E coli aminoglycoside 3-10% ESBL aminoglycoside (Table 2), cefotaxime S marcescens, imipenem Acinetobacter baumannii, vancomycint e i c o p l a n i n

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1 NCCLS Table 1-3 6, , 127 (234%) 344%, 75% Serratia marcescens (105%) A n t i m i c r o b i a l a g e n t E C O C F R K P N K O X E C L E A E S M A P M I P V U M M O P S T A B A S M P ( 993 ) ( 82 ) ( 655 ) ( 53 ) ( 240 ) ( 76 ) ( 166 ) ( 48 ) ( 25 ) ( 82 ) ( 9 ) ( 518 ) ( 153 ) A m p i c i l l i n A m p i c i l l i n - s u l b a c t a m Ticarcillin-clavulanic acid P i p e r a c i l l i n P i p e r a c i l l i n - t a z o b a c t a m C e p h a l o t h i n C e f o t a x i m e 11 b b 9 b C e f t a z i d i m e 13 b b 8 b C e f o p e r a z o n e - s u l b a c t a m C e f e p i m e C e f o t e t a n C e f o x i t i n A z t r e o n a m 12 b b 9 b I m i p e n e m A m i k a c i n G e n t a m i c i n I s e p a m i c i n N e t i l m i c i n To b r a m y c i n C o t r i m o x a z o l e L e v o f l o x a c i n Te t r a c y c l i n e a ECO, E c o l i; CFR, C f r e u n d i i; KPN, K p n e u m o n i a e; KOX, K o x y t o c a; ECL, E c l o a c a e; EAE, E a e r o g e n e s; SMA, S m a r c e s c e n s; PMI, P m i r a b i l i s; PVU,P vulgaris; MMO, M morganii; P S T, P stuartii; ABA, A baumannii;smp, S m a l t o p h i l i a; No tested b Extended-spectrum -lactamase (ESBL) breakpoint were not applied for resistance rate of E coli and Klebsiella spp to 3rdgeneration cephalosporins

2 E coli aminoglycoside 3-10% ESBL aminoglycoside (Table 2), cefotaxime S marcescens, imipenem Acinetobacter baumannii, vancomycint e i c o p l a n i n 1% 6% (Table 1) 26%12% imipenem Pseudomonas aeru g i n o s a (Table 3) 22 % 12 % - l a c t a m Antimicrobial agent R I S A n t i m i c r o b i a l S A U C N S E FA E F M a g e n t ( 995 ) ( 431 ) ( 526 ) ( 303 ) Piperacillin Piperacillin-tazobactam Ampicillin NT NT 0 96 Ticarcillin-clavulanic acid Penicillin G NT NT Ceftazidime Oxacillin NT NT Cefepime Clindamycin NT NT Cefoperazone-sulbactam Cotrimoxazole NT NT Aztreonam Erythromycin Imipenem Tetracycline Amikacin Ciprofloxacin NT NT Gentamicin Pefloxacin NT NT Isepamicin Fusidic acid 4 21 NT NT Netilmicin Teicoplanin Tobramycin Vancomycin Ciprofloxacin S A U, S aure u s; CNS, coagulase-negative S t a p h y l o c o c c u s; No tested, 971 E FA, E faecalis; EFM, E faecium; NT, not tested; No tested methodology for fusidic acid Diag Microbiol Infect Dis 40: , 2001] MRSA, vancomycin Fusidic acid, methicillin, C l o s t r i d i u m s p p, Corynebacterium spp fusidic acidnccls breakpoint Skov (1)NCCLS fusidic acidbreakpoint 1 [ Va n c o m y c i n S aure u s : (1) Skov R, Frimodt-Moller N, Espersen F: Correlation of MIC methods and tentative interpretive criteria for disk diffusion susceptibility testing using NCCLS VRSA, VISA GISA [7(4):5] v a n c o m y c i n 2

