Pilzinfektionen in der Intensivmedizin

Daniel C. Richter; Christoph Lichtenstern; Alexander Brinkmann; Markus A. Weigand

doi:10.1055/a-1338-9359

Krankenhaushygiene up2date, Table of Contents

Krankenhaushygiene up2date 2021; 16(01): 63-82
DOI: 10.1055/a-1338-9359

Infektiologie

Pilzinfektionen in der Intensivmedizin

Daniel C. Richter

,

Christoph Lichtenstern

,

Alexander Brinkmann

,

Markus A. Weigand

Abstract

All articles of this category

Invasive Pilzinfektionen sind zunehmend bedeutsam – als primäre Infektion und im Rahmen komplexer Infektionsgeschehen bei kritisch kranken sowie immunsupprimierten oder organtransplantierten Patienten. Neben Candida-Infektionen liegt das Augenmerk v. a. auf der invasiven pulmonalen Aspergillose und den selteneren Schimmelpilzinfektionen, wie z. B. den Mukormykosen. Neben den bekannten, häufig verwendeten Antimykotika möchten wir auch die Rolle neuerer Therapien diskutieren und einen Ausblick in die Zukunft der Antimykotika wagen.

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References

Literatur
1 Alexander BD, Pfaller MA. Contemporary tools for the diagnosis and management of invasive mycoses. Clin Infect Dis 2006; 43: S15-S27
2 Bitar D, Lortholary O, Le Strat Y. et al. Population-based analysis of invasive fungal infections, France, 2001-2010. Emerg Infect Dis 2014; 20: 1163
3 Webb BJ, Ferraro JP, Rea S. et al. Epidemiology and clinical Features of invasive fungal Infection in a US Health Care Network. In: Open Forum infectious Diseases. Oxford: Oxford University Press US; 2018
4 Ruhnke M, Groll AH, Mayser P. et al. Estimated burden of fungal infections in Germany. Mycoses 2015; 58: 22-28
5 von Lilienfeld-Toal M, Wagener J, Einsele H. et al. Invasive fungal infection: new treatments to meet new challenges. Dtsch Arztebl Int 2019; 116: 271-278
6 Bassetti M, Giacobbe DR, Vena A. et al. Incidence and outcome of invasive candidiasis in intensive care units (ICUs) in Europe: results of the EUCANDICU project. Crit Care 2019; 23: 219
7 Bongomin F, Gago S, Oladele R. et al. Global and multi-national prevalence of fungal diseases – estimate precision. J Fungi (Basel) 2017; 3: 57
8 Brunkhorst FM, Oppert M, Marx G. et al. Effect of empirical treatment with moxifloxacin and meropenem vs. meropenem on sepsis-related organ dysfunction in patients with severe sepsis: a randomized trial. JAMA 2012; 307: 2390-2399
9 Satoh K, Makimura K, Hasumi Y. et al. Candida auris sp. nov., a novel ascomycetous yeast isolated from the external ear canal of an inpatient in a Japanese hospital. Microbiol Immunol 2009; 53: 41-44
10 Chowdhary A, Sharma C, Meis JF. Candida auris: a rapidly emerging cause of hospital-acquired multidrug-resistant fungal infections globally. PLoS Pathog 2017; 13: e1006290
11 Cortegiani A, Misseri G, Fasciana T. et al. Epidemiology, clinical characteristics, resistance, and treatment of infections by Candida auris. J Intensive Care 2018; 6: 69
12 Schelenz S, Hagen F, Rhodes JL. et al. First hospital outbreak of the globally emerging Candida auris in a European hospital. Antimicrob Resist Infect Control 2016; 5: 35
13 León C, Ruiz-Santana S, Saavedra P. et al. A bedside scoring system (“Candida score”) for early antifungal treatment in nonneutropenic critically ill patients with Candida colonization. Crit Care Med 2006; 34: 730-737
14 Fishman JA, Rubin RH. Infection in organ-transplant recipients. N Engl J Med 1998; 338: 1741-1751
15 Timsit J-F, Sonneville R, Kalil AC. et al. Diagnostic and therapeutic approach to infectious diseases in solid organ transplant recipients. Intensive Care Med 2019; 45: 573-591
16 Chambers DC, Yusen RD, Cherikh WS. et al. The registry of the International Society for Heart and Lung Transplantation: thirty-fourth adult lung and heart-lung transplantation report-2017; focus theme: allograft ischemic time. J Heart Lung Transplantat 2017; 36: 1047-1059
