Introduction 1 6 2 3 6 4 5 In this review, we will describe the pathophysiological mechanisms and risk factors for IPA in non-neutropenic critically ill patients, limitations and advances in the diagnostic process, and alterations in treatment with antifungal therapy. A Medline/PubMed search was performed for all articles about IPA in critically ill patients in relation to risk factors, diagnosis and antifungal therapy. All publication types of human studies in the English language were searched and an extraction of relevant articles was made for the purpose of this narrative review. Pathophysiological mechanisms and risk factors Aspergillus Aspergillus Aspergillus fumigatus Aspergillus flavus, Aspergillus terreus Aspergillus niger Aspergillus nidulans 7 Aspergillus Aspergillus 8 9 10 Aspergillus 11 Aspergillus 12 13 12 14 15 16 17 Aspergillus 17 18 19 20 23 Aspergillus fumigatus 21 1 24 26 27 1 4 28 32 2 31 33 2 4 34 8 35 4 36 38 1 Aspergillus 3 31 Table 1 Risk factors for IPA in non-neutropenic critically ill patients in the ICU Risk factor Reference COPD in combination with prolonged corticosteroid use 1 24 26 High-dose systemic corticosteroids > 3 weeks (e. g. prednisone equivalent
    > 20 mg/day) 2 31 33 Chronic renal failure with RRT 8 35 Liver cirrhosis/acute hepatic failure 2 4 34 Near-drowning 4 36 38 Diabetes mellitus 2 3 31 33 COPD RRT Diagnostic features 39 1 39 Aspergillus Aspergillus 32 6 7 39 2 6 40 41 2 6 40 40 42 Aspergillus, Fusarium and Scedosporium Mucorales Mucorales Aspergillus, Fusarium and Scedosporium Aspergillus fumigatus 43 Aspergillus 44 50 51 47 3 6 52 Aspergillus Aspergillus Aspergillus 53 Aspergillus 54 57 Aspergillus 53 54 58 59 62 63 64 67 63 68 69 53 54 Aspergillus 39 53 54 70 72 3 Aspergillus Candida 73 33 74 75 79 80 81 Aspergillus 78 82 Aspergillus Aspergillus Antifungal therapy 83 84 85 86 87 88 Aspergillus 89 Aspergillus fumigatus 90 91 92 93 93 94 95 96 96 96 97 96 98 99 43 100 101 102 103 Candida Aspergillus 104 105 2 Table 2 Treatment options with antifungal drugs for IPA in critically ill patients in the ICU Setting First choice Alternatives Primary therapy of IPA Voriconazole 6 mg/kg q 12 h i. v. on day 1, then 4 mg/kg
    q 12 h i. v. Liposomal amphotericin B 3-5 mg/kg/day i. v.  or or  a Amphotericin B deoxycholate 1 mg/kg/day i. v.   or   b a b Combination therapy 106 107 108 108 109 110 113 114 115 116 Conclusion Aspergillus Aspergillus Aspergillus