Fusarium Infection

Fusarium species is a ubiquitous fungus that causes opportunistic infections. We present 26 cases of invasive fusariosis categorized according to the European Organization for Research and Treatment of Cancer/Mycoses Study Group (EORTC/MSG) criteria of fungal infections. All cases (20 proven and 6 probable) were treated from January 2000 until January 2010. We also review 97 cases reported since 2000. The most important risk factors for invasive fusariosis in our patients were compromised immune system, specifically lung transplantation (n = 6) and hematologic malignancies (n = 5), and burns (n = 7 patients with skin fusariosis), while the most commonly infected site was the skin in 11 of 26 patients. The mortality rates among our patients with disseminated, skin, and pulmonary fusariosis were 50%, 40%, and 37.5%, respectively. Fusarium solani was the most frequent species, isolated from 49% of literature cases. Blood cultures were positive in 82% of both current study and literature patients with disseminated fusariosis, while the remaining 16% had 2 noncontiguous sites of infection but negative blood cultures. Surgical removal of focal lesions was effective in both current study and literature cases. Skin lesions in immunocompromised patients should raise the suspicion for skin or disseminated fusariosis. The combination of medical monotherapy with voriconazole or amphotericin B and surgery in such cases is highly suggested. (Medicine 2013;92: 305Y316) Abbreviations: COPD = chronic obstructive pulmonary disease, EORTC = European Organization for Research and Treatment of Cancer, FSSC = Fusarium solani species complex, G-CSF = granulocyte colony-stimulating factor, GM-CSF = granulocyte macrophage colony-stimulating factor, HSCT = hematopoietic stem cell transplant, IFICG = Invasive Fungal Infection Cooperative Group, MIC = minimum inhibitory concentration, MSG = Mycoses Study Group, MGH = Massachusetts General Hospital, NIAID = National Institute of Allergy and Infectious Diseases. INTRODUCTION Fusarium species, Aspergillus species, and Zygomycetes are the most clinically important molds. Fusarium species isolates are universally found in the environment and cause infection in both humans and plants. In humans, infection starts with the inhalation of Fusarium conidia or direct contact with materials contaminated with Fusarium conidia. Subsequently, conidia germinate and form filaments that invade the surrounding tissue when a suitable environment is offered. There is a paucity of reports describing the predisposing factors and clinical characteristics of patients with Fusarium infection. The clinical presentation of fusariosis depends on the host’s immune status. Invasive infections, such as sinusitis, pneumonia, deep cutaneous infections, and disseminated infections, present in immunocompromised patients and most commonly manifest as fever not responding to antimicrobial medications. Specifically, neutropenia, deficits in cellular immunity, induction chemotherapy for leukemia, and hematopoietic cell transplantation are considered risk factors for the development of invasive fusariosis. On the other hand, immunocompetent patients present more frequently with superficial infections, such as keratitis and onychomycosis. In the current study, we describe the clinical characteristics of 26 patients with proven or probable invasive fusariosis managed at Massachusetts General Hospital (MGH) during a 10-year period and review the literature of cases with fusariosis published since January 2000, focusing on the therapeutic approach and outcome of patients. PATIENTS AND METHODS We identified patients with fusariosis treated at MGH from January 2000 to January 2010 by searching the records of the clinical microbiology laboratory at MGH, Boston, MA. We collected data by reviewing the electronic medical records of the patients; we retrieved their baseline characteristics, underlying diseases, treatment modalities, and outcome. We categorized all patients according to the revised 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/IFICG and NIAID/MSG) into proven and probable cases. We defined disseminated fusariosis as any case with at least 1 positive blood culture or with the concurrent involvement of 2 or more noncontiguous sites. Neutropenia was defined as an absolute neutrophil count e500 cells/KL, while steroid therapy was defined as the use of prednisone or prednisone-equivalent at a dose equal to or higher than 10mg/day. For simplicity, the term ‘‘skin infection’’ was used to describe fusariosis involving the skin with or without involvement of other soft tissues. The study was approved by the institutional review board of MGH. Medicine & Volume 92, Number 6, November 2013 www.md-journal.com 305 From the Division of Infectious Diseases (MM, TA, AD, TKK, HAC, JG-B, JJC, EM), Harvard Medical School, Massachusetts General Hospital, Boston, Massachusetts; and Division of Infectious Diseases (TA, JJC, EM), Warren Alpert Medical School of Brown University, Rhode Island Hospital, Providence, Rhode Island. *These authors contributed equally to the study. Financial support and conflicts of interest: This research was supported by a National Institutes of Health grant P01 AI 083214, a R01 award AI075286 and a R21 award AI079569 to EM, and a T32 AI007061 to JJC. The authors have no conflicts of interest to disclose. Reprints: Eleftherios Mylonakis, MD, PhD, Warren Alpert Medical School of Brown University, Rhode Island Hospital, 593 Eddy Street, Providence, RI 02903 (e<mail: [email protected]). Copyright * 2013 by Lippincott Williams & Wilkins ISSN: 0025-7974 DOI: 10.1097/MD.0000000000000008 Copyright © 2013 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited. TA B LE 1. 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