National surveillance of species distribution in blood isolates of Candida species in Japan and their susceptibility to six antifungal agents including voriconazole and micafungin

Takakura, Shunji; Fujihara, Noború; Saito, Takashi; Kudo, Takako; Iinuma, Yoshitsugu; Ichiyama, Satoshi

doi:10.1093/jac/dkh053

Cited by 103 publications

(82 citation statements)

References 36 publications

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“…Other studies report between 0 (12) and 15% (13) with intermediate values (14)(15)(16), and all the isolates stored as C. tropicalis in the CBS collection since 1912 exhibited 5FC MIC <0.5 μg/mL. When we started the YEASTS program in 2002, the proportion of R 5FC was already at 46% and the clone accounted for 85% of the R 5FC isolates.…”

Section: Discussionmentioning

confidence: 89%

Clonal Population of Flucytosine-ResistantCandida tropicalisfrom Blood Cultures, Paris, France

Desnos‐Ollivier

Bretagne²,

Bernède³

et al. 2008

Emerg. Infect. Dis.

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Candida tropicalis is a diploid ascomycetes yeast responsible for 4%-24% of candidemia. Resistance to fl ucytosine is rarely described for this species but was observed for 45 (35%) of 130 C. tropicalis isolates recovered from blood cultures in the Paris area in a 4-year survey. The aims of this study were to test the hypothesis that the fl ucytosine-resistant isolates could represent a subgroup and to determine the relationship between epidemiologic and genomic data. Epidemiologic data and gene sequences were analyzed, and molecular typing was performed. Our results suggest that a clone of fl ucytosine-resistant isolates, associated with malignancies and a lower mortality than that for other C. tropicalis isolates, is widespread in the Paris area. We propose the analysis of 2 polymorphic microsatellite markers coupled with URA3 sequencing to track the clone. C andida tropicalis is a diploid ascomycetes yeast commonly found on the skin and in digestive tracts of healthy human hosts worldwide (1). Infections caused by C. tropicalis are reported in 4%-24% of patients with candidemia, depending on the country of study, underlying risk factors, and period of study (2). Primary resistance to fl ucytosine (5FC) occurs in <5% of all Candida species except for C. krusei, in which it is detected in up to 28% of isolates (3). It was thus unexpected to observe 35% resistance to 5FC among C. tropicalis isolates recovered from blood cultures in the active surveillance program on yeast-related fungemia implemented by the French National Reference Center for Mycoses and Antifungals (NRCMA) in the Paris area. The YEASTS program is designed to analyze the epidemiologic trends of yeast fungemia by collecting isolates and epidemiologic and clinical data. The second objective is to study the clinical isolates in terms of species, antifungal susceptibility profi les, and genetic diversity to look for associations between subtypes of isolates and epidemiologic/clinical parameters. To test the hypothesis that the 5FC resistant ( R 5FC) isolates could represent a different species or a subgroup, the R 5FC and susceptible ( S 5FC)

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Section: Discussionmentioning

confidence: 89%

Clonal Population of Flucytosine-ResistantCandida tropicalisfrom Blood Cultures, Paris, France

Desnos‐Ollivier

Bretagne²,

Bernède³

et al. 2008

Emerg. Infect. Dis.

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“…Over 200 species of Candida have been described, but 95% of all Candida infections are caused by five species: C. glabrata, C. parapsilosis, C. tropicalis, C. krusei, and C. albicans. C. albicans is the most important cause of candidemia worldwide (1,6,13,33 . terreus, A. niger, and A. nidulans (36).…”

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confidence: 99%

Evaluation of Novel Broad-Range Real-Time PCR Assay for Rapid Detection of Human Pathogenic Fungi in Various Clinical Specimens

et al. 2008

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In the present study, a novel broad-range real-time PCR was developed for the rapid detection of human pathogenic fungi. The assay targets a part of the 28S large-subunit ribosomal RNA (rDNA) gene. We investigated its application for the most important human pathogenic fungal genera, including Aspergillus, Candida, Cryptococcus, Mucor, Penicillium, Pichia, Microsporum, Trichophyton, and Scopulariopsis. Species were identified in PCR-positive reactions by direct DNA sequencing. A noncompetitive internal control was applied to prevent false-negative results due to PCR inhibition. The minimum detection limit for the PCR was determined to be one 28S rDNA copy per PCR, and the 95% detection limit was calculated to 15 copies per PCR. To assess the clinical applicability of the PCR method, intensive-care patients with artificial respiration and patients with infective endocarditis were investigated. For this purpose, 76 tracheal secretion samples and 70 heart valve tissues were analyzed in parallel by real-time PCR and cultivation. No discrepancies in results were observed between PCR analysis and cultivation methods. Furthermore, the application of the PCR method was investigated for other clinical specimens, including cervical swabs, nail and horny skin scrapings, and serum, blood, and urine samples. The combination of a broad-range real-time PCR and direct sequencing facilitates rapid screening for fungal infection in various clinical specimens.Invasive fungal infections caused mainly by Candida and Aspergillus spp. have assumed an increasing importance over the last two decades, with a high mortality and morbidity among hospitalized and immunocompromised patients (36). Candida is a commensal of the human mucosa and has remained the fourth most important cause of nosocomial bloodstream infections. Over 200 species of Candida have been described, but 95% of all Candida infections are caused by five species: C. glabrata, C. parapsilosis, C. tropicalis, C. krusei, and C. albicans. C. albicans is the most important cause of candidemia worldwide (1,6,13,33 . terreus, A. niger, and A. nidulans (36). Fungal infections have also been considered in many superficial dermatological mycoses (22, 37) causing restricted infections of the corneocyte of skin, hair, and nails (27). Other important fungal pathogens that cause uncommon human diseases are Cryptococcus spp., Penicillium spp., Pichia spp., Fusarium spp., and Mucor spp. (19,35,36). The crucial factor in diagnosis and effective therapy is the identification of the etiologic agent. The standard method for the detection of fungal infections is mycological culture and direct microscopy of clinical specimen. Nevertheless, microscopy often lacks a satisfactory sensitivity, whereas diagnosis by mycological culture often require a long growth period. The application of serological tests for cryptococcus, aspergillus, and histoplasma antigens also lacks sufficient sensitivity (26). Furthermore, widely accepted antigen tests for Candida or dermatophytes are not available. In this...

