2 2 THE JAPANESE JOURNAL OF ANTIBIOTICS 67 1 Feb CRBSI Catheter related bloodstream infection 1. n 167 I. 4 4, % 7 10 Candida albicans
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1 Feb THE JAPANESE JOURNAL OF ANTIBIOTICS , 3 2, CRBSI compromised host CRBSI 4 CVC CVC D- / 1 ICU 2, 3 4
2 2 2 THE JAPANESE JOURNAL OF ANTIBIOTICS 67 1 Feb CRBSI Catheter related bloodstream infection 1. n 167 I. 4 4, % 7 10 Candida albicans % 50% non-albicans Candida 5 C. glabrata C. tropicalis, C. krusei C. albicans 40.7%, C. parapsilosis 23.0%, C. glabrata 17.9%, C. tropicalis 11.6%, C. krusei 2.4%, C. guilliermondii 1.3%, C. famata 0.7%, C. lusitaniae 0.6% C. albicans CVC: central venous catheter 12 CVC 68% 13 CRBSI NAGASAKI, Y.: 47th ICAAC JANIS 2011 CRBSI 0.7 /1,000 C. albicans 5.9% Staphylococcus S. epidermidis 15.1%, methicillin-resistant S. aureus MRSA 13.0%, coagulase-negative Staphylococci CNS 8.6%, methicillin-susceptible S. aureus MSSA 6.5% CRBSI % CVC 12 10% ICU CLABSI Central line-associated BSI , ,000 58% MRSA 15
3 Feb THE JAPANESE JOURNAL OF ANTIBIOTICS II % 16 CRBSI CVC D- 2 -D- 95% 2 2a 17 -D- Alcaligenes faecalis MK 18
4 4 4 THE JAPANESE JOURNAL OF ANTIBIOTICS 67 1 Feb a D- Med. Mycol. J. 54: , b. -D D- 20, 21 -D- CRBSI ELISA 2b 2 22 III in vitro CLSM C. albicans 3 60 m C. glabrata 30 1,000 MIC 26 C. albicans Planktonic cell MIC 3 FLCZ VRCZ MCFG CPFG B AMPH-B 26 B B L- AMB B ABLC
5 Feb THE JAPANESE JOURNAL OF ANTIBIOTICS BLANKENSHIP, J. R., et al.: Curr. Opin. Microbiol. 9: , C. albicans CLSM 3. C. albicans MIC KUHN, D. M., et al.: Antimicrob. Agents Chemother. 46: , 2002 in vitro 90% killing 4 MIC AMPH-B L-AMB FLCZ CRBSI C. albicans 1 MIC FLCZ MCFG AMPH-B L-AMB SEM
6 6 6 THE JAPANESE JOURNAL OF ANTIBIOTICS 67 1 Feb MIC 4. 2,000 CVC 27 CRBSI FLCZ SEM L-AMB SEM 28
7 Feb THE JAPANESE JOURNAL OF ANTIBIOTICS PAPPAS, P. G., et al.: Inf. Dis. Soc. Am. 48: , Sessile cell Persister cell CDR1, CDR2 MDR FLCZ -D- Sessile cell 32 Persister cell Tolerance IV % % 2 3, 12, C. albicans non-albicans Candida 5 Candida 3 FLCZ 3 12 FLCZ 39 B CRBSI APACHE 40, 41
8 8 8 THE JAPANESE JOURNAL OF ANTIBIOTICS 67 1 Feb CRBSI A: B: C: D: 2012 ESCMID , 43 CVC 44, 45 CRBSI 46 ESCMID 2012 CRBSI CVC 6 36, C. parapsilosis L-AMB 38 MCFG 100 mg/day L-AMB 3 mg/kg/day 47 89% 78.7% vs 77.9% 10.9% vs 11.6% L-AMB AMPH-B L-AMB mg/kg/day 49 C. albicans C. parapsilosis OR 2.33 OR 2.35 APACHE III OR , 51 Dispersed cell Planktonic cell 52 CLSI M27-S3
9 Feb THE JAPANESE JOURNAL OF ANTIBIOTICS M27-S4 5 C. albicans, C. glabrata, C. krusei, C. parapsilosis, C. tropicalis FLCZ, VRCZ CLSI Planktonic cell V. 3 X CT bacterial translocation % 54 CVC 4% 55 C. albicans 85 99% 25% CVC 2.5% non-albicans Candida FLCZ C. albicans C. krusei Y -D- 2 57
10 10 10 THE JAPANESE JOURNAL OF ANTIBIOTICS 67 1 Feb ESCMID FLCZ, VRCZ L-AMB 5-FC AMPH-B, VRCZ, FLCZ 7 35, % 30 50% 17.7% 58 L-AMB 5-FC 1 36 CRBSI
11 Feb THE JAPANESE JOURNAL OF ANTIBIOTICS PFALLER, M. A. & D. J. DIEKEMA: Epidemiology of invasive candidiasis: a persistent public health problem. Clin. Microbiol. Rev. 20: , MORRELL, M.; V. J. FRASER & M. H. KOLLEF: Delaying the empiric treatment of Candida bloodstream infection until positive blood culture results are obtained: a potential risk factor for hospital mortality. Antimicrob. Agents Chemother. 