17 Kalil AC, Levitsky J, Lyden E. et al. Meta-analysis: the efficacy of strategies to prevent organ disease by cytomegalovirus in solid organ transplant recipients. Ann Intern Med 2005; 143: 870-880
18 Kalil AC, Dakroub H, Freifeld AG. Sepsis and solid organ transplantation. Current Drug Targets 2007; 8: 533-541
19 Pfaller MA, Pappas PG, Wingard JR. Invasive fungal pathogens: current epidemiological trends. Clin Infect Dis 2006; 43: S3-S14
20 Pfaller M, Diekema D. Epidemiology of invasive candidiasis: a persistent public health problem. Clin Microbiol Rev 2007; 20: 133-163
21 Meyer E, Geffers C, Gastmeier P. et al. No increase in primary nosocomial candidemia in 682 German intensive care units during 2006 to 2011. Euro Surveill 2013; 18: 20505
22 Azie N, Neofytos D, Pfaller M. et al. The PATH (Prospective Antifungal Therapy) Alliance^® registry and invasive fungal infections: update 2012. Diagn Microbiol Infect Dis 2012; 73: 293-300
23 Maubon D, Garnaud C, Calandra T. et al. Resistance of Candida spp. to antifungal drugs in the ICU: where are we now?. Intensive Care Med 2014; 40: 1241-1255
24 Borst A, Raimer MT, Warnock DW. et al. Rapid acquisition of stable azole resistance by Candida glabrata isolates obtained before the clinical introduction of fluconazole. Antimicrob Agents Chemother 2005; 49: 783-787
25 Glöckner A, Cornely O. Candida glabrata-unique features and challenges in the clinical management of invasive infections. Mycoses 2015; 58: 445-450
26 Pfaller M, Castanheira M, Lockhart S. et al. Frequency of decreased susceptibility and resistance to echinocandins among fluconazole-resistant bloodstream isolates of Candida glabrata. J Clin Microbiol 2012; 50: 1199-1203
27 Klotz U, Schmidt D, Willinger B. et al. Echinocandin resistance and population structure of invasive Candida glabrata isolates from two university hospitals in Germany and Austria. Mycoses 2016; 59: 312-318
28 Alexander BD, Johnson MD, Pfeiffer CD. et al. Increasing echinocandin resistance in Candida glabrata: clinical failure correlates with presence of FKS mutations and elevated minimum inhibitory concentrations. Clin Infect Dis 2013; 56: 1724-1732
29 Playford EG, Marriott D, Nguyen Q. et al. Candidemia in nonneutropenic critically ill patients: risk factors for non-albicans Candida spp. Crit Care Med 2008; 36: 2034-2039
30 Shin JH, Kee SJ, Shin MG. et al. Biofilm production by isolates of Candida species recovered from nonneutropenic patients: comparison of bloodstream isolates with isolates from other sources. J Clin Microbiol 2002; 40: 1244-1248
31 Pappas PG, Rex JH, Lee J. et al. A prospective observational study of candidemia: epidemiology, therapy, and influences on mortality in hospitalized adult and pediatric patients. Clin Infect Dis 2003; 37: 634-643
32 Reboli AC, Rotstein C, Pappas PG. et al. Anidulafungin versus fluconazole for invasive candidiasis. N Engl J Med 2007; 356: 2472-2482
33 Lockhart SR, Etienne KA, Vallabhaneni S. et al. Simultaneous emergence of multidrug-resistant Candida auris on 3 continents confirmed by whole-genome sequencing and epidemiological analyses. Clin Infect Dis 2017; 64: 134-140
34 Kohlenberg A, Struelens MJ, Monnet DL. et al. Candida auris: epidemiological situation, laboratory capacity and preparedness in European Union and European Economic Area countries, 2013 to 2017. Euro Surveill 2018; 23: 18-00136
35 Perlroth J, Choi B, Spellberg B. Nosocomial fungal infections: epidemiology, diagnosis, and treatment. Med Mycol 2007; 45: 321-346
36 Walsh T, Groll A. Overview: non-fumigatus species of Aspergillus: perspectives on emerging pathogens in immunocompromised hosts. Curr Opin Investig Drugs 2001; 2: 1366-1367
37 Maertens J, Glasmacher A, Herbrecht R. et al. Multicenter, noncomparative study of caspofungin in combination with other antifungals as salvage therapy in adults with invasive aspergillosis. Cancer 2006; 107: 2888-2897
