Diagnosis and Treatment of Candidemia in the Intensive Care Unit

Matteo Bassetti; Daniele R. Giacobbe; Antonio Vena; Michel Wolff

doi:10.1055/s-0039-1693704

Seminars in Respiratory and Critical Care Medicine, Table of Contents

Semin Respir Crit Care Med 2019; 40(04): 524-539
DOI: 10.1055/s-0039-1693704

Review Article

Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Diagnosis and Treatment of Candidemia in the Intensive Care Unit

Matteo Bassetti

¹Department of Medicine, Infectious Diseases Clinic, University of Udine and Azienda Sanitaria Universitaria Integrata di Udine, Udine, Italy

²Department of Health Sciences, University of Genoa, Genoa, Italy

,

Daniele R. Giacobbe

²Department of Health Sciences, University of Genoa, Genoa, Italy

,

Antonio Vena

¹Department of Medicine, Infectious Diseases Clinic, University of Udine and Azienda Sanitaria Universitaria Integrata di Udine, Udine, Italy

,

Michel Wolff

³Service de Réanimation Neuro-Chirurgicale, Centre Hospitalier Saint-Anne, Paris, France

› Author Affiliations

Abstract

Candidemia is the fourth most frequent health care-associated bloodstream infection, and the most frequent severe fungal infection developing in critically ill patients in intensive care units (ICUs). Diagnosis of candidemia in ICU patients is a complex task made of both early and late assessments involving both conventional diagnostic methods and novel rapid tests. Management strategies to optimize treatment of candidemia can be challenging and include starting early adequate therapy, use of an adequate dose and duration of therapy, de-escalating treatment whenever possible, and early discontinuation of useless antifungals in those with no definitive diagnosis of fungal infection. Herein, we will discuss recent epidemiological data on candidemia in ICUs and current diagnostic techniques before concentrating on antifungal treatments.

Keywords

Candida - ICU - diagnosis - biomarker - pre-emptive - echinocandins - source control - antifungals

