Multifocal osteomyelitis caused by Candida dubliniensis

Abstract

Candida dubliniensis is an emerging fungal pathogen, especially in immunodeficient patients. We report what is to the best of our knowledge the first case of multifocal osteomyelitis following disseminated infection in a patient after haematopoietic stem cell transplantation. PFGE for typing of C. dubliniensis was developed and the necessity of long-term antifungal therapy is discussed. Case reportA 19-year-old white man with congenital haemolytic anaemia of undefined genetic origin, son of consanguineous parents, was referred for peripheral blood stem cell transplantation (PBSCT) to our institution. He suffered from the sequelae of lifelong transfusion therapy including haemosiderosis of the liver (histological grade IV), pancreas and endocrine system, and showed incompliance to chelate therapy.The conditioning regimen for PBSCT consisted of radioimmunotherapy with an yttrium-90-labelled CD66 antibody for myeloablation (calculated bone marrow dose 17 Gy), and chemotherapy with fludarabine (40 mg m 22 for 4 days) and melphalan (140 mg m 22 for 1 day). In addition, antithymocyte globulin [rabbit (Sangstadt) 3.3 mg kg 21 for 3 days] was given. On day 0 the patient received peripheral blood stem cells of a 10/10 human leukocyte antigen-matched unrelated female donor. The number of CD34 + cells in the graft was 4610 6 cells kg 21 , the CD3 cell count was adapted to 1610 7 cells (kg body weight)21 . Graft versus host disease prophylaxis included cyclosporine and mycophenolate.The patient developed fever on day 21 when ceftazidime was started (100 mg kg 21 per day). On day +4 vancomycin (40 mg kg 21 per day) was added, and on day +7 ceftazidime was changed to meropenem (80 mg kg 21 per day). However, spiking temperatures continued and C-reactive protein (CrP) increased to a peak level of 298 mg l 21 on day +10. No infectious focus was detected by computed tomography (CT) scan of the thorax. However, on day +8, he developed generalized papulopustulous skin efflorescences on his trunk and extremities suggestive of septic metastases.A skin biopsy was performed at day +9 and grew Candida spp. in pure culture after 24 h of incubation on Sabouraud dextrose agar. Blue colonies on Candida ID-2 agar (bioMérieux) (Eraso et al., 2006), an abundance of chlamydospores on rice agar, and growth on Sabouraud dextrose agar at 42 u C and 45 u C, suggested Candida albicans; however, biochemical identification by API ID32 (bioMérieux) was ambiguous, suggesting Candida dubliniensis after 48 h (code 7142140015, 99.3 %, T0.67) and C. albicans after 72 h incubation (code 7347150015, 98.4 %, T0.53). In the BichroDubli latex agglutination test (Fumouze) the isolate reacted positively. By sequencing a 550 bp fragment of the internal transcribed spacer regions 1 and 2 using the primers Fungi for (59-TCCGTAGGTGAACCTGCGG-39) and Fungi rev (59-TCCTCCGCTTATTGATATGC-3 9 ) identification of C. dubliniensis was confirmed. The strain showed 99.6 % homology to the C. dubliniensis reference strain DSM 13628 (GenBank accession number DQ105856) using the BL...

Hematogenous dissemination of Candida dubliniensis causing spondylodiscitis and spinal abscess in a HIV-1 and HCV-coinfected patient

“…So far, Wellinghausen and colleagues reported the only case of multifocal osteomyelitis following disseminated C. dubliniensis infection in a patient after haematopoietic stem cell transplantation (PBSCT) [11]. In line with our case, this patient reported was severely immunocompromised and showed a delayed T-cell reconstitution mediated by a lack of sufficient numbers of CD4 T-cells (<400/μl) until 6 month after the PBSCT.…”

Radioimmunotherapy-based conditioning for hematopoietic cell transplantation in children with malignant and nonmalignant diseases

“…Our study demonstrates that radioimmunotherapy with our conjugate can be used safely to target doses of [30][31][32][33][34][35][36][37][38][39][40] Gy to the marrow in children. Because antileukemic efficacy was not the primary end point of this phase 2 study, only a few preliminary remarks with respect to this issue can be made.…”

“…Three patients experienced bacterial sepsis, and 3 had systemic fungal infections. Patients A-4 and A-5 with active aspergillosis died of multiorgan failure; patient B-7 developed multifocal osteomyelitis due to Candida dubliniensis that required transient ventilation and prolonged antimycotic therapy (published in a report from Wellinghausen et al 40 ).…”

Importance of α- and β/α-linked mannooligosaccharides in antibody response against C. dubliniensis

“…C. dubliniensis was first recognized as a human pathogen in 1995, causing oral candidiasis in severely immunocompromised HIV positive patients [1][2][3][4]. Since then, numerous clinical cases of severe systemic candidiasis caused by this organism, irrespective of HIV co-infection were reported [5][6][7][8][9][10]. Recently, an environmental reservoir of C. dubliniensis has been discovered [11].…”