38 Maertens J, Raad I, Petrikkos G. et al. Efficacy and safety of caspofungin for treatment of invasive aspergillosis in patients refractory to or intolerant of conventional antifungal therapy. Clin Infect Dis 2004; 39: 1563-1571
39 Vandewoude K, Blot S, Benoit D. et al. Invasive aspergillosis in critically ill patients: attributable mortality and excesses in length of ICU stay and ventilator dependence. J Hospital Infection 2004; 56: 269-276
40 Formanek PE, Dilling DF. Advances in the Diagnosis and Management of Invasive Fungal Disease. Chest 2019; 156: 834-842
41 Arendrup MC, Sulim S, Holm A. et al. Diagnostic issues, clinical characteristics and outcome for patients with fungaemia. J Clin Microbiol 2011; 49: 3300-3308
42 Ben-Ami R, Weinberger M, Orni-Wasserlauff R. et al. Time to blood culture positivity as a marker for catheter-related candidemia. J Clin Microbiol 2008; 46: 2222-2226
43 Kami M, Machida U, Okuzumi K. et al. Effect of fluconazole prophylaxis on fungal blood cultures: an autopsy-based study involving 720 patients with haematological malignancy. Br J Haematol 2002; 117: 40-46
44 Thorn JL, Gilchrist KB, Sobonya RE. et al. Postmortem candidaemia: marker of disseminated disease. J Clin Pathol 2010; 63: 337-340
45 Richter DC, Heininger A, Schmidt K. et al. Diagnostik der Sepsis – Teil 2: Erregeridentifikation. Anästhesiol Intensivmed Notfallmed Schmerzther 2019; 54: 38-48
46 Avni T, Leibovici L, Paul M. PCR diagnosis of invasive candidiasis: systematic review and meta-analysis. J Clin Microbiol 2011; 49: 665-670
47 Bassetti M, Righi E, Montravers P. et al. What has changed in the treatment of invasive candidiasis? A look at the past 10 years and ahead. J Antimicrob Chemother 2018; 73: i14-i25
48 Bille J. New nonculture-based methods for the diagnosis of invasive candidiasis. Curr Opinion Crit Care 2010; 16: 460-464
49 Nguyen MH, Wissel MC, Shields RK. et al. Performance of Candida real-time polymerase chain reaction, β‑D-glucan assay, and blood cultures in the diagnosis of invasive candidiasis. Clin Infect Dis 2012; 54: 1240-1248
50 Mylonakis E, Clancy CJ, Ostrosky-Zeichner L. et al. T2 magnetic resonance assay for the rapid diagnosis of candidemia in whole blood: a clinical trial. Clin Infect Dis 2015; 60: 892-899
51 Beyda ND, Alam MJ, Garey KW. Comparison of the T2Dx instrument with T2Candida assay and automated blood culture in the detection of Candida species using seeded blood samples. Diagn Microbiol Infect Dis 2013; 77: 324-326
52 León C, Ruiz-Santana S, Saavedra P. Cava Trem Study Group Contribution of Candida biomarkers and DNA detection for the diagnosis of invasive candidiasis in ICU patients with severe abdominal conditions. Crit Care 2016; 20: 149
53 Mikulska M, Calandra T, Sanguinetti M. et al. 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. Crit Care 2010; 14: R222
54 Bassetti M, Marchetti M, Chakrabarti A. et al. A research agenda on the management of intra-abdominal candidiasis: results from a consensus of multinational experts. Intensive Care Med 2013; 39: 2092-2106
55 Cornely O, Bassetti M, Calandra T. et al. ESCMID guideline for the diagnosis and management of candida diseases 2012: non-neutropenic adult patients. Clin Microbiol Infect 2012; 18: 19-37
56 Patterson TF, Thompson 3rd GR, Denning DW. et al. Practice guidelines for the diagnosis and management of aspergillosis: 2016 update by the Infectious Diseases Society of America. Clin Infect Dis 2016; 63: e1-e60
57 Shin B, Koh W-J, Jeong B-H. et al. Serum galactomannan antigen test for the diagnosis of chronic pulmonary aspergillosis. J Infect 2014; 68: 494-499
58 Aquino VR, Nagel F, Andreolla HF. et al. The performance of real-time PCR, galactomannan, and fungal culture in the diagnosis of invasive aspergillosis in ventilated patients with chronic obstructive pulmonary disease (COPD). Mycopathologia 2012; 174: 163-169
