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Fungal Infections in Cancer Patients

  • Bruno P. GranwehrEmail author
  • Nikolaos V. Sipsas
  • Dimitrios P. Kontoyiannis
Reference work entry

Abstract

Invasive fungal infections (IFIs) are a leading cause of morbidity and mortality in cancer patients admitted to intensive care units (ICUs). The patients typically exhibit multiple risk factors for IFIs, including barrier injury due to surgery, drains and catheters, effects from chemotherapy, neutropenia, corticosteroid exposure, renal and/or hepatic dysfunction, intra-abdominal surgery, and total parenteral nutrition (TPN). Candida remains the most common etiology of IFI. Prompt treatment, control of the sources of infection (e.g., removal of central venous catheters, drainage of abscesses), and prompt and appropriate selection, including dosing, of antifungals remain keys to survival in invasive candidiasis. Although fluconazole has been replaced by echinocandins as the first-line agent for candidemia, knowledge of prior antifungal exposure and hospital epidemiology is essential to appropriate antifungal selection. The most common mold isolated in oncologic ICUs is Aspergillus. Aggressive anti-mold prophylaxis has resulted in breakthrough infections with uncommon and resistant molds, such as Fusarium, Lomentospora, and Mucorales, which are increasingly more common. Diagnosis of IFIs requires high index of suspicion and art of risk stratification for IFI risk. New diagnostic methods, including fungal biomarkers, mass spectrometry (MALDI-TOF), and magnetic resonance (T2MR), have led to more rapid diagnosis, but many questions remain unanswered regarding real-world use of these tools in highly complex patient populations in cancer center ICUs. Despite improvements in therapeutic and diagnostic modalities, the activity of underlying disease and comorbidities are the most important drivers for outcome.

Keywords

Invasive fungal infections (IFIs) Candida Aspergillus Mucormycosis Antifungals Biomarkers 

References

  1. 1.
    Chow JK, Golan Y, Ruthazer R, et al. Risk factors for albicans and non-albicans candidemia in the intensive care unit. Crit Care Med. 2008;36:1993–8.CrossRefPubMedGoogle Scholar
  2. 2.
    Wiederhold NP. The antifungal arsenal: alternative drugs and future targets. Int J Antimicrob Agents. 2018;51:333–9.CrossRefPubMedGoogle Scholar
  3. 3.
    Eggimann P, Garbino J, Pittet D. Management of Candida species infections in critically ill patients. Lancet Infect Dis. 2003;3:772–85.CrossRefPubMedGoogle Scholar
  4. 4.
    Pfaller MA, Diekema DJ. Epidemiology of invasive candidiasis: a persistent public health problem. Clin Microbiol Rev. 2007;20:133–63.CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    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;39:309–17.CrossRefPubMedGoogle Scholar
  6. 6.
    Hidron AI, Edwards JR, Patel J, et al. NHSN annual update: antimicrobial-resistant pathogens associated with healthcare-associated infections: annual summary of data reported to the National Healthcare Safety Network at the Centers for Disease Control and Prevention, 2006–2007. Infect Control Hosp Epidemiol. 2008;29:996–1011.CrossRefPubMedGoogle Scholar
  7. 7.
    Kullberg BJ, Arendrup MC. Invasive Candidiasis. N Engl J Med. 2015;373:1445–56.CrossRefPubMedGoogle Scholar
  8. 8.
    Cornely OA, Gachot B, Akan H, et al. Epidemiology and outcome of fungemia in a cancer Cohort of the Infectious Diseases Group (IDG) of the European Organization for Research and Treatment of Cancer (EORTC 65031). Clin Infect Dis. 2015;61:324–31.CrossRefPubMedGoogle Scholar
  9. 9.
    Luzzati R, Allegranzi B, Antozzi L, et al. Secular trends in nosocomial candidaemia in non-neutropenic patients in an Italian tertiary hospital. Clin Microbiol Infect. 2005;11:908–13.CrossRefPubMedGoogle Scholar
  10. 10.
    Trick WE, Fridkin SK, Edwards JR, Hajjeh RA, Gaynes RP, National Nosocomial Infections Surveillance System H. Secular trend of hospital-acquired candidemia among intensive care unit patients in the United States during 1989–1999. Clin Infect Dis. 2002;35:627–30.CrossRefPubMedGoogle Scholar
  11. 11.
    Bougnoux ME, Kac G, Aegerter P, d’Enfert C, Fagon JY, CandiRea Study G. Candidemia and candiduria in critically ill patients admitted to intensive care units in France: incidence, molecular diversity, management and outcome. Intensive Care Med. 2008;34:292–9.CrossRefPubMedGoogle Scholar
  12. 12.
    Bassetti M, Righi E, Costa A, et al. Epidemiological trends in nosocomial candidemia in intensive care. BMC Infect Dis. 2006;6:21.CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Mahr CC, Fildes JJ, Becker EJ, et al. The alarming rate of fungal recovery in critically ill trauma patients with unresolved sepsis. Crit Care Med. 1995;23:A154.CrossRefGoogle Scholar
  14. 14.
    Petri MG, Konig J, Moecke HP, et al. Epidemiology of invasive mycosis in ICU patients: a prospective multicenter study in 435 non-neutropenic patients. Paul-Ehrlich Society for Chemotherapy, Divisions of Mycology and Pneumonia Research. Intensive Care Med. 1997;23:317–25.CrossRefPubMedGoogle Scholar
  15. 15.
    Rangel-Frausto MS, Wiblin T, Blumberg HM, et al. National epidemiology of mycoses survey (NEMIS): variations in rates of bloodstream infections due to Candida species in seven surgical intensive care units and six neonatal intensive care units. Clin Infect Dis. 1999;29:253–8.CrossRefPubMedGoogle Scholar
  16. 16.
    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:E1–E50.CrossRefPubMedGoogle Scholar
  17. 17.
