1. Current Status of Antimicrobial Resistance
in Gram-Negative Bacilli from Korea
김 태라
미생물 파트

2. Antimicrobial resistance (%) in clinical isolates of
gram-negative bacilli from Korea in 2007
Strain
AMP
A/S
PIP
FOX
CTX
CAZ
FEP
IMP
MER AK FQ 67 27 8 13 11 11 3 32
E. coli ND 63
K. pneumoniae NR 34 20 34 36 25
0.2 ND 20 32 52 40 24 33 4
0.5 5 17
C. freundii NR NR ND
E. cloacae NR 63 42 NR 36 40 11
0.1 ND 6 10 NR 80 40 NR 28 24 14
0.5 16 19
S. marcescens ND NR 40 62 63 57 55 27 40 52 64
A. baumannii NR NR 30 NR 21 21 23 19 21 35
P. aeruginosa NR ND
NR, natural resistance; ND, not done.
Collection of routine susceptibility data from 12 university &
general hospitals in Korea in 2007

3. SHV & TEM enzymes: the classical ESBLs
Can hydrolyze:
penicillins
narrow-spect. cephalosporins
oxyimino-cephalosporins
monobactams
Cannot hydrolyze:
cephamycins
carbapenems
Inhibited by:
clavulanic acid, sulbactam,
tazobactam
Frequent loci for substitutions affecting the
substrate specificity of SHV & TEM -lactamases
(Page MGP, CMI, 2008).

4. CTX-M ESBLs: a rapidly growing family
CTX-M-1 cluster
CTX-M-9 cluster
CTX-M-2 cluster
CTX-M-25 cluster
CTX-M-8 cluster
CTX-M-45
The six known clusters of CTX-M ESBLs.

5. Worldwide distribution of CTX-M ESBLs
(Canton & Coque, 2006)

6. Prevalence of ESBLs in Korea
35.2% ◎
K. pneumoniae
23%
22% ◎ ◎
14.2% ■
9.3% ■
E. coli
4.8% ■
1997
2003
2007

7. Distribution of ESBLs in E. coli from Korea (2007)
Gangwon
CTX-M-3, -15
CTX-M-3, -15, -57
CTX-M-14
Seoul
CTX-M-14, -27
Gyeonggi
CTX-M-3, -15
Gyeongbuk
CTX-M-14
CTX-M-3, -15
CTX-M-14
CTX-M-3, -15
CTX-M-3, -15
Busan
CTX-M-9, -14
CTX-M-14
Gwangju
CTX-M-15
Jeju
CTX-M-14

8. Type of ESBLs in E. coli isolates from Korea (2007)
CTX-M + SHV % (1/78)
SHV-12, 1.3% (1/78)
CTX-M, 97.4% (76/78)

9. CTX-M ESBLs in E. coli isolates from Korea (2007)
CTX-M-1 cluster (n=42)
CTX-M-15 (n=27)
CTX-M-3 (n=10)
CTX-M-22 (n=2)
CTX-M-57 (n=2)
CTX-M-12 (n=1)
CTX-M-9 cluster (n=35)
CTX-M-14 (n=32)
CTX-M-9 (n=2)
CTX-M-27 (n=1)
Yellow: ceftazidimase

10. Type of ESBLs in K. pneumoniae isolates from Korea (2005)
CTX-M (n=11)
SHV-2a (n=1)
SHV-2a + CTX-M (n=1)
TEM-52 (n=1)
GES-5 (n=3)
CTX-M, (31/163)
SHV-12 + CTX-M, 11.7% (19/163)
SHV-12, 77.9% (127/163)

