{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T12:36:09Z","timestamp":1789994169484,"version":"4.0.1"},"reference-count":120,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2018,8,16]],"date-time":"2018-08-16T00:00:00Z","timestamp":1534377600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JoF"],"abstract":"<jats:p>Invasive candidiasis occurs frequently in hospitalized patients, and is associated with high mortality rates due to delays in recognition and initiation of appropriate antifungals. Management of invasive candidiasis must take into account multiple host, pathogen, and drug-related factors, including the site of infection, host immune status, severity of sepsis, resistance and tolerance to antifungal agents, biofilm formation, and pharmacokinetic\/pharmacodynamic considerations. Recent treatment directives have been shaped by the widespread introduction of echinocandins, highly potent and safe antifungals, into clinical use, as well as important changes in drug susceptibility patterns and the emergence of known and novel drug-resistant Candida species. Advances in molecular diagnostics have the potential to guide early targeted treatment of high-risk patients.<\/jats:p>","DOI":"10.3390\/jof4030097","type":"journal-article","created":{"date-parts":[[2018,8,16]],"date-time":"2018-08-16T11:39:08Z","timestamp":1534419548000},"page":"97","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":89,"title":["Treatment of Invasive Candidiasis: A Narrative Review"],"prefix":"10.3390","volume":"4","author":[{"given":"Ronen","family":"Ben-Ami","sequence":"first","affiliation":[{"name":"Infectious Diseases Unit, Tel Aviv Sourasky Medical Center, and the Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 64239, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2018,8,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1198","DOI":"10.1056\/NEJMoa1306801","article-title":"Multistate point-prevalence survey of health care-associated infections","volume":"370","author":"Magill","year":"2014","journal-title":"N. Engl. J. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1086\/421946","article-title":"Nosocomial bloodstream infections in US hospitals: Analysis of 24,179 cases from a prospective nationwide surveillance study","volume":"39","author":"Wisplinghoff","year":"2004","journal-title":"Clin. Infect. Dis."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2323","DOI":"10.1001\/jama.2009.1754","article-title":"International study of the prevalence and outcomes of infection in intensive care units","volume":"302","author":"Vincent","year":"2009","journal-title":"JAMA"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Bongomin, F., Gago, S., Oladele, R.O., and Denning, D.W. (2017). Global and Multi-National Prevalence of Fungal Diseases-Estimate Precision. J. Fungi (Basel), 3.","DOI":"10.3390\/jof3040057"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"3015","DOI":"10.1128\/IAI.00062-14","article-title":"Candida glabrata Intra-Abdominal Candidiasis Is Characterized by Persistence within the Peritoneal Cavity and Abscesses","volume":"82","author":"Cheng","year":"2014","journal-title":"Infect. Immun."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1612","DOI":"10.1097\/CCM.0b013e31819efac0","article-title":"Epidemiology, management, and risk factors for death of invasive Candida infections in critical care: A multicenter, prospective, observational study in France (2005\u20132006)","volume":"37","author":"Leroy","year":"2009","journal-title":"Crit. Care Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"7","DOI":"10.3201\/eid2301.161198","article-title":"Epidemiology of Hospitalizations Associated with Invasive Candidiasis, United States, 2002\u20132012(1)","volume":"23","author":"Strollo","year":"2016","journal-title":"Emerg. Infect. Dis."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1016\/j.diagmicrobio.2010.01.002","article-title":"Geographic variation in the frequency of isolation and fluconazole and voriconazole susceptibilities of Candida glabrata: An assessment from the ARTEMIS DISK Global Antifungal Surveillance Program","volume":"67","author":"Pfaller","year":"2010","journal-title":"Diagn. Microbiol. Infect. Dis."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1097\/MCC.0b013e32833e84d2","article-title":"Epidemiology of invasive candidiasis","volume":"16","author":"Arendrup","year":"2010","journal-title":"Curr. Opin. Crit. Care"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Cleveland, A.A., Harrison, L.H., Farley, M.M., Hollick, R., Stein, B., Chiller, T.M., Lockhart, S.R., and Park, B.J. (2015). Declining incidence of candidemia and the shifting epidemiology of Candida resistance in two US metropolitan areas, 2008\u20132013: Results from population-based surveillance. