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1 Infectious Agents Surveillance Report (IASR) 3, CRE 4, CRE 5, CRE 7, CRE 8, CRE 9, CRE 10, 11, 1 13, EHEC O121 : 14, D-68 4 : 15, 2014 : 16, 10 A : 18, Vol. 35 No Vol.35 No.12 No.418 ISSN Tel , 1,, 2 :,,, CRE, - CRE WHO, Antimicrobial resistance: global report on surveillance 2014, tance/documents/surveillancereport/en/,, CRE 5,,,,,,,,,, 1 1,, Klebsiella 10.4 Jacob JT, et al., MMWR 62 9: , 2013WHO,,,, C - 3 -,, 4, IMP,, NDM, KPC, OXA-48,, 5, CRE Escherichia coli 0.1, Klebsiella pneumoniae 0.2 Enterobacter cloacae 0.6,, Enterobacter aerogenes 0.2 7, IASR 35: , Citrobacter freundii 0.2 Citrobacter koseri : , : , 2013 Proteus mirabilis 0.1 CRE
2 2282 Vol. 35 No (n=113) (n=47) (n=66) , 2,, IASR 35: , 2014,,, Proteus,, , , , 65 88, 78,,, CRE 47 42, 27, , 1,, 23, , 41 2, Enterobacter Enterobacter cloacae 34 Enterobacter aerogenes 22 Escherichia coli 19 Klebsiella pneumoniae 15 Citrobacter spp Enterobacter,, C - -,, Q & A ja/id/495-source/drug-resistance/5011-carbapenemqa2.html,,,,,,,,, 9 10 CRE,,,, : ,,,,,
3 Vol. 35 No ,,, WHO / FDA/CVM,,, 2000,,,,, CRE CPE, A. - B. A, AmpC, 3540 kda Enterobacter, R :, DHA C CTX-M - ESBL, B, IMP NDM, KPC -- : MBL,, MBL a. IMP 1991 Serratia marcescens IMP-1, 1980,, IMP MBL IMP MBL,,, IMP-1 MBL,, IMP, VIM NDM, IMP MBL,,, IMP-1 1 IMP-6, IMP-6 R:,,, PCR IMP-1 b. VIM 1997 VIM-1 VIM, 2000 VIM-2, 2005 VIM-1, VIM MBL,, c. NDM 2007,, NDM , NDM- 1,,,,,,, NDM-1, R:, 2. a. KPC 1990,,, KPC KPC KPC-2,,,
4 4284 Vol. 35 No ,,, b. OXA-48 OXA-48 OXA-181 OXA , 2009,,, OXA-48,, OXA-48 OXA-181, 2006,, c. GES 2004 GES-4 GES-5 -, GES-5,,, 1. - extended-spectrum -lactamase: ESBL, carbapenemase CRE Klebsiella pneumoniae carbapenemase KPC, NDM-1, OXA-48,, CRE metallo--lactamase IMP CRE 1-3 IMP, meropenem imipenem 1g/ml MIC 4, 5,, S, CRE IMP , 6 A, 3,, meropenem 5, 3 IMP-1 Enterobacter cloacae Bacteroides sp., levof loxacin ampicillin/sulbactam 14, levof loxacin metronidazole, 6 3. IMP, 15 IMP E. cloacae , 53IMP E. cloacae 5, 4 3, 3, 2, , , 40, 3, 3, 2, 2 10 IMP E. cloacae , IMP E. cloacae 15,,,, 2.2, IMP E. cloacae 3, 29, 3, 3 IMP E. cloacae IMP E. cloacae meropenem imipenem minimum inhibitory concentration: MIC g/ml
5 Vol. 35 No Clinical and Laboratory Standards Institute CLSI M100-S22 8, MIC 1g/ml, IMP E. cloacae 10 IMP-1, 5 IMP-11,, E. cloacae,, 3, imipenem meropenem MIC 1g/ml, HMRZ-86 - I/MBL ESBL, --, AmpC 9, --, 10 IMP -- 5., CRE IMP --,,,,,, IMP,, CLSI M100-S22 M100-S22,, meropenem 1g/ ml, imipenem 1g/ml, 7 IMI-6 4, IMP, imipenem MIC 1g/ml IMP, 7 IMP,,, 1Shigemoto N, et al., Diagn Microbiol Infect Dis 76 1: , Sho T, et al., Microb Drug Resist 19 4: , Yano H, et al., Antimicrob Agents Chemother 56 8: , Shigemoto N, et al., Diagn Microbiol Infect Dis 72 1: , Hamada Y, et al., J Infect Chemother, Hamada Y, et al., J Infect Chemother 19 5: , Hayakawa K, et al., Antimicrob Agents Chemother 58 6: , Clinical and Laboratory Standards Institute: Performance standards for antimicrobial susceptibility testing; nineteenth informational supplement, CLSI document M100-S22, Livermore DM, et al., J Antimicrob Chemother 60 6: , Kitao T, et al., J Microbiol Methods 87 3: , 2011, -,, PCR,, 1, IMP-6 --, 2, Proteus mirabilis - 3,, MIC 0.564g/mg,, PCR A, B,
