during their hospitalization which the CRKP infec-
were implemented correctly. With all precautions in tion contributed to their death (Table 1).
place, the outbreak began to wane in September 2018
with only few newly infected patients and no additional Antimicrobial susceptibility testing and phenotypic assays
spread in the most affected wards (Fig. 1 and Table 1). Overall the antibiotics showing the highest susceptibil-
The outbreak essentially stopped in December 2018. ity were tigecycline (n = 31, 100%), colistin (n = 30,
Due to the successful control of the outbreak we are 96.8%), amikacin (n = 27, 87.1%) and fosfomycin (n =
now back to epidemiological stage before the outbreak 21, 67.7%). MIC range (mg/L) for different carbapen-
with sporadic CRKP occurrence. From May to June ems were imipenem 1- ≥ 256, meropenem 4- ≥ 256 and
2019, CRKP with KPC was detected in two newly ertapenem 0.5 - ≥ 256. Seven isolates had MIC ≤8 mg/L
CRKP-infected patients with indirect epidemiological for at least one carbapenem. PCR and sequence analysis
connection to the outbreak (Figs. 1 and 2). of carbapenemase genes identified blaNDM-1 in 14 iso-
A total of 31 patients were affected. These patients did lates and blaKPC-2 in 5 isolates. However, it was worth
not have a history of travel outside of China, but most of noting that, eight isolates were positive in mCIM com-
them had frequent hospitalizations in Shanxi province. bined eCIM while were negative by PCR (Table 1).
In 17 (54.8%) patients CRKPs were isolated from respira-
tory secretions. In seven (22.6%) patients CRKPs were Microbiological investigation of the outbreak
isolated from blood cultures, in four (12.9%) from cere- Of the 31 CRKP isolates, 20 (64.5%) were found to pro-
brospinal fluid, in two (6.5%) from the secretions and in duce carbapenemases. However, 6/31 K. pneumoniae
one case (3.2%) from Pus (Table 1). isolates were found to harbor genes encoding ESBLs
The age range of the patients was from 30 to 95 years, (mainly CTX-M-17 and CTX-M-3), whereas only one
with an average age of 62.4 years, and 71.0% were male. harbored AmpC genes (DHA-6). Only one strain was
The average score on the Acute Physiology and Chronic found to express 2 types carbapenemases which were
Health Evaluation II (APACHE II) index of these patients KPC-2 and NDM-1 (Table 1).
was 15.4 (Table 1). The analysis of CRKP revealed a structure dominated
The average number of days spent in hospital was by two major genetically distinct lineages; mostly MLST-
38.0 days. The average number of days for infection sequence type belonged to ST11 (21/31) and others such
development after first detection of CRKP from patients as ST147 (n = 1), ST1 (n = 1). Different strains producing
was 21.0 days, and the median was 12.0 days (Fig. 1). A different carbapenemases that were found in both major
total of 45.2% of CRKP patients received Carbapenem- related clusters belonging to different STs (Fig. 3).
Zhu et al. Antimicrobial Resistance and Infection Control (2020) 9:91 Page 6 of 9

wards during the outbreak. According to the dendro-

gram, the isolates were belonging to two closely related
clusters with different STs. Horizontal gene transfer via
highly transmissible plasmids from CRKP probably
occurred.
