FatalCandida dubliniensisSepticemia in a Patient with AIDS

SIR—Candida dubliniensis is a recently described, germ tube–producing yeast. It has been identified as a cause of oral candidiasis in HIV-infected persons [1]. Although most isolates show in vitro susceptibility to commonly used antifungal agents, fluconazole-resistant strains have been recovered from oropharyngeal specimens from HIV-infected persons. In vitro studies have proven that fluconazole-resistant strains can be generated from susceptible isolates by exposure to fluconazole [2]. There are increasing reports of C. dubliniensis fungemia in immunocompromised hosts [3–5]. To date, all of the isolates from such cases were fluconazole susceptible. In addition, there have been no documented cases of death attributed to C. dubliniensis infection. I describe a patient with acquired immunodeficiency syndrome (AIDS) who is, to my knowledge, the sentinel case of mortality attributable to C. dubliniensis infection. A 33-year-old man with AIDS (CD4 cell count, 100 cells/mL; viral load, 309,000 copies/mL) presented with a 3-day history of fever, abdominal pain, jaundice, and decreasing urine output. His medical history was notable for multiple episodes of oral candidiasis, which had been treated successfully with fluconazole. Three weeks before presentation, the patient had been hospitalized at our institution with methicillin-susceptible Staphylococcus aureus bacteremia and tricuspid valve endocarditis, secondary to intravenous drug use. A peripherally inserted central catheter (PICC) had been placed, and the patient had been transferred to a subacute care facility to complete a 4-week course of vancomycin therapy. He was not treated with any antiretroviral medications. At admission, the patient's medications included vancomycin. Allergies included a rash caused by penicillin. The patient's temperature was 39.2°C, blood pressure was 100/50 mm Hg, heart rate was 112 beats/min, and respiratory rate was 24 breaths/min. Physical examination revealed icteric sclerae and skin, a harsh systolic murmur, diffuse abdominal tenderness, and an intact PICC. The WBC count was 8200 cells/mm3 (83% neutrophils), the hemoglobin level was 7.6 g/dL, the platelet count was 53,000 platelets/mm3, the blood urea nitrogen level was 46 mg/dL, the creatinine level was 5.7 mg/dL, and the bilirubin level was 6.1 mg/dL. Cultures of blood obtained at admission both from a peripheral vein and from the PICC grew germ tube–producing yeast. The PICC was removed and fluconazole (400 mg/day) was added to the patient's treatment regimen on day 2 of hospitalization. Vancomycin therapy was continued. The patient's multiorgan dysfunction progressed, reflected by worsening anemia and thrombocytopenia, disseminated intravascular coagulation, anuric renal failure, deteriorating hepatic function, severe metabolic acidosis, and protracted hypotension. Multiple blood cultures grew germ tube–producing yeast. Results of a fluorescent in situ hybdrization assay indicated the yeast isolates were not Candida albicans. Serum samples tested negative for cryptococcus antigen. An echocardiogram showed no new valvular vegetations. Fluconazole was changed to caspofungin on day 3 of hospitalization. The yeast was C. dubliniensis. In vitro drug-susceptibility studies showed that the isolates were susceptible to fluconazole (MIC, 0.5 µg/mL). The patient died on day 8 of multi-organ failure due to C. dubliniensis septicemia. Autopsy findings confirmed disseminated C. dubliniensis infection with hepatic, renal, peritoneal, and bone marrow involvement. To my knowledge, this is the first reported fatality due to C. dubliniensis fungemia. Clinical vigilance, aggressive and early diagnosis, and appropriate therapy are essential to guard against this emerging pathogen. Prior azole exposure and the ability of C. dubliniensis to develop induced fluconazole resistance should also be considered when choosing antimicrobial treatment for C. dubliniensis fungemia in immunocompromised patients. Potential conflicts of interest. K.M.C-T.: no conflicts.