6 6286 Vol. 35 No , GES, IMI, SME, GIM, SMB,, AmpC -,,, Etest, 1 IASR 35: , Yano H, et al., Antimicrob Agents Chemother 56: , Neuwirth C, et al., J Antimicrob Chemother 36: , p IASR 34: , β- -β- Ambler IMP A -- 2, 4 IMP, IMP-1 40, IMP-1 IMP-6, IMP-1 IMP-1 IMP-6 1 1, NDM, KPC, OXA-48, 5, A, KPC IPM, MEPM 3- APB,, 3- AmpC -, KPC,, PCR KPC B, SMA IMP -- SMA B B 1 --,, SMA, IMP, NDM, PCR OXA-48, A, B, PCR PCR 5 3 class B IMP IMP-1 F: ACCGCAGCAGAGTCTTTGCC R: ACAACCAGTTTTGCCTTACC NDM VIM IMP-2 F: GTTTTATGTGTATGCTTCC R: AGCCTGTTCCCATGTAC F: TTGCCCAATATTATGCACCC R: ATTGGCATAAGTCGCAATCC VIM-2 F: ATGTTCAAACTTTTGAGTAAG R: CTACTCAACGACTGAGCG class A KPC F: ATGTCACTGTATCGCCGTCT R: TTTTCAGAGCCTTACTGCCC class D OXA-48 F: TTGGTGGCATCGATTATCGG R: GAGCACTTCTTTTGTGATGGC IPM IPMAPB 587bp 6 678bp 6 420bp 4 587bp 6 893bp 4 744bp 7 MEPM MEPMAPB *APB SMAEDTA DPA CAZ MEPM SMA A: 3-KPC B: SMAIMP-β- B
7 Vol. 35 No Shibata N, et al., J Clin Microbiol 41: , Poirel L, et al., Antimicrob Agents Chemother 48: 15-22, 2004,,, IMP, VIM, NDM, KPC, OXA-48 5,,, 5, IMP, NDM, KPC, OXA-48, ,, 46, NDM 16 25, KPC 4 15, OXA , Klebsiella pneumoniae 31, Escherichia coli 13,,, KPC 1, NDM,, KPC,, OXA-48,, 1,,, 46, NDM OXA-48,,,,, NDM, OXA-48 NDM, OXA MICNDM, 4g/ml, MIC, OXA-48 1g/ml, 2g/ml OXA-48,, MIC 0.12g/ml, NDM, NDM 16 Klebsiella pneumoniae (12) Escherichia coli (13) KPC 4 Klebsiella pneumoniae (13) Citrobacter freundii (1) Morganella morganii (1) OXA-48 2 Klebsiella pneumoniae (6)
8 8288 Vol. 35 No NDMN= (μg/ml) OXA-48N= (μg/ml) NDMOXA (MIC),,, 1Nordmann, et al., Clin Microbiol Infect 20: , EUCAST guidelines for detection of resistance mechanisms and specif ic resistances of clinical and/ or epidemiological importance, Version 1.0 December , CRE , , 19, 7 66, , 65 88, 78 2, 39, 22, 21, 18, 8, 2, 1, 22, 8,, 17 CRE,, -,,, ,,,, CRE, 27, 66, CRE, 32, 17,,, 2 113, 31, 41, , 105 Enterobacter cloacae 34, Enterobacter aerogenes 22 1 Enterobacter asburiae, 54 Enterobacter Enterobacter, Escherichia coli 19, Klebsiella pneumonia 15, Citrobacter 5, 2 1, Klebsiella oxytoca, Morganella morgannii, Serratia marcescens, Proteus mirabilis, Providencia rettgeri E. colis. marcescens 2
9 Vol. 35 No , ,, 23 CRE, CRE, VRE MDRA, , 1 1,000, CRE, 5 VRE, 100 MDRA , CRE 113 MDRA 7,, CRE , ICU A, Enterobacter aerogenes, SMA-- MBL A 1 4, MBL, MBL, A MBL, 5, , A, Escherichia coli Klebsiella pneumoniae 1, 0.1, 0.2,, ,, IMP-1, IMP-2, VIM-2, NDM PCR MBL MPE metallo- -lactamase producing Enterobacteriaceae, 289, A 15 AO23 MPE , 4 57, 2, Serratia marcescens Kluyvera intermedia 3. PCR 23 2 IMP- 1 MBL, PFGE S. marcescens, 4, S. marcescens,, AF 6 9. AMPEmetallo--lactamase producing Enterobacteriaceae A Enterobacter aerogenes Enterobacter cloacae 2 2 Klebsiella pneumoniae Klebsiella oxytoca Serratia marcescens Escherichia coli Citrobacter freundii
