AAC Accepts, published online ahead of print on 18 February 2014 Antimicrob. Agents Chemother. doi:10.1128/AAC.02047-13 Copyright © 2014, American Society for Microbiology. All Rights Reserved.
1
Spread of NDM-1-producing Enterobacteriaceae in a neonatal
2
intensive care unit, Istanbul, Turkey
3
Laurent Poirel,1,2 Mesut Yilmaz,3 Ayse Istanbullu4, Ferhat Arslan3, Ali Mert3,
4
Sandrine Bernabeu,2 and Patrice Nordmann1,2*
5 6
1
Medical and Molecular Microbiology Unit, Department of Medicine, Faculty of Science,
7
University of Fribourg, Switzerland, 2INSERM U914, South-Paris Medical School, K.-Bicêtre,
8
France, 3Infectious Diseases and Clinical Microbiology Department, and 4Medical Microbiology
9
Department, School of Medicine, Istanbul Medipol University, Istanbul, Turkey 4
10 11 12
Key words : NDM-1, Enterobacter cloacae, carbapenemase, Turkey.
13
Running title : NDM-1 outbreak in NICU
14 15
*Corresponding author. Mailing address: Medical and Molecular Microbiology Unit, Department
16
of Medicine, Faculty of Science, University of Fribourg, rue Albert-Gockel 3,
17
Fribourg, Switzerland. Phone: 41-26-300-9581. E-mail: [email protected]
CH-1700
18
1
19
Twenty-two consecutive carbapenem-resistant enterobacterial isolates were recovered
20
from patients hospitalized between January and April 2013 in different units at a University
21
hospital
22
carbapenemases OXA-48, NDM-1, and KPC-2, Enterobacter cloacae producing NDM-1, and
23
Escherichia coli producing OXA-48, respectively. Most of the OXA-48-producing K.
24
pneumoniae, and all the NDM-1-producing E. cloacae, respectively, were clonally-related. The
25
NDM-1-producing E. cloacae isolates recovered from a single neonatal intensive care unit
26
corresponded to a single cluster highlighting the spread of that clone on that setting.
in
Istanbul,
Turkey.
There
were
Klebsiella
pneumoniae
producing
the
27
2
28
Carbapenem-hydrolyzing β-lactamases belonging to Ambler classes A, B and D have been
29
reported worldwide among Enterobacteriaceae (1, 2). In Turkey, the wide dissemination of OXA-
30
48-producing isolates (Klebsiella pneumoniae, Escherichia coli, Citrobacter freundii, Enterobacter
31
cloacae) has been demonstrated, defining this country has endemic for OXA-48 (3-5). Apart from
32
OXA-48 producers, isolates producing other types of carbapenemases (NDM-1, IMP-1, KPC-2)
33
have been recently identified in Turkey as well. The non-OXA-48-producing carbapenemase
34
producers reported from Turkey are the followings ; six NDM-1-producing K. pneumoniae (6, 7),
35
four IMP-1-producing K. pneumoniae (7, 8), and a single KPC-2-producing K. pneumoniae (9).
36
The spread of NDM-1-producing Enterobacteriaceae is now considered to be almost global
37
(10). However, only few outbreaks of NDM-1 producers have been reported. So far most of the
38
reports in many countries have been scattered and corresponded mainly to importation cases (1).
39
Our study was designed to evaluate retrospectively the occurrence of carbapenemase-
40
producing Enterobacteriaceae in a University hospital in Istanbul, Turkey. Actually, an increased
41
number of carbapenem-resistant isolates recovered from patients hospitalized at the Neonatal
42
Intensive Care Unit (NICU) during a short period prompted us to perform such a study.
43
All enterobacterial isolates presenting with a reduced susceptibility to imipenem (MIC ≥ 0.5
44
µg/ml) were collected between Jan 1st to May 1st, 2013 (4 month-period), consisting in a total of
45
twenty-two isolates. The MICs of carbapenems were determined by Etest (AB bioMérieux; La 3
46
Balme-les-Grottes, France) on Mueller-Hinton agar plates at 37°C and results of susceptibility
47
testing were interpreted according to the CLSI guidelines (11). Those isolates were recovered from
48
urine mostly, and from rectal swabs (Table). All isolates were considered as colonizers. There were
49
K. pneumoniae (n = 12), E. cloacae (n = 8), and E. coli (n = 2) (Table 1). The isolates were resistant
50
to all β-lactams, including carbapenems for most isolates (Table 2). However, some isolates were
51
still categorized in the susceptibility range for carbapenems (Table 2). In addition, they were mostly
52
resistant to aminoglycosides, fluoroquinolones, chloramphenicol, sulfonamides, fosfomycin and
53
nitrofurantoin. All except two had low MIC values (
1
Spread of NDM-1-producing Enterobacteriaceae in a neonatal
2
intensive care unit, Istanbul, Turkey
3
Laurent Poirel,1,2 Mesut Yilmaz,3 Ayse Istanbullu4, Ferhat Arslan3, Ali Mert3,
4
Sandrine Bernabeu,2 and Patrice Nordmann1,2*
5 6
1
Medical and Molecular Microbiology Unit, Department of Medicine, Faculty of Science,
7
University of Fribourg, Switzerland, 2INSERM U914, South-Paris Medical School, K.-Bicêtre,
8
France, 3Infectious Diseases and Clinical Microbiology Department, and 4Medical Microbiology
9
Department, School of Medicine, Istanbul Medipol University, Istanbul, Turkey 4
10 11 12
Key words : NDM-1, Enterobacter cloacae, carbapenemase, Turkey.