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0120452"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1111\/1469-0691.12039","article-title":"ESCMID* guideline for the diagnosis and management of Candida diseases 2012: Non-neutropenic adult patients","volume":"18","author":"Cornely","year":"2012","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"e1","DOI":"10.1093\/cid\/civ933","article-title":"Clinical Practice Guideline for the Management of Candidiasis: 2016 Update by the Infectious Diseases Society of America","volume":"62","author":"Pappas","year":"2016","journal-title":"Clin. Infect. Dis."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1111\/1469-0691.12041","article-title":"ESCMID* guideline for the diagnosis and management of Candida diseases 2012: Adults with haematological malignancies and after haematopoietic stem cell transplantation (HCT)","volume":"18","author":"Ullmann","year":"2012","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1724","DOI":"10.1093\/cid\/cit136","article-title":"Increasing echinocandin resistance in Candida glabrata: Clinical failure correlates with presence of FKS mutations and elevated minimum inhibitory concentrations","volume":"56","author":"Alexander","year":"2013","journal-title":"Clin. Infect. Dis."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"726","DOI":"10.3389\/fmicb.2018.00726","article-title":"Candida auris: Disinfectants and Implications for Infection Control","volume":"9","author":"Ku","year":"2018","journal-title":"Front. Microbiol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1093\/cid\/ciw691","article-title":"Simultaneous Emergence of Multidrug-Resistant Candida auris on 3 Continents Confirmed by Whole-Genome Sequencing and Epidemiological Analyses","volume":"64","author":"Lockhart","year":"2016","journal-title":"Clin. Infect. Dis."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1093\/clinids\/21.2.323","article-title":"Meningitis caused by Candida species: An emerging problem in neurosurgical patients","volume":"21","author":"Nguyen","year":"1995","journal-title":"Clin. Infect. Dis."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1016\/j.jinf.2004.10.016","article-title":"A meta-analysis of medical versus surgical therapy for Candida endocarditis","volume":"51","author":"Steinbach","year":"2005","journal-title":"J. Infect."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2305","DOI":"10.1128\/AAC.00262-08","article-title":"A naturally occurring proline-to-alanine amino acid change in Fks1p in Candida parapsilosis, Candida orthopsilosis, and Candida metapsilosis accounts for reduced echinocandin susceptibility","volume":"52","author":"Katiyar","year":"2008","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2020","DOI":"10.1056\/NEJMoa021585","article-title":"Comparison of caspofungin and amphotericin B for invasive candidiasis","volume":"347","author":"Betts","year":"2002","journal-title":"N. Engl. J. Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1519","DOI":"10.1016\/S0140-6736(07)60605-9","article-title":"Micafungin versus liposomal amphotericin B for candidaemia and invasive candidosis: A phase III randomised double-blind trial","volume":"369","author":"Kuse","year":"2007","journal-title":"Lancet"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2472","DOI":"10.1056\/NEJMoa066906","article-title":"Anidulafungin versus fluconazole for invasive candidiasis","volume":"356","author":"Reboli","year":"2007","journal-title":"N. Engl. J. Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"883","DOI":"10.1086\/520980","article-title":"Micafungin versus caspofungin for treatment of candidemia and other forms of invasive candidiasis","volume":"45","author":"Pappas","year":"2007","journal-title":"Clin. Infect. Dis."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1676","DOI":"10.1086\/598933","article-title":"A Multicenter, double-blind trial of a high-dose caspofungin treatment regimen versus a standard caspofungin treatment regimen for adult patients with invasive candidiasis","volume":"48","author":"Betts","year":"2009","journal-title":"Clin. Infect. Dis."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1042\/bj2660475","article-title":"Interaction of azole antifungal antibiotics with cytochrome P-450-dependent 14 alpha-sterol demethylase purified from Candida albicans","volume":"266","author":"Hitchcock","year":"1990","journal-title":"Biochem. J."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1325","DOI":"10.1056\/NEJM199411173312001","article-title":"A randomized trial comparing fluconazole with amphotericin B for the treatment of candidemia in patients without neutropenia. Candidemia Study Group and the National Institute","volume":"331","author":"Rex","year":"1994","journal-title":"N. Engl. J. Med."