Successful Treatment with Caspofungin of Hepatosplenic Candidiasis Resistant to Liposomal Amphotericin B

Abstract

Sir—The recent review by Singh [1] pointed out the increase in the incidence of opportunistic fungal infections in immunocompromised hosts during the past decade. Singh [1] also described the dramatic increase in the prevalence of azole-resistant Candida species, which is probably the result of current antimicrobial prophylactic strategies. We describe a patient affected by acute myelogenous leukemia in first complete remission who developed Candida albicans sepsis with hepato-splenic abscesses that did not respond to conventional antifungal therapy (which included an azole and liposomal amphotericin B [AmBisome; Fujisawa Healthcare]) and that resolved only after prolonged administration of caspofungin. The patient was 19-year-old man who underwent autologous peripheral blood stem cell transplantation (PBSCT) after graft failure that occurred following matched unrelated donor transplantation. A few days after he underwent PBSCT, the patient had a neutrophil count of <100 cells/μL, and he developed fever and abdominal pain. Broad-spectrum antibiotic therapy was started with imipenem, vancomycin, and amikacin; after 72 h of persistent fever, liposomal amphotericin B (5 mg/kg per day) was added to the regimen. Four blood cultures yielded Pseudomonas aeruginosa that was resistant to imipenem, aminoglycosides, and quinolones, and the clinical features were initially attributed to disseminated P. aeruginosa infection. On day 10 after PBSCT, laparoscopy was performed because of worsening abdominal pain and peritonism and revealed only diffuse adenomesenteritis. Microbiological culture of peritoneal fluid showed the presence of P. aeruginosa. After prolonged antibiotic therapy, the patient's clinical condition improved, and fever resolved on day 19 after PBSCT. Meanwhile, during treatment with granulocyte colony-stimulating factor (5 μg/kg per day), hematological parameters improved; the neutropenia resolved, and examination of a bone marrow aspirate revealed complete remission of leukemia. On day 30 after PBSCT, the patient, who was still receiving liposomal amphotericin B, vancomycin, and imipenem, developed a new episode of iperpyressia, and microbiological and radiological investigations were performed. C. albicans was isolated from multiple sites: stool, a vesical catheter, and a central venous catheter. Total body CT was performed and revealed multiple and diffused low-density areas in hepato-splenic parenchyma suggestive of microabscesses and a fluid collection near the ascending colon. Ten days later (on day 40 after PBSCT), the patient underwent hemicolectomy because of increasing abdominal pain. Intestinal and hepatic biopsies and culture of biopsy specimens revealed infection with C. albicans and P. aeruginosa. The same microorganisms were isolated from peritoneal fluid cultures. Ketoconazole was empirically added to the ongoing antifungal therapy with liposomal amphotericin B, but the patient's clinical condition did not improve. On day 100 after PBSCT, fever persisted, and a CT was performed, which revealed no improvement of the hepato-splenic involvement. Therefore, the antibiotic and antifungal therapy was stopped (total dose of liposomal amphotericin B administered, 18 g), and treatment with caspofungin was initiated at a dosage of 50 mg/day after a starting dose of 70 mg. After 30 days, the fever had resolved and the clinical condition of the patient had improved. The echinocandin was administered daily for 60 days until the patient was discharged from the hospital. CT was performed 30 days after the end of the caspofungin therapy and showed that the lesions in the liver and spleen persisted in the absence of symptoms. Six months later, nuclear MRI was performed and revealed hepatosplenic areas with low signal intensity without perilesional ring on all imaging sequences; this finding was interpreted as chronic healed lesions [2, 3]. Twelve months after PBSCT, leukemia relapsed, and chemotherapy was administered; no evidence of C. albicans reactivation was detected during therapy-related profound neutropenia. Caspofungin is highly active against oral and esophageal candidiasis, and it has recently been approved by the US Food and Drug Administration for the treatment of adults with invasive aspergillosis refractory to other therapy and adults with this infection who are intolerant of other drugs [4, 5]. However, few data are available on the use of caspofungin in the treatment of chronic disseminated candidiasis [6]. In our experience, caspofungin was an effective and well-tolerated drug for the treatment of invasive candidiasis that was resistant to conventional treatment that included an azole and amphotericin B, and no side effects were detected during prolonged treatment in our patient.