3 , v a n c o m y c i n N C C L S v a n c o m y c i nm I C8-16 m l V I S A MIC 4 / m l Linares (1), 32 / m l Hiramatsu Mu50 v a n c o m y c i nm I C8 / m l, V I S A v a n c o m y c i n VRSA 1, 2, 4, 8, /ml v a n c o m y c i nm I C5-7 / m l (,, /ml) Etest M u l l e r-hinton agar MIC (5-15) 16 /ml VISA [ : Linares J: The VISA/GISA problem: therapeutic implications Clin Microbiol Infect 7:S8-15, 2001], biofilm,, cystic fibrosis ( ), : Costerton (1)biofilm, (MIC) biofilm,, biofilm Biofilmgel biofilm, bacteriophage,, biofilm,, biocide Biofilm Biofilm, Plastic, 1) (microcolony) 2) biofilm biofilm polymer, 3) pili, lipopolysaccharide O, teichoic acid, exopolysaccharide, e x o p o l y s a c c h a r i d e P s e u d o m o n a s 4) glycocalyx polymer, 3

4 pacemaker S aureus Biofilmtransparent dressing,, biofilm Biocide,,, Hickman biofilm silastic cardiac catheter,, Swan-Ganz catheter, dacron, cardiac pacemaker,, Te n c k o ff c a t h e t e r, Foley Johnson ( 3 )n i t r o f u r a z o n e catheter vancomycin E c a t h e t e r,,,, f a e c i u m E coli, K pneumoniae, C Biofilm freundii, S aureus CNS 5 nitrofurazone biofilm cm Catheter Candida albicansbiofilm : Catheter C albicans b i o f i l m, hyphae R h o d o c o c c u s, pseudohyphae, amphotericin B, fluconazole Mycobacterium avium-intracellulare, Cory n e b a c t e r i u m BasileDouglas (4) acquaticum, Pseudomonas mesophilia, P putida,, C Agrobacterium radiobacter, albicans biofilm amphotericin B 01 coagulase / m l b i o f i l m Staphylococcus (CNS) catheter ( a d h e r e ), (colonize), (2) C N Splastic catheter Plastic d i ffuse panbronchitis (5) Diff u s e CNS SlimeCNS panbronchitis 70% P aeruginosa, biofilm exopolysaccharide CNS2/3slime, alginate, P aeruginosa CNS2/3slime alginate biofilm catheter biofilm Slime P aeru g i n o s a, biofilm (2), P aeruginosa alginate : Biofilm, alginate,, Alginate g u a n o s i n e (planktonic cell) diphospho-d-mannose dehydrogenase( G M D ) Mitsuya biocide,,, (5) P aeruginosa PAO-1, GMD biofilm, P aeruginosa P aeru g i n o s a 50 / m l GMD tobramycin8, biofilm 1000 / m l m a c r o l i d ee r y t h r o m y c i n1 6 m i d e c a m y c i np aeru g i n o s a Endocardial erythromycinalginate pacemaker S aureus biofilm 6 cloxacillinrifampicin 4

5 erythromycin GMD Microbiol Rev 6:176-92, 1993; (3) Johnson JR, Delavari, midecamycin GMD P, Azar M: Activities of a nitrofurazone-containing urinary erythromycinteflon catheter and a silver hydrogel catheter against multidrugresistant bacteria characteristic of catheter - a s s o c i a t e d f i l t e rb i o f i l m, e r y t h r o m y c i nd i ffuse panbronchitis urinary tract infection AAC 43:2990-5, 1999; (4) Basille biofilm G, Douglas LJ: Iron-limited biofilm of Candida albicans clarithromycin azithromycin and their susceptibility to amphotericin B Antimicrob [ : (1) Costerton JW, Agents Chemother 42:2146-9, 1999; (5) Mitsuya Y, Lewandowski Z, Caldwell DE, Korber DR, Lappin-Scott Kawai S, Kobayashi H: Influence of macrolides on HM: Microbial biofilms Ann Rev Microbiol 49:711-45, guanosine diphospho-d-mannose dehydrgenase activity in 1995; (2) Goldmann DA, Pier GB: Pathogenesis of Pseudomonas biofilm J Infect Chemother 6: 45-50, 2000] infections related to intravascular catheterization Clin,,, (1) (: ) (2) (1, 2) (2) 1),,, penicillin 2),,, 3), [ (1) Levin BR: Minimizing potential resistance: A population dynamics view Clin Infect Dis 33:S161-9, 2001; (2), Kristinson KG: Mathematical models as tools for evaluating the effectiveness of interventions: a comment on Levin Clin Infect Dis 33:S174-9, 2001], 5