Full Text

References

References
1 Marchetti O, Bille J, Fluckiger U. , et al; Fungal Infection Network of Switzerland. Epidemiology of candidemia in Swiss tertiary care hospitals: secular trends, 1991–2000. Clin Infect Dis 2004; 38 (03) 311-320
2 Wisplinghoff H, Bischoff T, Tallent SM, Seifert H, Wenzel RP, Edmond MB. Nosocomial bloodstream infections in US hospitals: analysis of 24,179 cases from a prospective nationwide surveillance study. Clin Infect Dis 2004; 39 (03) 309-317
3 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 (06) 839-845
4 Bouza E, Muñoz P. Epidemiology of candidemia in intensive care units. Int J Antimicrob Agents 2008; 32 (Suppl. 02) S87-S91
5 Bougnoux ME, Kac G, Aegerter P, d'Enfert C, Fagon JY. ; CandiRea Study Group. Candidemia and candiduria in critically ill patients admitted to intensive care units in France: incidence, molecular diversity, management and outcome. Intensive Care Med 2008; 34 (02) 292-299
6 Bassetti M, Giacobbe DR, Vena A. , et al. O0042 Incidence of invasive candidiasis in intensive care units (ICU): results from the first phase of the candidaemia/intra-abdominal candidiasis in European ICU project (EUCANDICU). Paper presented at: 29th ECCMID, Amsterdam, Netherlands, 13–16 April 2019
7 Klingspor L, Tortorano AM, Peman J. , et al. Invasive Candida infections in surgical patients in intensive care units: a prospective, multicentre survey initiated by the European Confederation of Medical Mycology (ECMM) (2006–2008). Clin Microbiol Infect 2015; 21 (01) 87.e1-87.e10
8 Tortorano AM, Dho G, Prigitano A. , et al; ECMM-FIMUA Study Group. Invasive fungal infections in the intensive care unit: a multicentre, prospective, observational study in Italy (2006–2008). Mycoses 2012; 55 (01) 73-79
9 Vincent JL, Rello J, Marshall J. , et al; EPIC II Group of Investigators. International study of the prevalence and outcomes of infection in intensive care units. JAMA 2009; 302 (21) 2323-2329
10 Baldesi O, Bailly S, Ruckly S. , et al; REA-RAISIN network. ICU-acquired candidaemia in France: epidemiology and temporal trends, 2004–2013 - a study from the REA-RAISIN network. J Infect 2017; 75 (01) 59-67
11 Kett DH, Azoulay E, Echeverria PM, Vincent JL. ; Extended Prevalence of Infection in ICU Study (EPIC II) Group of Investigators. Candida bloodstream infections in intensive care units: analysis of the extended prevalence of infection in intensive care unit study. Crit Care Med 2011; 39 (04) 665-670
12 Paiva JA, Pereira JM, Tabah A. , et al. Characteristics and risk factors for 28-day mortality of hospital acquired fungemias in ICUs: data from the EUROBACT study. Crit Care 2016; 20: 53
13 Tabah A, Koulenti D, Laupland K. , et al. Characteristics and determinants of outcome of hospital-acquired bloodstream infections in intensive care units: the EUROBACT International Cohort Study. Intensive Care Med 2012; 38 (12) 1930-1945
14 Playford EG, Lipman J, Jones M. , et al. Problematic dichotomization of risk for intensive care unit (ICU)-acquired invasive candidiasis: results using a risk-predictive model to categorize 3 levels of risk from a multicenter prospective cohort of Australian ICU patients. Clin Infect Dis 2016; 63 (11) 1463-1469
15 Puig-Asensio M, Pemán J, Zaragoza R. , et al; Prospective Population Study on Candidemia in Spain (CANDIPOP) Project; Hospital Infection Study Group (GEIH); Medical Mycology Study Group (GEMICOMED) of the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC); Spanish Network for Research in Infectious Diseases. Impact of therapeutic strategies on the prognosis of candidemia in the ICU. Crit Care Med 2014; 42 (06) 1423-1432
16 Angus DC, Yealy DM, Kellum JA. , ProCESS Investigators. Protocol-based care for early septic shock. N Engl J Med 2014; 371 (04) 386
17 Martin-Loeches I, Antonelli M, Cuenca-Estrella M. , et al. ESICM/ESCMID task force on practical management of invasive candidiasis in critically ill patients. Intensive Care Med 2019; 45 (06) 789-805
18 Bassetti M, Garnacho-Montero J, Calandra T. , et al. Intensive care medicine research agenda on invasive fungal infection in critically ill patients. Intensive Care Med 2017; 43 (09) 1225-1238
19 Bassetti M, Righi E, Montravers P, Cornely OA. What has changed in the treatment of invasive candidiasis? A look at the past 10 years and ahead. J Antimicrob Chemother 2018; 73 (Suppl. 01) i14-i25
20 Pappas PG, Lionakis MS, Arendrup MC, Ostrosky-Zeichner L, Kullberg BJ. Invasive candidiasis. Nat Rev Dis Primers 2018; 4: 18026
21 Fraser VJ, Jones M, Dunkel J, Storfer S, Medoff G, Dunagan WC. Candidemia in a tertiary care hospital: epidemiology, risk factors, and predictors of mortality. Clin Infect Dis 1992; 15 (03) 414-421
22 Edwards Jr JE. Should all patients with candidemia be treated with antifungal agents?. Clin Infect Dis 1992; 15 (03) 422-423
23 Wey SB, Mori M, Pfaller MA, Woolson RF, Wenzel RP. Hospital-acquired candidemia. The attributable mortality and excess length of stay. Arch Intern Med 1988; 148 (12) 2642-2645
24 Young RC, Bennett JE, Geelhoed GW, Levine AS. Fungemia with compromised host resistance. A study of 70 cases. Ann Intern Med 1974; 80 (05) 605-612
25 Toala P, Schroeder SA, Daly AK, Finland M. Candida at Boston City Hospital. Clinical and epidemiological characteristics and susceptibility to eight antimicrobial agents. Arch Intern Med 1970; 126 (06) 983-989
26 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 (01) 25-31
27 Kollef M, Micek S, Hampton N, Doherty JA, Kumar A. Septic shock attributed to Candida infection: importance of empiric therapy and source control. Clin Infect Dis 2012; 54 (12) 1739-1746
28 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 (09) 3640-3645
29 Clancy CJ, Nguyen MH. Finding the "missing 50%" of invasive candidiasis: how nonculture diagnostics will improve understanding of disease spectrum and transform patient care. Clin Infect Dis 2013; 56 (09) 1284-1292
30 Pfeiffer CD, Samsa GP, Schell WA, Reller LB, Perfect JR, Alexander BD. Quantitation of Candida CFU in initial positive blood cultures. J Clin Microbiol 2011; 49 (08) 2879-2883
31 Telenti A, Steckelberg JM, Stockman L, Edson RS, Roberts GD. Quantitative blood cultures in candidemia. Mayo Clin Proc 1991; 66 (11) 1120-1123
32 Arendrup MC, Sulim S, Holm A. , et al. Diagnostic issues, clinical characteristics, and outcomes for patients with fungemia. J Clin Microbiol 2011; 49 (09) 3300-3308
33 Giacobbe DR, Esteves P, Bruzzi P. , et al. Initial serum (1,3)-β-D-glucan as a predictor of mortality in proven candidaemia: findings from a retrospective study in two teaching hospitals in Italy and Brazil. Clin Microbiol Infect 2015; 21 (10) 954.e9-954.e17