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1007\/BF01726360","article-title":"Multicenter randomized trial of fluconazole versus amphotericin B for treatment of candidemia in non-neutropenic patients. Canadian Candidemia Study Group","volume":"16","author":"Phillips","year":"1997","journal-title":"Eur. J. Clin. Microbiol. Infect. Dis."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1221","DOI":"10.1086\/374850","article-title":"A randomized and blinded multicenter trial of high-dose fluconazole plus placebo versus fluconazole plus amphotericin B as therapy for candidemia and its consequences in nonneutropenic subjects","volume":"36","author":"Rex","year":"2003","journal-title":"Clin. Infect. Dis."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1435","DOI":"10.1016\/S0140-6736(05)67490-9","article-title":"Voriconazole versus a regimen of amphotericin B followed by fluconazole for candidaemia in non-neutropenic patients: A randomised non-inferiority trial","volume":"366","author":"Kullberg","year":"2005","journal-title":"Lancet"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"686","DOI":"10.1086\/319211","article-title":"Mortality and costs of acute renal failure associated with amphotericin B therapy","volume":"32","author":"Bates","year":"2001","journal-title":"Clin. Infect. Dis."},{"key":"ref_31","unstructured":"Clinical and Laboratory Standards Institute (2008). Reference Method for Broth Dilution Antifungal Susceptibility Testing of Yeasts, National Committee for Clinical Laboratory Standards. Approved Standard M27-A3."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"EUCAST (2008). Definitive document EDef 7.1: Method for the determination of broth dilution MICs of antifungal agents for fermentative yeasts. Clin. Microbiol. Infect., 14, 398\u2013405.","DOI":"10.1111\/j.1469-0691.2007.01935.x"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1016\/j.diagmicrobio.2014.02.008","article-title":"The impact of new epidemiological cutoff values on Candida glabrata resistance rates and concordance between testing methods","volume":"79","author":"Hilerowicz","year":"2014","journal-title":"Diagn. Microbiol. Infect. Dis."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"6361","DOI":"10.1128\/AAC.01451-13","article-title":"Anidulafungin and micafungin MIC breakpoints are superior to that of caspofungin for identifying FKS mutant Candida glabrata strains and Echinocandin resistance","volume":"57","author":"Shields","year":"2013","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1897","DOI":"10.1128\/AAC.02163-13","article-title":"Real-world experience with echinocandin MICs against Candida species in a multicenter study of hospitals that routinely perform susceptibility testing of bloodstream isolates","volume":"58","author":"Eschenauer","year":"2014","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"3965","DOI":"10.1128\/AAC.00355-12","article-title":"Caspofungin Etest susceptibility testing of Candida species: Risk of misclassification of susceptible isolates of C. glabrata and C. krusei when adopting the revised CLSI caspofungin breakpoints","volume":"56","author":"Arendrup","year":"2012","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2257","DOI":"10.1128\/AAC.00095-07","article-title":"Paradoxical effect of Echinocandins across Candida species in vitro: Evidence for echinocandin-specific and candida species-related differences","volume":"51","author":"Chamilos","year":"2007","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1007\/s10096-007-0411-4","article-title":"Paradoxical growth effects of the echinocandins caspofungin and micafungin, but not of anidulafungin, on clinical isolates of Candida albicans and C. dubliniensis","volume":"27","author":"Fleischhacker","year":"2008","journal-title":"Eur. J. Clin. Microbiol. Infect. Dis."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"2641","DOI":"10.1128\/AAC.00999-10","article-title":"Paradoxical effect of caspofungin against Candida bloodstream isolates is mediated by multiple pathways but eliminated in human serum","volume":"55","author":"Shields","year":"2011","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1007\/s12275-010-9221-y","article-title":"In vivo studies with a Candida tropicalis isolate exhibiting paradoxical growth in vitro in the presence of high concentration of caspofungin","volume":"48","author":"Bayegan","year":"2010","journal-title":"J. Microbiol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"4862","DOI":"10.1128\/AAC.00027-12","article-title":"The presence of an FKS mutation rather than MIC is an independent risk factor for failure of echinocandin therapy among patients with invasive candidiasis due to Candida glabrata","volume":"56","author":"Shields","year":"2012","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"3528","DOI":"10.1128\/AAC.00136-13","article-title":"Caspofungin MICs correlate with treatment outcomes among patients with Candida glabrata invasive candidiasis and prior echinocandin exposure","volume":"57","author":"Shields","year":"2013","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"626","DOI":"10.1093\/infdis\/jir351","article-title":"Fitness and Virulence Costs of Candida albicans FKS1 Hot Spot Mutations Associated With Echinocandin Resistance","volume":"204","author":"Lewis","year":"2011","journal-title":"J. Infect. Dis."