    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;63:1463–9.CrossRefPubMedGoogle Scholar
  18. 18.
    Morgan J. Global trends in candidemia: review of reports from 1995–2005. Curr Infect Dis Rep. 2005;7:429–39.CrossRefPubMedGoogle Scholar
  19. 19.
    Shorr AF, Lazarus DR, Sherner JH, et al. Do clinical features allow for accurate prediction of fungal pathogenesis in bloodstream infections? Potential implications of the increasing prevalence of non-albicans candidemia. Crit Care Med. 2007;35:1077–83.CrossRefPubMedGoogle Scholar
  20. 20.
    Hajjeh RA, Sofair AN, Harrison LH, et al. Incidence of bloodstream infections due to Candida species and in vitro susceptibilities of isolates collected from 1998 to 2000 in a population-based active surveillance program. J Clin Microbiol. 2004;42:1519–27.CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Slavin MA, Sorrell TC, Marriott D, et al. Candidaemia in adult cancer patients: risks for fluconazole-resistant isolates and death. J Antimicrob Chemother. 2010;65:1042–51.CrossRefPubMedGoogle Scholar
  22. 22.
    Sipsas NV, Lewis RE, Tarrand J, et al. Candidemia in patients with hematologic malignancies in the era of new antifungal agents (2001–2007) stable incidence but changing epidemiology of a still frequently lethal infection. Cancer. 2009;115:4745–52.CrossRefPubMedGoogle Scholar
  23. 23.
    Nguyen MH, Peacock JE, Morris AJ, et al. The changing face of candidemia: emergence of non-Candida albicans species and antifungal resistance. Am J Med. 1996;100:617–23.CrossRefPubMedGoogle Scholar
  24. 24.
    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;36:2034–9.CrossRefPubMedGoogle Scholar
  25. 25.
    Holley A, Dulhunty J, Blot S, et al. Temporal trends, risk factors and outcomes in albicans and non-albicans candidaemia: an international epidemiological study in four multidisciplinary intensive care units. Int J Antimicrob Agents. 2009;33:554 e551–7.CrossRefGoogle Scholar
  26. 26.
    Jung DS, Farmakiotis D, Jiang Y, Tarrand JJ, Kontoyiannis DP. Uncommon Candida species fungemia among cancer patients, Houston, Texas, USA. Emerg Infect Dis. 2015;21:1942–50.PubMedPubMedCentralGoogle Scholar
  27. 27.
    Golan Y, Wolf MP, Pauker SG, Wong JB, Hadley S. Empirical anti-Candida therapy among selected patients in the intensive care unit: a cost-effectiveness analysis. Ann Intern Med. 2005;143:857–69.CrossRefPubMedGoogle Scholar
  28. 28.
    Rodriguez-Adrian LJ, King RT, Tamayo-Derat LG, Miller JW, Garcia CA, Rex JH. Retinal lesions as clues to disseminated bacterial and candidal infections: frequency, natural history, and etiology. Medicine (Baltimore). 2003;82:187–202.Google Scholar
  29. 29.
    Lamaris GA, Esmaeli B, Chamilos G, et al. Fungal endophthalmitis in a tertiary care cancer center: a review of 23 cases. Eur J Clin Microbiol Infect Dis. 2008;27:343–7.CrossRefPubMedGoogle Scholar
  30. 30.
    Anttila VJ, Elonen E, Nordling S, Sivonen A, Ruutu T, Ruutu P. Hepatosplenic candidiasis in patients with acute leukemia: incidence and prognostic implications. Clin Infect Dis. 1997;24:375–80.CrossRefPubMedGoogle Scholar
  31. 31.
    Kontoyiannis DP, Luna MA, Samuels BI, Bodey GP. Hepatosplenic candidiasis. A manifestation of chronic disseminated candidiasis. Infect Dis Clin N Am. 2000;14:721–39.CrossRefGoogle Scholar
  32. 32.
    Mean M, Marchetti O, Calandra T. Bench-to-bedside review: candida infections in the intensive care unit. Crit Care. 2008;12:204.CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Morris AJ, Byrne TC, Madden JF, Reller LB. Duration of incubation of fungal cultures. J Clin Microbiol. 1996;34:1583–5.PubMedPubMedCentralGoogle Scholar
  34. 34.
    Horvath LL, George BJ, Hospenthal DR. Detection of fifteen species of Candida in an automated blood culture system. J Clin Microbiol. 2007;45:3062–4.CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    Lewis RE, Cahyame-Zuniga L, Leventakos K, et al. Epidemiology and sites of involvement of invasive fungal infections in patients with haematological malignancies: a 20-year autopsy study. Mycoses. 2013;56:638–45.CrossRefPubMedGoogle Scholar
  36. 36.
    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;51:433–42.CrossRefPubMedGoogle Scholar
  37. 37.
    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;41:654–9.CrossRefPubMedGoogle Scholar
  38. 38.
    Morace G, Pagano L, Sanguinetti M, et al. PCR-restriction enzyme analysis for detection of Candida DNA in blood from febrile patients with hematological malignancies. J Clin Microbiol. 1999;37:1871–5.PubMedPubMedCentralGoogle Scholar
  39. 39.
    Clancy CJ, Nguyen MH. Diagnosing invasive Candidiasis. J Clin Microbiol. 2018;56:e01909.CrossRefPubMedPubMedCentralGoogle Scholar
  40. 40.
    Reischies FM, Prattes J, Woelfler A, Eigl S, Hoenigl M. Diagnostic performance of 1,3-beta-D-glucan serum screening in patients receiving hematopoietic stem cell transplantation. Transpl Infect Dis. 2016;18:466–70.CrossRefPubMedGoogle Scholar
  41. 41.
    Giacobbe DR, Del Bono V, Viscoli C, Mikulska M. Use of 1,3-beta-D-glucan in invasive fungal diseases in hematology patients. Expert Rev Anti-Infect Ther. 2017;15:1101–12.CrossRefPubMedGoogle Scholar
  42. 42.