10 10290 Vol. 35 No , MBL IMP-1 MBL, Inc L/M, B, C, D, E, F Inc L/M, A 3 Inc L/M,, BF Inc L/M MBL, bla IMP-1 100,, 4.,,,, MBL 5. MBL,, A,, 1http:// metallo--lactamase: MBL MBL-Ent Klebsiella pneumoniae,,, MBL-Ent 1, , ,, MBL MBL-Ent, , 76 : 2888 MBL-Ent, Escherichia coli, Klebsiella oxytoca, Enterobacter cloacae, K. pneumoniae, Enterobacter aerogenes , 4 14, 12 41, , 22 MBL-Ent MBL-Ent MBL-Ent 1, 18 62, 29, , E. coli 9, K. oxytoca 8, E. cloacae 7, K. pneumoniae 3 Pulsed-f ield gel electrophoresis: PFGE, K. oxytoca 8, E. coli 2, E. cloacae 2,, 17 18, PFGE, IMP- 6 MBL,,,,, MBL-Ent,,, MBL-Ent, MBL-Ent, MBL- Ent, MBL-Ent 1 : 2, 13, 24,,, MBL-Ent,,
11 Vol. 35 No ,,,, MBL-Ent,,,,,,,,,,, IMP-6 MBL CRE IMP-6 MBL 2, 3,,, CRE, IMP-6 MBL, 1,, 24 1: 9-16, Yano H, et al., Antimicrob Agents Chemother 45 5: , Shigemoto N, et al., Diagn Microbiol Infect Dis 72 1: , 2012, , Acinetobacter baumannii A. baumannii,,, International clone II IC II
12 12292 Vol. 35 No IC II A. baumannii A. baumannii IC II A. baumannii (IC II) (non-ic II) [n=245] [n=621] / 24.5 % 0.8 % / 8.2 % 0.0 % 69.8 % 1.6 % 48.2 % 2.6 % 3.7 % 0.6 % 3.7 % 0.8 % 51.0 % 4.8 % 24.5 % 0.0 % 87.8 % 9.3 % 100 % 18.4 % 13.5 % 0.0 % / 0.0 % 0.0 % 0.0 % 0.8 % B 0.0 % 0.3 % CLSI M100-S23 6 MIC64μg/ml 1, IC II 86, rpob 2, IC II, bla OXA-51-like SNP 3, , 932, 866, A. baumannii , Acinetobacter nosocomialis , Acinetobacter pittii A. baumannii IC II 245, 28 IC II IC II IC II A. baumannii A. baumannii ; non-ic II,, IC II, 3.7, non-ic II 0.6, 0.8 9, IC II non-ic II, IC II, IC II,,, 3, 2 0.2, IC II ,, IC II 12,,, 7 IC II,, IC II 4, IC II,, IC II, 3.7 5, IC II, IC II 28, 46, IC II IC II, non-ic II, IC II, IC II,,,
13 Vol. 35 No taiseikin nih.go.jp : 1Diancourt L, et al., PLoS One 5, e10034, La Scola B, et al., J Clin Microbiol 44: , Matsui M, et al., J Microbiol Methods 94: , Karah N, et al., Drug Resist Updates 15: , JANIS 6Clinical and Laboratory Standards Institute CLSIM100-S23, ,, 1 1, Hib 3, 4 1, 39, ,,,,, DZP4 mg, 39,, 3,,,, 40, 5,,, WBC 10,500/l Neut 76, CRP 6.93mg/dl, Na 129mEq/l, K 2.6mEq/l,, SIADH 5, CBZ 50mg,,, 19, PB15mg/kg, PB 10mg/kg/day,,, CT,,,, CT,,,,,,,, CTX, MEPM,, ACV,, 6 5,, ABPC400mg/kg/day, ICU,,, MEPM, CTX, GM30mg/kg/day CTRX 100mg/kg/day,,, 7, 8 Listeria monocytogenes, CTRX,, 9,, 36 L. monocytogenes, L. monocytogenes, 1,, 60, 1 L. monocytogenes 1958, 80,,, 21 2,,,,,,, 1570, /100, 3/4,
14 14294 Vol. 35 No ,, 6 L. monocytogenes ,, 314, L. monocytogenes 3 5,, Hib,, 4 6, L. monocytogenes ,, 20: 8-14, ,, IASR 33: , ,, 60: , ,, 85: , ,, 118: , 2014 PL O , 3,, 4 1 Vero VT 2 EHECO121 : H19, , 3,,, 1,, 6, 2, 3,, 2 1, 1, 1, 1, 4 29,, M M 1-4 :, :, M:S. Braenderup H9812, : Xba I. PFGE 3 1, 5 3 EHEC O121, EHEC, 5, 2, O121 2, 3 O121,,, 5 9, O121 EHEC O O121, PFGEO121 1,,,,, O121 : H19, VT2 PCR, PFGE, 11 7, 4 1 2, O121,,,,,,,