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“…are the fourth most common cause of nosocomial bloodstream infection (13,14). These infections result in increased mortality (5) and longer hospital stays (3,18) with associated higher health care costs. Of special concern has been the emergence of non-Candida albicans species exhibiting resistance to the current spectrum of azoles (6,8,(12)(13)(14).…”

mentioning

confidence: 99%

Activities of Micafungin against 315 Invasive Clinical Isolates of Fluconazole-Resistant Candida spp

Messer¹,

Diekema

Boyken³

et al. 2006

J Clin Microbiol

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Micafungin is a new echinocandin exhibiting broad-spectrum activity against Candida spp. The activity of the echinocandins against Candida species known to express intrinsic or acquired resistance to fluconazole is of interest. We determined the MICs of micafungin and caspofungin against 315 invasive clinical (bloodstream and other sterile-site) isolates of fluconazole-resistant Candida species obtained from geographically diverse medical centers between 2001 and 2004. MICs were determined using broth microdilution according to the CLSI reference method M27-A2. RPMI 1640 was used as the test medium, and we used the MIC endpoint of prominent growth reduction at 24 h. Among the 315 fluconazole-resistant Candida isolates, 146 (46%) were C. krusei, 110 (35%) were C. glabrata, 41 (13%) were C. albicans, and 18 (6%) were less frequently isolated species. Micafungin had good in vitro activity against all fluconazole-resistant Candida spp. tested; the MICs at which 50% (MIC 50 ) and 90% (MIC 90 ) of isolates were inhibited were 0.03 g/ml and 0.06 g/ml, respectively. All the fluconazole-resistant Candida spp. were inhibited at a micafungin MIC that was <1 g/ml. Among the most common fluconazole-resistant Candida spp. tested in the collection, C. glabrata exhibited the lowest micafungin MICs (MIC 90 , <0.015 g/ml), followed by C. albicans (MIC 90 , 0.03 g/ml) and C. krusei (MIC 90 , 0.06 g/ml). The new echinocandin micafungin has excellent in vitro activity against 315 invasive clinical isolates of fluconazole-resistant Candida, which represents the largest collection to date of fluconazole-resistant Candida isolates tested against micafungin. Micafungin may prove useful in the treatment of infections due to azoleresistant Candida.In the United States, Candida spp. are the fourth most common cause of nosocomial bloodstream infection (13,14). These infections result in increased mortality (5) and longer hospital stays (3, 18) with associated higher health care costs. Of special concern has been the emergence of non-Candida albicans species exhibiting resistance to the current spectrum of azoles (6,8,(12)(13)(14). Treatment of azole-resistant infections has remained a challenge for clinicians and has driven the need for alternative agents having novel mechanisms of action.The development of the echinocandin class of systemic antifungal agents has added to the limited number of drugs used against Candida spp. In contrast to the azoles, which inhibit ergosterol synthesis, echinocandins interrupt the synthesis of 1,3-␤-D glucan, an important component of the fungal cell wall (2). The echinocandins have been shown to exhibit in vitro activity against both Candida spp. and Aspergillus spp. (4,10,11,15,17,19).Micafungin is the most recently available echinocandin, currently FDA approved for use in esophageal candidiasis and for the prophylaxis of invasive fungal infections in hematopoietic stem cell transplant patients. The activity of micafungin against clinical isolates of azole-resistant Candida spp. is of interest. We examine...

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National surveillance of species distribution in blood isolates of Candida species in Japan and their susceptibility to six antifungal agents including voriconazole and micafungin

Cited by 103 publications

References 36 publications

Clonal Population of Flucytosine-ResistantCandida tropicalisfrom Blood Cultures, Paris, France

Clonal Population of Flucytosine-ResistantCandida tropicalisfrom Blood Cultures, Paris, France

Evaluation of Novel Broad-Range Real-Time PCR Assay for Rapid Detection of Human Pathogenic Fungi in Various Clinical Specimens

Activities of Micafungin against 315 Invasive Clinical Isolates of Fluconazole-Resistant Candida spp

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