This article has been corrected. The original version (PDF) is appended to this article as a Supplement. Invasive aspergillosis (IA) is associated with poor outcomes in patients with hematologic malignancies (HMs) and hematopoietic cell transplantation (HCT). Small studies suggest a role for combination antifungal therapy. To assess the safety and efficacy of voriconazole and anidulafungin compared with voriconazole monotherapy for treatment of IA. Randomized, double-blind, placebo-controlled multicenter trial. (ClinicalTrials.gov: NCT00531479) 93 international sites. 454 patients with HM or HCT and suspected or documented IA were randomly assigned to treatment with voriconazole and anidulafungin or placebo. Primary analysis was done in the modified intention-to-treat population of 277 patients in whom IA was confirmed. The primary outcome was 6-week mortality; secondary outcomes included 12-week mortality, mortality in major subgroups, and safety measures. Mortality rates at 6 weeks were 19.3% (26 of 135) for combination therapy and 27.5% (39 of 142) for monotherapy (difference, −8.2 percentage points [95% CI, −19.0 to 1.5]; P = 0.087). Secondary mortality outcomes favored combination therapy. Multivariable regression analysis suggested that maximum galactomannan value, Karnofsky score, and baseline platelet count had prognostic significance. Most patients (218 of 277 [78.7%]) had IA diagnosis established by radiographic findings and maximum galactomannan positivity. In a post hoc analysis of this dominant subgroup, 6-week mortality was lower in combination therapy than monotherapy (15.7% [17 of 108] vs. 27.3% [30 of 110]; difference, −11.5 percentage points [CI, −22.7 to −0.4]; P = 0.037). Safety measures, including hepatotoxicity, were not different. Mortality at 6 weeks was higher than expected, and the difference in mortality was lower than expected, which reduced power to detect a treatment effect. Enrollment was restricted to patients with HM or HCT, which limited generalizability. Compared with voriconazole monotherapy, combination therapy with anidulafungin led to higher survival in subgroups of patients with IA. Limitations in power preclude definitive conclusions about superiority. Pfizer.

Infectious complications after allogeneic haematopoietic stem cell transplantation (allo-HCT) remain a clinical challenge. This is a guideline provided by the AGIHO (Infectious Diseases Working Group) of the DGHO (German Society for Hematology and Medical Oncology). A core group of experts prepared a preliminary guideline, which was discussed, reviewed, and approved by the entire working group. The guideline provides clinical recommendations for the preventive management including prophylactic treatment of viral, bacterial, parasitic, and fungal diseases. The guideline focuses on antimicrobial agents but includes recommendations on the use of vaccinations. This is the updated version of the AGHIO guideline in the field of allogeneic haematopoietic stem cell transplantation utilizing methods according to evidence-based medicine criteria.

Invasive fusariosis (IF) is a leading mycosis affecting immunocompromised patients [¹ x 1 Nucci, M and Anaissie, E. Fusarium infections in immunocompromised patients. Clin Microbiol Rev. 2007; 20: 695–704 Crossref | PubMed | Scopus (454) | Google Scholar See all References ]. The disease is usually invasive and disseminated, affecting mostly neutropenic patients with acute leukaemia [² x 2 Nucci, M, Anaissie, EJ, Queiroz-Telles, F et al. Outcome predictors of 84 patients with hematologic malignancies and Fusarium infection. Cancer. 2003; 98: 315–319 Crossref | PubMed | Scopus (169) | Google Scholar See all References ] or patients with severe T-cell immunodeficiency, especially haematopoietic cell transplant recipients receiving corticosteroids for the treatment of severe graft-versus-host disease (GVHD) [³ x 3 Nucci, M, Marr, KA, Queiroz-Telles, F et al. Fusarium infection in hematopoietic stem cell transplant recipients. Clin Infect Dis. 2004; 38: 1237–1242 Crossref | PubMed | Scopus (208) | Google Scholar See all References ]. Most infections in humans are caused by Fusarium solani species complex and Fusarium oxysporum species complex [¹ x 1 Nucci, M and Anaissie, E. Fusarium infections in immunocompromised patients. Clin Microbiol Rev. 2007; 20: 695–704 Crossref | PubMed | Scopus (454) | Google Scholar See all References ].

Invasive zygomycosis accounts for a significant proportion of all invasive fungal diseases (IFD), but clinical data on the clinical course and treatment response are limited. Fungiscope™—A Global Rare Fungal Infection Registry is an international university-based case registry that collects data of patients with rare IFD, using a web-based electronic case form at www.fungiscope.net. Forty-one patients with invasive zygomycosis from central Europe and Asia were registered. The most common underlying conditions were malignancies (n = 26; 63.4%), diabetes mellitus (n = 7; 17.1%) and solid organ transplantation (n = 4; 9.8%). Diagnosis was made by culture in 28 patients (68.3%) and by histology in 26 patients (63.4%). The main sites of infection were the lungs (n = 24; 58.5%), soft tissues (n = 8; 19.5%), rhino-sinu-orbital region (n = 8; 19.5%) and brain (n = 6; 14.6%). Disseminated infection of more than one non-contiguous site was seen in six patients (14.6%). Mycocladus corymbifer was the most frequently identified species (n = 10, 24.4%). A favourable response was observed in 23 patients (56.1%). Overall survival was 51.2% (n = 21). At diagnosis, four patients (9.8%) were on continuous antifungal prophylaxis with itraconazole (n = 1; 2.4%) or posaconazole (n = 3; 7.3%). Initial targeted treatment with activity against zygomycetes was administered to 34 patients (82.9%). Liposomal amphotericin B was associated with improved response (P = 0.012) and survival rates (P = 0.004). Pathogen distribution and, consequently, drug susceptibility seem to vary across different geographic regions. Furthermore, protection from invasive zygomycosis for patients on posaconazole prophylaxis is not absolute. Our findings indicate that the use of liposomal amphotericin B as first-line treatment for patients diagnosed with zygomycoses merits further investigation, preferably in the form of a clinical trial.