11. Other resistance genes in ESBL-producing E. coli
AmpC
16S rRNA
Methylase
qnr
aac(6’)-Ib-cr

12. Carbapenem resistance in gram-negative bacilli
Strain
AMP
A/S
PIP
FOX
CTX
CAZ
FEP
IMP
MER AK FQ 67 27 ND 8 13 11 11 3 32
E. coli 63
K. pneumoniae NR 34 20 34 36 25
0.2 ND 20 32 52 40 24 33 4
0.5 5 17
C. freundii NR NR ND
E. cloacae NR 63 42 NR 36 40 11
0.1 ND 6 10 NR 80 40 NR 28 24 14
0.5 16 19
S. marcescens ND
A. baumannii NR 40 62 63 57 55 27 40 52 64 NR NR NR 30 NR ND 21 21 23 19 21 35
P. aeruginosa
Collection of routine susceptibility data from 12 university &
general hospitals in Korea in 2007
NR, natural resistance; ND, not done.

13. Carbapenem resistance mechanisms
Loss of porin, over expression of efflux system
-lactamases
A. Non-carbapenemases (plasmid-mediated ESBL or AmpC
-lactamases plus porin loss)
B. Carbapenemases
1. Serine -lactamases
1) Class A : KPC-1 to -5, GES-2, -4, -5, & -6
2) Class D (group 2d): OXA carbapenemases
2. Metallo--lactamases- mainly in Pseudomonas &
Acinetobacter spp.

14. Carbapenem resistance in K. pneumoniae
42 imipenem-non-susceptible K. pneumoniae between 2002 and 2004 in a Korean hospital (Lee et al., IJAA, 2007).
VIM-2 MBL (2), CMY-2 (24), DHA-1 (16)
Effect of addition of BA on MICs of imipenem
IMP
IMP+BA
MIC (mg/L)
Range
MIC50
blaCMY-2 (n = 24)
blaDHA-1 (n = 16)
8-32
1-4 32 1 2

15. SDS-PAGE profile of OMPs
(A) 1: Control 2: CMY (B) 1: Control 2: DHA-1
Lee et al. (IJAA, 2007)

16. Carbapenem resistance in Acinetobacter spp.
OXA-51 (-), 7.6% (15/197)
OXA-51 (+), 92.4% (182/197)
Imipenem-resistant or intermediate isolates from 12 university and general hospital laboratories in Korea in 2007 (n=197).

17. Carbapenem resistance in A. baumannii
OXA-23/MBL (-), 20.3% (37/182)
VIM-2 (+), 1.1% (2/182)
OXA-23 (+), 78.6% (143/182)

18. Carbapenem resistance in Acinetobacter spp.
OXA/MBL (-), 20% (3/15)
MBL (+), 80% (12/15)
IMP-1 (9)
VIM-2 (2)
SIM-1 (1)

19. Carbapenem resistance in P. aeruginosa
MBL (+), 13% (50/373)
IMP-6 (19)
VIM-2 (30)
SIM-1 (1)
MBL (-), 87% (323/373)
Carbapenem resistance in P. aeruginosa
Imipenem-resistant or intermediate isolates (n = 373) from 12 university and general hospital laboratories in Korea in 2007.

20. Summary I Prevalence of ESBL-producers: Dominant types of ESBLs:
E. coli: 4.8% (1997)  14.2% (2007)
K. pneumoniae: 22% (1997)  35.2% (2007)
Dominant types of ESBLs:
E. coli, CTX-M-14 & CTX-M-15; K. pneumoniae, SHV-12
Other resistance genes in ESBL-producing E. coli:
AmpC -lactamase, 9.8%; 16S rRNA methylase, 18.5%
qnr gene, ~8%; aac(6’)-Ib-cr, 70.4%
Carbapenem-resistant K. pneumoniae:
CMY-2/DHA-1 + diminished expression of OmpK35/36

21. Summary II OXA-23 carbapenemase – main problem in A. baumannii
MBL – Acinetobacter spp. other than A. baumannii
Only 13% (50/373) of carbapenem-resistant P. aeruginosa isolates in 2007 produced MBLs.
Further study: What’s the main mechanism in P. aeruginosa?