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Singh-Babak, S.D., Babak, T., Diezmann, S., Hill, J.A., Xie, J.L., Chen, Y.L., Poutanen, S.M., Rennie, R.P., Heitman, J., and Cowen, L.E. (2012). Global Analysis of the Evolution and Mechanism of Echinocandin Resistance in Candida glabrata. PLoS Pathog., 8.","DOI":"10.1371\/journal.ppat.1002718"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"86","DOI":"10.3201\/eid1801.110556","article-title":"Candida spp. with acquired echinocandin resistance, France, 2004-2010","volume":"18","author":"Dannaoui","year":"2012","journal-title":"Emerg. Infect. Dis."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"982","DOI":"10.1086\/342384","article-title":"Has antifungal susceptibility testing come of age?","volume":"35","author":"Rex","year":"2002","journal-title":"Clin. Infect. Dis."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1016\/j.drup.2010.09.002","article-title":"Wild-type MIC distributions, epidemiological cutoff values and species-specific clinical breakpoints for fluconazole and Candida: Time for harmonization of CLSI and EUCAST broth microdilution methods","volume":"13","author":"Pfaller","year":"2010","journal-title":"Drug. Resist. Updat."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1002\/yea.962","article-title":"Function of Candida glabrata ABC transporter gene, PDH1","volume":"20","author":"Izumikawa","year":"2003","journal-title":"Yeast"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1482","DOI":"10.1128\/AAC.41.7.1482","article-title":"Increased mRNA levels of ERG16, CDR, and MDR1 correlate with increases in azole resistance in Candida albicans isolates from a patient infected with human immunodeficiency virus","volume":"41","author":"White","year":"1997","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1289","DOI":"10.1128\/EC.00215-12","article-title":"Gain-of-function mutations in UPC2 are a frequent cause of ERG11 upregulation in azole-resistant clinical isolates of Candida albicans","volume":"11","author":"Flowers","year":"2012","journal-title":"Eukaryot Cell"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"2753","DOI":"10.1128\/AAC.43.11.2753","article-title":"The ATP binding cassette transporter gene CgCDR1 from Candida glabrata is involved in the resistance of clinical isolates to azole antifungal agents","volume":"43","author":"Sanglard","year":"1999","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1695","DOI":"10.1128\/AAC.42.7.1695","article-title":"Fluconazole resistance associated with drug efflux and increased transcription of a drug transporter gene, PDH1, in Candida glabrata","volume":"42","author":"Miyazaki","year":"1998","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"704","DOI":"10.1111\/j.1365-2958.2006.05235.x","article-title":"Pdr1 regulates multidrug resistance in Candida glabrata: Gene disruption and genome-wide expression studies","volume":"61","author":"Vermitsky","year":"2006","journal-title":"Mol. Microbiol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"3773","DOI":"10.1128\/AAC.48.10.3773-3781.2004","article-title":"Azole resistance in Candida glabrata: Coordinate upregulation of multidrug transporters and evidence for a Pdr1-like transcription factor","volume":"48","author":"Vermitsky","year":"2004","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Ferrari, S., Ischer, F., Calabrese, D., Posteraro, B., Sanguinetti, M., Fadda, G., Rohde, B., Bauser, C., Bader, O., and Sanglard, D. (2009). Gain of function mutations in CgPDR1 of Candida glabrata not only mediate antifungal resistance but also enhance virulence. PLoS Pathog., 5.","DOI":"10.1371\/journal.ppat.1000268"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1384","DOI":"10.1128\/AAC.50.4.1384-1392.2006","article-title":"Candida glabrata PDR1, a transcriptional regulator of a pleiotropic drug resistance network, mediates azole resistance in clinical isolates and petite mutants","volume":"50","author":"Tsai","year":"2006","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1773","DOI":"10.1128\/AAC.48.5.1773-1777.2004","article-title":"Mechanism of increased fluconazole resistance in Candida glabrata during prophylaxis","volume":"48","author":"Bennett","year":"2004","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_58","first-page":"195","article-title":"Multidrug-Resistant Candida haemulonii and C. auris, Tel Aviv, Israel","volume":"23","author":"Berman","year":"2017","journal-title":"Emerg. Infect. Dis."