6 vancomycinmic >16 / m l4 / m l, 2 S aureus vancomycin MIC 18 4 / m l, 24 8 / m l Oxacillin MIC >16 / m l 05 / m l E t e s t vancomycin MIC 6 / m l, vancomycin 6 / m l BHI Vancomycin-intermediate Staphylococcus aure u s CDC V I S A, ( V I S A )1 997 o x a c i l l i nm I C05 / m l,,, 10, m e c A MSSA V I S A C D CV I S A h V I S A, 1) VISA 2 VISA, 2) VISAvancomycin S aureus VISA 24, UCLAMarlowe (1) 3) VISA, 4) VISA VISA Va n c o m y c i n S aureusvisa, 5) VISA UCLA 20006vancomycin VISA S aureus 1 S [ (1): Marlowe EM, Cohen MD, Hindler JF, a u re u s o x a c i l l i nv a n c o m y c i n Ward KW, Bruckner DA: Practical strategies for MIC >16 / m l2 / m l detecting and confirming vancomycin-intermediate S Staphylococcus aureus : a tertiary-care hospital aureus, oxacillin laboratory's experience 39: , 2001] VISA MIC Vancomycin MIC 2 g/ml 4 g/ml VISA VISA VISA Vancomycin MIC 2 g/ml 4 g/ml VISA VISA : BHI-Vancomycin (6 g/ml) Etest : Vancomycin MIC 6 g/ml : Vancomycin MIC 8 g/ml 1 VISA 6

K pneumoniae imipenem meropenem 10% ESBL 1983, Imipenemmeropenem imipenem, MICmeropenem ESBL E coli98%klebsiella spp256%esbl meropenem (1) ESBL 1995 (1) ESBL 36 2000 119 (2) ESBL P a t e r s o n (3)

7 K pneumoniae imipenem meropenem 10% ESBL 1983, Imipenemmeropenem imipenem, MICmeropenem ESBL E coli98%klebsiella spp256%esbl meropenem (1) ESBL 1995 (1) ESBL (2) ESBL P a t e r s o n (3) ESBL 3 cephalosporin, ESBL ESBL piperacillin-tazobactam %, % CarbapenemESBL ESBL carbapenemamikacin aminoglycoside, carbapenem ESBL aminoglycoside - l a c t a m Quinolone ceftazidime MIC >256 / m l, ceftriaxone ESBL quinolone cefotaximemic<16 / m l NCCLS 3 c e p h a l o s p o r i nesbl Cefepime 4 c e p h a l o s p o r i n3 cephalosporin ESBL, Imipenem m e r o p e n e m 3 cephalosporin Imipenem m e r o p e n e m MIC cefepimeesbl Imipenem meropenem 1 Fluoroquinolone F l u o r o q u i n o l o n e F l u o r o q u i n o l o n e F l u o r o q u i n o l o n e A m o x i c i l l i n - c l a v u l a n a t e, aminoglycoside Meropenem Polymixin B Cephamycin ESBL carbapenem, [ (1),,,,, : 12 e x t e n d e d - 2 spectrum -lactamase Escherichia coli Klebsiella pneumoniae 18 : lactam -lactamase ESBL 410, 2000; (2) Bush K: New -lactamases in gram-, 3negative bacteria: diversity and impact on the selection cephalosporin of antimicrobial therapy Clin Infect Dis 32;1085-9, MIC, ESBL 2001; (3) Paternson DL: Recommendation for treatment of severe infections caused by E n t e ro b a c t e r i a c e a e producing extended-spectrum -lactamases (ESBLs), Clin Microbiol Infect 6: , 2000] 7

