Breakthrough C. parapsilosis (Cp) and C. guillermondii (Cg) Blood Stream Infections in Allogeneic Hematopoetic Stem Cell (HSC) Recipients Receiving Long Term Caspofungin (C) Therapy.
Authors: Kabbara Nabil , Lacroix Claire , Robin Marie , Rocha Vanderson , de Latour Regis Peffault , Esperou Helene , Devergie Agnes , Gluckman Eliane , Socie Gerard , Ribaud Patricia 
Published: October 2019

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 1st 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 2nd 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 1st 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 1st 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.

Minimal Inhibitory Concentrations (MICs, μg/ml) of first blood isolates (EUCAST) C. parapsilosis (pt1) C. parapsilosis (pt2) C. guillermondii (pt3) Amphotericin B 0.03 0.03 ≤0.015 Fluorocytosine 0.5 ≤0.125 ≤0.125 Fluconazole 2 1 8 Itraconazole 0.06 0.06 0.5 Voriconazole 0.03 0.03 0.06 Caspofungin 0.5 0.125 0.06