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Opportunistic Infections in Heart Transplant Patients: The Role of Thymoglobulin and Corticosteroid Dosing

Nicolasora, Nelson P. MD*; Malani, Preeti N. MD*†∥; Riddell, James IV MD*; Dorsch, Michael P. PharmD; Reaume, Kristen T. PharmD; Dyke, David B. MD; Pagani, Francis D. MD, PhD§; Aaronson, Keith D. MD; Kaul, Daniel R. MD*

Infectious Diseases in Clinical Practice: September 2010 - Volume 18 - Issue 5 - p 318-323
doi: 10.1097/IPC.0b013e3181e9b7e8
Original Articles

Background: We observed an outbreak of severe opportunistic infections (OIs) among heart transplant patients coincident with a change from muromonab-CD3 (OKT3) to rabbit anti-thymocyte globulin (Thymoglobulin) for induction immunosuppression. The purpose of this study was to describe the outbreak and, because Thymoglobulin use alone would not be expected to result in such a high rate of OIs, to assess for other risk factors.

Methods: Based on the clustering of cases, the outbreak period was defined as May 2005 to December 2006. The preoutbreak period was defined as January 2003 to April 2005. Clinical and demographic data were collected on all patients who received a transplant during this period, and occurrence of OI was tracked on 14 consecutive patients who received a transplant after resolution of the outbreak.

Results: One hundred two patients underwent heart transplantation during the period studied. Thirteen patients developed severe OIs: 10 during the outbreak period (rate, 10/48 [21%]), 2 before the outbreak (2/50 [4%]), and 1 (1/14 [7%]) in limited follow-up after the outbreak. Opportunistic infections included aspergillosis, nocardiosis, disseminated histoplasmosis, cryptococcal meningitis, mucormycosis, and cytomegalovirus syndrome. In multivariate analysis, patients who received a transplant during the outbreak had a higher risk of OI and were more likely to receive Thymoglobulin than patients who received a transplant before the outbreak. Maintenance prednisone dosing in our patients was higher than in other published series of solid organ transplant recipients treated with Thymoglobulin.

Conclusions: Thymoglobulin induction combined with higher maintenance dosing of prednisone may result in a high rate of serious OIs in heart transplant recipients.

From the *Division of Infectious Diseases, Department of Internal Medicine, †Division of Geriatric Medicine, ‡Division of Cardiology, and §Division of Cardiac Surgery, Department of Surgery, University of Michigan Medical School, Ann Arbor, MI; ∥Geriatric Research Education and Clinical Center (GRECC), Veterans Affairs Ann Arbor Healthcare System and ¶College of Pharmacy, University of Michigan, Ann Arbor, MI.

Correspondence to: Daniel R. Kaul, MD, Division of Infectious Diseases, University of Michigan Medical Center, 3120 Taubman Center, Box 0378, Ann Arbor, MI 48109-0378. E-mail:

The authors have no funding or conflicts of interest to disclose.

© 2010 Lippincott Williams & Wilkins, Inc.