Identifying Predictors of Central Nervous System Disease in Solid Organ Transplant Recipients With Cryptococcosis

• Authors: Ryosuke Osawa, University of Pittsburgh; Barbara D. Alexander, Duke University; Olivier Lortholary, Institut Pasteur; Françoise Dromer, Institut Pasteur; Graeme N. Forrest, University of Maryland; G. Lyon, Emory University; Jyoti Somani, Emory University; Krishan L. Gupta, Postgraduate Institute of Medical Education and Research; Ramon del Busto, Henry Ford Hospital; Timothy L. Pruett, University of Virginia; Costi D. Sifri, University of Virginia; Ajit P. Limaye, University of Washington; George T. John, Christian Medical College Hospital; Goran B. Klintmalm, Baylor University; Kenneth Pursell, University of Chicago; Valentina Stosor, Northwestern University; Michele I. Morris, University of Miami; Lorraine A. Dowdy, University of Miami; Patricia Munoz, Hospital General Universitario Gregorio Marañón; Andre C. Kalil, University of Nebraska; Julia Garcia-Diaz, Ochsner Clinic; Susan Orloff, Oregon Health Sciences University; Andrew A. House, University of Western Ontario; Sally Houston, Tampa General Hospital; Dannah Wray, Medical University of South Carolina; Shirish Huprikar, Mount Sinai Medical Center; Leonard B. Johnson, St. John Medical Center; Atul Humar, Toronto General Hospital; Raymund R. Razonable, Mayo Clinic; Robert A. Fisher, Virginia Commonwealth University
• Journal Title: Transplantation
• Volume: Volume 89, Number 1
• Publisher: Lippincott, Williams & Wilkins | 2010-01-15, Pages 69-74
• Type of Work: Article | Post-print: After Peer Review
• Publisher DOI: http://doi.org/10.1097/TP.0b013e3181bcda41
• Subjects: Health Sciences, Pathology; Health Sciences, Medicine and Surgery
• Keywords: Science & Technology; Life Sciences & Biomedicine; Immunology; Surgery; Transplantation; Cryptococcosis; Solid organ transplant; Central nervous system disease; HEMATOPOIETIC STEM-CELL; NEOFORMANS INFECTION; PRACTICE GUIDELINES; MENINGITIS; MANAGEMENT

Abstract

BACKGROUND: Cerebrospinal fluid (CSF) analysis is often deferred in patients with cryptococcal disease, particularly in the absence of neurologic manifestations. We sought to determine whether a subset of solid organ transplant (SOT) recipients with high likelihood of central nervous system (CNS) disease could be identified in whom CSF analysis must be performed. METHODS: Patients comprised a multicenter cohort of SOT recipients with cryptococcosis. RESULTS: Of 129 (88%) of 146 SOT recipients with cryptococcosis who underwent CSF analysis, 80 (62%) had CNS disease. In the overall study population, abnormal mental status, time to onset of cryptococcosis more than 24 months posttransplantation (late-onset disease), serum cryptococcal antigen titer more than 1:64, and fungemia were independently associated with an increased risk of CNS disease. Of patients with abnormal mental status, 95% had CNS cryptococcosis. When only patients with normal mental status were considered, three predictors (serum antigen titer >1:64, fungemia, and late-onset disease) independently identified patients with CNS cryptococcosis; the risk of CNS disease was 14% if none, 39% if one, and 94% if two of the aforementioned predictors existed (χ for trend P<0.001). CONCLUSIONS: CSF analysis should be strongly considered in SOT recipients with cryptococcosis who have late-onset disease, fungemia, or serum cryptococcal antigen titer more than 1:64 even in the presence of normal mental status.