Rhodotorula mucilaginosa catheter-related fungemia in a patient with sickle cell disease: case presentation and literature review.Abstract: Rhodotorula mucilaginosa (formerly Rhodotorula rubra) is a ubiquitous, environmental, urease-positive yeast that does not ferment sugars and can assimilate various carbohydrates. Characterized by the salmon-pink to coral-red color of its colonies, Rhodotorula mucilaginosa can disseminate and cause significant disease. We present a case of sustained Rhodotorula mucilaginosa catheter-related fungemia in a patient with sickle cell anemia sickle cell anemia n. A chronic, usually fatal inherited form of anemia marked by crescent-shaped red blood cells, occurring almost exclusively in Blacks, and characterized by fever, leg ulcers, jaundice, and episodic pain in the joints. who refused removal of the implanted port. The patient remained clinically stable, with blood cultures persistently growing Rhodotorula mucilaginosa, despite appropriate antifungal therapy. An extensive literature review revealed a wide range of clinical manifestations in immunocompromised immunocompromised /im·mu·no·com·pro·mised/ (-kom´pro-mizd) having the immune response attenuated by administration of immunosuppressive drugs, by irradiation, by malnutrition, or by certain disease processes (e.g., cancer). patients. Susceptibility patterns to different antifungal agents antifungal agents, n.pl agents that inhibit, control, or kill fungi. The most common yeastlike fungus occurring in or near the oral cavity is C. albicans. and therapeutic considerations are thoroughly discussed. Rhodotorula mucilaginosa can be a significant, recalcitrant pathogen in immunocompromised patients and prompt treatment should be instituted. Key Words: Rhodotorula mucilaginosa (formerly rubra), catheter-related fungemia, sickle-cell disease ********** Rhodotorula mucilaginosa is a ubiquitous yeast that in the appropriate setting may disseminate and cause significant disease. A few cases of catheter-related R mucilaginosa fungemia have been reported thus far. We report a case of sustained, catheter-related R mucilaginosa fungemia in a patient with sickle cell anemia and review the medical literature regarding this organism. Case Report A 31-year-old man with a history of sickle cell anemia presented to the emergency department with a sickle cell crisis sickle cell crisis, n an acute, episodic condition that occurs in children with sickle cell anemia. The crisis may be vasoocclusive, resulting from the aggregation of misshapen erythrocytes, or anemic, resulting from bone marrow aplasia. . Blood cultures from the patient's subclavian vein subclavian vein n. A continuation of the axillary vein at the lateral border of the first rib, passing medially to join the internal jugular vein and forming the brachiocephalic vein on each side. Infusaport, inserted two months prior, were obtained at presentation. After five days, blood cultures were positive for R mucilaginosa. The patient completed a 14-day course of oral fluconazole fluconazole /flu·con·a·zole/ (floo-kon´ah-zol) a triazoleantifungal used in the systemic treatment of candidiasis and cryptococcal meningitis. flu·con·a·zole n. (400 mg daily), but the port was not removed. Two months later, he presented with another sickle cell crisis and blood cultures were again positive for R mucilaginosa. The patient denied any constitutional symptoms and the Infusaport site was intact. Blood was inoculated into Bactec blood culture bottles (Bactec 9240, Becton, Dickinson, MD, USA). Five days later, the blood cultures were positive for yeast and the yeast was subsequently subcultured on Sabouraud dextrose dextrose: see glucose. agar (Remel, Lenexa, KS, USA) and incubated at 30[degrees]C. The isolate was tested with the API-20C Aux (Biomerieux) yeast identification system and was identified as R mucilaginosa (APIC (Advanced Programmable Interrupt Controller) A circuit that handles the priority of interrupts in a computer. Designed to support symmetric multiprocessing (SMP), the APIC handles more interrupts and is more flexible than the programmable interrupt controller number 2620073). Susceptibilities to amphotericin B, caspofungin. fluconazole and voriconazole are shown on the Table. Voriconazole (maintenance dose of 4 mg/kg orally every 12 hours) was prescribed. The patient refused to have his port removed. Most of the blood cultures that were drawn through the Infusaport and peripheral veins remained positive for R mucilaginosa. The patient was discharged home on oral voriconazole, and remained asymptomatic until the last follow-up one month after his discharge. He was lost to follow-up thereafter. Discussion Rhodotorula is a genus of fungi that belongs to the family Cryptococcaceae. It contains several species, with R minuta, R glutinis, and R mucilaginosa (formerly R rubra) being isolated most frequently in humans. Rhodotorula species usually grow in Sabouraud dextrose agar, occasionally produce a few