15 Vol. 35 No ,,, EHEC O121 PFGE, , EHEC, 1, IASR 25: , ,, IASR 33: , 2012 D EV-D68, 1962, 4,, 1 1, , nesid3g.mhlw.go.jp/byogentai/pdf/data60j.pdf pdf,, 4 EV-D68, 1 : EV,, 5 BGM, HEp-2, RD-18S, Vero, FL, Vero EV CPE, EV, 5NCR VP2 OL68-1, EVP4, EV VP1 CODEHOP PCR,, BLAST, EV-D68,, RS,,,, 2 : ,,, FL EV CPE, OL68-1 EVP4,, BLAST EV- D68, 3 : ,, 23,,,, , FL EV CPE, CODEHOP PCR,, BLAST EV-D68, 4 : ,,, CT, 11 3, 11 5, RD-18S, RD-A, Vero, FL, CODEHOP PCR,, BLAST EV-D68 EV-D68 : 1, 3, 4 CODEHOP PCR VP1, 343bp 3 346bp MEGA5, 3 Case 3, , 2,
16 16296 Vol. 35 No , 3, , 1 Case 1 4 Case 4, , EV-D68, 1, 4,, , 23 2 EV-D68, 5,, EV-D68, 9 4 EV-D68 6, EV-D68 7, 4 1, 2,, 3, 4, 3, EV-D68,, 1Ikeda T, et al., Microbiol Immunol 56: , Prachayangprecha S, et al., J Clin. Microbiol 52 10: , Piralla A, et al., J Med Virol 86 9: , Rahamat-Langendoen J, et al., J Clin Virol 52: , MMWR Weekly, October 10, 2014/6340: MMWR Weekly, October 10, 2014/63 40: IASR 35: 250, 2014 JA KM361524Thailand2011 JQ CHN-2011 KC Italy-2012 JQ UK-2009 AB Okinawa-2010 AB PHI-2011 AB Yamagata-2005 AB Yamagata-2007 AY Fermon-EV68 ON T-2013 (Case 4) HA (Case 1). EV-D68VP1343bpK bp 2014, , ,, , 1 A, B , [ , , ], , A , B , B , A 20, B 20, A B n=45 An=23 Bn=22 0% 20% 40% 60% 80% 100%
17 Vol. 35 No B A , A B, 45 A 23, B 22 t A B A : , B : , P=0.12, , A , B 1 : 4, A 23 15, 8, 9 : 6, 1, 1, 1, 14 B, , 1 4, B 0, A, 3 A B3 9 5, 4 H1 1, D , H1 5 1, , , B3 2, 7, 8, 10, 9, 33, 8 9 7, 1 2, : 22 : 5 30,,,, 25 : 611, 33 : 613,, 1 33 : 6 12, 3 H1,, 0 14,,,, 1,
18 18298 Vol. 35 No ,, 2014, H1, D8, B3 5, 6 H1,, 13 29,,,, 1IASR 35: , A A RVA,, ,,, 10, RVA, 2003/ /13 10, 1,179, RVA VP4VP7 RT-PCR RVA G2P[4] 2 G9P[8] 3 G4P[8] 1 G3P[8] 23 G6P[9] 1 G12P[9] 1 G1P[8] RVA 2003/ / / / / / / / / /13 2. RVA G12P[9] G9P[8] G6P[9] G4P[8] G3P[8] G2P[4] G1P[8] 10, 500l 10,000rpm 10, QIAampViral RNA Mini Kit QIAGEN RNA G VP7-F 1 VP7-R 1, P Con-3 2 Con-2 2 RT-PCR,, RotaC MEGA5 10 RVA G1P[8] 52.3, G3P[8] 35.4, G9P[8] 4.6, G2P[4] 3.1 1, 2004/05, 2005/06, 2011/ /13 G1P[8], 2003 /04, 2006/07, 2008/09 G3P[8] 2, G6P[9] G12P[9] 1 G6P[9] M72S , 2, G12P[9]M392S G6,,, Iizuka 3 G6 PA151 AU-1
19 Vol. 35 No / RNA-RNA hybridization Yamamoto 4, G6P[9] KF17, KF17AU-1 / M72S11, KF17VP7 VP4, ,, M72S11 KF17, 3 & 4, G12, Lineage I 5, G12P[9],, Lineage II 6, 7, G12 Lineage III, G12P[6] G12P[8] 8 M392S09 VP7 Lineage II G12, , G12P[9] M392S09, G12P[9] 2001 CP727 6, VP7 99.1, VP4 99.3, Lineage II G12 5,,,,,, M72S11, M392S09VP7 VP4 GenBank, AB M72S11, VP7, AB M72S11, VP4, AB M392S09, VP7, AB M392S09, VP4 : 1Iturriza-G ómara M, et al., J Clin Virol 31: , Gentsch JR, et al., J Clin Microbiol 30: RVA G6VP7714bp 4. RVAVP4739bp Lineage Lineage Lineage Lineage 5. RVA G12VP7752pb 1373, Iizuka M, et al., Arch Virol 135: , Yamamoto D, et al., Virus Genes 43: , Kobayashi N, et al., Arch Virol 109: 11-23, Shinozaki K, et al., J Med Virol 73: , 2014