It is likely that our patients obtained the isolates within
wards from an unknown source after admission. The most
frequent sources in hospital outbreaks are the patients
themselves, the health care staff, or the environment [20],
with the former being the most important epidemiologi-
cally. Factors such as immunosuppression, ICU admission,
antibiotics exposure including carbapenems, invasive de-
vices are making patients at risk of infections by CRKP
[21]. The 31 patients involved in the outbreak had com-
plex, extended or repeated, and overlapping inpatient
stays, which lead to an increased risk of multidrug resist-
ance strains infection [22, 23]. Mostly of the patients who
received Carbapenem-including treatment in the 90 days
before the strains isolated. Extended-spectrum antibiotics
use could have played a major role in the loss of intestinal
microbiota diversity and made CRKP detection possible in
subsequent cultures [24–27]. The duration of CRKP
colonization is difficult to anticipate and while many
patients do experience spontaneous decolonization within
6 months to a year, multiple hospitalizations and CRE
disease can extend duration of carriage [28]. Also several
studies emphasize the importance of early identification of
carriers for infectious control purposes [29, 30]. According
to this, the AMS workers asked physicians to submission
of active surveillance cultures timely. Invasive devices and
ICU admission has been reported that significantly associ-
ated with CRKP strains [31–33]. Here we found that 12 of
our patients at ICU and 29 of our patients received inva-
sive devices including 5 neurosurgery patients. Thus, our
AMS workers have recommended that surveillance
culture of feces or rectal swabs or perianal swabs should
be performed as soon as possible after hospital admission
or risk exposure. Besides our AMS workers have required
all patients with cerebrospinal fluid drawn sanitized by
using 0.05% chlorhexidine.
The other CRKP sources are the environment, healthcare
workers’ and environmental cleaning staffs’ hands, gloves
Fig. 3 Phylogeny by the seven MLST gene sequences of 31 strains. or gowns contaminated by CRKP isolates, especially some
Patient numbers are shown on the right. The refined maximum high-touch surfaces in the CRKP positive patient zone, and
likelihood phylogeny constructed by MEGA7. ST: sequence type
thus increase potential for transmission [34–36]. During
the outbreak, transfer of unknown carriers between health-
Discussion care workers and environmental contamination probably
We report the investigation of the first hospital outbreak happened. An indirect epidemiological link for some
of CRKP in the Second Hospital of Shanxi Medical CRKP-positive cases were likely obtained the strain from
University, which demonstrated extensive clonal dissem- environmental source or via undetected intermediate
ination. The epidemiological investigation shown the patient. Outbreaks of K. pneumoniae with persisting envir-
two index patients had been transferred to regular wards onmental reservoir and high resistance to cleaning efforts
respectively. With frequent transfer of patients between have been previously reported [37]. According to this, the
the different wards, the CRKPs were disseminated to ten AMS workers isolated infected patients in a single room,
Zhu et al. Antimicrobial Resistance and Infection Control (2020) 9:91 Page 7 of 9

enhanced chlorhexidine disinfection of the rooms at least Our patients did not have a history of travel outside of
three times daily [29, 38] and training sessions in hand- China, but a number had frequent hospitalizations in
washing for healthcare workers. Shanxi province, raising concerns regarding the possi-
It also turned out that the infection control methods bility of increasing but unrecognized prevalence of
used previously were not effective in controlling the spread. NDM-1 and potential decline in value of travel history
Our infection control strategies have changed from decen- a marker of colonization risk. Although 11 strains were
tralized management to integrated management now. The negative by PCR, they were highly suspected to be other
assignment of dedicated AMS workers guided by local untested carbapenem enzymes. In Asia, the dominant
epidemiology, resource availability and the likely clinical clone is ST11 CRKP, which accounts for up to 60% of
impact of the CRKP outbreak. To support surveillance, CRKP in China [44]. Consequently, in recent years,
enhanced training on epidemiological methods, appropri- ST11 has been regarded as the most transmissible clone
ate data collection and management infrastructure have contributing to the increasing prevalence of CRKP in
also implemented. Under the comprehensive management China [40]. Our study showed that ST11 was the most
of unified leadership, timely communication, multidiscip- abundant K. pneumoniae ST type. Most ST11 CRKP
linary cooperation and effective surveillance, we success- isolates carried NDM-1 carbapenemase.
fully controlled the outbreak. There have been a few effective drugs to treat CRKP
We are now back to epidemiological stage with spor- infections, such as ceftazidime-avibactam and colistin.
