Breakthrough C. parapsilosis (Cp) and C. guillermondii (Cg) Blood Stream Infections in Allogeneic Hematopoetic Stem Cell (HSC) Recipients Receiving Long Term Caspofungin (C) Therapy.

Between July 2004 and June 2006, 209 transplants were performed in our department. Only 3 patients (pts) developed candidemia (Cp n=2; Cg n=1) during that period. They were all receiving long-term C therapy. Pt 1 A 18 year-old male with severe aplastic anemia received a 1^st unrelated HSCT in January 2004 without sustained engraftment. Two months later, he developed a definite lung invasive aspergillosis (IA) successfully treated with Voriconazole (V). He received a 2^nd unrelated cord blood transplant on May 12, 2005. V was continued as secondary prophylaxis. Due to liver function test abnormalities V was switched to C on day (d) 7. On d 48, he was febrile, and a blood culture (BC) was positive (+) for Cp. C was stopped [total treatment duration (TTD)=47 d] and liposomal amphotericin B (LAB) was initiated. Due to the pt’s poor condition, the CVC was not removed. BCs remained + until d 53 (9 + BCs). He ultimately died from multi-organ failure and no engraftment on d 72. Skin and throat colonization (Co) with Cp was documented from d 39 on. Pt 2 A 46-year old male with ALL in 1^st complete remission (CR) underwent a genoidentical HSCT on May 26, 2005. Antifungal prophylaxis consisted of fluconazole (F). C was empirically introduced on d 6. Granulocytes (G) recovery occurred on d 28. He further experienced a severe acute graft-versus-host disease (GvHD) treated with increased immunosuppression (IS), and a CMV infection. On d 58–60, although he was afebrile, 3 BCs were + for Cp. C was stopped [TTD=50 d], LAB and F were initiated, and the CVC was replaced. The BCs became negative. However, the pt ultimately died from GvHD and respiratory failure of unknown origin on d 86. Skin, GI and respiratory tracks Co with Cp was documented from d 33 on. Pt 3 A 32-year old male with lymphoblastic T cell lymphoma in 1^st CR underwent an unrelated HSCT on November 10, 2005. Antifungal prophylaxis consisted of F. G recovery occurred on d 21. He experienced recurrent episodes of acute GvHD treated with increased IS and developed several episodes of CMV infections and bacteremias, including a septic shock on d 61 which lead to CVC replacement. Antifungal prophylaxis was switched to C on d 95. On d 118, he was febrile, and a single BC was + for Cg. Noteworthy, he developed a probable lung IA concomitantly. C was stopped [TTD=26 d], and V was initiated. The BCs became negative, and the IA resolved. He ultimately died from GvHD and respiratory failure on d 197. GI and respiratory racks Co with Cp was documented between d 116–123. [Table 1] The MICs of Cp and of Cg are known to be slightly higher than those of other Candida spp., which is in accordance with our results for the 2 Cp isolates. In deeply immunocompromised pts, the emergence of Candida known to have a decreased susceptibility to C could become an increasing problem. Persisting Co with such Candida spp may be an indication, in C treated pts, for switching to an alternative antifungal drug.