20 20300 Vol. 35 No Castello AA, et al., J Med Virol 81: , Uchida R, et al., J Clin Microbiol 44: , Human parainf luenzavirus: HPIV, 1 RNA, 1,,, 1, 2,,, 2 HPIV-2, 9 9, , 13 40,,,,,,,, 1 5,,,,, HPIV 1 3, RS,,,, 6, 7,, B19 Real-timeRT-PCR, HRV,,,,, RT-PCR Tong L RT-PCR 3, Real-time RT-PCR HPIV-2 HPIV /5l, /5l, RT-PCR RT-PCR, 490bp 1, 100, DDBJ BLAST, HPIV2/ V94 AF , HPIV-2, RD-A, VeroE6, HEp-2, CaCo-2 MDCK,, 1, HPIV-2 HPIV,, 2, 4,, HPIV-3 1 5,,, HPIV-2 1, HPIV-2,, HPIV, 1,, Karron RA and Collins PL, Parainfluenza Viruses, Vol.1, , Fields Virology, Tong S, et al., J Clin Microbiol 46: , Reed G, et al., J Infect Dis 175: , Aronson MD, et al., Ann Intern Med 81 6: , , 33 : , 2006
21 Vol. 35 No IASR Vol. 35 No. 12 December 2014 Infectious Agents Surveillance Report Mechanism of carbapenem resistance among Enterobacteriaceae -characteristics and trends Clinical features of carbapenem-resistant Enterobacteriaceae infection cases in Japan Laboratory testing of carbapenem-resistant Enterobacteriaceae Isolation of carbapenemase-producing Enterobacteriaceae from overseas travelers returning to Japan Situation update on reported cases of carbapenem-resistant Enterobacteriaceae infections under the National Epidemiological Surveillance of Infectious Diseases, week 38-44, 2014 Japan Nosocominal infection involving horizontal transmission of plasmid(s) bearing carbapenem resistance gene, May Persistent and large-scale nosocominal transmission of carbapenem-resistant Enterobacteriaceae in a community hospital in Osaka City, July 2013-May ISSN National Institute of Infectious Diseases and Tuberculosis and Infectious Diseases Control Division, Ministry of Health, Labour and Welfare Molecular epidemiology of Acinetobacter spp. isolated in Japan, October 2011-March Infant Listeria meningitis-a case report Osaka Prefecture An EHEC O121 infection through contact with breeding cattle, May 2014-Hyogo Prefecture Isolation of enterovirus D-68 from 4 infant cases, September 2010-November 2013-Hiroshima Prefecture Measles epidemic in Osaka Prefecture, first half of Trends in group A rotavirus infection in Miyagi Prefecture during the past 10 years Isolation of parainfluenza virustype 2 from a patient with pneumonia, gastroenteritis and neurological symptoms, August 2014-Chiba City <THE TOPIC OF THIS MONTH> Carbapenem-resistant Enterobacteriaceae Infection, Japan Carbapenem-resistant Enterobacteriaceae (CRE) is a group of Enterobacteriaceae, such as Escherichia coli and Klebsiella pneumoniae that are resistant to both carbapenems and broad-spectrum ß-lactams. CREs cause respiratory tract infections such as pneumonia, urinary tract infections, surgical site infections, catheter-related bacteremia, sepsis and meningitis. While more common among immune compromised patients, postoperative patients or patients treated with antimicrobials for an extended period of time, CREs