Candida species distribution and antifungal susceptibility testing according to European Committee on Antimicrobial Susceptibility Testing and new vs. old Clinical and Laboratory Standards Institute clinical breakpoints: a 6-year prospective candidaemia s
We analyzed the species distribution of Candida blood isolates (CBIs), prospectively collected between 2004 and 2009 within FUNGINOS, and compared their antifungal susceptibility according to clinical breakpoints defined by the European Committee on Antimicrobial Susceptibility Testing (EUCAST) in 2013, and the Clinical and Laboratory Standards Institute (CLSI) in 2008 (old CLSI breakpoints) and 2012 (new CLSI breakpoints). CBIs were tested for susceptiblity to fluconazole, voriconazole and caspofungin by microtitre broth dilution (Sensititre® YeastOne™ test panel). Of 1090 CBIs, 675 (61.9%) were C. albicans, 191 (17.5%) C. glabrata, 64 (5.9%) C. tropicalis, 59 (5.4%) C. parapsilosis, 33 (3%) C. dubliniensis, 22 (2%) C. krusei and 46 (4.2%) rare Candida species. Independently of the breakpoints applied, C. albicans was almost uniformly (>98%) susceptible to all three antifungal agents. In contrast, the proportions of fluconazole- and voriconazole-susceptible C. tropicalis and F-susceptible C. parapsilosis were lower according to EUCAST/new CLSI breakpoints than to the old CLSI breakpoints. For caspofungin, non-susceptibility occurred mainly in C. krusei (63.3%) and C. glabrata (9.4%). Nine isolates (five C. tropicalis, three C. albicans and one C. parapsilosis) were cross-resistant to azoles according to EUCAST breakpoints, compared with three isolates (two C. albicans and one C. tropicalis) according to new and two (2 C. albicans) according to old CLSI breakpoints. Four species (C. albicans, C. glabrata, C. tropicalis and C. parapsilosis) represented >90% of all CBIs. In vitro resistance to fluconazole, voriconazole and caspofungin was rare among C. albicans, but an increase of non-susceptibile isolates was observed among C. tropicalis/C. parapsilosis for the azoles and C. glabrata/C. krusei for caspofungin according to EUCAST and new CLSI breakpoints compared with old CLSI breakpoints.
Orasch C
，Marchetti O
，Garbino J
，Schrenzel J
，Zimmerli S
，Mühlethaler K
，Pfyffer G
，Ruef C
，Fehr J
，Zbinden R
，Calandra T
，Bille J
，FUNGINOS
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Non-albicans Candida spp. causing fungaemia: pathogenicity and antifungal resistance.
Non-albicans Candida (NAC) species cause 35-65% of all candidaemias in the general patient population. They occur more frequently in cancer patients, mainly in those with haematological malignancies and bone marrow transplant (BMT) recipients (40-70%), but are less common among intensive care unit (ITU) and surgical patients (35-55%), children (1-35%) or HIV-positive patients (0-33%). The proportion of NAC species among Candida species is increasing: over the two decades to 1990, NAC represented 10-40% of all candidaemias. In contrast, in 1991-1998, they represented 35-65% of all candidaemias. The most common NAC species are C. parapsilosis (20-40% of all Candida species), C. tropicalis (10-30%), C. krusei (10-35%) and C. glabrata (5-40%). Although these four are the most common, at least two other species are emerging: C. lusitaniae causing 2-8% of infections, and C. guilliermondii causing 1-5%. Other NAC species, such as C. rugosa, C. kefyr, C. stellatoidea, C. norvegensis and C. famata are rare, accounting for less than 1% of fungaemias in man. In terms of virulence and pathogenicity, some NAC species appear to be of lower virulence in animal models, yet behave with equal or greater virulence in man, when comparison is made with C. albicans. Mortality due to NAC species is similar to C. albicans, ranging from 15% to 35%. However, there are differences in both overall and attributable mortality among species: the lowest mortality is associated with C. parapsilosis, the highest with C. tropicalis and C. glabrata (40-70%). Other NAC species including C. krusei are associated with similar overall mortality to C. albicans (20-40%). Mortality in NAC species appears to be