34 Berenguer J, Buck M, Witebsky F, Stock F, Pizzo PA, Walsh TJ. Lysis-centrifugation blood cultures in the detection of tissue-proven invasive candidiasis. Disseminated versus single-organ infection. Diagn Microbiol Infect Dis 1993; 17 (02) 103-109
35 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 (01) 40-46
36 Ness MJ, Vaughan WP, Woods GL. Candida antigen latex test for detection of invasive candidiasis in immunocompromised patients. J Infect Dis 1989; 159 (03) 495-502
37 Arendrup MC, Bille J, Dannaoui E, Ruhnke M, Heussel CP, Kibbler C. ECIL-3 classical diagnostic procedures for the diagnosis of invasive fungal diseases in patients with leukaemia. Bone Marrow Transplant 2012; 47 (08) 1030-1045
38 Cuenca-Estrella M, Verweij PE, Arendrup MC. , et al; ESCMID Fungal Infection Study Group. ESCMID* guideline for the diagnosis and management of Candida diseases 2012: diagnostic procedures. Clin Microbiol Infect 2012; 18 (Suppl. 07) 9-18
39 De Carolis E, Vella A, Florio AR. , et al. Use of matrix-assisted laser desorption ionization-time of flight mass spectrometry for caspofungin susceptibility testing of Candida and Aspergillus species. J Clin Microbiol 2012; 50 (07) 2479-2483
40 De Pauw B, Walsh TJ, Donnelly JP. , et al; European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group; National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) Consensus Group. Revised definitions of invasive fungal disease from the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) Consensus Group. Clin Infect Dis 2008; 46 (12) 1813-1821
41 Delavy M, Dos Santos AR, Heiman CM, Coste AT. Investigating antifungal susceptibility in Candida species with MALDI-TOF MS-based assays. Front Cell Infect Microbiol 2019; 9: 19
42 Sanguinetti M, Posteraro B. Susceptibility testing of fungi to antifungal drugs. J Fungi (Basel) 2018; 4 (03) 4
43 Saracli MA, Fothergill AW, Sutton DA, Wiederhold NP. Detection of triazole resistance among Candida species by matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS). Med Mycol 2015; 53 (07) 736-742
44 Vella A, De Carolis E, Mello E. , et al. Potential use of MALDI-ToF mass spectrometry for rapid detection of antifungal resistance in the human pathogen Candida glabrata. Sci Rep 2017; 7 (01) 9099
45 Vella A, De Carolis E, Vaccaro L. , et al. Rapid antifungal susceptibility testing by matrix-assisted laser desorption ionization-time of flight mass spectrometry analysis. J Clin Microbiol 2013; 51 (09) 2964-2969
46 Vatanshenassan M, Boekhout T, Lass-Flörl C. , et al. Proof of concept for MBT ASTRA, a rapid matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS)-based method to detect caspofungin resistance in Candida albicans and Candida glabrata. J Clin Microbiol 2018; 56: e00420-18
47 Gorton RL, Ramnarain P, Barker K. , et al. Comparative analysis of Gram's stain, PNA-FISH and Sepsityper with MALDI-TOF MS for the identification of yeast direct from positive blood cultures. Mycoses 2014; 57 (10) 592-601
48 Wattal C, Oberoi JK, Goel N, Raveendran R, Khanna S. Matrix-assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF MS) for rapid identification of micro-organisms in the routine clinical microbiology laboratory. Eur J Clin Microbiol Infect Dis 2017; 36 (05) 807-812
49 Huang AM, Newton D, Kunapuli A. , et al. Impact of rapid organism identification via matrix-assisted laser desorption/ionization time-of-flight combined with antimicrobial stewardship team intervention in adult patients with bacteremia and candidemia. Clin Infect Dis 2013; 57 (09) 1237-1245
50 Stone NR, Gorton RL, Barker K, Ramnarain P, Kibbler CC. Evaluation of PNA-FISH yeast traffic light for rapid identification of yeast directly from positive blood cultures and assessment of clinical impact. J Clin Microbiol 2013; 51 (04) 1301-1302
51 Micek ST, Arnold H, Juang P. , et al. Effects of empiric antifungal therapy for septic shock on time to appropriate therapy for Candida infection: a pilot study. Clin Ther 2014; 36 (09) 1226-1232
52 Schuster MG, Edwards Jr JE, Sobel JD. , et al. Empirical fluconazole versus placebo for intensive care unit patients: a randomized trial. Ann Intern Med 2008; 149 (02) 83-90
53 Bernhardt HE, Orlando JC, Benfield JR, Hirose FM, Foos RY. Disseminated candidiasis in surgical patients. Surg Gynecol Obstet 1972; 134 (05) 819-825
54 Pittet D, Monod M, Suter PM, Frenk E, Auckenthaler R. Candida colonization and subsequent infections in critically ill surgical patients. Ann Surg 1994; 220 (06) 751-758
55 Solomkin JS, Flohr AM, Simmons RL. Indications for therapy for fungemia in postoperative patients. Arch Surg 1982; 117 (10) 1272-1275
56 Paphitou NI, Ostrosky-Zeichner L, Rex JH. Rules for identifying patients at increased risk for candidal infections in the surgical intensive care unit: approach to developing practical criteria for systematic use in antifungal prophylaxis trials. Med Mycol 2005; 43 (03) 235-243
57 Michalopoulos AS, Geroulanos S, Mentzelopoulos SD. Determinants of candidemia and candidemia-related death in cardiothoracic ICU patients. Chest 2003; 124 (06) 2244-2255
58 Ostrosky-Zeichner L, Sable C, Sobel J. , et al. Multicenter retrospective development and validation of a clinical prediction rule for nosocomial invasive candidiasis in the intensive care setting. Eur J Clin Microbiol Infect Dis 2007; 26 (04) 271-276
59 Guillamet CV, Vazquez R, Micek ST, Ursu O, Kollef M. Development and validation of a clinical prediction rule for candidemia in hospitalized patients with severe sepsis and septic shock. J Crit Care 2015; 30 (04) 715-720
60 Hermsen ED, Zapapas MK, Maiefski M, Rupp ME, Freifeld AG, Kalil AC. Validation and comparison of clinical prediction rules for invasive candidiasis in intensive care unit patients: a matched case-control study. Crit Care 2011; 15 (04) R198
61 León C, Ruiz-Santana S, Saavedra P. , et al; EPCAN Study Group. A bedside scoring system (“Candida score”) for early antifungal treatment in nonneutropenic critically ill patients with Candida colonization. Crit Care Med 2006; 34 (03) 730-737
62 Leroy G, Lambiotte F, Thévenin D. , et al. Evaluation of “Candida score” in critically ill patients: a prospective, multicenter, observational, cohort study. Ann Intensive Care 2011; 1 (01) 50
63 Ostrosky-Zeichner L. Clinical prediction rules for invasive candidiasis in the ICU: ready for prime time?. Crit Care 2011; 15 (05) 189
64 Timsit JF, Chemam S, Bailly S. Empiric/pre-emptive anti-Candida therapy in non-neutropenic ICU patients. F1000Prime Rep 2015; 7: 21
65 Giacobbe DR, Del Bono V, Viscoli C, Mikulska M. Use of 1,3-β-D-glucan in invasive fungal diseases in hematology patients. Expert Rev Anti Infect Ther 2017; 15 (12) 1101-1112