may also cause infection in otherwise healthy patients. CREs are often the cause of nosocomial infections. So far in Japan, the prevalence of CRE has been relatively low. For example, in 2013, meropenem-resistant isolates occupied less than 1% of the various representative Enterobacteriaceae bacteria isolates (Table 1). Meanwhile, in many other countries, the proportion of carbapenem resistance is increasing, and in the United States, 10.4% of the isolates belonging to the genus Klebsiella were carbapenem-resistant [MMWR, 62(9): , 2013]. The World Health Organization (WHO) considers strengthening the surveillance of antimicrobial resistance as a critical priority for member states (WHO, Antimicrobial resistance: global report on surveillance 2014, Carbapenem resistance mechanisms Mechanism of carbapenem resistance includes production of various carbapenemases, production of AmpC type or extendedspectrum ß-lactamases combined with mutation(s) resulting in the decreased permeability of the cellular membrane (see p. 283 of this issue). Carbapenemase-producing bacteria are clinically important as they are often resistant not only to broad-spectrum ß-lactams but also to other classes of antimicrobials (see p. 284 of this issue). Carbapenemase producers isolated in Japan are mostly of IMP genotype (see p. 285 of this issue), which can be easily detected by the sodium mercaptoacetic acid (SMA) disk method widely used in medical facilities in Japan. Isolates abroad, however, carry carbapenemases of NDM, KPC, or OXA-48 genotypes, whose detection requires use of methods other than SMA disk method (see p. 285 of this issue). As nosocomial infections due to CRE are more frequent abroad, patients who were treated in foreign medical facilities should be investigated for possible carriage of CREs so as to prevent the spread from such imported cases in Japan (see p. Table 1. Proportion of Enterobacteriaceae resistant to meropenem, 2013, Japan Enterobacteriaceae species Meropenem resistant (%) Escherichia coli 0.1 Klebsiella pneumoniae 0.2 Enterobacter cloacae 0.6 Enterobacter aerogenes 0.2 Citrobacter freundii 0.2 Citrobacter koseri 0.1 Proteus mirabilis Annual Report of Clinical Laboratory Division, Japan Nosocomial Infections Surveillance (JANIS: Ministry of Health, Labour and Welfare Table 2. Laboratory criteria required for fulfilling definition of carbapenem resistance a. MIC for meropenem 2µg/ml, or zone diameter of meropenem disk (KB) 22mm b. Fulfillment of both i) and ii): i) MIC for imipenem 2µg/ml, or zone diameter of imipenem disk (KB) 22mm ii) MIC for cefmetazole 64µg/ml, or zone diameter of cefmetazole disk (KB) 12mm MIC: minimum inhibitory concentration See notification criteria ( Continued on page 282