13
Running title : NDM-1 outbreak in NICU
14 15
*Corresponding author. Mailing address: Medical and Molecular Microbiology Unit, Department
16
of Medicine, Faculty of Science, University of Fribourg, rue Albert-Gockel 3,
17
Fribourg, Switzerland. Phone: 41-26-300-9581. E-mail: [email protected]
CH-1700
18
1
19
Twenty-two consecutive carbapenem-resistant enterobacterial isolates were recovered
20
from patients hospitalized between January and April 2013 in different units at a University
21
hospital
22
carbapenemases OXA-48, NDM-1, and KPC-2, Enterobacter cloacae producing NDM-1, and
23
Escherichia coli producing OXA-48, respectively. Most of the OXA-48-producing K.
24
pneumoniae, and all the NDM-1-producing E. cloacae, respectively, were clonally-related. The
25
NDM-1-producing E. cloacae isolates recovered from a single neonatal intensive care unit
26
corresponded to a single cluster highlighting the spread of that clone on that setting.
in
Istanbul,
Turkey.
There
were
Klebsiella
pneumoniae
producing
the
27
2
28
Carbapenem-hydrolyzing β-lactamases belonging to Ambler classes A, B and D have been
29
reported worldwide among Enterobacteriaceae (1, 2). In Turkey, the wide dissemination of OXA-
30
48-producing isolates (Klebsiella pneumoniae, Escherichia coli, Citrobacter freundii, Enterobacter
31
cloacae) has been demonstrated, defining this country has endemic for OXA-48 (3-5). Apart from
32
OXA-48 producers, isolates producing other types of carbapenemases (NDM-1, IMP-1, KPC-2)
33
have been recently identified in Turkey as well. The non-OXA-48-producing carbapenemase
34
producers reported from Turkey are the followings ; six NDM-1-producing K. pneumoniae (6, 7),
35
four IMP-1-producing K. pneumoniae (7, 8), and a single KPC-2-producing K. pneumoniae (9).
36
The spread of NDM-1-producing Enterobacteriaceae is now considered to be almost global
37
(10). However, only few outbreaks of NDM-1 producers have been reported. So far most of the
38
reports in many countries have been scattered and corresponded mainly to importation cases (1).
39
Our study was designed to evaluate retrospectively the occurrence of carbapenemase-
40
producing Enterobacteriaceae in a University hospital in Istanbul, Turkey. Actually, an increased
41
number of carbapenem-resistant isolates recovered from patients hospitalized at the Neonatal
42
Intensive Care Unit (NICU) during a short period prompted us to perform such a study.
43
All enterobacterial isolates presenting with a reduced susceptibility to imipenem (MIC ≥ 0.5
44
µg/ml) were collected between Jan 1st to May 1st, 2013 (4 month-period), consisting in a total of
45
twenty-two isolates. The MICs of carbapenems were determined by Etest (AB bioMérieux; La 3
46
Balme-les-Grottes, France) on Mueller-Hinton agar plates at 37°C and results of susceptibility
47
testing were interpreted according to the CLSI guidelines (11). Those isolates were recovered from
48
urine mostly, and from rectal swabs (Table). All isolates were considered as colonizers. There were
49
K. pneumoniae (n = 12), E. cloacae (n = 8), and E. coli (n = 2) (Table 1). The isolates were resistant
50
to all β-lactams, including carbapenems for most isolates (Table 2). However, some isolates were
51
still categorized in the susceptibility range for carbapenems (Table 2). In addition, they were mostly
52
resistant to aminoglycosides, fluoroquinolones, chloramphenicol, sulfonamides, fosfomycin and
53
nitrofurantoin. All except two had low MIC values (
