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      Osteoarticular Infections Caused by Non- Aspergillus Filamentous Fungi in Adult and Pediatric Patients : A Systematic Review

      review-article
      , PhD, DABMM, , MD, PhD, , MD, PhD, MPH, , MD, PhD, , MD, , MD, PhD, , MD, ScD, , MD, , MD, , MD, PhD, , MD, PhD
      Medicine
      Wolters Kluwer Health

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          Abstract

          Osteoarticular mycoses due to non- Aspergillus moulds are uncommon and challenging infections.

          A systematic literature review of non- Aspergillus osteoarticular mycoses was performed using PUBMED and EMBASE databases from 1970 to 2013.

          Among 145 patients were 111 adults (median age 48.5 [16–92 y]) and 34 pediatric patients (median age 7.5 [3–15 y]); 114 (79.7%) were male and 88 (61.9%) were immunocompromised. Osteomyelitis was due to direct inoculation in 54.5%. Trauma and puncture wounds were more frequent in children (73.5% vs 43.5%; P = 0.001). Prior surgery was more frequent in adults (27.7% vs 5.9%; P = 0.025). Vertebral (23.2%) and craniofacial osteomyelitis (13.1%) with neurological deficits predominated in adults. Lower limb osteomyelitis (47.7%) and knee arthritis (67.8%) were predominantly seen in children. Hyalohyphomycosis represented 64.8% of documented infections with Scedosporium apiospermum (33.1%) and Lomentospora prolificans (15.8%) as the most common causes. Combined antifungal therapy and surgery was used in 69% of cases with overall response in 85.8%. Median duration of therapy was 115 days (range 5–730). When voriconazole was used as single agent for treatment of hyalohyphomycosis and phaeohyphomycosis, an overall response rate was achieved in 94.1% of cases.

          Non- Aspergillus osteoarticular mycoses occur most frequently in children after injury and in adults after surgery. Accurate early diagnosis and long-course therapy (median 6 mo) with a combined medical-surgical approach may result in favorable outcome.

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          Most cited references126

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          Infections caused by Scedosporium spp.

          Scedosporium spp. are increasingly recognized as causes of resistant life-threatening infections in immunocompromised patients. Scedosporium spp. also cause a wide spectrum of conditions, including mycetoma, saprobic involvement and colonization of the airways, sinopulmonary infections, extrapulmonary localized infections, and disseminated infections. Invasive scedosporium infections are also associated with central nervous infection following near-drowning accidents. The most common sites of infection are the lungs, sinuses, bones, joints, eyes, and brain. Scedosporium apiospermum and Scedosporium prolificans are the two principal medically important species of this genus. Pseudallescheria boydii, the teleomorph of S. apiospermum, is recognized by the presence of cleistothecia. Recent advances in molecular taxonomy have advanced the understanding of the genus Scedosporium and have demonstrated a wider range of species than heretofore recognized. Studies of the pathogenesis of and immune response to Scedosporium spp. underscore the importance of innate host defenses in protection against these organisms. Microbiological diagnosis of Scedosporium spp. currently depends upon culture and morphological characterization. Molecular tools for clinical microbiological detection of Scedosporium spp. are currently investigational. Infections caused by S. apiospermum and P. boydii in patients and animals may respond to antifungal triazoles. By comparison, infections caused by S. prolificans seldom respond to medical therapy alone. Surgery and reversal of immunosuppression may be the only effective therapeutic options for infections caused by S. prolificans.
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            Candida osteomyelitis: analysis of 207 pediatric and adult cases (1970-2011).

            The epidemiology, pathogenesis, clinical manifestations, management, and outcome of Candida osteomyelitis are not well understood.
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              Voriconazole in the treatment of aspergillosis, scedosporiosis and other invasive fungal infections in children.