adic CRKP occurrence before the outbreak. The control The new antimicrobial drug ceftazidime-avibatan can be
of CRKPs spread is still possible in hospital settings and used to treat CRKP which has no metalloenzyme [45],
relies on the use of rapid diagnostic techniques and and therefore the detection of genotype is also necessary.
strict implementation of hygiene measures. The assign- During the outbreak, Clinical pharmacists put forward
ment of dedicated AMS workers proved to be crucial suggestions on rational drug use according to the result
and a multimodal and multidisciplinary infection control of phenotypic assays. In cases where there is a lack of
strategy seems to be most effective. A study compared effective drugs, combinations of two or more antibiotics
infection control practices among nine neighboring are often used in the hopes of achieving a synergistic
hospitals in New York (NY, USA) and found that hospi- effect. The Result of mCIM combine with eCIM showed
tals that used active surveillance cultures had most NDM was the main mechanism of carbapenem resistance
success in reducing the acquisition rate of KPC-positive during the outbreak. NDM-1 confers broad spectrum
organisms [39]. Nevertheless, in our study, it is difficult beta-lactam resistance mediated by hydrolysis of all β-
to say which infection control intervention is the most lactam antimicrobials, with the exception of monobac-
effective. Infection control interventions generally are tams, such as aztreonam [9]. Therefore, our AMS workers
implemented as bundles, since no one action can be sin- used tigecycline or colistin in combination with aztreonam
gled out as effective [5]. for patients with NDM strains in controlling the outbreak.
The China Antimicrobial Resistance Surveillance Report This study have several limitations. The transmission
(http://www.carss.cn/), the largest survey of antimicrobial chain can be further elucidated with a detailed epidemio-
resistance in China, reported that the rate of carbapenem logical investigation, an analysis of plasmids and the use of
resistance in K. pneumoniae increased from 8.7% in 2016 more discriminatory genotyping such as whole-genome se-
(including 1412 tertiary-care hospital and 378 Second-level quencing or pulsed-field gel electrophoresis. Unfortunately,
hospital) to 10.1% in 2018(including 1353 tertiary-care hos- it’s impossible for us now due to the limitation of experi-
pital and 349 Second-level hospital). Fortunately, despite the mental conditions. Another limitation of our study is the
increasing CRKP prevalence recently in our hospital, cross- lack of active surveillance cultures results that could prob-
species transfer of blaNDM-1 and blaKPC-2 from K. pneu- ably give useful information about the mode of transmis-
moniae to other Enterobacteriaceae species, particularly sion and the colonization burden of the outbreak-strain.
Escherichia coli, was not detected during the outbreak. Further work is needed to determine the importance of en-
CRKP strains harboring KPC are prevalent in China [40], vironmental contamination with CRKP and the effect of ef-
the United States, Israel, Romania, Greece, Italy, and some fective decontamination on hospital infection rates. Finally,
parts of the Mediterranean region [41]. According to a CRE the other limitation of our study was retrospective design.
network to investigate the epidemiology of CRE in China
starting from 2014, only CRKP from the Northwest pro- Conclusions
duced a high level of NDM [40]. Our study showed that This study describes an outbreak of 31 CRKP strains
NDM-1 (15/31) was the main mechanism of carbapenem presumably cross-transmitted among patients hospital-
resistance during the outbreak. Currently, contact with en- ized in our hospital from October 2017 to August 2019.
demic countries, either by tourism or by healthcare, is con- The assignment of dedicated AMS workers proved to be
sidered the main risk factor for NDM-1 acquisition [42, 43]. crucial. The multimodal and multidisciplinary infection
Zhu et al. Antimicrobial Resistance and Infection Control (2020) 9:91 Page 8 of 9

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Abbreviations Characterization of a new metallo-beta-lactamase gene, bla(NDM-1), and a
CRKP: Carbapenem-resistant Klebsiella pneumoniae; AMS: Antimicrobial novel erythromycin esterase gene carried on a unique genetic structure in
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