RENAL TOXICITY DUE TO INHALED TOBRAMYCIN IN LUNG TRANSPLANT RECIPIENTS To the Editor: We read with great interest the article by Ahya et al 1 related to renal toxicity caused by inhaled tobramycin. We want to report our experience with 2 lung trans- plantation patients who developed renal failure when nebulized tobramycin was started. A 63-year-old man underwent bilateral lung transplan- tation in June 2001 because of idiopathic pulmonary fibrosis. The immunosuppression protocol included cyclosporine, mycophenolate, and steroids. His serum creatinine level was 2.5 mg/dl secondary to calcineurin inhibitor nephrotoxicity. The patient had multiple bronchial infections caused by Pseudomonas aerugi- nosa, so inhaled tobramycin was started at a dose of 300 mg twice daily. Ten days after commencing this therapy, his creatinine level rose to 3.5 mg/dl despite cyclosporine adjustments. Tobramycin toxicity was sus- pected; therefore, the drug was withdrawn. Within 1 week the creatinine level decreased to the previous value without any other therapeutic modification. The second case was a 55-year-old man who received a transplant in October 1999 because of emphysema. Bronchiolitis obliterans was diagnosed, and the immu- nosuppression regime was switched to tacrolimus, my- cophenolate, and steroids. Inhaled tobramycin was started because of repeated bronchial infections by P. aeruginosa. His baseline creatinine level was 1.4 to 1.6 mg/dl. After starting tobramycin, the creatinine value rose to 4 mg/dl, potassium levels reached 7 mEq/liter, and the patient required temporary hemodialysis. Other conditions that could induce renal failure were ex- cluded, and renal function was recovered 15 days after tobramycin was withdrawn. Renal toxicity caused by inhaled tobramycin could be more frequent than previously thought, especially in patients with previous renal function impairment. The concomitant administration of other nephrotoxic drugs, such as calcineurin inhibitors or anti-virals, could be confounding factors and could also favor aminoglycoside renal toxicity. The safety results of tobramycin use in cystic fibrosis patients 2 cannot be extrapolated to patients who re- ceive a lung transplant. In their article, Ahya et al 1 observed that systemic absorption could provoke toxic effects such as nephrotoxicity and ototoxicity. Our data, together with a case reported in cardiac transplan- tation, 3 could support this issue, as renal function seriously deteriorated when inhaled tobramycin was administered. Although tobramycin levels in the blood were not measured in our patients, other causes of renal failure were excluded and there was a clear relationship between beginning tobramycin inhalation and the increase in creatinine levels. In each case, renal function improved after the withdrawal of tobramycin. In the light of these clinical experiences, pharmacoki- netic studies of inhaled tobramycin in lung transplant are warranted. Rosalía Laporta, MD Piedad Ussetti, MPhd M. Cruz Carreño, MPhd Lung Transplant Unit Hospital Universitario Clínica Puerta de Hierro Madrid, Spain REFERENCES 1. Ahya VN, Doyle AM, Mendez JD, et al. Renal and vestibular toxicity due to inhaled tobramycin in a lung transplant recipient. J Heart Lung Transplant 2005;24:932–5. 2. Geller D, Pitlick W, Nardella P, Tracewell W, Ramsey B. Pharmacokinetics and bioavailability of aerosolized tobra- mycin in cystic fibrosis. Chest 2002;122:219 –26. 3. Kahler DA, Schowengerdt KO, Fricker FK, Mansfield M, Visner GA, Faro A. Toxic serum trough concentrations after administration of nebulized tobramycin. Pharmaco- therapy 2003;23:543–5. ADMINISTRATION OF RABBIT ANTI-THYMOCYTE GLOBULIN DURING CARDIOPULMONARY BYPASS: A NOVEL APPROACH TO THE HIGHLY SENSITIZED CARDIAC TRANSPLANT PATIENT To the Editor: Sensitization, the presence of circulating pre-formed antibodies, poses a dilemma for cardiac transplant recipients, particularly multiparous women, re-opera- tive sternotomy patients, those exposed to transfusions, and those supported with left ventricular assist devices (LVADs). This patient population faces longer waiting times, lower survival to transplant, and a higher incidence of rejection. The most common approach to treating this problem involves immunomodulation with intravenous immunoglobulin (IVIg) and cyclophosphamide. 1 This reg- imen is given pre-operatively while awaiting transplant, followed by monthly doses of cyclophosphamide, as an adjunct to standard immunosuppressive therapy. Signifi- cant toxicity may occur with this approach. Thymoglobulin (Sangstat, Cambridge, MA) is a pasteur- ized polyclonal rabbit anti-thymocyte immunoglobulin. Although its exact mechanism of action is unknown, Thymoglobulin is thought to induce immunosuppression via T-cell depletion and immunomodulation; multiple an- tibodies attack many T-cell receptor sites. FDA-approved use of Thymoglobulin in the USA is for acute rejection in doi:10.1016/j.healun.2005.12.002 608 LETTERS TO THE EDITOR