              To describe the safety and efficacy of voriconazole in children treated within the compassionate release program. Children received voriconazole on a compassionate basis for treatment of an invasive fungal infection if they were refractory to or intolerant of conventional antifungal therapy. Voriconazole was administered as a loading dose of 6 mg/kg every 12 h i.v. on Day 1 followed by 4 mg/kg every 12 h i.v. thereafter. When feasible the route of administration of voriconazole was changed from i.v. to oral (100 or 200 mg twice a day for patients weighing or = 40 kg, respectively). Outcome was assessed by investigators at the end of therapy or at the last visit as success (complete or partial response), stable infection, or failure, based on protocol-defined criteria. Sixty-nine children (ages 9 months to 15 years; median, 7 years) received voriconazole; 58 had a proven or probable fungal infection. Among these 58 patients 27 had hematologic malignancies and 13 had chronic granulomatous disease as the most frequent underlying conditions. Forty-two patients had aspergillosis, 8 had scedosporiosis, 4 had invasive candidiasis and 4 had other invasive fungal infections. The median duration of voriconazole therapy was 93 days. At the end of therapy 26 patients (45%) had a complete or partial response. Four patients (7%) had a stable response, 25 (43%) failed therapy and 4 (7%) were discontinued from voriconazole because of intolerance. Success rates were highest in patients with chronic granulomatous disease (62%) and lowest in patients with hematologic malignancies (33%). Two patients experienced treatment-related serious adverse events (ulcerated lips with rash, elevated hepatic transaminases or bilirubin). A total of 23 patients had voriconazole-related adverse events, 3 (13%) of which caused discontinuation of voriconazole therapy. The most commonly reported adverse events included elevation in hepatic transaminases or bilirubin (n = 8), skin rash (n = 8), abnormal vision (n = 3) and a photosensitivity reaction (n = 3). These data support the use of voriconazole for treatment of invasive fungal infections in pediatric patients who are intolerant of or refractory to conventional antifungal therapy.
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                Author and article information

                Journal
                Medicine (Baltimore)
                Medicine (Baltimore)
                MEDI
                Medicine
                Wolters Kluwer Health
                0025-7974
                1536-5964
                December 2015
                18 December 2015
                : 94
                : 50
                : e2078
                Affiliations
                From the Mycology Unit, Microbiology Division, Department of Laboratory Medicine and Pathology, Hamad Medical Corporation, Doha, Qatar (SJT-A); Center for Osteoarticular Mycoses, Hospital for Special Surgery (SJT-A, BR, MG, NVS, ER, AOM, VP, TJW, OL); International Osteoarticular Mycoses Study Consortium, NY (SJT-A, BR, MG, NVS, ER, AOM, VP, TJW, OL); Weill Cornell Medical College, Doha, Qatar (SJT-A); Université Paris-Descartes, Sorbonne Paris Cité, APHP, Service des Maladies Infectieuses et Tropicales, Hôpital Necker-Enfants Malades, Centre d’Infectiologie Necker-Pasteur, Institut Imagine (BR, OL); Institut Pasteur, Mycology Molecular Unit, Paris, France (BR, OL); Transplantation-Oncology Infectious Diseases Program, Department of Medicine, Weill Cornell Medical Center of Cornell University (MG, AOM, VP, TJW); Pediatrics, and Microbiology & Immunology, Weill Cornell Medical Center of Cornell University, New York, NY (MG, NVS, TJW); National and Kapodistrian University of Athens, Athens, Greece (MG, NVS); Osteoarticular Reference Center, Groupe Hospitalier Diaconesses-Croix Saint-Simon, Paris, France (VZ); Infectious Diseases Unit, 3rd Department of Pediatrics, Faculty of Medicine, Aristotle University, School of Health Sciences, and Hippokration Hospital, Thessaloniki, Greece (ER); and MD Anderson Cancer Center, Houston, TX (DPK).
                Author notes
                Correspondence: Saad J. Taj-Aldeen, Mycology Unit Microbiology Division, Department of Laboratory Medicine and Pathology, Hamad Medical Corporation, P.O. Box 3050, Doha, Qatar (e-mail: saadtaj51@ 123456gmail.com ).
                Article
                02078
                10.1097/MD.0000000000002078
                5058889
                26683917
                829a164f-ccd8-4a3d-9593-e35e61bed820
                Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.

                This is an open access article distributed under the Creative Commons Attribution License 4.0, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. http://creativecommons.org/licenses/by/4.0

                History
                : 14 May 2015
                : 10 September 2015
                : 24 October 2015
                Categories
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                Research Article
                Systematic Review and Meta-Analysis
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