Trimethoprim‐Sulfamethoxazole as Toxoplasmosis Prophylaxis for Heart Transplant Recipients

Sir—Toxoplasmosis is a disease that is highly transmissible to D+/R- patients (i.e., patients who are seronegative for Toxoplasma gondii IgG antibodies and who receive a heart transplant from donors who are seropositive for T. gondii IgG antibodies). This disease, along with disseminated aspergillosis, is associated with the highest mortality rate attributable to an infectious complication in heart transplant recipients. For these high-risk patients, 25 mg of pyrimethamine is given as toxoplasmosis prophylaxis for 6 weeks after surgery [1–3]. We read with interest the article on heart transplantation by Montoya et al. [1]. In their extensive review of the experience with heart transplantation patients at Stanford Medical Center (Stanford, CA), there was not enough data to assess whether administration of trimethoprim-sulfamethoxazole (TMP-SMZ) for prophylaxis against Pneumocystis jiroveci (formerly known as “Pneumocystis carinii”) is sufficient to prevent toxoplasmosis in D+/R- patients. The authors concluded that, until more data are available, it seems prudent to recommend a 6-week course of pyrimethamine for these patients [1]. The problem is that pyrimethamine does not provide effective prophylaxis against P. jiroveci, so both drugs should be used simultaneously [4]. In 1994, reported experience with HIV-infected patients showed that TMP-SMZ might be useful as toxoplasmosis prophylaxis for heart transplant recipients [5]. On the basis of this experience, we decided to begin a trial of TMP-SMZ (a single double-strength tablet given 3 times each week) as prophylaxis against toxoplasmosis and P. jiroveci. Before the start date of the trial, we had followed standard recommendations and had used pyrimethamine for toxoplasmosis prophylaxis and TMP-SMZ for Pneumocystis pneumonia prophylaxis. Since 1988, a total of 315 patients have undergone heart transplantation at Hospital General Universitario Gregorio Marañón (Madrid, Spain); of these patients, 32 (10.2%) were considered to be D+/R- patients with regard to Toxoplasma IgG antibody serostatus. Twelve of the patients received pyrimethamine, 17 received TMP-SMZ, and 3 did not receive any prophylaxis. Two cases of toxoplasmosis occurred among all our heart transplant recipients; one case occurred in 1990 and was associated with pulmonary involvement, and the other case occurred in 1991 and was associated with meningitis, chorioretinitis, and myocardial involvement (the latter of which was proven by biopsy). None of the patients had been receiving any kind of prophylaxis. The first case of toxoplasmosis developed only 5 days after transplantation and before prophylaxis was started. Prophylaxis was not administered for the second case because the patient had severely impaired liver function. The 2 affected patients were treated with pyrimethamine and sulfadiazine with satisfactory outcome. The third D+/R- patient, who did not receive prophylaxis, died of noninfectious causes soon after surgery. Seroconversion occurred in only 1 patient who received pyrimethamine but was not associated with clinically evident disease. Neither seroconversion not toxoplasmosis occurred in any patient who was receiving TMP-SMZ. Very little data are available on the use of TMP-SMZ as toxoplasmosis prophylaxis for solid-organ transplant recipients. Nevertheless, in one trial [6], 126 consecutively seen cardiac transplant recipients were given this drug for either 6 months (n = 48) or 12 months (n = 78); no patient who received TMP-SMZ for either 6 months or 12 months developed either toxoplasmosis or Pneumocystis pneumonia while receiving this prophylaxis. In 1 patient, toxoplasmosis occurred 77 days after cessation of a 6-month course of prophylaxis. The 126 patients receiving TMP-SMZ were compared with a group of 143 patients who were not receiving prophylaxis, 6 of whom developed clinically evident toxoplasmosis (P =.05). It is unfortunate that no serological analyses were performed. There also are some observational data for liver transplant recipients that allow us to infer the effectiveness of TMP-SMZ in the prevention of toxoplasmosis as well as P. jiroveci infection, which was the initial indication for its use [7]. Our data support the safety and effectiveness of the use of a single tablet of TMP-SMZ (double-strength) given 3 times each week for the prevention of toxoplasmosis in D+/R- heart transplant recipients.