49: , PAPPAS, P. G.; C. A. KAUFFMAN, D. ANDES, et al.: Clinical practice guidelines for the management of candidiasis: 2009 update by the Infectious Diseases Society of America. Clin. Inf. Dis. 48: , WISPLINGHOFF, H.; T. BISCHOFF, S. M. TALLENT, et al.: Nosocomial bloodstream infections in US hospitals: analysis of 24,179 cases from a prospective nationwide surveillance study. Clin. Inf. Dis. 39: , ZILBERBERG, M. D.; A. F. SHORR & M. H. KOLLEF: Secular trends in candidemia-related hospitalization in the United States, Inf. Contr. Hosp. Epidemiol. 29: , EDMOND, M. B.; S. E. WALLACE, D. K. MCCLISH, et al.: Nosocomial bloodstream infections in United States hospitals: a three-year analysis. Clin. Inf. Dis. 29: , FALAGAS, M. E.; K. E. APOSTOLOU & V. D. PAPPAS: Attributable mortality of candidemia: a systematic review of matched cohort and casecontrol studies. Eur. J. Clin. Microbiol. Inf. Dis. 25: , GUDLAUGSSON, O.; S. GILLESPIE, K. LEE, et al.: Attributable mortality of nosocomial candidemia, revisited. Clin. Inf. Dis. 37: , WEY, S. B.; M. MORI, M. A. PFALLER, et al.: Hospital-acquired candidemia. The attributable mortality and excess length of stay. Arch. Int. Med. 148: , ARENDRUP, M. C.; S. SULIM, A. HOLM, et al.: Diagnostic issues, clinical characteristics, and outcomes for patients with fungemia. J. Clin. Microbiol. 49: , TAKAKURA, S.; N. FUJIHARA, T. SAITO, et al.: National surveillance of species distribution in blood isolates of Candida species in Japan and their susceptibility to six antifungal agents including voriconazole and micafungin. J. Antimicr. Chemother. 53: , MERMEL, L. A.; M. ALLON, E. BOUZA, et al.: Clinical practice guidelines for the diagnosis and management of intravascular catheterrelated infection: 2009 Update by the Infectious Diseases Society of America. Clin. Inf. Dis. 49: 1 45, SHERERTZ, R. J.; I. I. RAAD, A. BELANI, et al.: Three-year experience with sonicated vascular catheter cultures in a clinical microbiology laboratory. J. Clin. Microbiol. 28: 76 82, PITTET, D.; N. LI, R. F. WOOLSON, et al.: of nosocomial bloodstream infections: a 6-year validated, population-based model. Clin. Inf. Dis. 24: , Vital signs: Central line--associated blood stream infections--united States, 2001, 2008, and MMWR 60: , CUENCA-ESTRELLA, M.; P. E. VERWEIJ, M. C. ARENDRUP, et al.: ESCMID* guideline for the diagnosis and management of Candida diseases 2012: diagnostic procedures. Clin. Microbiol. Inf. 18 Suppl. 7 : 9 18, Med. Mycol. J. 54: , KARAGEORGOPOULOS, D. E.; E. K. VOULOUMANOU, F. NTZIORA, et al.: Beta-D-glucan assay for the diagnosis of invasive fungal infections: a metaanalysis. Clin. Inf. Dis. 52: , ODABASI, Z.; G. MATTIUZZI, E. ESTEY, et al.: Beta-D-glucan as a diagnostic adjunct for invasive fungal infections: validation, cutoff development, and performance in patients with acute myelogenous leukemia and myelodysplastic syndrome. Clin. Inf. Dis. 39: , NETT, J.; L. LINCOLN, K. MARCHILLO, et al.: Putative role of beta-1,3 glucans in Candida
12 12 12 THE JAPANESE JOURNAL OF ANTIBIOTICS 67 1 Feb albicans Chemother. 51: , NETT, J.; L. LINCOLN, K. MARCHILLO, et al.: Beta- 1,3 glucan as a test for central venous catheter 1712, MUKHERJEE, P. K.; G. ZHOU, R. MUNYON, et al.: Candida environment. Med. Mycol. 43: , KOJIC, E. M. & R. O. DAROUICHE: Candida infections of medical devices. Clin. Microbiol. Rev. 17: , BLANKENSHIP, J. R. & A. P. MITCHELL: How to Opin. Microbiol. 9: , KUHN, D. M.; T. GEORGE, J. CHANDRA, et al.: Antifungal susceptibility of Candida unique efficacy of amphotericin B lipid formulations and echinocandins. Antimicrob. Agents Chemother. 