66 Obayashi T, Yoshida M, Mori T. , et al. Plasma (1-->3)-beta-D-glucan measurement in diagnosis of invasive deep mycosis and fungal febrile episodes. Lancet 1995; 345 (8941): 17-20
67 Odabasi Z, Paetznick VL, Rodriguez JR, Chen E, McGinnis MR, Ostrosky-Zeichner L. Differences in beta-glucan levels in culture supernatants of a variety of fungi. Med Mycol 2006; 44 (03) 267-272
68 Dagens A, Mughal N, Sisson A, Moore LSP. Experience of using beta-D-glucan assays in the intensive care unit. Crit Care 2018; 22 (01) 125
69 Del Bono V, Delfino E, Furfaro E. , et al. Clinical performance of the (1,3)-β-D-glucan assay in early diagnosis of nosocomial Candida bloodstream infections. Clin Vaccine Immunol 2011; 18 (12) 2113-2117
70 Donato L, González T, Canales M, Legarraga P, García P, Rabagliati R. The 1,3-β-d-glucan in critical adult patients as diagnostic tool for invasive Candida spp. infection, performance evaluation [in Spanish]. Rev Chilena Infectol 2017; 34 (04) 340-346
71 Giacobbe DR, Mikulska M, Tumbarello M. , et al; ISGRI-SITA (Italian Study Group on Resistant Infections of the Società Italiana Terapia Antinfettiva). Combined use of serum (1,3)-β-D-glucan and procalcitonin for the early differential diagnosis between candidaemia and bacteraemia in intensive care units. Crit Care 2017; 21 (01) 176
72 Nucci M, Nouér SA, Esteves P. , et al. Discontinuation of empirical antifungal therapy in ICU patients using 1,3-β-d-glucan. J Antimicrob Chemother 2016; 71 (09) 2628-2633
73 Poissy J, Sendid B, Damiens S. , et al. Presence of Candida cell wall derived polysaccharides in the sera of intensive care unit patients: relation with candidaemia and Candida colonisation. Crit Care 2014; 18 (03) R135
74 Posteraro B, De Pascale G, Tumbarello M. , et al. Early diagnosis of candidemia in intensive care unit patients with sepsis: a prospective comparison of (1→3)-β-D-glucan assay, Candida score, and colonization index. Crit Care 2011; 15 (05) R249
75 Posteraro B, Tumbarello M, De Pascale G. , et al. (1,3)-β-d-Glucan-based antifungal treatment in critically ill adults at high risk of candidaemia: an observational study. J Antimicrob Chemother 2016; 71 (08) 2262-2269
76 Rautemaa-Richardson R, Rautemaa V, Al-Wathiqi F. , et al. Impact of a diagnostics-driven antifungal stewardship programme in a UK tertiary referral teaching hospital. J Antimicrob Chemother 2018; 73 (12) 3488-3495
77 Talento AF, Dunne K, Joyce EA. , et al. A prospective study of fungal biomarkers to improve management of invasive fungal diseases in a mixed specialty critical care unit. J Crit Care 2017; 40: 119-127
78 Mikulska M, Giacobbe DR, Furfaro E. , et al. Lower sensitivity of serum (1,3)-β-d-glucan for the diagnosis of candidaemia due to Candida parapsilosis. Clin Microbiol Infect 2016; 22 (07) 646.e5-646.e8
79 Ostrosky-Zeichner L, Alexander BD, Kett DH. , et al. Multicenter clinical evaluation of the (1-->3) beta-D-glucan assay as an aid to diagnosis of fungal infections in humans. Clin Infect Dis 2005; 41 (05) 654-659
80 Martín-Mazuelos E, Loza A, Castro C. , et al. β-D-Glucan and Candida albicans germ tube antibody in ICU patients with invasive candidiasis. Intensive Care Med 2015; 41 (08) 1424-1432
81 Albert O, Toubas D, Strady C. , et al. Reactivity of (1→3)-β-d-glucan assay in bacterial bloodstream infections. Eur J Clin Microbiol Infect Dis 2011; 30 (11) 1453-1460
82 Digby J, Kalbfleisch J, Glenn A, Larsen A, Browder W, Williams D. Serum glucan levels are not specific for presence of fungal infections in intensive care unit patients. Clin Diagn Lab Immunol 2003; 10 (05) 882-885
83 Duffner U, Abdel-Mageed A, Dahl K, Fogg G, Hester J. Serum (1 → 3)-β-D-glucan levels (Fungitell assay) is not useful as a screening test for recipients of an allogeneic HSCT while on immunoglobulin replacement. Bone Marrow Transplant 2012; 47 (01) 151-152
84 Furfaro E, Viscoli C, Giacobbe DR, Ratto S, Mikulska M. The Beta-d-glucan test: time to re-visit its utility in IFI diagnosis. Curr Fungal Infect Rep 2015; 9: 292-301
85 Koo S, Bryar JM, Page JH, Baden LR, Marty FM. Diagnostic performance of the (1-->3)-beta-D-glucan assay for invasive fungal disease. Clin Infect Dis 2009; 49 (11) 1650-1659
86 Marty FM, Lowry CM, Lempitski SJ, Kubiak DW, Finkelman MA, Baden LR. Reactivity of (1-->3)-beta-d-glucan assay with commonly used intravenous antimicrobials. Antimicrob Agents Chemother 2006; 50 (10) 3450-3453
87 Nagasawa K, Yano T, Kitabayashi G. , et al. Experimental proof of contamination of blood components by (1-->3)-beta-D-glucan caused by filtration with cellulose filters in the manufacturing process. J Artif Organs 2003; 6 (01) 49-54
88 Nakao A, Yasui M, Kawagoe T, Tamura H, Tanaka S, Takagi H. False-positive endotoxemia derives from gauze glucan after hepatectomy for hepatocellular carcinoma with cirrhosis. Hepatogastroenterology 1997; 44 (17) 1413-1418
89 Otto GP, Ludewig K, Jacobsen ID, Schaarschmidt B, Hube B, Bauer M. Limitation of (1→3)-β-D-glucan monitoring in major elective surgery involving cardiopulmonary bypass. Crit Care 2013; 17 (03) 437
90 Pickering JW, Sant HW, Bowles CA, Roberts WL, Woods GL. Evaluation of a (1->3)-beta-D-glucan assay for diagnosis of invasive fungal infections. J Clin Microbiol 2005; 43 (12) 5957-5962
91 Racil Z, Kocmanova I, Lengerova M. , et al. Difficulties in using 1,3-beta-D-glucan as the screening test for the early diagnosis of invasive fungal infections in patients with haematological malignancies--high frequency of false-positive results and their analysis. J Med Microbiol 2010; 59 (Pt 9): 1016-1022
92 Sulahian A, Porcher R, Bergeron A. , et al. Use and limits of (1-3)-β-d-glucan assay (Fungitell), compared to galactomannan determination (Platelia Aspergillus), for diagnosis of invasive aspergillosis. J Clin Microbiol 2014; 52 (07) 2328-2333
93 Usami M, Ohata A, Horiuchi T, Nagasawa K, Wakabayashi T, Tanaka S. Positive (1-->3)-beta-D-glucan in blood components and release of (1-->3)-beta-D-glucan from depth-type membrane filters for blood processing. Transfusion 2002; 42 (09) 1189-1195
94 Furfaro E, Mikulska M, Del Bono V. , et al. Bloodstream infections are an improbable cause of positive serum (1,3)-β-D-glucan in hematology patients. Clin Vaccine Immunol 2014; 21 (09) 1357-1359
95 Kanamori H, Kanemitsu K, Miyasaka T. , et al. Measurement of (1-3)-beta-D-glucan derived from different gauze types. Tohoku J Exp Med 2009; 217 (02) 117-121
96 Metan G, Agkus C, Nedret Koc A, Elmali F, Finkelman MA. Does ampicillin-sulbactam cause false positivity of (1,3)-beta-D-glucan assay? A prospective evaluation of 15 patients without invasive fungal infections. Mycoses 2012; 55 (04) 366-371