8 1 Mutant selection window MICMPC mutant selection window, Drlica (1) Mutation selection window Selection window H e t e r o r e s i s t a n c e M R S A ( M I C5 0) Tomasz (1)MRSA Selection window 1 (%) (/ml)methicillin M R S A4 expression class 2 Hiramatsu (2) vancomycin MIC 2 M R S A h e t e r o - v a n c o m y c i n - r e s i s t a n t S aure u s (hetero-vrsa; vancomycin MIC2 / m l fluoroquinolone 10-7, NCCLS 2 ) ( 7(4) p 5 ) Alam (3)vancomycin E faecium h e t e r o r e s i s t a n c e s e l e c t i o n 31 MRSA window v a n c o m y c i n6 E mutant prevention f a e c i u m, concentration (MPC) vancomycin (MIC 025/ m l), Fluoroquinolone MICMPC (MIC 256 / m l) NorfloxacinMIC031 / m l Etest MIC10 / m l MPC70 / m l 23 M I CM P C selection window PCRvanA C-8-methoxy, heteroresistant VRE VRE fluoroquinolonemic011 / m l MPC04 / m l 36,, Etest, [ (1) Tomasz A, Nachman S, isoniazidempc Leaf H: Stable classes of phenotypic expression in rifampin methicillin-resistant clinical isolates of staphylococci E coli MPC Antimicrob Agents Chemother 35:124-9, 1991; (2) Hiramatsu K, Aritaka N, Kobayashi I: Dissemination in [ : (1) Drlica K: A Japanese hospitals of strains of Staphylococcus aure u s strategy for fighting antibiotic resistance ASM News heterogeneously resistant to vancomycin Lancet 67:27-33, 2001] 350:1670-3, 1997; (3) Alam MR, Donabedian S, Brown 8

9 W, Gordon J, Chow JW, Zervos MJ, Hershberger E: Penicillin tolerancepenicillin Heteroresistance to vancomycin in Enterococcus faecium J Clin Microbiol 39: , 2001] tolerance, lysis-and-kill curve tolerance [ (1) McCullers JA, English BK, Novak R: Isolation and characterization of vancomycin-tolerant S t re p t o c o c c u s B a c t e ro i d e s p n e u m o n i a e from cerebrospinal fluid of a patient who B a c t e ro i d e s 5 - developed recrudescent meningitis J Infect Dis nitroimidazole (5-Ni), metronidazole, 181: , 2000] tinidazole ornidazole Bacteroides n i m5-nitroimidazole 5-Ni B a c t e ro i d e s 4 n i m nima, nimb, nimc n i m D p l a s m i d, i n t e g r o n ( c o n j u g a t i o n ) B a c t e ro i d e s P re v o t e l l a (antibiotic associated diarrhea) B a c t e ro i d e s m e t r o n i d a z o l e, S aureus tinidazole o r n i d a z o l em I C4 /ml, C difficile n i m [ C perfringens : (1) Haggoud A, M'Hand RA, Reysset G, M'Daghri C difficile NE, Benbachir M, Moumni M: Prevalence and characteristics of n i m genes encoding 5-nitroimidazole (pseudomembranous colitis) resistance among B a c t e ro i d e s strains isolated in Morocco, Microb Drug Resist 7: , 2001] A (, ) B (, ), B C difficile C difficile diseasec difficile C difficile 21 % antibiotic associated diarrhea p e n i c i l l i ncefotaxime, 1%, v a n c o m y c i n vancomycin tolerance (1) McCullers ( 1 ) C difficile vancomycincefotaxime c e p h a l o s p o r i n, ampicillinamoxicillin, clindamycin, p e n i c i l l i n, erythromycin v a n c o m y c i nt o l e r a n c e macrolide, tetracycline, t r i m e t h o p r i m - s u l f o m e t h o x a z o l e [ : (1) Garcia-Lechuz JM, Hernangomez S, San Juan R, tolerance Peldez T, Alcala L, Bouza E: Extra-intestinal infections vancomycin tolerance caused by Clostridium difficile Clin Microbiol Infect 7:453- penicillin tolerance , 2001] 9