    Clancy CJ, Pappas PG, Vazquez J, et al. Detecting infections rapidly and easily for Candidemia trial, part 2 (DIRECT2): a prospective, multicenter study of the T2Candida panel. Clin Infect Dis. 2018;66:1678–86.CrossRefPubMedGoogle Scholar
  43. 43.
    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;60:892–9.CrossRefPubMedGoogle Scholar
  44. 44.
    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;49:2879–83.CrossRefPubMedPubMedCentralGoogle Scholar
  45. 45.
    Arendrup MC, Sulim S, Holm A, et al. Diagnostic issues, clinical characteristics, and outcomes for patients with fungemia. J Clin Microbiol. 2011;49:3300–8.CrossRefPubMedPubMedCentralGoogle Scholar
  46. 46.
    Antoniadou A, Torres HA, Lewis RE, et al. Candidemia in a tertiary care cancer center: in vitro susceptibility and its association with outcome of initial antifungal therapy. Medicine (Baltimore). 2003;82:309–21.CrossRefGoogle Scholar
  47. 47.
    Raad I, Hanna H, Boktour M, et al. Management of central venous catheters in patients with cancer and candidemia. Clin Infect Dis. 2004;38:1119–27.CrossRefPubMedGoogle Scholar
  48. 48.
    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;46:2222–6.CrossRefPubMedPubMedCentralGoogle Scholar
  49. 49.
    Kontoyiannis DP, Reddy BT, Torres HA, et al. Pulmonary candidiasis in patients with cancer: an autopsy study. Clin Infect Dis. 2002;34:400–3.CrossRefPubMedGoogle Scholar
  50. 50.
    Wood GC, Mueller EW, Croce MA, Boucher BA, Fabian TC. Candida sp. isolated from bronchoalveolar lavage: clinical significance in critically ill trauma patients. Intensive Care Med. 2006;32:599–603.CrossRefPubMedGoogle Scholar
  51. 51.
    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.CrossRefPubMedGoogle Scholar
  52. 52.
    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;15:414–21.CrossRefPubMedGoogle Scholar
  53. 53.
    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;26:271–6.CrossRefPubMedGoogle Scholar
  54. 54.
    Faiz S, Neale B, Rios E, et al. Risk-based fluconazole prophylaxis of Candida bloodstream infection in a medical intensive care unit. Eur J Clin Microbiol Infect Dis. 2009;28:689–92.CrossRefPubMedGoogle Scholar
  55. 55.
    Pittet D, Monod M, Suter PM, Frenk E, Auckenthaler R. Candida colonization and subsequent infections in critically ill surgical patients. Ann Surg. 1994;220:751–8.CrossRefPubMedPubMedCentralGoogle Scholar
  56. 56.
    Playford EG, Lipman J, Kabir M, et al. Assessment of clinical risk predictive rules for invasive candidiasis in a prospective multicentre cohort of ICU patients. Intensive Care Med. 2009;35:2141–5.CrossRefPubMedGoogle Scholar
  57. 57.
    Leon C, Ruiz-Santana S, Saavedra P, et al. 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;37:1624–33.CrossRefPubMedGoogle Scholar
  58. 58.
    Eggimann P, Francioli P, Bille J, et al. Fluconazole prophylaxis prevents intra-abdominal candidiasis in high-risk surgical patients. Crit Care Med. 1999;27:1066–72.CrossRefPubMedGoogle Scholar
  59. 59.
    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;233:542–8.CrossRefPubMedPubMedCentralGoogle Scholar
  60. 60.
    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;28:1708–17.CrossRefPubMedGoogle Scholar
  61. 61.
    Playford EG, Webster AC, Sorrell TC, Craig JC. Antifungal agents for preventing fungal infections in non-neutropenic critically ill patients. Cochrane Database Syst Rev. 2006;1:CD004920.Google Scholar
  62. 62.
    Rocco TR, Reinert SE, Simms HH. Effects of fluconazole administration in critically ill patients: analysis of bacterial and fungal resistance. Arch Surg. 2000;135:160–5.CrossRefPubMedGoogle Scholar
  63. 63.
    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;64:625–9.CrossRefPubMedGoogle Scholar
  64. 64.
    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;49:3640–5.CrossRefPubMedPubMedCentralGoogle Scholar
  65. 65.
    Piarroux R, Grenouillet F, Balvay P, et al. Assessment of preemptive treatment to prevent severe candidiasis in critically ill surgical patients. Crit Care Med. 2004;32:2443–9.CrossRefPubMedGoogle Scholar
  66. 66.
    Tsuruta R, Mizuno H, Kaneko T, et al. Preemptive therapy in nonneutropenic patients with Candida infection using the Japanese guidelines. Ann Pharmacother. 2007;41:1137–43.CrossRefPubMedGoogle Scholar
  67. 67.
    Schuster MG, Edwards JE Jr, Sobel JD, et al. Empirical fluconazole versus placebo for intensive care unit patients: a randomized trial. Ann Intern Med. 2008;149:83–90.CrossRefPubMedGoogle Scholar
  68. 68.
    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;58:1219–26.CrossRefPubMedGoogle Scholar
  69. 69.
    Timsit JF, 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;316:1555–64.CrossRefPubMedGoogle Scholar
  70. 70.
    Leventakos K, Lewis RE, Kontoyiannis DP. Fungal infections in leukemia patients: how do we prevent and treat them? Clin Infect Dis. 2010;50:405–15.CrossRefPubMedGoogle Scholar
  71. 71.
    Kontoyiannis DP, Lewis RE. Antifungal drug resistance of pathogenic fungi. Lancet. 2002;359:1135–44.CrossRefPubMedGoogle Scholar
  72. 72.
    Sinnollareddy MG, Roberts JA, Lipman J, et al. Pharmacokinetic variability and exposures of fluconazole, anidulafungin, and caspofungin in intensive care unit patients: data from multinational Defining Antibiotic Levels in Intensive care unit (DALI) patients study. Crit Care. 2015;19:33.CrossRefPubMedPubMedCentralGoogle Scholar
  73. 73.