highest in ITU and surgical patients, and somewhat lower in cancer patients, children and HIV-positive patients. There is no difference between overall and attributable mortality, with the exception of C. glabrata which tends to infect immunocompromised individuals. While the crude mortality is low, attributable mortality (fungaemia-associated mortality) is higher than with C. albicans. There are several specific risk factors for particular NAC species: C. parapsilosis is related to foreign body insertion, neonates and hyperalimentation; C. krusei to azole prophylaxis and along with C. tropicalis to neutropenia and BMT; C. glabrata to azole prophylaxis, surgery and urinary or vascular catheters; C. lusitaniae and C. guilliermondii to previous polyene (amphotericin B or nystatin) use; and C. rugosa to burns. Antifungal susceptibility varies significantly in contrast to C. albicans: some NAC species are inherently or secondarily resistant to fluconazole; for example, 75% of C. krusei isolates, 35% of C. glabrata, 10-25% of C. tropicalis and C. lusitaniae. Amphotericin B resistance is also seen in a small proportion: 5-20% of C. lusitaniae and C. rugosa, 10-15% of C. krusei and 5-10% of C. guilliermondii. Other NAC species are akin to C. albicans-susceptible to both azoles and polyenes (C. parapsilosis, the majority of C. guilliermondii strains and C. tropicalis). Therefore, 'species directed' therapy should be administered for fungaemia according to the species identified-amphotericin B for C. krusei and C. glabrata, fluconazole for other species, including polyene-resistant or tolerant Candida species (C. lusitaniae, C. guilliermondii). In vitro susceptibility testing should be performed for most species of NAC in addition to removal of any foreign body to optimize management.
Krcmery V
，Barnes AJ
《JOURNAL OF HOSPITAL INFECTION》
Candida bloodstream infections: comparison of species distribution and resistance to echinocandin and azole antifungal agents in Intensive Care Unit (ICU) and non-ICU settings in the SENTRY Antimicrobial Surveillance Program (2008-2009).
Minimum inhibitory concentration (MIC) data from the SENTRY Antimicrobial Surveillance Program generated by reference methods were analysed to compare the antifungal resistance profiles and species distribution of Candida bloodstream infection (BSI) isolates obtained from patients in the Intensive Care Unit (ICU) and those from non-ICU locations. Results from 79 medical centres between 2008 and 2009 were tabulated. MIC values were obtained for anidulafungin, caspofungin, micafungin, fluconazole, posaconazole and voriconazole. Recently revised Clinical and Laboratory Standards Institute breakpoints for resistance were employed. A total of 1752 isolates of Candida spp. were obtained from ICU (779; 44.5%) and non-ICU (973; 55.5%) settings. The frequency of ICU-associated Candida BSI was higher in Latin America (56.5%) compared with Europe (44.4%) and North America (39.6%). The frequency of candidaemia in the ICU decreased both in Latin America and North America over the 2-year study period. Approximately 96% of isolates both in ICU and non-ICU settings were caused by only five species (Candida albicans, Candida glabrata, Candida parapsilosis, Candida tropicalis and Candida krusei). Resistance both to azoles and echinocandins was uncommon in ICU and non-ICU settings. Overall, fluconazole resistance was detected in 5.0% of ICU isolates and 4.4% of non-ICU isolates. Candida glabrata was the only species in which resistance to azoles and echinocandins was noted, and this multidrug-resistant phenotype was found in both settings. In conclusion, the findings from this global survey indicate that invasive candidiasis can no longer be considered to be just an ICU-related infection, and efforts to design preventive and diagnostic strategies must be expanded to include other at-risk populations and hospital environments. Concern regarding C. glabrata must now include resistance to echinocandins as well as azole antifungal agents.
Pfaller MA
，Messer SA
，Moet GJ
，Jones RN
，Castanheira M
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