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Chowdhary, A., Sharma, C., and Meis, J.F. (2017). Candida auris: A rapidly emerging cause of hospital-acquired multidrug-resistant fungal infections globally. PLoS Pathog., 13.","DOI":"10.1371\/journal.ppat.1006290"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1287","DOI":"10.1128\/AAC.50.4.1287-1292.2006","article-title":"Evaluation of amphotericin B interpretive breakpoints for Candida bloodstream isolates by correlation with therapeutic outcome","volume":"50","author":"Park","year":"2006","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1086\/514193","article-title":"Do in vitro susceptibility data predict the microbiologic response to amphotericin B? Results of a prospective study of patients with Candida fungemia","volume":"177","author":"Nguyen","year":"1998","journal-title":"J. Infect. Dis."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"E27","DOI":"10.1111\/j.1469-0691.2011.03644.x","article-title":"EUCAST technical note on Amphotericin B","volume":"17","author":"Arendrup","year":"2011","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"4527","DOI":"10.1128\/AAC.00348-10","article-title":"Identification and characterization of four azole-resistant erg3 mutants of Candida albicans","volume":"54","author":"Martel","year":"2010","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"3578","DOI":"10.1128\/AAC.00303-10","article-title":"A clinical isolate of Candida albicans with mutations in ERG11 (encoding sterol 14alpha-demethylase) and ERG5 (encoding C22 desaturase) is cross resistant to azoles and amphotericin B","volume":"54","author":"Martel","year":"2010","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"2404","DOI":"10.1128\/AAC.47.8.2404-2412.2003","article-title":"Candida albicans mutations in the ergosterol biosynthetic pathway and resistance to several antifungal agents","volume":"47","author":"Sanglard","year":"2003","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"2551","DOI":"10.1093\/jac\/dkv140","article-title":"Stepwise emergence of azole, echinocandin and amphotericin B multidrug resistance in vivo in Candida albicans orchestrated by multiple genetic alterations","volume":"70","author":"Jensen","year":"2015","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"11128","DOI":"10.1038\/ncomms11128","article-title":"Prevalent mutator genotype identified in fungal pathogen Candida glabrata promotes multi-drug resistance","volume":"7","author":"Healey","year":"2016","journal-title":"Nat. Commun."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"eE00655-16","DOI":"10.1128\/mBio.00655-16","article-title":"Heteroresistance to Fluconazole Is a Continuously Distributed Phenotype among Candida glabrata Clinical Strains Associated with In Vivo Persistence","volume":"7","author":"Zimmerman","year":"2016","journal-title":"mBio"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1128\/CMR.00058-14","article-title":"Antimicrobial heteroresistance: An emerging field in need of clarity","volume":"28","author":"Valvano","year":"2015","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"3640","DOI":"10.1128\/AAC.49.9.3640-3645.2005","article-title":"Delaying the empiric treatment of candida bloodstream infection until positive blood culture results are obtained: A potential risk factor for hospital mortality","volume":"49","author":"Morrell","year":"2005","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1086\/504810","article-title":"Time to initiation of fluconazole therapy impacts mortality in patients with candidemia: A multi-institutional study","volume":"43","author":"Garey","year":"2006","journal-title":"Clin. Infect. Dis."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/j.cmi.2014.07.006","article-title":"Early initiation of appropriate treatment is associated with increased survival in cancer patients with Candida glabrata fungaemia: A potential benefit from infectious disease consultation","volume":"21","author":"Farmakiotis","year":"2015","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1739","DOI":"10.1093\/cid\/cis305","article-title":"Septic shock attributed to Candida infection: Importance of empiric therapy and source control","volume":"54","author":"Kollef","year":"2012","journal-title":"Clin. Infect. Dis."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1284","DOI":"10.1093\/cid\/cit006","article-title":"Finding the \u201cMissing 50%\u201d of Invasive Candidiasis: How Nonculture Diagnostics Will Improve Understanding of Disease Spectrum and Transform Patient Care","volume":"56","author":"Clancy","year":"2013","journal-title":"Clin. Infect. Dis."