    Mora-Duarte J, Betts R, Rotstein C, et al. Comparison of caspofungin and amphotericin B for invasive candidiasis. N Engl J Med. 2002;347:2020–9.CrossRefPubMedGoogle Scholar
  74. 74.
    Kuse ER, Chetchotisakd P, da Cunha CA, et al. Micafungin versus liposomal amphotericin B for candidaemia and invasive candidosis: a phase III randomised double-blind trial. Lancet. 2007;369:1519–27.CrossRefPubMedGoogle Scholar
  75. 75.
    Reboli AC, Rotstein C, Pappas PG, et al. Anidulafungin versus fluconazole for invasive candidiasis. N Engl J Med. 2007;356:2472–82.CrossRefPubMedGoogle Scholar
  76. 76.
    Pappas PG, Rotstein CM, Betts RF, et al. Micafungin versus caspofungin for treatment of candidemia and other forms of invasive candidiasis. Clin Infect Dis. 2007;45:883–93.CrossRefPubMedGoogle Scholar
  77. 77.
    Sipsas NV, Lewis RE, Raad II, Kontoyiannis DP. Monotherapy with caspofungin for candidaemia in adult patients with cancer: a retrospective, single institution study. Int J Antimicrob Agents. 2009;34:95–8.CrossRefPubMedGoogle Scholar
  78. 78.
    Betts R, Glasmacher A, Maertens J, et al. Efficacy of caspofungin against invasive Candida or invasive Aspergillus infections in neutropenic patients. Cancer. 2006;106:466–73.CrossRefPubMedGoogle Scholar
  79. 79.
    van der Elst KC, Veringa A, Zijlstra JG, et al. Low caspofungin exposure in patients in intensive care units. Antimicrob Agents Chemother. 2017;61:e01582.PubMedPubMedCentralGoogle Scholar
  80. 80.
    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:e01398.CrossRefPubMedPubMedCentralGoogle Scholar
  81. 81.
    Chen SC, Slavin MA, Sorrell TC. Echinocandin antifungal drugs in fungal infections: a comparison. Drugs. 2011;71:11–41.CrossRefPubMedGoogle Scholar
  82. 82.
    Colombo AL, Ngai AL, Bourque M, et al. Caspofungin use in patients with invasive candidiasis caused by common non-albicans Candida species: review of the caspofungin database. Antimicrob Agents Chemother. 2010;54:1864–71.CrossRefPubMedPubMedCentralGoogle Scholar
  83. 83.
    Kontoyiannis DP, Bassetti M, Nucci M, et al. Anidulafungin for the treatment of candidaemia caused by Candida parapsilosis: analysis of pooled data from six prospective clinical studies. Mycoses. 2017;60:663–7.CrossRefPubMedGoogle Scholar
  84. 84.
    Kullberg BJ, Sobel JD, Ruhnke M, et al. Voriconazole versus a regimen of amphotericin B followed by fluconazole for candidaemia in non-neutropenic patients: a randomised non-inferiority trial. Lancet. 2005;366:1435–42.CrossRefPubMedGoogle Scholar
  85. 85.
    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. 2018. https://www.ncbi.nlm.nih.gov/pubmed/30289478.  https://doi.org/10.1093/cid/ciy827
  86. 86.
    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.CrossRefPubMedPubMedCentralGoogle Scholar
  87. 87.
    Farmakiotis D, Kyvernitakis A, Tarrand JJ, Kontoyiannis DP. Early initiation of appropriate treatment is associated with increased survival in cancer patients with Candida glabrata fungaemia: a potential benefit from infectious disease consultation. Clin Microbiol Infect. 2015;21:79–86.CrossRefPubMedGoogle Scholar
  88. 88.
    Lee RA, Zurko J, Camins BC, et al. Impact of infectious disease consultation on clinical management and mortality in patients with candidemia. Clin Infect Dis. 2018. https://www.ncbi.nlm.nih.gov/pubmed/30281081.  https://doi.org/10.1093/cid/ciy849
  89. 89.
    Ostrosky-Zeichner L, Oude Lashof AM, Kullberg BJ, Rex JH. Voriconazole salvage treatment of invasive candidiasis. Eur J Clin Microbiol Infect Dis. 2003;22:651–5.CrossRefPubMedGoogle Scholar
  90. 90.
    Rex JH, Pappas PG, Karchmer AW, et al. 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. Clin Infect Dis. 2003;36:1221–8.CrossRefPubMedGoogle Scholar
  91. 91.
    Kullberg BJ, Oude Lashof AM, Netea MG. Design of efficacy trials of cytokines in combination with antifungal drugs. Clin Infect Dis. 2004;39(Suppl 4):S218–23.CrossRefPubMedGoogle Scholar
  92. 92.
    Sobel JD. Combination therapy for invasive mycoses: evaluation of past clinical trial designs. Clin Infect Dis. 2004;39(Suppl 4):S224–7.CrossRefPubMedGoogle Scholar
  93. 93.
    West KA, Gea-Banacloche J, Stroncek D, Kadri SS. Granulocyte transfusions in the management of invasive fungal infections. Br J Haematol. 2017;177:357–74.CrossRefPubMedPubMedCentralGoogle Scholar
  94. 94.
    Toya SP, Schraufnagel DE, Tzelepis GE. Candiduria in intensive care units: association with heavy colonization and candidaemia. J Hosp Infect. 2007;66:201–6.CrossRefPubMedGoogle Scholar
  95. 95.
    Alvarez-Lerma F, Nolla-Salas J, Leon C, et al. Candiduria in critically ill patients admitted to intensive care medical units. Intensive Care Med. 2003;29:1069–76.CrossRefPubMedGoogle Scholar
  96. 96.