10 ,, K p n e u m o n i a e [ : (1) Essack S, Hall LMC, Pillay DG, McFadyen ML, Livermore DM: Complexity and diversity of Klebsiella pneumoniae strains with extendedspectrum -lactamase isolated in 1994 and 1996 at a TEM-52 E S B L C T X - ME S B Lceftazidime c e f o t a x i m e teaching hospital in Durban, South Africa (Toho), Antimicrob Agents Chemother 45:88-95, 2001] E colisalmonella Ty p h i m u r i u m T E M S H VESBL, CTX-M Shigella sonnei C T X - M - 14E S B L (1) C T X - M - 14 E colik pneumoniae E S B L [ : (1) : 12:48, 2001; Glycopeptide MRSA (2) Pai H, Choi E-H, Lee H-J, Hong JY, Jacoby GA:, glycopeptide Identification of CTX-M-14 extended-spectrum - Quinupristin-dalfopristin lactamase in clinical isolates of Shigella sonnei, l i n e z o l i d MRSA Escherichia coli, a n d Klebsiella pneumoniae i n Quinupristin-dalfopristin Korea J Clin Microbiol 39:3747-9, 2001] q u i n u p r i s t i nstreptogramin B dalfopristinstreptogramin A, m a c r o l i d e Staphylococcus Werner (1) , 052 S aure u s 35 q u i n u p r i s t i n - dalfopristin (MIC 2 / m l) ESBL quinupristin-dalfopristin Essack (1) 3 cephalosporin 25 pristinamycin Klebsiella pneumoniae 20 ESBL, S HV- 2, - 5, - 19, S aure u s -20, -21, -22 TEM-53, -63 streptogramin SHV-19, -20, -21, -22, TEM-63 S aureus [ : (1) Werner G, Cuny C, Schmitz F-J, ESBL Witte W: Methicillin-resistant, quinupristindalfopristin-resistant Staphylococcus aure u s w i t h, 3 (clonal spread) reduced sensitivity to glycopeptides J Clin ESBL (horizontal transfer) Microbiol 39: , 2001] 10

11 - penicillin, 1 :11 - -lactamase-negative ampicillin-resistant H influenzae, 3 :11 - Gentamicin S aureus MRSA?, 1:11 - avoparcinvirginiamycin, 1:6 -, 4:5 - Fluoroquinolone, 2:8 - breakpoint, 3:3 - imipenem ampicillin, 3: 2 - breakpoint, 2:3 - vancomycin tolerance, 4:9 - fusidic acidbreakpoint, 4:2 - Class B -lactamasesubclass, 2:9 - Cefditoren, 2:2 - EagleMRSA, 2:9 - Colistinpolymixin B, 1:3 - HeteroVancomyan E faecium, 4:8 - VISA/GISAbreakpoint, 4:2 - Lantibiotics, 3:10 - Macrolide, lincosamide streptogramin (MLS), 1:9 - ESBL, 1:8 - MurM, 3:10 - ESBL, 4:7 -Mutant selection windowmutant prevention concentration, - Ketolidetelithromycin, 3:6 4:8 - nim, 4:9 - Photobactericide, 2: , 1:1 - Tolerance, 3: , 2:1 - Vancomycin-resistant S aureus, 2: , 3: , 4:1 - ESBL!, 1:11 -, 2:11 - BLNAR H influenzae, 3:9 - CTX-MESBL, Quinupristin-dalfopristin - Haemophilus influenzae, 1:6 g l y c o p e p t i d e MRSA, - Vancomycin ESBL, 4:10 practical strategy, 4:6 -, 3:11 - WHO, 2:7 - Janthinobacterium lividumm e t a l l o -- l a c t a m a s e!!, 2:11 -, 1:3 - Biofilm, 4:3 - Carbapenem-hydrolyzing OXA-type enzyme, 2:5-3 cephalosporin?, 2:11 - Coagulase Staphylococcusglycopeptide, 2:4 - ciprofloxacin?, 4:11 - Fluoroquinolone, 3:4 11

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(59-69)Kjcm13.hwp Korean J Clin Microbiol Vol. 10, No. 1, April, 2007 Antimicrobial Resistance of Clinically Important Bacteria Isolated from 12 Hospitals in Korea in 2005 and 2006 Hyukmin Lee 1, Chang Ki Kim 2, Jongwook