97 Metan G, Koc AN, Ağkuş Ç, Kaynar LG, Alp E, Eser B. Can bacteraemia lead to false positive results in 1,3-beta-D-glucan test? Analysis of 83 bacteraemia episodes in high-risk patients for invasive fungal infections. Rev Iberoam Micol 2012; 29 (03) 169-171
98 Prattes J, Schneditz D, Prüller F. , et al. 1,3-ß-d-Glucan testing is highly specific in patients undergoing dialysis treatment. J Infect 2017; 74 (01) 72-80
99 Racil Z, Kocmanova I, Toskova M. , et al. Reactivity of the 1,3-β-D-glucan assay during bacteraemia: limited evidence from a prospective study. Mycoses 2013; 56 (02) 101-104
100 Giacobbe DR, Signori A, Tumbarello M. , et al. Desirability of outcome ranking (DOOR) for comparing diagnostic tools and early therapeutic choices in patients with suspected candidemia. Eur J Clin Microbiol Infect Dis 2019; 38 (02) 413-417
101 Timsit JF, Azoulay E, Schwebel C. , et al; EMPIRICUS Trial Group. 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 (15) 1555-1564
102 Rouzé A, Loridant S, Poissy J. , et al; S-TAFE study group. Biomarker-based strategy for early discontinuation of empirical antifungal treatment in critically ill patients: a randomized controlled trial. Intensive Care Med 2017; 43 (11) 1668-1677
103 Bloos F, Held J, Schlattmann P. , et al. (1,3)-β-D-glucan-based diagnosis of invasive Candida infection versus culture-based diagnosis in patients with sepsis and with an increased risk of invasive Candida infection (CandiSep): study protocol for a randomized controlled trial. Trials 2018; 19 (01) 472
104 Klis FM. Review: cell wall assembly in yeast. Yeast 1994; 10 (07) 851-869
105 Mikulska M, Calandra T, Sanguinetti M, Poulain D, Viscoli C. ; Third European Conference on Infections in Leukemia Group. 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 (06) R222
106 Sendid B, Tabouret M, Poirot JL, Mathieu D, Fruit J, Poulain D. New enzyme immunoassays for sensitive detection of circulating Candida albicans mannan and antimannan antibodies: useful combined test for diagnosis of systemic candidiasis. J Clin Microbiol 1999; 37 (05) 1510-1517
107 Sendid B, Poirot JL, Tabouret M. , et al. Combined detection of mannanaemia and antimannan antibodies as a strategy for the diagnosis of systemic infection caused by pathogenic Candida species. J Med Microbiol 2002; 51 (05) 433-442
108 Yera H, Sendid B, Francois N, Camus D, Poulain D. Contribution of serological tests and blood culture to the early diagnosis of systemic candidiasis. Eur J Clin Microbiol Infect Dis 2001; 20 (12) 864-870
109 Duettmann W, Koidl C, Krause R, Lackner G, Woelfler A, Hoenigl M. Specificity of mannan antigen and anti-mannan antibody screening in patients with haematological malignancies at risk for fungal infection. Mycoses 2016; 59 (06) 374-378
110 Verduyn Lunel FM, Donnelly JP, van der Lee HA, Blijlevens NM, Verweij PE. Circulating Candida-specific anti-mannan antibodies precede invasive candidiasis in patients undergoing myelo-ablative chemotherapy. Clin Microbiol Infect 2009; 15 (04) 380-386
111 Alam FF, Mustafa AS, Khan ZU. Comparative evaluation of (1, 3)-beta-D-glucan, mannan and anti-mannan antibodies, and Candida species-specific snPCR in patients with candidemia. BMC Infect Dis 2007; 7: 103
112 Ellis M, Al-Ramadi B, Bernsen R, Kristensen J, Alizadeh H, Hedstrom U. Prospective evaluation of mannan and anti-mannan antibodies for diagnosis of invasive Candida infections in patients with neutropenic fever. J Med Microbiol 2009; 58 (Pt 5): 606-615
113 Persat F, Topenot R, Piens MA, Thiebaut A, Dannaoui E, Picot S. Evaluation of different commercial ELISA methods for the serodiagnosis of systemic candidosis. Mycoses 2002; 45 (11–12): 455-460
114 Prella M, Bille J, Pugnale M. , et al. Early diagnosis of invasive candidiasis with mannan antigenemia and antimannan antibodies. Diagn Microbiol Infect Dis 2005; 51 (02) 95-101
115 Sendid B, Caillot D, Baccouch-Humbert B. , et al. Contribution of the Platelia Candida-specific antibody and antigen tests to early diagnosis of systemic Candida tropicalis infection in neutropenic adults. J Clin Microbiol 2003; 41 (10) 4551-4558
116 White PL, Archer AE, Barnes RA. Comparison of non-culture-based methods for detection of systemic fungal infections, with an emphasis on invasive Candida infections. J Clin Microbiol 2005; 43 (05) 2181-2187
117 León C, Ruiz-Santana S, Saavedra P. , et al; 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 (01) 149
118 Clancy CJ, Nguyen MH. Non-culture diagnostics for invasive candidiasis: promise and unintended consequences. J Fungi (Basel) 2018; 4 (01) E27
119 Martínez-Jiménez MC, Muñoz P, Guinea J. , et al. Potential role of Candida albicans germ tube antibody in the diagnosis of deep-seated candidemia. Med Mycol 2014; 52 (03) 270-275
120 Fortún J, Meije Y, Buitrago MJ. , et al. Clinical validation of a multiplex real-time PCR assay for detection of invasive candidiasis in intensive care unit patients. J Antimicrob Chemother 2014; 69 (11) 3134-3141
121 Martínez-Jiménez MC, Muñoz P, Valerio M, Vena A, Guinea J, Bouza E. 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 2016; 71 (09) 2679
122 Parra-Sánchez M, Zakariya-Yousef Breval I, Castro Méndez C. , et al; CAVA Trem Study Group. Candida albicans germ-tube antibody: evaluation of a new automatic assay for diagnosing invasive candidiasis in ICU patients. Mycopathologia 2017; 182 (7–8): 645-652
123 León C, Ruiz-Santana S, Saavedra P. , et al. Value of β-D-glucan and Candida albicans germ tube antibody for discriminating between Candida colonization and invasive candidiasis in patients with severe abdominal conditions. Intensive Care Med 2012; 38 (08) 1315-1325
124 Martínez-Jiménez MC, Muñoz P, Valerio M. , et al. Candida biomarkers in patients with candidaemia and bacteraemia. J Antimicrob Chemother 2015; 70 (08) 2354-2361
125 Pazos C, Moragues MD, Quindós G, Pontón J, del Palacio A. Diagnostic potential of (1,3)-beta-D-glucan and anti-Candida albicans germ tube antibodies for the diagnosis and therapeutic monitoring of invasive candidiasis in neutropenic adult patients. Rev Iberoam Micol 2006; 23 (04) 209-215
126 Wei S, Wu T, Wu Y, Ming D, Zhu X. Diagnostic accuracy of Candida albicans germ tube antibody for invasive candidiasis: systematic review and meta-analysis. Diagn Microbiol Infect Dis 2019; 93 (04) 339-345
127 Berzaghi R, Colombo AL, Machado AM, de Camargo ZP. New approach for diagnosis of candidemia based on detection of a 65-kilodalton antigen. Clin Vaccine Immunol 2009; 16 (11) 1538-1545
128 Ellepola AN, Morrison CJ. Laboratory diagnosis of invasive candidiasis. J Microbiol 2005; 43 (Spec No): 65-84
129 Held J, Kohlberger I, Rappold E, Busse Grawitz A, Häcker G. Comparison of (1->3)-β-D-glucan, mannan/anti-mannan antibodies, and Cand-Tec Candida antigen as serum biomarkers for candidemia. J Clin Microbiol 2013; 51 (04) 1158-1164