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"2879","DOI":"10.1128\/JCM.00609-11","article-title":"Quantitation of Candida CFU in initial positive blood cultures","volume":"49","author":"Pfeiffer","year":"2011","journal-title":"J. Clin. Microbiol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"730","DOI":"10.1097\/01.CCM.0000202208.37364.7D","article-title":"A bedside scoring system (\u201cCandida score\u201d) for early antifungal treatment in nonneutropenic critically ill patients with Candida colonization","volume":"34","author":"Leon","year":"2006","journal-title":"Crit. Care Med."},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Bruyere, R., Quenot, J.P., Prin, S., Dalle, F., Vigneron, C., Aho, S., Leon, C., and Charles, P.E. (2014). Empirical antifungal therapy with an echinocandin in critically-ill patients: Prospective evaluation of a pragmatic Candida score-based strategy in one medical ICU. BMC Infect. Dis., 14.","DOI":"10.1186\/1471-2334-14-385"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"R249","DOI":"10.1186\/cc10507","article-title":"Early diagnosis of candidemia in intensive care unit patients with sepsis: A prospective comparison of (1-->3)-beta-d-glucan assay, Candida score, and colonization index","volume":"15","author":"Posteraro","year":"2011","journal-title":"Crit. Care"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1186\/2110-5820-1-50","article-title":"Evaluation of \u201cCandida score\u201d in critically ill patients: A prospective, multicenter, observational, cohort study","volume":"1","author":"Leroy","year":"2011","journal-title":"Ann. Intensive Care"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"750","DOI":"10.1093\/cid\/ciq206","article-title":"beta-D-glucan assay for the diagnosis of invasive fungal infections: A meta-analysis","volume":"52","author":"Karageorgopoulos","year":"2011","journal-title":"Clin. Infect. Dis."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"R222","DOI":"10.1186\/cc9365","article-title":"The use of mannan antigen and anti-mannan antibodies in the diagnosis of invasive candidiasis: Recommendations from the Third European Conference on Infections in Leukemia","volume":"14","author":"Mikulska","year":"2010","journal-title":"Crit. Care"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1128\/JCM.01602-10","article-title":"PCR diagnosis of invasive candidiasis: Systematic review and meta-analysis","volume":"49","author":"Avni","year":"2011","journal-title":"J. Clin. Microbiol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1678","DOI":"10.1093\/cid\/cix1095","article-title":"Detecting Infections Rapidly and Easily for Candidemia Trial, Part 2 (DIRECT2): A Prospective, Multicenter Study of the T2Candida Panel","volume":"66","author":"Clancy","year":"2018","journal-title":"Clin. Infect. Dis."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1110","DOI":"10.1093\/cid\/cis021","article-title":"Impact of treatment strategy on outcomes in patients with candidemia and other forms of invasive candidiasis: A patient-level quantitative review of randomized trials","volume":"54","author":"Andes","year":"2012","journal-title":"Clin. Infect. Dis."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"532","DOI":"10.1128\/AAC.01128-10","article-title":"Recent exposure to caspofungin or fluconazole influences the epidemiology of candidemia: A prospective multicenter study involving 2441 patients","volume":"55","author":"Lortholary","year":"2011","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1016\/j.jinf.2007.10.014","article-title":"Increasing incidence of Candida parapsilosis candidemia with caspofungin usage","volume":"56","author":"Forrest","year":"2008","journal-title":"J. Infect."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"4745","DOI":"10.1002\/cncr.24507","article-title":"Candidemia in patients with hematologic malignancies in the era of new antifungal agents (2001\u20132007): Stable incidence but changing epidemiology of a still frequently lethal infection","volume":"115","author":"Sipsas","year":"2009","journal-title":"Cancer"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"1413","DOI":"10.1093\/cid\/ciu158","article-title":"Initial use of echinocandins does not negatively influence outcome in Candida parapsilosis bloodstream infection: A propensity score analysis","volume":"58","author":"Aguado","year":"2014","journal-title":"Clin. Infect. Dis."},{"key":"ref_89","unstructured":"Centers for Disease Control (2018, May 23). Recommendations for Treatment of Candida auris, Available online: https:\/\/www.cdc.gov\/fungal\/candida-auris\/c-auris-treatment.html."},{"key":"ref_90","doi-asserted-by":"crossref","unstructured":"Ruiz-Gaitan, A., Moret, A.M., Tasias-Pitarch, M., Aleixandre-Lopez, A.I., Martinez-Morel, H., Calabuig, E., Salavert-Lleti, M., Ramirez, P., Lopez-Hontangas, J.L., and Hagen, F. (2018). An outbreak due to Candida auris with prolonged colonization and candidemia in a tertiary care European hospital. Mycoses.","DOI":"10.1111\/myc.12781"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"1794","DOI":"10.1093\/jac\/dkx034","article-title":"Candida auris candidaemia in Indian ICUs: Analysis of risk factors","volume":"72","author":"Rudramurthy","year":"2017","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"S73","DOI":"10.1093\/ofid\/ofx163.003","article-title":"Assessment of Candida auris response to antifungal drugs using time-kill assays and an animal model","volume":"4","author":"Novikov","year":"2017","journal-title":"Open Forum Infect. Dis."