Current Status of Antimicrobial Resistance

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Presentation transcript:

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

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

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).

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.

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

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

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

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

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

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)

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

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.

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.

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

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

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).

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

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

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.

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

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?