130 López-Ribot JL, Casanova M, Murgui A, Martínez JP. Antibody response to Candida albicans cell wall antigens. FEMS Immunol Med Microbiol 2004; 41 (03) 187-196
131 Martínez JP, Gil ML, López-Ribot JL, Chaffin WL. Serologic response to cell wall mannoproteins and proteins of Candida albicans. Clin Microbiol Rev 1998; 11 (01) 121-141
132 Na BK, Song CY. Use of monoclonal antibody in diagnosis of candidiasis caused by Candida albicans: detection of circulating aspartyl proteinase antigen. Clin Diagn Lab Immunol 1999; 6 (06) 924-929
133 Pitarch A, Nombela C, Gil C. Diagnosis of invasive candidiasis: from gold standard methods to promising leading-edge technologies. Curr Top Med Chem 2018; 18 (16) 1375-1392
134 Walsh TJ, Hathorn JW, Sobel JD. , et al. Detection of circulating candida enolase by immunoassay in patients with cancer and invasive candidiasis. N Engl J Med 1991; 324 (15) 1026-1031
135 Yang Q, Su QP, Wang GY. , et al. Production of hybrid phage displaying secreted aspartyl proteinase epitope of Candida albicans and its application for the diagnosis of disseminated candidiasis. Mycoses 2007; 50 (03) 165-171
136 Christensson B, Sigmundsdottir G, Larsson L. D-arabinitol--a marker for invasive candidiasis. Med Mycol 1999; 37 (06) 391-396
137 Yeo SF, Huie S, Sofair AN, Campbell S, Durante A, Wong B. Measurement of serum D-arabinitol/creatinine ratios for initial diagnosis and for predicting outcome in an unselected, population-based sample of patients with Candida fungemia. J Clin Microbiol 2006; 44 (11) 3894-3899
138 Charles PE, Dalle F, Aho S. , et al. Serum procalcitonin measurement contribution to the early diagnosis of candidemia in critically ill patients. Intensive Care Med 2006; 32 (10) 1577-1583
139 Cortegiani A, Russotto V, Montalto F. , et al. Procalcitonin as a marker of Candida species detection by blood culture and polymerase chain reaction in septic patients. BMC Anesthesiol 2014; 14: 9
140 Hoeboer SH, van der Geest PJ, Nieboer D, Groeneveld AB. The diagnostic accuracy of procalcitonin for bacteraemia: a systematic review and meta-analysis. Clin Microbiol Infect 2015; 21 (05) 474-481
141 Martini A, Gottin L, Menestrina N, Schweiger V, Simion D, Vincent JL. Procalcitonin levels in surgical patients at risk of candidemia. J Infect 2010; 60 (06) 425-430
142 Raineri SM, Cortegiani A, Vitale F, Iozzo P, Giarratano A. Procalcitonin for the diagnosis of invasive candidiasis: what is the evidence?. J Intensive Care 2017; 5: 58
143 Wacker C, Prkno A, Brunkhorst FM, Schlattmann P. Procalcitonin as a diagnostic marker for sepsis: a systematic review and meta-analysis. Lancet Infect Dis 2013; 13 (05) 426-435
144 Avni T, Leibovici L, Paul M. PCR diagnosis of invasive candidiasis: systematic review and meta-analysis. J Clin Microbiol 2011; 49 (02) 665-670
145 Chang SS, Hsieh WH, Liu TS. , et al. Multiplex PCR system for rapid detection of pathogens in patients with presumed sepsis - a systemic review and meta-analysis. PLoS One 2013; 8 (05) e62323
146 Desmet S, Maertens J, Bueselinck K, Lagrou K. Broad-range PCR coupled with electrospray ionization time of flight mass spectrometry for detection of bacteremia and fungemia in patients with neutropenic fever. J Clin Microbiol 2016; 54 (10) 2513-2520
147 Metzgar D, Frinder MW, Rothman RE. , et al. The IRIDICA BAC BSI assay: rapid, sensitive and culture-independent identification of bacteria and Candida in blood. PLoS One 2016; 11 (07) e0158186
148 White PL, Hibbitts SJ, Perry MD. , et al. Evaluation of a commercially developed semiautomated PCR-surface-enhanced raman scattering assay for diagnosis of invasive fungal disease. J Clin Microbiol 2014; 52 (10) 3536-3543
149 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 2016; 62 (04) e1-e50
150 Clancy CJ, Nguyen MH. T2 magnetic resonance for the diagnosis of bloodstream infections: charting a path forward. J Antimicrob Chemother 2018; 73 (Suppl. 04) iv2-iv5
151 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 (06) 892-899
152 Arendrup MC, Andersen JS, Holten MK. , et al. Diagnostic performance of T2Candida among ICU patients with risk factors for invasive candidiasis. Open Forum Infect Dis 2019; 6 (05) ofz136
153 Giannella M, Paolucci M, Roncarati G. , et al. Potential role of T2Candida in the management of empirical antifungal treatment in patients at high risk of candidaemia: a pilot single-centre study. J Antimicrob Chemother 2018; 73 (10) 2856-2859
154 Muñoz P, Vena A, Machado M. , et al; T2MadRid study group. T2Candida MR as a predictor of outcome in patients with suspected invasive candidiasis starting empirical antifungal treatment: a prospective pilot study. J Antimicrob Chemother 2018; 73 (Suppl. 04) iv6-iv12
155 Bouza E, Vena A, Munoz P. ; T2MadRid study group. T2Candida MR as a predictor of outcome in patients with suspected invasive candidiasis starting empirical antifungal treatment: a prospective pilot study-authors' response. J Antimicrob Chemother 2019; 74 (02) 533-534
156 Walker B, Powers-Fletcher MV, Schmidt RL, Hanson KE. Cost-effectiveness analysis of multiplex PCR with magnetic resonance detection versus empiric or blood culture-directed therapy for management of suspected candidemia. J Clin Microbiol 2016; 54 (03) 718-726
157 White PL, Barnes RA, Gorton R, Cruciani M, Loeffler J. ; Fungal PCR Initiative (Working Group of the International Society of Human and Animal Mycology). Comment on: T2Candida MR as a predictor of outcome in patients with suspected invasive candidiasis starting empirical antifungal treatment: a prospective pilot study. J Antimicrob Chemother 2019; 74 (02) 532-533
158 Ostrosky-Zeichner L, Andes D. The role of in vitro susceptibility testing in the management of Candida and aspergillus. J Infect Dis 2017; 216 (Suppl. 03) S452-S457
159 Ferrari S, Sanguinetti M, De Bernardis F. , et al. Loss of mitochondrial functions associated with azole resistance in Candida glabrata results in enhanced virulence in mice. Antimicrob Agents Chemother 2011; 55 (05) 1852-1860
160 Morio F, Loge C, Besse B, Hennequin C, Le Pape P. Screening for amino acid substitutions in the Candida albicans Erg11 protein of azole-susceptible and azole-resistant clinical isolates: new substitutions and a review of the literature. Diagn Microbiol Infect Dis 2010; 66 (04) 373-384
161 Sanguinetti M, Posteraro B. New approaches for antifungal susceptibility testing. Clin Microbiol Infect 2017; 23 (12) 931-934
162 Vandeputte P, Ferrari S, Coste AT. Antifungal resistance and new strategies to control fungal infections. Int J Microbiol 2012; 2012: 713687
163 Dudiuk C, Gamarra S, Leonardeli F. , et al. Set of classical PCRs for detection of mutations in Candida glabrata FKS genes linked with echinocandin resistance. J Clin Microbiol 2014; 52 (07) 2609-2614