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1007\/s10096-002-0854-6","article-title":"Duration of antifungal treatment and development of delayed complications in patients with candidaemia","volume":"22","author":"Donnelly","year":"2003","journal-title":"Eur. J. Clin. Microbiol. Infect. Dis."},{"key":"ref_94","doi-asserted-by":"crossref","unstructured":"Vazquez, J., Reboli, A.C., Pappas, P.G., Patterson, T.F., Reinhardt, J., Chin-Hong, P., Tobin, E., Kett, D.H., Biswas, P., and Swanson, R. (2014). Evaluation of an early step-down strategy from intravenous anidulafungin to oral azole therapy for the treatment of candidemia and other forms of invasive candidiasis: Results from an open-label trial. BMC Infect. Dis., 14.","DOI":"10.1186\/1471-2334-14-97"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1016\/j.diagmicrobio.2012.10.003","article-title":"Epidemiology and outcomes of candidemia in 3648 patients: Data from the Prospective Antifungal Therapy (PATH Alliance(R)) registry, 2004\u20132008","volume":"74","author":"Pfaller","year":"2012","journal-title":"Diagn. Microbiol. Infect. Dis."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1016\/j.jinf.2008.12.008","article-title":"Candidemia in cancer patients: Impact of early removal of non-tunneled central venous catheters on outcome","volume":"58","author":"Liu","year":"2009","journal-title":"J. Infect."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"2429","DOI":"10.1001\/archinte.1995.00430220087009","article-title":"Therapeutic approaches in patients with candidemia. Evaluation in a multicenter, prospective, observational study","volume":"155","author":"Nguyen","year":"1995","journal-title":"Arch. Intern. Med."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1086\/653935","article-title":"Early removal of central venous catheter in patients with candidemia does not improve outcome: Analysis of 842 patients from 2 randomized clinical trials","volume":"51","author":"Nucci","year":"2010","journal-title":"Clin. Infect. Dis."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"2566","DOI":"10.1128\/JCM.00605-14","article-title":"Diagnostic usefulness of differential time to positivity for catheter-related candidemia","volume":"52","author":"Park","year":"2014","journal-title":"J. Clin. Microbiol."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"2222","DOI":"10.1128\/JCM.00214-08","article-title":"Time to blood culture positivity as a marker for catheter-related candidemia","volume":"46","author":"Weinberger","year":"2008","journal-title":"J. Clin. Microbiol."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1016\/j.diagmicrobio.2016.04.001","article-title":"Time-to-reporting of blood culture positivity and central venous catheter-associated Candida glabrata fungemia in cancer patients","volume":"85","author":"Stempel","year":"2016","journal-title":"Diagn Microbiol. Infect. Dis."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1086\/599376","article-title":"Clinical Practice Guidelines for the Diagnosis and Management of Intravascular Catheter-Related Infection: 2009 Update by the Infectious Diseases Society of America","volume":"49","author":"Allon","year":"2009","journal-title":"Clin. Infect. Dis."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1128\/AAC.01351-12","article-title":"Antifungal lock therapy","volume":"57","author":"Walraven","year":"2013","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"7601","DOI":"10.1128\/AAC.04134-14","article-title":"Abdominal candidiasis is a hidden reservoir of echinocandin resistance","volume":"58","author":"Shields","year":"2014","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"1543","DOI":"10.1007\/s10096-015-2384-z","article-title":"The search for endocarditis in patients with candidemia: A systematic recommendation for echocardiography? A prospective cohort","volume":"34","author":"Munoz","year":"2015","journal-title":"Eur. J. Clin. Microbiol. Infect. Dis."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1093\/cid\/cir355","article-title":"Ocular manifestations of candidemia","volume":"53","author":"Rothova","year":"2011","journal-title":"Clin. Infect. Dis."