title: Aspergillus osteomyelitis: epidemiology, clinical manifestations, management, and outcome.
abstract: BACKGROUND
  The epidemiology, pathogenesis, diagnosis, and management of Aspergillus osteomyelitis are not well understood.
  
  
  METHODS
  Protocol-defined cases of Aspergillus osteomyelitis published in the English literature were reviewed for comorbidities, microbiology, mechanisms of infection, clinical manifestations, radiological findings, inflammatory biomarkers, antifungal therapy, and outcome.
  
  
  RESULTS
  Among 180 evaluable patients, 127 (71%) were males. Possible predisposing medical conditions in 103 (57%) included pharmacological immunosuppression, primary immunodeficiency, and neutropenia. Seventy-three others (41%) had prior open fracture, trauma or surgery. Eighty (44%) followed a hematogenous mechanism, 58 (32%) contiguous infections, and 42 (23%) direct inoculation. Aspergillus osteomyelitis was the first manifestation of aspergillosis in 77%. Pain and tenderness were present in 80%. The most frequently infected sites were vertebrae (46%), cranium (23%), ribs (16%), and long bones (13%). Patients with vertebral Aspergillus osteomyelitis had more previous orthopedic surgery (19% vs 0%; P = 0.02), while those with cranial osteomyelitis had more diabetes mellitus (32% vs 8%; P = 0.002) and prior head/neck surgery (12% vs 0%; P = 0.02). Radiologic findings included osteolysis, soft-tissue extension, and uptake on T2-weighted images. Vertebral body Aspergillus osteomyelitis was complicated by spinal-cord compression in 47% and neurological deficits in 41%. Forty-four patients (24%) received only antifungal therapy, while 121 (67%) were managed with surgery and antifungal therapy. Overall mortality was 25%. Median duration of therapy was 90 days (range, 10-772 days). There were fewer relapses in patients managed with surgery plus antifungal therapy in comparison to those managed with antifungal therapy alone (8% vs 30%; P = 0.006).
  
  
  CONCLUSIONS
  Aspergillus osteomyelitis is a debilitating infection affecting both immunocompromised and immunocompetent patients. The most common sites are vertebrae, ribs, and cranium. Based upon this comprehensive review, management of Aspergillus osteomyelitis optimally includes antifungal therapy and selective surgery to avoid relapse and to achieve a complete response.
authors.affiliation: Weill Cornell Medical Center of Cornell University, New York, NY, USA; National and Kapodistrian University of Athens, Athens, Greece; Center for Osteoarticular Mycoses, Hospital for Special Surgery, New York, NY, USA; International Osteoarticular Mycoses Study Consortium, USA.
authors.forename: Maria N
authors.initials: MN
authors.lastname: Gamaletsou
authors.affiliation: Center for Osteoarticular Mycoses, Hospital for Special Surgery, New York, NY, USA; International Osteoarticular Mycoses Study Consortium, USA; Université Paris-Descartes, Sorbonne Paris Cité, APHP, Service des Maladies Infectieuses et Tropicales, Hôpital Necker-Enfants Malades, Centre d'Infectiologie Necker-Pasteur, Institut Imagine, Paris, France; Unité de Mycologie Moléculaire, Institut Pasteur, Paris, France.
authors.forename: Blandine
authors.initials: B
authors.lastname: Rammaert
authors.affiliation: Weill Cornell Medical Center of Cornell University, New York, NY, USA.
authors.forename: Marimelle A
authors.initials: MA
authors.lastname: Bueno
authors.affiliation: Department of Pharmacy, NIH Clinical Center, Bethesda, MD, USA.
authors.forename: Brad
authors.initials: B
authors.lastname: Moriyama
authors.affiliation: National and Kapodistrian University of Athens, Athens, Greece; Center for Osteoarticular Mycoses, Hospital for Special Surgery, New York, NY, USA; International Osteoarticular Mycoses Study Consortium, USA.
authors.forename: Nikolaos V
authors.initials: NV
authors.lastname: Sipsas
authors.affiliation: MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Dimitrios P
authors.initials: DP
authors.lastname: Kontoyiannis
authors.affiliation: Center for Osteoarticular Mycoses, Hospital for Special Surgery, New York, NY, USA; International Osteoarticular Mycoses Study Consortium, USA; Infectious Diseases Unit, 3rd Department of Pediatrics, Faculty of Medicine, Aristotle University School of Health Sciences, and Hippokration Hospital, Thessaloniki, Greece.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Roilides
authors.affiliation: Osteoarticular Reference Center, Groupe Hospitalier Diaconesses-Croix Saint-Simon, Paris, France.
authors.forename: Valerie
authors.initials: V
authors.lastname: Zeller
authors.affiliation: Infectious Disease Department, San Martino di Genoa Hospital, University of Genoa, Genoa, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Prinapori
authors.affiliation: Mycology Unit, Department of Laboratory Medicine and Pathology, Hamad Medical Corporation, Doha, Qatar.
authors.forename: Saad J
authors.initials: SJ
authors.lastname: Taj-Aldeen
authors.affiliation: Weill Cornell Medical Center of Cornell University, New York, NY, USA; Center for Osteoarticular Mycoses, Hospital for Special Surgery, New York, NY, USA; International Osteoarticular Mycoses Study Consortium, USA.
authors.forename: Barry
authors.initials: B
authors.lastname: Brause
authors.affiliation: Center for Osteoarticular Mycoses, Hospital for Special Surgery, New York, NY, USA; International Osteoarticular Mycoses Study Consortium, USA; Université Paris-Descartes, Sorbonne Paris Cité, APHP, Service des Maladies Infectieuses et Tropicales, Hôpital Necker-Enfants Malades, Centre d'Infectiologie Necker-Pasteur, Institut Imagine, Paris, France; Unité de Mycologie Moléculaire, Institut Pasteur, Paris, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Lortholary
authors.affiliation: Weill Cornell Medical Center of Cornell University, New York, NY, USA; Center for Osteoarticular Mycoses, Hospital for Special Surgery, New York, NY, USA; International Osteoarticular Mycoses Study Consortium, USA. Electronic address: thw2003@med.cornell.edu.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Walsh
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000935:Antifungal Agents / Q000627:therapeutic use; D001228:Aspergillosis / Q000175:diagnosis* / Q000453:epidemiology / Q000473:pathology / Q000628:therapy*; D001230:Aspergillus / Q000302:isolation & purification*; D002648:Child; D002675:Child, Preschool; D003646:Debridement; D003955:Diagnostic Tests, Routine / Q000379:methods; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D010019:Osteomyelitis / Q000175:diagnosis* / Q000453:epidemiology / Q000473:pathology / Q000628:therapy*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000935:Antifungal Agents
keywords: Aspergillus; Osteomyelitis