    Georgiadou SP, Tarrand J, Sipsas NV, Kontoyiannis DP. Candiduria in haematologic malignancy patients without a urinary catheter: nothing more than a frailty marker? Mycoses. 2013;56:311–4.CrossRefPubMedGoogle Scholar
  97. 97.
    Sobel JD, Kauffman CA, McKinsey D, et al. Candiduria: a randomized, double-blind study of treatment with fluconazole and placebo. The National Institute of Allergy and Infectious Diseases (NIAID) Mycoses Study Group. Clin Infect Dis. 2000;30:19–24.CrossRefPubMedGoogle Scholar
  98. 98.
    Drew RH, Arthur RR, Perfect JR. Is it time to abandon the use of amphotericin B bladder irrigation? Clin Infect Dis. 2005;40:1465–70.CrossRefPubMedGoogle Scholar
  99. 99.
    Pappas PG, Lionakis MS, Arendrup MC, Ostrosky-Zeichner L, Kullberg BJ. Invasive candidiasis. Nat Rev Dis Primers. 2018;4:18026.CrossRefPubMedGoogle Scholar
  100. 100.
    Davidson L, Netea MG, Kullberg BJ. Patient susceptibility to candidiasis-a potential for adjunctive immunotherapy. J Fungi (Basel). 2018;4:E9.CrossRefGoogle Scholar
  101. 101.
    Rex JH, Bennett JE, Sugar AM, et al. Intravascular catheter exchange and duration of candidemia. NIAID Mycoses Study Group and the Candidemia Study Group. Clin Infect Dis. 1995;21:994–6.CrossRefPubMedGoogle Scholar
  102. 102.
    Anaissie EJ, Rex JH, Uzun O, Vartivarian S. Predictors of adverse outcome in cancer patients with candidemia. Am J Med. 1998;104:238–45.CrossRefPubMedGoogle Scholar
  103. 103.
    Nucci M, Anaissie E. Should vascular catheters be removed from all patients with candidemia? An evidence-based review. Clin Infect Dis. 2002;34:591–9.CrossRefPubMedGoogle Scholar
  104. 104.
    Epstein L, See I, Edwards JR, Magill SS, Thompson ND. Mucosal Barrier Injury Laboratory-Confirmed Bloodstream Infections (MBI-LCBI): descriptive analysis of data reported to National Healthcare Safety Network (NHSN), 2013. Infect Control Hosp Epidemiol. 2016;37:2–7.CrossRefPubMedGoogle Scholar
  105. 105.
    Raad II, Hachem RY, Hanna HA, et al. Role of ethylene diamine tetra-acetic acid (EDTA) in catheter lock solutions: EDTA enhances the antifungal activity of amphotericin B lipid complex against Candida embedded in biofilm. Int J Antimicrob Agents. 2008;32:515–8.CrossRefPubMedGoogle Scholar
  106. 106.
    Jones TM, Drew RH, Wilson DT, Sarubbi C, Anderson DJ. Impact of automatic infectious diseases consultation on the management of fungemia at a large academic medical center. Am J Health Syst Pharm. 2017;74:1997–2003.CrossRefPubMedGoogle Scholar
  107. 107.
    Antworth A, Collins CD, Kunapuli A, et al. Impact of an antimicrobial stewardship program comprehensive care bundle on management of candidemia. Pharmacotherapy. 2013;33:137–43.CrossRefPubMedGoogle Scholar
  108. 108.
    Gouliouris T, Micallef C, Yang H, Aliyu SH, Kildonaviciute K, Enoch DA. Impact of a candidaemia care bundle on patient care at a large teaching hospital in England. J Infect. 2016;72:501–3.CrossRefPubMedGoogle Scholar
  109. 109.
    Blot SI, Vandewoude KH, Hoste EA, Colardyn FA. Effects of nosocomial candidemia on outcomes of critically ill patients. Am J Med. 2002;113:480–5.CrossRefPubMedGoogle Scholar
  110. 110.
    Dimopoulos G, Karabinis A, Samonis G, Falagas ME. Candidemia in immunocompromised and immunocompetent critically ill patients: a prospective comparative study. Eur J Clin Microbiol Infect Dis. 2007;26:377–84.CrossRefPubMedGoogle Scholar
  111. 111.
    Zaoutis TE, Argon J, Chu J, Berlin JA, Walsh TJ, Feudtner C. The epidemiology and attributable outcomes of candidemia in adults and children hospitalized in the United States: a propensity analysis. Clin Infect Dis. 2005;41:1232–9.CrossRefPubMedGoogle Scholar
  112. 112.
    Voss A, le Noble JL, Verduyn Lunel FM, Foudraine NA, Meis JF. Candidemia in intensive care unit patients: risk factors for mortality. Infection. 1997;25:8–11.CrossRefPubMedGoogle Scholar
  113. 113.
    Cesaro S, Tridello G, Blijlevens N, et al. Incidence, risk factors, and long-term outcome of acute leukemia patients with early candidemia after allogeneic stem cell transplantation: a study by the acute leukemia and infectious diseases working parties of European Society for Blood and Marrow Transplantation. Clin Infect Dis. 2018;67:564–72.CrossRefPubMedGoogle Scholar
  114. 114.
    Vandewoude KH, Blot SI, Benoit D, Colardyn F, Vogelaers D. Invasive aspergillosis in critically ill patients: attributable mortality and excesses in length of ICU stay and ventilator dependence. J Hosp Infect. 2004;56:269–76.CrossRefPubMedGoogle Scholar
  115. 115.
    Meersseman W, Lagrou K, Maertens J, Van Wijngaerden E. Invasive aspergillosis in the intensive care unit. Clin Infect Dis. 2007;45:205–16.CrossRefPubMedGoogle Scholar
  116. 116.
    Lahmer T, Held J, Rasch S, et al. Usage of 1,3-beta-D-glucan for early detection of invasive mycoses and outcome parameter in immunocompromised critically ill patients. Mycopathologia. 2016;181:815–21.CrossRefPubMedGoogle Scholar
  117. 117.