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"1302","DOI":"10.1016\/S0161-6420(94)31175-4","article-title":"Intraocular candidiasis in patients with candidemia. Clinical implications derived from a prospective multicenter study","volume":"101","author":"Donahue","year":"1994","journal-title":"Ophthalmology"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1093\/clinids\/20.3.657","article-title":"Use of fluconazole in the treatment of candidal endophthalmitis","volume":"20","author":"Akler","year":"1995","journal-title":"Clin. Infect. Dis."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"4027","DOI":"10.1128\/AAC.02300-12","article-title":"Intraocular penetration of intravenous micafungin in inflamed human eyes","volume":"57","author":"Mochizuki","year":"2013","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"E27","DOI":"10.1086\/431761","article-title":"Subtherapeutic ocular penetration of caspofungin and associated treatment failure in Candida albicans endophthalmitis","volume":"41","author":"Gauthier","year":"2005","journal-title":"Clin. Infect. Dis."},{"key":"ref_111","doi-asserted-by":"crossref","unstructured":"Schell, W.A., Jones, A.M., Borroto-Esoda, K., and Alexander, B.D. (2017). Antifungal Activity of SCY-078 and Standard Antifungal Agents against 178 Clinical Isolates of Resistant and Susceptible Candida Species. Antimicrob. Agents Chemother., 61.","DOI":"10.1128\/AAC.01102-17"},{"key":"ref_112","doi-asserted-by":"crossref","unstructured":"Larkin, E., Hager, C., Chandra, J., Mukherjee, P.K., Retuerto, M., Salem, I., Long, L., Isham, N., Kovanda, L., and Borroto-Esoda, K. (2017). The Emerging Pathogen Candida auris: Growth Phenotype, Virulence Factors, Activity of Antifungals, and Effect of SCY-078, a Novel Glucan Synthesis Inhibitor, on Growth Morphology and Biofilm Formation. Antimicrob. Agents Chemother., 61.","DOI":"10.1128\/AAC.02396-16"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1093\/jac\/dkx422","article-title":"Oral glucan synthase inhibitor SCY-078 is effective in an experimental murine model of invasive candidiasis caused by WT and echinocandin-resistant Candida glabrata","volume":"73","author":"Wiederhold","year":"2018","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_114","doi-asserted-by":"crossref","unstructured":"Jimenez-Ortigosa, C., Perez, W.B., Angulo, D., Borroto-Esoda, K., and Perlin, D.S. (2017). De Novo Acquisition of Resistance to SCY-078 in Candida glabrata Involves FKS Mutations That both Overlap and Are Distinct from Those Conferring Echinocandin Resistance. Antimicrob. Agents Chemother., 61.","DOI":"10.1128\/AAC.00833-17"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/j.jgar.2018.02.013","article-title":"Rezafungin (CD101), a next-generation echinocandin: A systematic literature review and assessment of possible place in therapy","volume":"14","author":"Sofjan","year":"2018","journal-title":"J. Glob. Antimicrob. Resist."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"624.e1","DOI":"10.1016\/j.ajog.2018.03.001","article-title":"A phase 2, randomized, double-blind, placebo-controlled, dose-ranging study to evaluate the efficacy and safety of orally administered VT-1161 in the treatment of recurrent vulvovaginal candidiasis","volume":"218","author":"Brand","year":"2018","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1093\/jac\/dkx352","article-title":"VT-1161 protects mice against oropharyngeal candidiasis caused by fluconazole-susceptible and -resistant Candida albicans","volume":"73","author":"Break","year":"2018","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_118","doi-asserted-by":"crossref","unstructured":"Hager, C.L., Larkin, E.L., Long, L., Zohra Abidi, F., Shaw, K.J., and Ghannoum, M.A. (2018). In Vitro and In Vivo Evaluation of the Antifungal Activity of APX001A\/APX001 against Candida auris. Antimicrob. Agents Chemother., 62.","DOI":"10.1128\/AAC.02319-17"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"2356","DOI":"10.1128\/AAC.44.9.2356-2360.2000","article-title":"Efficacy of oral cochleate-amphotericin B in a mouse model of systemic candidiasis","volume":"44","author":"Santangelo","year":"2000","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"1463","DOI":"10.1128\/AAC.44.6.1463-1469.2000","article-title":"Antifungal activity of amphotericin B cochleates against Candida albicans infection in a mouse model","volume":"44","author":"Zarif","year":"2000","journal-title":"Antimicrob. Agents Chemother."}],"container-title":["Journal of Fungi"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2309-608X\/4\/3\/97\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T15:19:04Z","timestamp":1760195944000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2309-608X\/4\/3\/97"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,8,16]]},"references-count":120,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2018,9]]}},"alternative-id":["jof4030097"],"URL":"https:\/\/doi.org\/10.3390\/jof4030097","relation":{},"ISSN":["2309-608X"],"issn-type":[{"value":"2309-608X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,8,16]]}}}