46: , SEIDLER, M.; S. SALVENMOSER & F. M. MULLER: Liposomal amphotericin B eradicates Candida albicans model. FEMS Yeast Res. 10: , SCHINABECK, M. K.; L. A. LONG, M. A. HOSSAIN, et al.: Rabbit model of Candida albicans antifungal lock therapy. Antimicrob. Agents Chemother. 48: , CUELLAR-CRUZ, M.; A. VEGA-GONZALEZ, B. MENDOZA-NOVELO, et al.: The effect of biomaterials and antifungals on biofilm formation by Candida species: a review. Eur. J. Clin. Microbiol. Inf. Dis. 31: , RAMAGE, G.; S. BACHMANN, T. F. PATTERSON, et al. Candida albicans 49: , MUKHERJEE, P. K.; J. CHANDRA, D. M. KUHN, et al. Candida albicans Immun. 71: , NETT, J. & D. ANDES: Candida albicans development, modeling a host-pathogen interaction. Curr. Opin. Microbiol. 9: , LAFLEUR, M. D.; C. A. KUMAMOTO & K. LEWIS: Candida albicans tolerant persister cells. Antimicrob. Agents Chemother. 50: , : 72 79, , CORNELY, O. A.; M. BASSETTI, T. CALANDRA, et al.: ESCMID guideline for the diagnosis and management of Candida diseases 2012: nonneutropenic adult patients. Clin. Microbiol. Inf. 18 Suppl. 7 : 19 37, ULLMANN, A. J.; M. AKOVA, R. HERBRECHT, et al.: ESCMID* guideline for the diagnosis and management of Candida diseases 2012: adults with haematological malignancies and after haematopoietic stem cell transplantation HCT. Clin. Microbiol. Inf. 18 Suppl. 7 : 53 67, , LEROY, O.; J. P. GANGNEUX, P. MONTRAVERS, et al.: Epidemiology, management, and risk factors for death of invasive Candida infections in critical care: a multicenter, prospective, observational study in France Crit. Care Med. 37: , NUCCI, M.; E. ANAISSIE, R. F. BETTS, et al.: Early removal of central venous catheter in patients with candidemia does not improve outcome: analysis of 842 patients from 2 randomized clinical trials. Clin. Inf. Dis. 51: , ANDES, D. R.; N. SAFDAR, J. W. BADDLEY, et al.: Impact of treatment strategy on outcomes in patients with candidemia and other forms of invasive candidiasis: a patient-level quantitative review of randomized trials. Clin. Inf. Dis. 54: , REX, J. H.; J. E. BENNETT, A. M. SUGAR, et al.: Intravascular catheter exchange and duration of
13 Feb THE JAPANESE JOURNAL OF ANTIBIOTICS candidemia. Clin. Infect. Dis. 21: , NGUYEN, M. H.; J. E. PEACOCK, JR., D. C. TANNER, et al.: Therapeutic approaches in patients with candidemia. Evaluation in a multicenter, prospective, observational study. Arch. Intern. Med. 155: , WEINBERGER, M.; L. LEIBOVICI, S. PEREZ, et al.: Characteristics of candidaemia with Candidaalbicans compared with non-albicans Candida species and predictors of mortality. J. Hosp. Infect. 61: , ALMIRANTE, B.; D. RODRIGUEZ, B. J. PARK, et al.: Epidemiology and predictors of mortality in cases of Candida bloodstream infection: results from population-based surveillance, barcelona, Spain, from 2002 to J. Clin. Microbiol. 43: , TAKAKURA, S.; N. FUJIHARA, T. SAITO, et al.: Improved clinical outcome of patients with Candida bloodstream infections through direct consultation by infectious diseases physicians in a Japanese university hospital. Inf. Contr. Hosp. Epidemiol. 27: , KUSE, E. R.; P. CHETCHOTISAKD, C. A. DA CUNHA, et al.: Micafungin versus liposomal amphotericin B for candidaemia and invasive candidosis: a phase III randomised double-blind trial. Lancet 369: , ALVAREZ-LERMA, F.; F. MARISCAL, E. QUINTANA, et al.: Use of liposomal amphotericin B in critically Ill patients: A retrospective, multicenter, clinical study. J. Chemother. 