    Roosen J, Frans E, Wilmer A, Knockaert DC, Bobbaers H. Comparison of premortem clinical diagnoses in critically ill patients and subsequent autopsy findings. Mayo Clin Proc. 2000;75:562–7.CrossRefPubMedGoogle Scholar
  118. 118.
    Gayet-Ageron A, Iten A, van Delden C, et al. In-hospital transfer is a risk factor for invasive filamentous fungal infection among hospitalized patients with hematological malignancies: a matched case-control study. Infect Control Hosp Epidemiol. 2015;36:320–8.CrossRefPubMedGoogle Scholar
  119. 119.
    Patterson TF, Thompson GR 3rd, 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.CrossRefPubMedPubMedCentralGoogle Scholar
  120. 120.
    Lat A, Bhadelia N, Miko B, Furuya EY, Thompson GR 3rd. Invasive aspergillosis after pandemic (H1N1) 2009. Emerg Infect Dis. 2010;16:971–3.CrossRefPubMedPubMedCentralGoogle Scholar
  121. 121.
    Crum-Cianflone NF. Invasive aspergillosis associated with severe influenza infections. Open Forum Infect Dis. 2016;3:ofw171.CrossRefPubMedPubMedCentralGoogle Scholar
  122. 122.
    Schauwvlieghe A, Rijnders BJA, Philips N, et al. Invasive aspergillosis in patients admitted to the intensive care unit with severe influenza: a retrospective cohort study. Lancet Respir Med. 2018;6:782–92.CrossRefPubMedGoogle Scholar
  123. 123.
    Skoetz N, Bauer K, Elter T, et al. Alemtuzumab for patients with chronic lymphocytic leukaemia. Cochrane Database Syst Rev. 2012;2:CD008078.Google Scholar
  124. 124.
    Chamilos G, Lionakis MS, Kontoyiannis DP. Call for action: invasive fungal infections associated with ibrutinib and other small molecule kinase inhibitors targeting immune signaling pathways. Clin Infect Dis. 2018;66:140–8.CrossRefPubMedGoogle Scholar
  125. 125.
    Postow MA, Sidlow R, Hellmann MD. Immune-related adverse events associated with immune checkpoint blockade. N Engl J Med. 2018;378:158–68.CrossRefPubMedGoogle Scholar
  126. 126.
    Khasawneh F, Mohamad T, Moughrabieh MK, Lai Z, Ager J, Soubani AO. Isolation of Aspergillus in critically ill patients: a potential marker of poor outcome. J Crit Care. 2006;21:322–7.CrossRefPubMedGoogle Scholar
  127. 127.
    Horvath JA, Dummer S. The use of respiratory-tract cultures in the diagnosis of invasive pulmonary aspergillosis. Am J Med. 1996;100:171–8.CrossRefPubMedGoogle Scholar
  128. 128.
    Chamilos G, Marom EM, Lewis RE, Lionakis MS, Kontoyiannis DP. Predictors of pulmonary zygomycosis versus invasive pulmonary aspergillosis in patients with cancer. Clin Infect Dis. 2005;41:60–6.CrossRefPubMedGoogle Scholar
  129. 129.
    Colombo AL, de Almeida Junior JN, Slavin MA, Chen SC, Sorrell TC. Candida and invasive mould diseases in non-neutropenic critically ill patients and patients with haematological cancer. Lancet Infect Dis. 2017;17:e344–56.CrossRefPubMedGoogle Scholar
  130. 130.
    Vandewoude KH, Vogelaers D. Medical imaging and timely diagnosis of invasive pulmonary aspergillosis. Clin Infect Dis. 2007;44:380–1.CrossRefPubMedGoogle Scholar
  131. 131.
    Fernandez-Cruz A, Magira E, Heo ST, Evans S, Tarrand J, Kontoyiannis DP. Bronchoalveolar lavage fluid cytology in culture-documented invasive pulmonary aspergillosis in patients with hematologic diseases: analysis of 67 episodes. J Clin Microbiol. 2018;56:e00962.CrossRefPubMedPubMedCentralGoogle Scholar
  132. 132.
    Meersseman W, Lagrou K, Maertens J, et al. Galactomannan in bronchoalveolar lavage fluid: a tool for diagnosing aspergillosis in intensive care unit patients. Am J Respir Crit Care Med. 2008;177:27–34.CrossRefPubMedGoogle Scholar
  133. 133.
    Rose SR, Vallabhajosyula S, Velez MG, et al. The utility of bronchoalveolar lavage beta-D-glucan testing for the diagnosis of invasive fungal infections. J Infect. 2014;69:278–83.CrossRefPubMedPubMedCentralGoogle Scholar
  134. 134.
    De Pauw B, Walsh TJ, Donnelly JP, et al. 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;46:1813–21.CrossRefPubMedPubMedCentralGoogle Scholar
  135. 135.
    Segal BH. Aspergillosis. N Engl J Med. 2009;360:1870–84.CrossRefPubMedGoogle Scholar
  136. 136.
    Herbrecht R, Denning DW, Patterson TF, et al. Voriconazole versus amphotericin B for primary therapy of invasive aspergillosis. N Engl J Med. 2002;347:408–15.CrossRefPubMedGoogle Scholar
  137. 137.
    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;387:760–9.CrossRefPubMedGoogle Scholar
  138. 138.
    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;39:1563–71.CrossRefPubMedGoogle Scholar
  139. 139.
    Walsh TJ, Raad I, Patterson TF, et al. Treatment of invasive aspergillosis with posaconazole in patients who are refractory to or intolerant of conventional therapy: an externally controlled trial. Clin Infect Dis. 2007;44:2–12.CrossRefPubMedGoogle Scholar
  140. 140.
