0041-1337/03/7503-326/0 TRANSPLANTATION Vol. 75, 326–329, No. 3, February 15, 2003 Copyright © 2003 by Lippincott Williams & Wilkins, Inc. Printed in U.S.A. THE ISOLATION OF ASPERGILLUS FUMIGATUS FROM RESPIRATORY TRACT SPECIMENS IN HEART TRANSPLANT RECIPIENTS IS HIGHLY PREDICTIVE OF INVASIVE ASPERGILLOSIS 1 PATRICIA MUN ˜ OZ, 2,4 LUIS ALCAL ´ A, 2 MATILDE S ´ ANCHEZ CONDE, 2 JES ´ US PALOMO, 3 JUAN Y ´ AN ˜ EZ, 3 TERESA PELAEZ, 2 AND EMILIO BOUZA 2 Background. Prompt recognition of invasive pulmo- nary aspergillosis (IPA) after heart transplantation is essential for achieving a successful outcome. How- ever, the significance of the isolation of Aspergillus from respiratory specimens in heart transplant recip- ients is not established. Methods. From 1990 to 1999, we analyzed first respi- ratory specimens with Aspergillus spp. growth from heart transplant patients in our institution. All speci- mens were cultured in both fungal and conventional media. Diagnosis of proven and probable IPA or colo- nization was made according to criteria of the Myco- ses Study Group. Results. During the 10-year study period, Aspergillus spp. was recovered from 30 episodes from 27 heart transplant recipients (incidence: 10.5%). Three epi- sodes were classified as indeterminate and were in- cluded in the analysis in a double way, first consider- ing them as true positives and afterward as true negatives, so ranges were obtained. After applying di- agnostic criteria, 18 of 30 episodes were proven or probable IPA, and 9 episodes were colonizations. Ac- cordingly, 7 to 8% of heart transplant recipients suf- fered an IPA, and the overall positive predictive value (PPV) was 60% to 70%. When analyzed by species, the PPV of recovering Aspergillus fumigatus was 78% to 91%, whereas it was 0% for other species. The PPV increased to 88% to 100% when A. fumigatus was re- covered from a respiratory specimen other than spu- tum and decreased to 50% to 67% when it was recov- ered from sputum. The sensitivities of fungal and conventional media for the recovery of Aspergillus spp. were 95% to 100% and 33% to 38%, respectively. Conclusion. The isolation of A. fumigatus from the respiratory tract of a heart transplant recipient is highly predictive of invasive aspergillosis. Invasive pulmonary aspergillosis (IPA) is the most com- mon invasive mycosis after heart transplantation (HT) and affects 3.3% to 14% of patients (1-6). Prompt recognition of this fungal infection is essential for achieving a successful outcome with intensive antifungal therapy. However, both clinical symptoms and radiologic manifestations may be non- specific at early stages of the disease (7,8). The isolation of Aspergillus species from nonsterile respiratory samples may indicate invasive infection, colonization, or laboratory con- tamination and therefore make treatment of symptomatic transplant recipients difficult (9-14). The positive predictive value (PPV) of the isolation of As- pergillus from sputum has been described in liver (41%–72%) and kidney (30%– 45%) transplant recipients (1) but not after HT. Our aims were to analyze the incidence of Aspergillus spp. isolation from symptomatic heart transplant recipients and the PPV for IPA of the first positive respiratory specimen of each episode. We also considered the influence of the type of sample Aspergillus spp. was recovered from, the Aspergil- lus species, and the culture media used. MATERIALS AND METHODS Ours is a 1,750-bed teaching institution with approximately 50,000 admissions per year. Our period of study was January 1990 to December 1999. During this time, 258 patients underwent HT in our hospital. The general methodology of the transplantation was standard and has been described elsewhere (15). In summary, the immunosuppressive regimen consisted of induction with three doses of antithymocyte globulin and maintenance with cyclosporine, azathioprine, and cor- ticosteroids until 1998. Since then, mycophenolate mofetil and ta- crolimus have been more common. Doses of cyclosporine were set to achieve a plasma level of 200 to 400 ng/mL (determined by immu- noassay) during the first month after transplantation. Thereafter, levels of 100 to 200 ng/mL were targeted. Rejection episodes were diagnosed by endomyocardial biopsy and treated with intravenous boluses of methylprednisolone (250 –500 mg/day) for 3 days. Antithy- mocyte globulin was administered when resistance to steroids was observed and in patients with severe allograft dysfunction. We analyzed the significance of Aspergillus spp. recovered from the respiratory tract of heart transplant patients for the first time. It is important to underline that cultures were ordered under clinical suspicion of infection and not for surveillance. Sputum samples were obtained from all the patients able to produce them, and different invasive techniques were used depending on the type of infiltrate, availability of personnel to perform a bronchoscopy, and clinical situation. All patients were prospectively followed up by at least one infec- tious disease physician who collaborated in the diagnosis and treat- ment of all invasive aspergillosis episodes. All samples with even a single colony of Aspergillus from a heart transplant recipient were retrieved from our database and organized by date and by patient. Cultures were classified into different episodes in patients who had sets of positive cultures separated by at least 6 months. 1 This article was partially presented at the 40th Interscience Conference in Antimicrobial Agents and Chemotherapy, Toronto, Ontario, Canada, September 17 to 20, 2000. 2 Department of Clinical Microbiology and Infectious Diseases, Hospital General Universitario “Gregorio Maran ˜ ´ on,” Madrid, Spain. 3 Department of Cardiology, Hospital General Universitario “Gre- gorio Maran ˜ ´ on,” Madrid, Spain. 4 Address correspondence to: Patricia Mun ˜ oz, M.D., Ph.D., Hospi- tal General Universitario “Gregorio Maran ˜ ´ on,” Servicio de Microbio- log ´ ia y Enfermedades Infecciosas, Doctor Esquerdo 46, 28007 Ma- drid, Spain. E-mail: pmunoz@micro.hggm.es. Received 8 February 2002. Revision Requested 8 July 2002. Accepted 2 October 2002. 326 DOI: 10.1097/01.TP.0000044358.99414.B8