Duration of prophylaxis with trimethoprim–sulfamethoxazole in patients undergoing solid organ transplantation

Abstract

Patients undergoing solid organ transplantation (SOT) are at risk for opportunistic infections. Prophylaxis with trimethoprim–sulfamethoxazole (TMP-SMX) has been widely used after SOT for the prevention of opportunistic infections, including Pneumocystis jirovecii (PCP). The drug has the added benefit of preventing infections with Toxoplasma gondii, Isospora belli, Cyclospora cayetanensis, Nocardia sp., Listeria sp., and many bacterial pathogens that may cause urinary, gastrointestinal, and respiratory infections [1]. The recommended duration of TMP-SMX prophylaxis varies among centers that perform transplant operations and is dependent upon the type of organ transplanted, perceived degree of immunosuppression, episodes of rejection, and history of any prior opportunistic infections. Most centers administer TMP-SMX prophylaxis after renal transplantation for a period of 3–6 months [1]. Lifelong prophylaxis is recommended at many centers after heart, liver, and lung transplantation [2]. The recommendations of the American Society of Transplantation (AST) are for PCP prophylaxis to be administered after SOT in centers having a prevalence of 3–5 % for 6–12 months post-transplantation. In patients with lung, small bowel transplants or those with prior PCP or chronic cytomegalovirus (CMV) disease, lifelong prophylaxis may be indicated [3]. Heart transplant recipients who are at high risk for disseminated toxoplasmosis (donor seropositive and recipient seronegative) receive prophylaxis such as pyrimethamine– sulfadiazine instead of TMP-SMX for the first 6 months [4]. We briefly present two cases of renal transplant recipients who received the ‘‘recommended duration of prophylaxis’’ but developed PCP and central nervous system (CNS) toxoplasmosis, respectively, after their TMP-SMX treatment was discontinued. A 43-year-old Hispanic woman who had end-stage renal disease secondary to hypertension had undergone living related donor renal transplantation 13 months prior to presentation. The patient received antithymocyte globulin (ATG) induction prior to the transplant. Three months after transplant, the patient was treated for an episode of acute rejection with solumedrol 500 mg intravenously for three doses. The patient received TMP-SMX for 6 months after transplant. The patient presented to our institution with a 1-month history of dry cough and dyspnea. A 7-day course of levofloxacin had not led to improvement. There were no fevers, chills, or hemoptysis. A review of her other systems was unremarkable. Physical examination was significant for coarse crackles in both lung bases. A computed tomography (CT) scan of the chest without contrast revealed bilateral interstitial opacities. At the time of presentation, the patient was receiving mycophenolate mofetil (MMF) 750 mg po bid, tacrolimus 10 mg po bid, and prednisone 80 mg po daily. The patient was admitted to the hospital and respiratory failure developed. Intubation and mechanical ventilation was required. She was treated with vancomycin, piperacillin–tazobactam, micafungin, and intravenous TMP-SMX 20 mg/kg/day in four divided doses. High doses of corticosteroids were administered. Bronchoalveolar fluid collected by flexible transbronchial bronchoscopy demonstrated PCP on silver methenamine stain. MMF was discontinued. She had P. Malhotra (&) S. D. Rai D. Hirschwerk Department of Medicine, Division of Infectious Diseases, Hofstra North Shore LIJ School of Medicine, 400 Community Drive, Manhasset, NY 11030, USA e-mail: pmalhotr@nshs.edu