    Kontoyiannis DP, Ratanatharathorn V, Young JA, et al. Micafungin alone or in combination with other systemic antifungal therapies in hematopoietic stem cell transplant recipients with invasive aspergillosis. Transpl Infect Dis. 2009;11:89–93.CrossRefPubMedGoogle Scholar
  141. 141.
    Cornely OA, Maertens J, Bresnik M, et al. Liposomal amphotericin B as initial therapy for invasive mold infection: a randomized trial comparing a high-loading dose regimen with standard dosing (AmBiLoad trial). Clin Infect Dis. 2007;44:1289–97.CrossRefPubMedGoogle Scholar
  142. 142.
    Marr KA, Boeckh M, Carter RA, Kim HW, Corey L. Combination antifungal therapy for invasive aspergillosis. Clin Infect Dis. 2004;39:797–802.CrossRefPubMedGoogle Scholar
  143. 143.
    Marr KA, Schlamm HT, Herbrecht R, et al. Combination antifungal therapy for invasive aspergillosis: a randomized trial. Ann Intern Med. 2015;162:81–9.CrossRefPubMedGoogle Scholar
  144. 144.
    Taccone FS, Van den Abeele AM, Bulpa P, et al. Epidemiology of invasive aspergillosis in critically ill patients: clinical presentation, underlying conditions, and outcomes. Crit Care. 2015;19:7.CrossRefPubMedPubMedCentralGoogle Scholar
  145. 145.
    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;43:1225–38.CrossRefPubMedGoogle Scholar
  146. 146.
    Raad II, Zakhem AE, Helou GE, Jiang Y, Kontoyiannis DP, Hachem R. Clinical experience of the use of voriconazole, caspofungin or the combination in primary and salvage therapy of invasive aspergillosis in haematological malignancies. Int J Antimicrob Agents. 2015;45:283–8.CrossRefPubMedGoogle Scholar
  147. 147.
    Heo ST, Tatara AM, Jimenez-Ortigosa C, et al. Changes in in vitro susceptibility patterns of aspergillus to triazoles and correlation with aspergillosis outcome in a tertiary care cancer center, 1999–2015. Clin Infect Dis. 2017;65:216–25.CrossRefPubMedPubMedCentralGoogle Scholar
  148. 148.
    Davoudi S, Kumar VA, Jiang Y, Kupferman M, Kontoyiannis DP. Invasive mould sinusitis in patients with haematological malignancies: a 10 year single-centre study. J Antimicrob Chemother. 2015;70:2899–905.CrossRefPubMedGoogle Scholar
  149. 149.
    Kontoyiannis DP, Selleslag D, Mullane K, et al. Impact of unresolved neutropenia in patients with neutropenia and invasive aspergillosis: a post hoc analysis of the SECURE trial. J Antimicrob Chemother. 2018;73:757–63.CrossRefPubMedGoogle Scholar
  150. 150.
    Kontoyiannis DP, Lionakis MS, Lewis RE, et al. Zygomycosis in a tertiary-care cancer center in the era of Aspergillus-active antifungal therapy: a case-control observational study of 27 recent cases. J Infect Dis. 2005;191:1350–60.CrossRefPubMedGoogle Scholar
  151. 151.
    Roden MM, Zaoutis TE, Buchanan WL, et al. Epidemiology and outcome of zygomycosis: a review of 929 reported cases. Clin Infect Dis. 2005;41:634–53.CrossRefPubMedGoogle Scholar
  152. 152.
    Trifilio SM, Bennett CL, Yarnold PR, et al. Breakthrough zygomycosis after voriconazole administration among patients with hematologic malignancies who receive hematopoietic stem-cell transplants or intensive chemotherapy. Bone Marrow Transplant. 2007;39:425–9.CrossRefPubMedGoogle Scholar
  153. 153.
    Pongas GN, Lewis RE, Samonis G, Kontoyiannis DP. Voriconazole-associated zygomycosis: a significant consequence of evolving antifungal prophylaxis and immunosuppression practices? Clin Microbiol Infect. 2009;15(Suppl 5):93–7.CrossRefPubMedGoogle Scholar
  154. 154.
    Wahba H, Truong MT, Lei X, Kontoyiannis DP, Marom EM. Reversed halo sign in invasive pulmonary fungal infections. Clin Infect Dis. 2008;46:1733–7.CrossRefPubMedGoogle Scholar
  155. 155.
    Chamilos G, Lewis RE, Kontoyiannis DP. Delaying amphotericin B-based frontline therapy significantly increases mortality among patients with hematologic malignancy who have zygomycosis. Clin Infect Dis. 2008;47:503–9.CrossRefPubMedGoogle Scholar
  156. 156.
    Kyvernitakis A, Torres HA, Jiang Y, Chamilos G, Lewis RE, Kontoyiannis DP. Initial use of combination treatment does not impact survival of 106 patients with haematologic malignancies and mucormycosis: a propensity score analysis. Clin Microbiol Infect. 2016;22:811.e1–8.CrossRefGoogle Scholar
  157. 157.
    Reed C, Bryant R, Ibrahim AS, et al. Combination polyene-caspofungin treatment of rhino-orbital-cerebral mucormycosis. Clin Infect Dis. 2008;47:364–71.CrossRefPubMedPubMedCentralGoogle Scholar
  158. 158.
    Chitasombat MN, Kontoyiannis DP. Treatment of mucormycosis in transplant patients: role of surgery and of old and new antifungal agents. Curr Opin Infect Dis. 2016;29:340–5.CrossRefPubMedGoogle Scholar
  159. 159.
    Spellberg B, Walsh TJ, Kontoyiannis DP, Edwards J Jr, Ibrahim AS. Recent advances in the management of mucormycosis: from bench to bedside. Clin Infect Dis. 2009;48:1743–51.CrossRefPubMedPubMedCentralGoogle Scholar
  160. 160.
    Nucci M, Marr KA, Queiroz-Telles F, et al. Fusarium infection in hematopoietic stem cell transplant recipients. Clin Infect Dis. 2004;38:1237–42.CrossRefPubMedGoogle Scholar
  161. 161.
