NCCLS Table 1-3 6,326 4-6 5, 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 75 94 99 98 98 96 99 38 92 100 89 96 99 A m p i c i l l i n - s u l b a c t a m 27 50 47 17 59 43 95 0 8 56 44 26 89 Ticarcillin-clavulanic acid 8 40 28 9 40 18 27 0 0 6 0 45 9 P i p e r a c i l l i n 47 44 58 26 44 29 47 0 0 20 22 67 80 P i p e r a c i l l i n - t a z o b a c t a m 3 18 17 6 17 17 21 0 0 0 0 41 49 C e p h a l o t h i n 38 85 56 24 96 88 100 4 92 99 56 99 99 C e f o t a x i m e 11 b 28 24 b 9 b 28 18 34 0 0 15 0 73 92 C e f t a z i d i m e 13 b 29 38 b 8 b 35 24 9 0 0 13 0 67 39 C e f o p e r a z o n e - s u l b a c t a m 2 16 8 8 4 0 10 0 0 0 0 16 9 C e f e p i m e 1 1 3 4 1 0 5 0 0 0 0 56 50 C e f o t e t a n 3 32 8 8 36 28 10 0 0 4 0 93 11 C e f o x i t i n 9 93 26 15 96 88 66 2 0 38 0 96 99 A z t r e o n a m 12 b 23 35 b 9 b 29 12 7 0 0 1 0 83 97 I m i p e n e m 0 0 0 0 0 0 0 0 0 0 0 6 100 A m i k a c i n 13 22 27 8 21 9 26 0 0 11 0 51 80 G e n t a m i c i n 34 35 47 17 39 17 33 17 0 33 67 68 76 I s e p a m i c i n 5 21 13 2 6 0 22 2 0 11 11 74 81 N e t i l m i c i n 15 27 41 8 34 17 31 2 0 11 33 64 54 To b r a m y c i n 30 35 53 17 46 17 68 8 0 16 78 68 77 C o t r i m o x a z o l e 57 39 39 19 38 4 43 27 33 39 22 62 20 L e v o f l o x a c i n 41 15 12 9 15 2 9 5 9 13 14 59 12 Te t r a c y c l i n e 71 28 38 19 22 24 90 100 80 73 89 68 93 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
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 49-51 Piperacillin-tazobactam 35-65 Ampicillin NT NT 0 96 Ticarcillin-clavulanic acid 56-44 Penicillin G 97 87 NT NT Ceftazidime 16 4 80 Oxacillin 71 71 NT NT Cefepime 15 10 75 Clindamycin 66 48 NT NT Cefoperazone-sulbactam 21 24 56 Cotrimoxazole 10 52 NT NT Aztreonam 19 28 54 Erythromycin 74 62 73 95 Imipenem 12 4 85 Tetracycline 62 33 82 17 Amikacin 33 3 64 Ciprofloxacin NT NT 47 92 Gentamicin 54 3 43 Pefloxacin 69 51 NT NT Isepamicin 38 5 57 Fusidic acid 4 21 NT NT Netilmicin 47 6 48 Teicoplanin 0 0 1 12 Tobramycin 51 2 47 Vancomycin 0 0 1 26 Ciprofloxacin 52 3 45 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 40:111-116, 2001] MRSA, vancomycin 5 20 17 19-24 14-18 10 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 21 18 20-25 15-20 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
, 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, 4 5-7 8-16 32 /ml 4-4-16 16 v a n c o m y c i nm I C5-7 / m l (,, 4 5-7 - 8 5-8 /ml) Etest 4 5-8 - 8 M u l l e r-hinton agar MIC 6 4 - (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
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 3 100 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 12 14 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
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
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 39:2637-2639, 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) ESBL 3 cephalosporin, ESBL ESBL piperacillin-tazobactam 1994 31 %, 1997-1998 63% 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 : 401 - -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 6:460-463, 2000] 7
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 ) 10 14 Alam (3)vancomycin E faecium 10 10 10 14 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
W, Gordon J, Chow JW, Zervos MJ, Hershberger E: Penicillin tolerancepenicillin Heteroresistance to vancomycin in Enterococcus faecium J Clin Microbiol 39:3379-81, 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, 181:369-373, 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: 177-181, 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 1 0 457, 2001] 9
,, 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 200010 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)1997-1998 3, 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 39:3586-90, 2001] 10
- 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, 2:10-20001-12, 1:1 - Tolerance, 3:10-20011-3, 2:1 - Vancomycin-resistant S aureus, 2:8-20014-6, 3:1-20017-9, 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