164 Hou X, Lee A, Jiménez-Ortigosa C, Kordalewska M, Perlin DS, Zhao Y. Rapid detection of ERG11-associated azole resistance and FKS-associated echinocandin resistance in Candida auris. Antimicrob Agents Chemother 2018; 63 (01) e01811-18
165 Morales-López S, Dudiuk C, Vivot W, Szusz W, Córdoba SB, Garcia-Effron G. Phenotypic and molecular evaluation of echinocandin susceptibility of Candida glabrata, Candida bracarensis, and Candida nivariensis strains isolated during 30 years in Argentina. Antimicrob Agents Chemother 2017; 61: e00170-17
166 Pham CD, Bolden CB, Kuykendall RJ, Lockhart SR. Development of a Luminex-based multiplex assay for detection of mutations conferring resistance to echinocandins in Candida glabrata. J Clin Microbiol 2014; 52 (03) 790-795
167 Posteraro B, Vella A, De Carolis E, Sanguinetti M. Molecular detection of resistance to echinocandins. Methods Mol Biol 2017; 1508: 413-421
168 Zhao Y, Nagasaki Y, Kordalewska M. , et al. Rapid detection of FKS-associated echinocandin resistance in Candida glabrata. Antimicrob Agents Chemother 2016; 60 (11) 6573-6577
169 Scudeller L, Viscoli C, Menichetti F. , et al; ITALIC Group. An Italian consensus for invasive candidiasis management (ITALIC). Infection 2014; 42 (02) 263-279
170 Lee CH, Lin C, Ho CL, Lin JC. Primary fungal prophylaxis in hematological malignancy: a network meta-analysis of randomized controlled trials. Antimicrob Agents Chemother 2018; 62 (08) e00355-18
171 Maertens JA, Girmenia C, Brüggemann RJ. , et al; European Conference on Infections in Leukaemia (ECIL), a joint venture of the European Group for Blood and Marrow Transplantation (EBMT), the European Organization for Research and Treatment of Cancer (EORTC), the Immunocompromised Host Society (ICHS) and; European Conference on Infections in Leukaemia (ECIL), a joint venture of the European Group for Blood and Marrow Transplantation (EBMT), the European Organization for Research and Treatment of Cancer (EORTC), the Immunocompromised Host Society (ICHS) and the European LeukemiaNet (ELN). European guidelines for primary antifungal prophylaxis in adult haematology patients: summary of the updated recommendations from the European Conference on Infections in Leukaemia. J Antimicrob Chemother 2018; 73 (12) 3221-3230
172 Zaragoza R, Aguado JM, Ferrer R. , et al; EPICO Project Group. EPICO 3.0. Antifungal prophylaxis in solid organ transplant recipients. Rev Iberoam Micol 2016; 33 (04) 187-195
173 León C, Ostrosky-Zeichner L, Schuster M. What's new in the clinical and diagnostic management of invasive candidiasis in critically ill patients. Intensive Care Med 2014; 40 (06) 808-819
174 López-Cortés LE, Almirante B, Cuenca-Estrella M. , et al; members of the CANDIPOP Project from GEIH-GEMICOMED (SEIMC) and REIPI. Empirical and targeted therapy of candidemia with fluconazole versus echinocandins: a propensity score-derived analysis of a population-based, multicentre prospective cohort. Clin Microbiol Infect 2016; 22 (08) 733.e1-733.e8
175 Gafter-Gvili A, Vidal L, Goldberg E, Leibovici L, Paul M. Treatment of invasive candidal infections: systematic review and meta-analysis. Mayo Clin Proc 2008; 83 (09) 1011-1021
176 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 (Suppl. 06) S622-S629
177 Bienvenu AL, Leboucher G, Picot S. Comparison of fks gene mutations and minimum inhibitory concentrations for the detection of Candida glabrata resistance to micafungin: a systematic review and meta-analysis. Mycoses 2019 (e-pub ahead of print). Doi: 10.1111/myc.12929
178 Pristov KE, Ghannoum MA. Resistance of Candida to azoles and echinocandins worldwide. Clin Microbiol Infect 2019; 25 (07) 792-798
179 Bassetti M, Righi E. Overview of fungal infections--the Italian experience. Semin Respir Crit Care Med 2015; 36 (05) 796-805
180 Mora-Duarte J, Betts R, Rotstein C. , et al; Caspofungin Invasive Candidiasis Study Group. Comparison of caspofungin and amphotericin B for invasive candidiasis. N Engl J Med 2002; 347 (25) 2020-2029
181 Kuse ER, Chetchotisakd P, da Cunha CA. , et al; Micafungin Invasive Candidiasis Working Group. Micafungin versus liposomal amphotericin B for candidaemia and invasive candidosis: a phase III randomised double-blind trial. Lancet 2007; 369 (9572): 1519-1527
182 Reboli AC, Rotstein C, Pappas PG. , et al; Anidulafungin Study Group. Anidulafungin versus fluconazole for invasive candidiasis. N Engl J Med 2007; 356 (24) 2472-2482
183 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 (12) 1981-1989
184 Andes DR, Safdar N, Baddley JW. , et al; Mycoses Study Group. 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 Infect Dis 2012; 54 (08) 1110-1122
185 Garnacho-Montero J, Díaz-Martín A, Cantón-Bulnes L. , et al. Initial antifungal strategy reduces mortality in critically ill patients with candidemia: a propensity score-adjusted analysis of a multicenter study. Crit Care Med 2018; 46 (03) 384-393
186 Chiotos K, Vendetti N, Zaoutis TE. , et al. Comparative effectiveness of echinocandins versus fluconazole therapy for the treatment of adult candidaemia due to Candida parapsilosis: a retrospective observational cohort study of the Mycoses Study Group (MSG-12). J Antimicrob Chemother 2016; 71 (12) 3536-3539
187 Cornely OA, Bassetti M, Calandra T. , et al; ESCMID Fungal Infection Study Group. ESCMID* guideline for the diagnosis and management of Candida diseases 2012: non-neutropenic adult patients. Clin Microbiol Infect 2012; 18 (Suppl. 07) 19-37
188 Weiler S, Falkensammer G, Hammerer-Lercher A. , et al. Pulmonary epithelial lining fluid concentrations after use of systemic amphotericin B lipid formulations. Antimicrob Agents Chemother 2009; 53 (11) 4934-4937
189 Seyedmousavi S, Rafati H, Ilkit M, Tolooe A, Hedayati MT, Verweij P. Systemic antifungal agents: current status and projected future developments. Methods Mol Biol 2017; 1508: 107-139
190 Lakota EA, Ong V, Flanagan S, Rubino CM. Population pharmacokinetic analyses for rezafungin (CD101) efficacy using phase 1 data. Antimicrob Agents Chemother 2018; 62 (06) 62
191 Sofjan AK, Mitchell A, Shah DN. , et al. Rezafungin (CD101), a next-generation echinocandin: a systematic literature review and assessment of possible place in therapy. J Glob Antimicrob Resist 2018; 14: 58-64
192 Pfaller MA, Messer SA, Rhomberg PR, Castanheira M. Activity of a long-acting echinocandin (CD101) and seven comparator antifungal agents tested against a global collection of contemporary invasive fungal isolates in the SENTRY 2014 Antifungal Surveillance Program. Antimicrob Agents Chemother 2017; 61 (03) e02045-16