59 Vergidis P, Razonable RR, Wheat LJ. et al. Reduction in falsepositive Aspergillus serum galactomannan enzyme immunoassay results associated with use of piperacillin-tazobactam in the United States. J Clin Microbiol 2014; 52: 2199-2201
60 Musher B, Fredricks D, Leisenring W. et al. Aspergillus galactomannan enzyme immunoassay and quantitative PCR for diagnosis of invasive aspergillosis with bronchoalveolar lavage fluid. J Clin Microbiol 2004; 42: 5517-5522
61 DʼHaese J, Theunissen K, Vermeulen E. et al. Detection of galactomannan in bronchoalveolar lavage fluid samples of patients at risk for invasive pulmonary aspergillosis: analytical and clinical validity. J Clin Microbiol 2012; 50: 1258-1263
62 DʼHaese J, Theunissen K, Vermeulen E. et al. Detection of galactomannan in bronchoalveolar lavage fluid samples of patients at risk for invasive pulmonary aspergillosis: analytical and clinical validity. J Clin Microbiol 2012; 50: 1258-1263
63 Gonzalez-Lara MF, Ostrosky-Zeichner L. Update on the Diagnosis of Candidemia and Invasive Candidiasis. Curr Fungal Infect Rep 2019; 13: 301-307
64 Hanson KE, Pfeiffer CD, Lease ED. et al. β‑D-glucan surveillance with preemptive anidulafungin for invasive candidiasis in intensive care unit patients: a randomized pilot study. PloS One 2012; 7: e42282
65 Digby J, Kalbfleisch J, Glenn A. et al. Serum glucan levels are not specific for presence of fungal infections in intensive care unit patients. Clin Diagn Lab Immunol 2003; 10: 882-885
66 Tissot F, Lamoth F, Hauser PM. et al. β-Glucan antigenemia anticipates diagnosis of blood culture-negative intraabdominal candidiasis. Am J Resp Crit Care Med 2013; 188: 1100-1109
67 Jaijakul S, Vazquez JA, Swanson RN. et al. (1, 3)-β‑D-glucan as a prognostic marker of treatment response in invasive candidiasis. Clin Infect Dis 2012; 55: 521-526
68 Koo S, Baden LR, Marty FM. Post-diagnostic kinetics of the (1→3)-β‑D-glucan assay in invasive aspergillosis, invasive candidiasis and Pneumocystis jirovecii pneumonia. Clin Microb Infect 2012; 18: E122-E127
69 Cornely O, Arikan-Akdagli S, Dannaoui E. et al. ESCMID and ECMM joint clinical guidelines for the diagnosis and management of mucormycosis 2013. Clin Microb Infect 2014; 20: 5-26
70 León C, Ruiz-Santana S, Saavedra P. et al. Contribution of Candida biomarkers and DNA detection for the diagnosis of invasive candidiasis in ICU patients with severe abdominal conditions. Crit Care 2016; 20: 149
71 Martínez-Jiménez MC, Muñoz P, Valerio M. et al. Combination of Candida biomarkers in patients receiving empirical antifungal therapy in a Spanish tertiary hospital: a potential role in reducing the duration of treatment. J Antimicrob Chemother 2015; 70: 3107-3115
72 Taccone FS, Van den Abeele A-M, Bulpa P. et al. Epidemiology of invasive aspergillosis in critically ill patients: clinical presentation, underlying conditions, and outcomes. Crit Care 2015; 19: 7
73 Kollef M, Micek S, Hampton N. et al. Septic shock attributed to Candida infection: importance of empiric therapy and source control. Clin Infect Dis 2012; 54: 1739-1746
74 Bassetti M, Righi E, Ansaldi F. et al. A multicenter study of septic shock due to candidemia: outcomes and predictors of mortality. Intensive Care Med 2014; 40: 839-845
75 Garey KW, Rege M, Pai MP. et al. Time to initiation of fluconazole therapy impacts mortality in patients with candidemia: a multi-institutional study. Clin Infect Dis 2006; 43: 25-31
76 Morrell M, Fraser VJ, Kollef MH. 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 2005; 49: 3640-3645
77 Bassetti M, Molinari M, Mussap M. et al. Candidaemia in internal medicine departments: the burden of a rising problem. Clin Microbiol Infect 2013; 19: E281-E284