21: , Liposomal amphotericin B L-AMB 61: , TUMBARELLO, M.; B. POSTERARO, E. M. TRECARICHI, et al. Candida species and inadequate antifungal therapy as predictors of mortality for patients with candidemia. J. Clin. Microbiol. 45: , TUMBARELLO, M.; B. FIORI, E. M. TRECARICHI, et al.: Risk factors and outcomes of candidemia care hospital. PloS One 7: e33705, UPPULURI, P.; A. K. CHATURVEDI, A. SRINIVASAN, et al.: Dispersion as an important step in the Candida albicans PLoS Pathog. 6: e , LINGAPPAN, A.; C. C. WYKOFF, T. A. ALBINI, et al.: Endogenous fungal endophthalmitis: causative organisms, management strategies, and visual acuity outcomes. Am. J. Ophthalmol. 153: e161, OMUTA, J.; K. UCHIDA, H. YAMAGUCHI, et al.: Histopathological study on experimental endophthalmitis induced by bloodstream infection with Candida albicans. Jpn. J. Infect. Dis. 60: 33 39, TAKEBAYASHI, H.; A. MIZOTA & M. TANAKA: Relation between stage of endogenous fungal endophthalmitis and prognosis. Graefe s Arch. Clin. Exp. Ophthalmol. 244: , NAJMI, N. G.; H. F. SONG & R. R. OBER: Presumed Candida endogenous fungal endophthalmitis: a case report and literature review. Optometry 78: , KRISHNA, R.; D. AMUH, C. Y. LOWDER, et al.: Should all patients with candidaemia have an ophthalmic examination to rule out ocular candidiasis? Eye 14: 30 34, LEFORT, A.; L. CHARTIER, B. SENDID, et al.: Diagnosis, management and outcome of Candida endocarditis. Clin. Microbiol. Infect. 18: E99 E109, 2012
14 14 14 THE JAPANESE JOURNAL OF ANTIBIOTICS 67 1 Feb Candida catheter related-blood stream infection MASAKO KADOWAKI 1, 3 2, 3 and NOBUYUKI SHIMONO 1 Department of Clinical Chemistry and Laboratory Medicine, Kyushu University Hospital 2 Center for the Study of Global Infection, Kyushu University Hospital 3 Department of Medicine and Biosystemic Science, Graduate School of Medical Sciences, Kyushu University Candida catheter-related bloodstream infection CRBSI is usually refractory because antifungals show limited effect. With medical development and increase in number of compromised hosts, CRBSI became more frequent. Candida, which is one of the opportunistic pathogens, ranks the fourth causative organism of bacteremia. The onset of bacteremia is greatly associated with the presence of catheter. Repeated blood cultures and the central venous catheter CVC tip culture are done for the definitive diagnosis of Candida CRBSI. Additionally serological examinations such as 1 3 -beta-d-glucan and mannan antigen are also useful for early diagnosis. It is important for the appropriate treatment to remove choice of antifungals, we should also take into account the ability of antibiofilm effect of antifungals as well as immunological state of host including neutropenia, prior administration of azoles, isolated or estimated Candida species, sensitivity against antifungals, administration route, pharmacokinetics bioavailability, metabolic and excretion pathway, distribution and drug interaction. As to complication of Candida which occurs frequently and leads to the loss of eyesight, as well as infective endocarditis, arthritis, metastatic infections such as embolic pneumonia and suppurative thrombotic phlebitis of catheter insertion site. Lastly we emphasize that the appropriate treatment based on the character of Candida
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