22 252 Vol. 35 No THE TOPIC OF THIS MONTH-Continued Figure. Age distribution of carbapenem-resistant Enterobacteriaceaeinfection cases, by gender, week 38 to 44 of 2014, Japan 30 No. of cases (n=113) Females (n=47) Males (n=66) IASR Vol. 35 No. 12 Dec Table 3. Notified cases of carbapenem-resistant Enterobacteriaceae infection, week 38 to 44 of 2014, Japan Enterobacteriaceae species Number of cases Enterobacter cloacae 34 Enterobacter aerogenes 22 Escherichia coli 19 Klebsiella pneumoniae 15 Citrobacter spp. 5 Others & not described 18 Total 113 [National Epidemiological Surveillance of Infectious Diseases, as of November 5, 2014, since compulsory reporting of all cases started in week 38 (September 19, 2014)] Age group (years) (National Epidemiological Surveillance of Infectious Diseases: as of November 5, 2014) 287 of this issue, IASR 35: , 2014, IASR 34: , 2013 and IASR 34: , 2013). National Epidemiological Surveillance of Infectious Diseases reporting criteria and current trends CRE infection is a category V infectious disease under the Infectious Diseases Control Law. Physicians who make the diagnosis of CRE infection must notify all cases (see for reporting criteria). Only infections determined to be caused by CRE are notifiable; asymptomatic CRE carriers are not. For determining carbapenem resistance, resistance to meropenem or resistance to both imipenem and cefmetazole are methods currently used (Table 2). Among them, use of meropenem is most recommended on account of its sensitivity and specificity (IASR 35: , 2014). Imipenem resistance was included in the reporting criteria because imipenem has been widely used as an indicator in the clinical setting. However, in order to exclude those that are resistant to imipenem but susceptible to other cephem antimicrobials and do not produce carbapenemase (e.g. Genus Proteus), reporting is limited to those resistant to both imipenem and cefmetazole. Since compulsory reporting of all cases started in week 38 (19 September 2014), 113 CRE infection cases were notified through week 44, among whom 66 were male and 47 female (see p. 288 of this issue). The age of the patients ranged from 0 year to 97 years; among them 88 (78% of all the cases) were aged 65 years or above (Figure). CRE was isolated from 47 (42%) aseptic specimens, such as blood, ascites, and cerebrospinal fluid; the isolation was most frequent from blood (n=27). Among 113 cases, 109 cases were reported as domestically acquired and one case abroad. Twenty three cases were considered as healthcare-associated infections, such as infection due to medical devices or surgical site infections. Among 113 cases diagnosed as CRE infection, 31 cases were based on resistance to meropenem, 41 cases by resistance to both imipenem and cefmetazole and 39 cases based on both methods. Half of the reported CRE cases were infections by Enterobacter spp. (Table 3). Most carbapenem resistance of Enterobacter spp. was not due to production of carbapenemases but rather due to production of class C ß-lactamase associated with reduced cellular membrane permeability. The