78 Leroy O, Gangneux J-P, Montravers P. et al. Epidemiology, management, and risk factors for death of invasive Candida infections in critical care: a multicenter, prospective, observational study in France (2005-2006). Crit Care Med 2009; 37: 1612-1618
79 Leroy O, Bailly S, Gangneux J-P. et al. Systemic antifungal therapy for proven or suspected invasive candidiasis: the Amar-CAND 2 study. Ann Intensive Care 2016; 6: 2
80 Timsit J-F, Azoulay E, Schwebel C. et al. Empirical micafungin treatment and survival without invasive fungal infection in adults with ICU-acquired sepsis, Candida colonization, and multiple organ failure: the EMPIRICUS randomized clinical trial. JAMA 2016; 316: 1555-1564
81 Dupont H, Mahjoub Y, Chouaki T. et al. Antifungal Prevention of Systemic Candidiasis in Immunocompetent ICU Adults: Systematic Review and Meta-Analysis of Clinical Trials. Crit Care Med 2017; 45: 1937-1945
82 Pfaller M, Diekema D. Rare and emerging opportunistic fungal pathogens: concern for resistance beyond Candida albicans and Aspergillus fumigatus. J Clin Microbiol 2004; 42: 4419-4431
83 Pappas PG, Kauffman CA, Andes DR. et al. Clinical practice guideline for the management of candidiasis: 2016 update by the Infectious Diseases Society of America. Clin Infect Dis 2015; 62: e1-e50
84 Rex JH, Bennett JE, Sugar AM. et al. Intravascular catheter exchange and duration of candidemia. Clin Infect Dis 1995; 21: 994-996
85 Hope W, Castagnola E, Groll A. et al. ESCMID* guideline for the diagnosis and management of Candida diseases 2012: prevention and management of invasive infections in neonates and children caused by Candida spp. Clin Microbiol Infect 2012; 18: 38-52
86 Montravers P, Dupont H, Gauzit R. et al. Candida as a risk factor for mortality in peritonitis. Crit Care Med 2006; 34: 646-652
87 Montravers P, Mira JP, Gangneux JP. et al. A multicentre study of antifungal strategies and outcome of Candida spp. peritonitis in intensive-care units. Clin Microbiol Infect 2011; 17: 1061-1067
88 Montravers P, Lepape A, Dubreuil L. et al. Clinical and microbiological profiles of community-acquired and nosocomial intraabdominal infections: results of the French prospective, observational EBIIA study. J Antimicrob Chemother 2009; 63: 785-794
89 Masur H, Rosen PP, Armstrong D. Pulmonary disease caused by Candida species. Am J Med 1977; 63: 914-925
90 Kontoyiannis D, Reddy B, Torres H. et al. Pulmonary candidiasis in patients with cancer: an autopsy study. Clin Infect Dis 2002; 34: 400-403
91 Pascual A, Calandra T, Bolay S. et al. Voriconazole therapeutic drug monitoring in patients with invasive mycoses improves efficacy and safety outcomes. Clin Infect Dis 2008; 46: 201-211
92 Herbrecht R, Denning DW, Patterson TF. et al. Voriconazole versus amphotericin B for primary therapy of invasive aspergillosis. N Engl J Med 2002; 347: 408-415
93 Maertens JA, Raad II, Marr KA. et al. Isavuconazole versus voriconazole for primary treatment of invasive mould disease caused by Aspergillus and other filamentous fungi (SECURE): a phase 3, randomised-controlled, non-inferiority trial. Lancet 2016; 387: 760-769
94 Vehreschild J, Heussel C, Groll A. et al. Serial assessment of pulmonary lesion volume by computed tomography allows survival prediction in invasive pulmonary aspergillosis. Eur Radiol 2017; 27: 3275-3282
95 Kovanda LL, Kolamunnage-Dona R, Neely M. et al. Pharmacodynamics of isavuconazole for invasive mold disease: role of galactomannan for real-time monitoring of therapeutic response. Clin Infect Dis 2017; 64: 1557-1563
96 Paul M. ESCMID and ECMM guidelines for the management of rare and emerging fungal infections. Clin Microbiol Infect 2014; 20: 1-98
97 Marty FM, Ostrosky-Zeichner L, Cornely OA. et al. Isavuconazole treatment for mucormycosis: a single-arm open-label trial and case-control analysis. Lancet Infect Dis 2016; 16: 828-837