    McCarthy MW, Katragkou A, Iosifidis E, Roilides E, Walsh TJ. Recent advances in the treatment of scedosporiosis and fusariosis. J Fungi (Basel). 2018;4:E73.CrossRefGoogle Scholar
  162. 162.
    Boutati EI, Anaissie EJ. Fusarium, a significant emerging pathogen in patients with hematologic malignancy: ten years’ experience at a cancer center and implications for management. Blood. 1997;90:999–1008.PubMedGoogle Scholar
  163. 163.
    Perfect JR, Marr KA, Walsh TJ, et al. Voriconazole treatment for less-common, emerging, or refractory fungal infections. Clin Infect Dis. 2003;36:1122–31.CrossRefPubMedGoogle Scholar
  164. 164.
    Raad II, Hachem RY, Herbrecht R, et al. Posaconazole as salvage treatment for invasive fusariosis in patients with underlying hematologic malignancy and other conditions. Clin Infect Dis. 2006;42:1398–403.CrossRefPubMedGoogle Scholar
  165. 165.
    Campo M, Lewis RE, Kontoyiannis DP. Invasive fusariosis in patients with hematologic malignancies at a cancer center: 1998–2009. J Infect. 2010;60:331–7.CrossRefPubMedGoogle Scholar
  166. 166.
    Kontoyiannis DP, Torres HA, Chagua M, et al. Trichosporonosis in a tertiary care cancer center: risk factors, changing spectrum and determinants of outcome. Scand J Infect Dis. 2004;36:564–9.CrossRefPubMedGoogle Scholar
  167. 167.
    Girmenia C, Pagano L, Martino B, et al. Invasive infections caused by Trichosporon species and Geotrichum capitatum in patients with hematological malignancies: a retrospective multicenter study from Italy and review of the literature. J Clin Microbiol. 2005;43:1818–28.CrossRefPubMedPubMedCentralGoogle Scholar
  168. 168.
    Walsh TJ, Melcher GP, Rinaldi MG, et al. Trichosporon beigelii, an emerging pathogen resistant to amphotericin B. J Clin Microbiol. 1990;28:1616–22.PubMedPubMedCentralGoogle Scholar
  169. 169.
    Lamaris GA, Chamilos G, Lewis RE, Safdar A, Raad II, Kontoyiannis DP. Scedosporium infection in a tertiary care cancer center: a review of 25 cases from 1989–2006. Clin Infect Dis. 2006;43:1580–4.CrossRefPubMedGoogle Scholar
  170. 170.
    Kovacs JA, Masur H. Evolving health effects of Pneumocystis: one hundred years of progress in diagnosis and treatment. JAMA. 2009;301:2578–85.CrossRefPubMedGoogle Scholar
  171. 171.
    Azoulay EM, Roux A, Vincent F, Kouatchet A, Argaud L, Rabbat A, Mayaux J, Perez P, Frédéric PM, Nyunga M, Bruneel F, Klouche K, Djamel MM, Darmon M, Chevret S, Lemiale V, Groupe de, (GRRR-OH) RReRO-H. A multivariable prediction model for pneumocystis jirovecii pneumonia in hematology patients with acute respiratory failure. Am J Respir Crit Care Med. 2018;198:1519–26.CrossRefPubMedGoogle Scholar
  172. 172.
    Lahmer T, da Costa CP, Held J, et al. Usefulness of 1,3 beta-D-glucan detection in non-HIV immunocompromised mechanical ventilated critically ill patients with ARDS and suspected pneumocystis jirovecii pneumonia. Mycopathologia. 2017;182:701–8.CrossRefPubMedGoogle Scholar
  173. 173.
    Maschmeyer G, Helweg-Larsen J, Pagano L, et al. ECIL guidelines for treatment of Pneumocystis jirovecii pneumonia in non-HIV-infected haematology patients. J Antimicrob Chemother. 2016;71:2405–13.CrossRefPubMedGoogle Scholar
  174. 174.
    Wieruszewski PM, Barreto JN, Frazee E, et al. Early corticosteroids for pneumocystis pneumonia in adults without HIV are not associated with better outcome. Chest. 2018;154:636–44.CrossRefPubMedGoogle Scholar
  175. 175.
    Williams KM, Ahn KW, Chen M, et al. The incidence, mortality and timing of Pneumocystis jiroveci pneumonia after hematopoietic cell transplantation: a CIBMTR analysis. Bone Marrow Transplant. 2016;51:573–80.CrossRefPubMedPubMedCentralGoogle Scholar
  176. 176.
    Farmakiotis D, Kontoyiannis DP. Epidemiology of antifungal resistance in human pathogenic yeasts: current viewpoint and practical recommendations for management. Int J Antimicrob Agents. 2017;50:318–24.CrossRefPubMedGoogle Scholar
  177. 177.
    Hamdy RF, Zaoutis TE, Seo SK. Antifungal stewardship considerations for adults and pediatrics. Virulence. 2017;8:658–72.CrossRefGoogle Scholar
  178. 178.
    Ben-Ami R, Lewis RE, Raad II, Kontoyiannis DP. Phaeohyphomycosis in a tertiary care cancer center. Clin Infect Dis. 2009;48:1033–41.CrossRefPubMedGoogle Scholar
  179. 179.
    Ostrosky-Zeichner L, Pappas PG. Invasive candidiasis in the intensive care unit. Crit Care Med. 2006;34:857–63.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2020

Authors and Affiliations

  • Bruno P. Granwehr
    • 1
    Email author
  • Nikolaos V. Sipsas
    • 2
  • Dimitrios P. Kontoyiannis
    • 1
  1. 1.Department of Infectious Diseases, Infection Control and Employee HealthThe University of Texas MD Anderson Cancer CenterHoustonUSA
  2. 2.Athens Laikon General Hospital and Medical SchoolNational and Kapodistrian University of AthensAthensGreece

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