Relapsing Brucellosis After Liver Transplantation in a Child

Abstract

Brucellosis is still an important infectious disease worldwide, especially in the Mediterranean area and in developing countries (1). The treatment of brucellosis is challenging because of relatively high rates of relapse and treatment failure. Obviously, relapse occurs more frequently within the first year if the full course of treatment is not completed (2). It is hypothesized that immunocompromised patients and organ transplant recipients have an increased rate of relapse (3). The hepatotoxicity of drugs used for brucellosis therapy and the drug interactions with immunosuppressive agents are important considerations in the treatment of brucellosis in immunocompromised patients and organ transplant recipients. No guidelines exist in the literature concerning the appropriate regimen and duration of therapy for brucellosis/relapsebrucellosis in these populations. In this report, we describe a child with relapsing brucellosis after liver transplantation, who was treated with two different courses of trimethoprim sulfamethoxazole (TMP-SMZ) and rifampin. A 7-year-old girl with fulminant hepatitis due to Wilson’s disease who had undergone liver transplantation 2 years ago presented to us with a fever that had lasted for more than 2 weeks. Due to the fact that the patient lives in a rural area and had consumed unpasteurized fresh cheese, she was evaluated forbrucellosis. The standard tube agglutination test and immunocapture test were positive at a titer of 1:640. The patientdid not have a history of brucellosis or similar symptoms before transplantation and the donor (mother) had no clinical or serologic evidence of brucellosis. Therefore, we postulated that the immunosuppressive therapy (tacrolimus and mycophenolate mofetil) was the predisposing factor for this infectious disease. The patient was treated with TMP-SMZ and rifampin. After treatment, her clinical and laboratory findings improved dramatically. Tacrolimus levels decreased because of increased cytochrome P450 activity due to rifampin. To prevent acute cellular rejection, the tacrolimus dosage was tripled to maintain normal drug blood levels. TMP-SMZ and rifampin were given for 12 weeks. Brucella serology was negative 4 months after treatment. One year later, the patient was evaluated for another fever of unknown origin. Although the patient was not in contact with infected animals or contaminated milk or milk products, her standard tube agglutination test and immunocapture titers were 1:320 and 1:160, respectively. TMP-SMZ and rifampin therapy were started. The patient’s response to therapy was excellent. Despite the fourfold increase in the dose of tacrolimus, normal blood levels of the drug were not achieved. To prevent acute cellular rejection during brucellosis treatment, mycophenolate mofetil, which had been previously discontinued, was restarted. Antibiotic therapy was used for a periodof 6 months to treat the brucellosis relapse. Despite fluctuations in immunosuppressive therapy, rejection and drug-induced hepatotoxicity were not observed. Antibiotic therapy was successful with no recurrence of infection during 3 years of follow-up. In conclusion, we believe that TMP-SMZ and rifampin therapy seem to be effective and reliable for the treatment of brucellosis in children after liver transplantation and that the length of treatment should be extended compared with that given in nonimmunosuppressed individuals. Ali Islek 1 Ersin Sayar1 Aygen Yilmaz1 Filiz Günseren2 Reha Artan1 1 Department of Pediatric Gastroenterology Akdeniz University Faculty of Medicine Antalya, Turkey 2 Department of Infectious Diseases and Clinical Microbiology Akdeniz University Faculty of Medicine Antalya, Turkey