98 Desai A, Kovanda L, Kowalski D. et al. Population pharmacokinetics of isavuconazole from phase 1 and phase 3 (SECURE) trials in adults and target attainment in patients with invasive infections due to Aspergillus and other filamentous fungi. Antimicrob Agents Chemother 2016; 60: 5483-5491
99 Schmitt-Hoffmann A, Desai A, Kowalski D. et al. Isavuconazole absorption following oral administration in healthy subjects is comparable to intravenous dosing, and is not affected by food, or drugs that alter stomach pH. International J Clin Pharmacol Ther 2016; 54: 572
100 Kieu V, Jhangiani K, Dadwal S. et al. Effect of isavuconazole on tacrolimus and sirolimus serum concentrations in allogeneic hematopoietic stem cell transplant patients: A drug-drug interaction study. Transplant Infect Dis 2019; 21: e13007
101 McCarthy MW, Moriyama B, Petraitiene R. et al. Clinical pharmacokinetics and pharmacodynamics of isavuconazole. Clin Pharmacokinet 2018; 57: 1483-1491
102 Kullberg BJ, Viscoli C, Pappas PG. et al. Isavuconazole versus caspofungin in the treatment of candidemia and other invasive candida infections: the ACTIVE trial. Clin Infect Dis 2019; 68: 1981-1989
103 Vehreschild MJ, Vehreschild JJ, Marty FM. et al. Primary Treatment of Invasive Mucormycosis (IM) with Isavuconazole (VITAL Study) or Amphotericin Formulations (FungiScope™): Case matched analysis. Washington, DC: American Society of Hematology; 2014
104 Denning DW. Echinocandin antifungal drugs. Lancet 2003; 362: 1142-1151
105 Katragkou A, Roilides E, Walsh TJ. Role of echinocandins in fungal biofilm-related disease: vascular catheter-related infections, immunomodulation, and mucosal surfaces. Clin Infect Dis 2015; 61: S622-S629
106 Krishnan BR, James KD, Polowy K. et al. CD101, a novel echinocandin with exceptional stability properties and enhanced aqueous solubility. J Antibiot 2017; 70: 130-135
107 Zhao Y, Perez WB, Jiménez-Ortigosa C. et al. CD101: a novel long-acting echinocandin. Cell Microbiol 2016; 18: 1308-1316
108 Ong V, Hough G, Schlosser M. et al. Preclinical evaluation of the stability, safety, and efficacy of CD101, a novel echinocandin. Antimicrob Agents Chemother 2016; 60: 6872-6879
109 Pfaller MA, Messer SA, Rhomberg PR. et al. Activity of a longacting echinocandin, CD101, determined using CLSI and EUCAST reference methods, against Candida and Aspergillus spp. including echinocandin-and azole-resistant isolates. J Antimicrob Chemother 2016; 71: 2868-2873
110 Sandison T, Ong V, Lee J. et al. Safety and pharmacokinetics of CD101 IV, a novel echinocandin, in healthy adults. Antimicrob Agents Chemother 2017; 61
111 Bader JC, Bhavnani SM, Andes DR. et al. We can do better: a fresh look at echinocandin dosing. J Antimicrob Chemother 2018; 73: i44-i50
112 Craig WA. Pharmacokinetic/pharmacodynamic parameters: rationale for antibacterial dosing of mice and men. Clin Infect Dis 1998; 26: 1-10
113 Thompson GR, Soriano A, Skoutelis A. et al. Rezafungin versus caspofungin in a phase 2, randomized, double-blind study for the treatment of candidemia and invasive candidiasis-The STRIVE Trial. Clin Infect Dis 2020;
114 Nishikawa H, Yamada E, Shibata T. et al. Uptake of T-2307, a novel arylamidine, in Candida albicans. J Antimicrob Chemother 2010; 65: 1681-1687
115 Wiederhold NP, Najvar LK, Fothergill AW. et al. The novel arylamidine T-2307 demonstrates in vitro and in vivo activity against echinocandin-resistant Candida glabrata. J Antimicrob Chemother 2016; 71: 692-695
116 Wring SA, Randolph R, Park S. et al. Preclinical pharmacokinetics and pharmacodynamic target of SCY‑078, a first-inclass orally active antifungal glucan synthesis inhibitor, in murine models of disseminated candidiasis. Antimicrob Agents Chemother 2017; 61: e02068-16
117 Lepak AJ, Marchillo K, Andes DR. Pharmacodynamic target evaluation of a novel oral glucan synthase inhibitor, SCY‑078 (MK-3118), using an in vivo murine invasive candidiasis model. Antimicrob Agents Chemother 2015; 59: 1265-1272