A “proven” IFI was defined according to the definitions of 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 [43 (link)]. Infections during ongoing critical care treatment were rated as “probable” upon the recommendations of the EORTC/MSGERC ICU Working Group [44 (link)].
Besides clinical symptoms of an infectious disease process, fundoscopic findings or hepatosplenic lesions by computed tomography were accepted as clinical criteria. Mycological criteria were defined by positive serum 1,3-β-d-glucan in two consecutive samples or recovery of Candida in an intra-abdominal specimen obtained surgically or within 24 h from external drainage. Candidemia was defined as the isolation of Candida spp. from at least one blood culture. An isolated Candida peritonitis without candidemia was rated as invasive only in cases with histopathologic or direct microscopic examination of perioperatively sampled sterile fluid or tissue. Positive samples taken from drains more than 24 h after surgery, as well as Candida isolation from respiratory secretions, stool, skin, and wound sites, and an asymptomatic candiduria were interpreted as colonization or “possible” infection in the case of clinical signs of sepsis [33 (link),44 (link),45 (link),46 (link),47 (link)].
Detection of Aspergillus spp. was only rated as “probable” invasive aspergillosis (IA) after positive mycological evidence of Aspergillus spp. either via cytology, direct microscopy, and/or culture in a lower respiratory tract specimen, or via a galactomannan antigen index >0.5 in plasma/serum, and/or galactomannan antigen >0.8 in bronchoalveolar lavage fluid (BALF) in the case of at least one diagnostic sign in computed tomography or bronchoscopic proof of a tracheobronchitis.
In the case of an IFI, computed tomography, transesophageal echocardiography, and fundoscopy were routinely performed to detect organ involvement.
Breakthrough IFI was defined as any IFI occurring during ongoing prophylaxis, including fungi outside its spectrum of activity. The time of b-IFI occurrence was defined as the first attributable clinical sign or symptom, mycological finding, or radiological feature. A relapse IFI was defined as occurrence after treatment and being caused by the same pathogen at the same site, although dissemination can occur [48 (link)].
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