193 Arendrup MC, Meletiadis J, Zaragoza O. , et al. Multicentre determination of rezafungin (CD101) susceptibility of Candida species by the EUCAST method. Clin Microbiol Infect 2018; 24 (11) 1200-1204
194 Gonzalez-Lara MF, Sifuentes-Osornio J, Ostrosky-Zeichner L. Drugs in clinical development for fungal infections. Drugs 2017; 77 (14) 1505-1518
195 Bailly S, Bouadma L, Azoulay E. , et al. Failure of empirical systemic antifungal therapy in mechanically ventilated critically ill patients. Am J Respir Crit Care Med 2015; 191 (10) 1139-1146
196 Jacobs S, Price Evans DA, Tariq M, Al Omar NF. Fluconazole improves survival in septic shock: a randomized double-blind prospective study. Crit Care Med 2003; 31 (07) 1938-1946
197 Pelz RK, Hendrix CW, Swoboda SM. , et al. Double-blind placebo-controlled trial of fluconazole to prevent candidal infections in critically ill surgical patients. Ann Surg 2001; 233 (04) 542-548
198 Garbino J, Lew DP, Romand JA, Hugonnet S, Auckenthaler R, Pittet D. Prevention of severe Candida infections in nonneutropenic, high-risk, critically ill patients: a randomized, double-blind, placebo-controlled trial in patients treated by selective digestive decontamination. Intensive Care Med 2002; 28 (12) 1708-1717
199 Cortegiani A, Russotto V, Maggiore A. , et al. Antifungal agents for preventing fungal infections in non-neutropenic critically ill patients. Cochrane Database Syst Rev 2016; (01) CD004920
200 Playford EG, Eggimann P, Calandra T. Antifungals in the ICU. Curr Opin Infect Dis 2008; 21 (06) 610-619
201 Slavin MA, Sorrell TC, Marriott D. , et al; Australian Candidemia Study, Australasian Society for Infectious Diseases. Candidaemia in adult cancer patients: risks for fluconazole-resistant isolates and death. J Antimicrob Chemother 2010; 65 (05) 1042-1051
202 Bassetti M, Ansaldi F, Nicolini L. , et al. Incidence of candidaemia and relationship with fluconazole use in an intensive care unit. J Antimicrob Chemother 2009; 64 (03) 625-629
203 León C, Ruiz-Santana S, Saavedra P. , et al; Cava Study Group. Usefulness of the “Candida score” for discriminating between Candida colonization and invasive candidiasis in non-neutropenic critically ill patients: a prospective multicenter study. Crit Care Med 2009; 37 (05) 1624-1633
204 Ostrosky-Zeichner L, Shoham S, Vazquez J. , et al. MSG-01: a randomized, double-blind, placebo-controlled trial of caspofungin prophylaxis followed by preemptive therapy for invasive candidiasis in high-risk adults in the critical care setting. Clin Infect Dis 2014; 58 (09) 1219-1226
205 González de Molina FJ, León C, Ruiz-Santana S, Saavedra P. ; CAVA I Study Group. Assessment of candidemia-attributable mortality in critically ill patients using propensity score matching analysis. Crit Care 2012; 16 (03) R105
206 Presterl E, Parschalk B, Bauer E, Lassnigg A, Hajdu S, Graninger W. Invasive fungal infections and (1,3)-beta-D-glucan serum concentrations in long-term intensive care patients. Int J Infect Dis 2009; 13 (06) 707-712
207 Mohr JF, Sims C, Paetznick V. , et al. Prospective survey of (1→3)-beta-D-glucan and its relationship to invasive candidiasis in the surgical intensive care unit setting. J Clin Microbiol 2011; 49 (01) 58-61
208 Arendrup MC, Bergmann OJ, Larsson L, Nielsen HV, Jarløv JO, Christensson B. Detection of candidaemia in patients with and without underlying haematological disease. Clin Microbiol Infect 2010; 16 (07) 855-862
209 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 (09) 1240-1248
210 Bailly S, Leroy O, Montravers P. , et al. Antifungal de-escalation was not associated with adverse outcome in critically ill patients treated for invasive candidiasis: post hoc analyses of the AmarCAND2 study data. Intensive Care Med 2015; 41 (11) 1931-1940
211 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 (12) 2092-2106
212 Bow EJ, Evans G, Fuller J. , et al. Canadian clinical practice guidelines for invasive candidiasis in adults. Can J Infect Dis Med Microbiol 2010; 21 (04) e122-e150
213 Vazquez J, Reboli AC, Pappas PG. , et al. 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 2014; 14: 97
214 Fernández-Cruz A, Cruz Menárguez M, Muñoz P. , et al; GAME Study Group (Grupo de Apoyo al Manejo de la Endocarditis). The search for endocarditis in patients with candidemia: a systematic recommendation for echocardiography? A prospective cohort. Eur J Clin Microbiol Infect Dis 2015; 34 (08) 1543-1549
215 Schein M, Marshall J. Source control for surgical infections. World J Surg 2004; 28 (07) 638-645
216 Martínez ML, Ferrer R, Torrents E. , et al; Edusepsis Study Group. Impact of source control in patients with severe sepsis and septic shock. Crit Care Med 2017; 45 (01) 11-19
217 Nucci M, Anaissie E, Betts RF. , 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 Infect Dis 2010; 51 (03) 295-303
218 Cuervo G, Garcia-Vidal C, Puig-Asensio M. , et al; for Grupo de Estudio de Micología Médica (GEMICOMED), Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica (SEIMC); and Red Española de Investigación en Patología Infecciosa (REIPI). Echinocandins compared to fluconazole for candidemia of a urinary tract source: a propensity score analysis. Clin Infect Dis 2017; 64 (10) 1374-1379
219 Bloos F, Rüddel H, Thomas-Rüddel D. , et al; MEDUSA study group. Effect of a multifaceted educational intervention for anti-infectious measures on sepsis mortality: a cluster randomized trial. Intensive Care Med 2017; 43 (11) 1602-1612
220 Azuhata T, Kinoshita K, Kawano D. , et al. Time from admission to initiation of surgery for source control is a critical determinant of survival in patients with gastrointestinal perforation with associated septic shock. Crit Care 2014; 18 (03) R87
221 Sinnollareddy MG, Roberts MS, Lipman J. , et al. In vivo microdialysis to determine subcutaneous interstitial fluid penetration and pharmacokinetics of fluconazole in intensive care unit patients with sepsis. Antimicrob Agents Chemother 2015; 60 (02) 827-832
222 Baddley JW, Patel M, Bhavnani SM, Moser SA, Andes DR. Association of fluconazole pharmacodynamics with mortality in patients with candidemia. Antimicrob Agents Chemother 2008; 52 (09) 3022-3028
223 Jullien V, Azoulay E, Schwebel C. , et al; EMPIRICUS Trial Study Group. Population pharmacokinetics of micafungin in ICU patients with sepsis and mechanical ventilation. J Antimicrob Chemother 2017; 72 (01) 181-189
224 van der Elst KC, Veringa A, Zijlstra JG. , et al. Low caspofungin exposure in patients in intensive care units. Antimicrob Agents Chemother 2017; 61 (02) e01582-16
225 Boonstra JM, van der Elst KC, Veringa A. , et al. Pharmacokinetic properties of micafungin in critically ill patients diagnosed with invasive candidiasis. Antimicrob Agents Chemother 2017; 61 (12) e01398-17