current practice of notifying carbapenemase non-producing bacteria resistant to broadspectrum ß-lactams is being reviewed with regards to implications for public health. Horizontal gene transfer and nosocomial infection In most cases, the carbapenemase gene is found on plasmids. It is transmitted to other bacteria belonging to Enterobacteriaceae by conjugation or other horizontal gene transfer mechanisms. Some Enterobacteriaceae bacteria possessing carbapenemase gene may be phenotypically susceptible to carbapenems. Such bacteria may become carbapenem-resistant through elevated expression of the drug resistance gene(s) or through cellular membrane change and capable of transmitting the resistance gene(s) to other bacteria of other species. As such events may go unnoticed, such possibilities should be kept in mind for surveillance. In fact, dissemination of the carbapenem resistance gene to multiple bacteria species in the clinical setting has already been reported (see pp. 289 & 290 of this issue). Asymptomatic CRE carriers are not rare. Although they are not notifiable, if they are hospitalized and a nosocomial outbreak is suspected, such carriers should be reported to health centers according to the notice issued by the Director of Guidance of Medical Service Division, Health Policy Bureau, Ministry of Health, Labour and Welfare (17 June 2011: Isei-shi-hatsu 0617 No.1), and necessary measures taken promptly with assistance of an existing local network of medical institutions. Though this notice will be updated soon, the requirements for notification will remain unchanged. If genotyping or further analysis of resistance gene(s) is deemed necessary for infection control purposes, research institutes, including the National Institute of Infectious Diseases, should be consulted. The statistics in this report are based on 1) the data concerning patients and laboratory findings obtained by the National Epidemiological Surveillance of Infectious Diseases undertaken in compliance with the Law Concerning the Prevention of Infectious Diseases and Medical Care for Patients of Infections, and 2) other data covering various aspects of infectious diseases. The prefectural and municipal health centers and public health institutes (PHIs), the Department of Food Safety, the Ministry of Health, Labour and Welfare, and quarantine stations, have provided the above data. Infectious Disease Surveillance Center, National Institute of Infectious Diseases Toyama , Shinjuku-ku, Tokyo , JAPAN Tel (+81-3)
CHEMOTHERAPY aureus 0.10, Enterococcus faecalis 3.13, Escherichia coli 0.20, Klebsiella pneumoniae, Enterobacter spp., Serratia marcescens 0.78, Prote
aureus 0.10, Enterococcus faecalis 3.13, Escherichia coli 0.20, Klebsiella pneumoniae, Enterobacter spp., Serratia marcescens 0.78, Proteus mirabilis 3.13, Proteus vulgaris 1.56, Citrobacter freundii 0.39,
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