rudimentary pseudohyphae and do not ferment sugars. (1,2) They are always urease urease /ure·ase/ (u´re-as) an enzyme that catalyzes the hydrolysis of urea to ammonia and carbon dioxide; it is a nickel protein of microorganisms and plants that is used in clinical assays of plasma urea concentrations. positive and can assimilate various carbohydrates. (1) Rhodotorula species produce carotenoid Carotenoid Any of a class of yellow, orange, red, and purple pigments that are widely distributed in nature. Carotenoids are generally fat-soluble unless they are complexed with proteins. pigments, which give their smooth and moist colonies a salmon-pink to coral-red appearance. Rhodotorula species live in the environment (eg, soil, water) and can colonize col·o·nize v. col·o·nized, col·o·niz·ing, col·o·niz·es v.tr. 1. To form or establish a colony or colonies in. 2. To migrate to and settle in; occupy as a colony. 3. humans (eg, skin, respiratory, gastrointestinal tracts). They can occasionally behave as pathogens and cause disease. Risk factors for infection include underlying immunosuppression immunosuppression Suppression of immunity with drugs, usually to prevent rejection of an organ transplant. Its aim is to allow the recipient to accept the organ permanently with no unpleasant side effects. , broad-spectrum antibiotics, and the presence of central venous catheters. (3-6) Reports of R mucilaginosa infection have been described in patients with HIV HIV (Human Immunodeficiency Virus), either of two closely related retroviruses that invade T-helper lymphocytes and are responsible for AIDS. There are two types of HIV: HIV-1 and HIV-2. HIV-1 is responsible for the vast majority of AIDS in the United States. infection, rheumatoid arthritis, renal insufficiency, diabetes mellitus and debilitation debilitation being in a state of debility. . (7-10) Although R mucilaginosa may be considered less virulent than most yeasts, (6,11) several descriptions of R mucilaginosa catheter-related fungemia have been reported. (3-6) Patients with endocarditis endocarditis (ĕn'dōkärdī`tĭs), bacterial or fungal infection of the endocardium (inner lining of the heart) that can be either acute or subacute. , (12-14) meningitis, (9,15) ventriculitis, (16) endophthalmitis, (17) keratitis keratitis Inflammation of the cornea (see eye). The conjunctiva may also be inflamed (keratoconjunctivitis). Depending on the cause, including dryness of the eye (from low tear production or inability to close the eye), chemical or physical injury, or certain , (7) or peritonitis peritonitis (pĕr'ĭtənī`tĭs), acute or chronic inflammation of the peritoneum, the membrane that lines the abdominal cavity and surrounds the internal organs. due to R mucilaginosa (8) have also been described. A cluster of 11 cases of R mucilaginosa isolated from bronchoscopy Bronchoscopy Definition Bronchoscopy is a procedure in which a cylindrical fiberoptic scope is inserted into the airways. This scope contains a viewing device that allows the visual examination of the lower airways. specimens was attributed to contamination of the suction channel of a flexible bronchoscope bronchoscope (brŏng`kəskōp'), long, tubular instrument with a light at the tip that is inserted through the windpipe and bronchial tubes to examine these structures. . (18) In addition, patients with sepsis due to this organism have also been described. (19-21) To our knowledge, this is the first description of R mucilaginosa fungemia in a patient with sickle cell anemia. Interestingly, the patient presented did not have any systemic signs or symptoms of infection. This relatively quiescent clinical presentation may be explained by his underlying immune status. Although sickle cell anemia certainly predisposes to bloodstream infection, it is possible that his underlying immune status resulted in less obvious signs of infection. Rhodotorula species are consistently resistant to fluconazole. Diekema et al (11) studied 64 isolates of Rhodotorula species (24 of which were R mucilaginosa) between 1987 and 2003 (Table). Antifungal susceptibilities were according to the recommendations of the National Committee for Clinical Laboratory Standards (NCCLS NCCLS National Committee for Clinical Laboratory Standards ). The most active agent was found to be 5-flucytocine (MIC [less than or equal to]0.5 [micro]/mL). Amphotericin B had an MIC [less than or equal to]1.0 [micro]g/mL, but E-test detected 8 isolates with an MIC >1 [micro]g/mL. All isolates in this study were resistant to echinocandins and fluconazole. Among the broad-spectrum azoles, MICs for both voriconazole and posaconazole were [less than or equal to]4.0 [micro]g/mL. (11) In another review from Spain, 25 isolates of R mucilaginosa were tested against several antifungal agents using the Antifungal Susceptibility Testing Subcommittee of the European Committee on Antibiotic Susceptibility Testing recommendations (AFST-EUCAST, discussion document 7.1). Gomez-Lopez et al reported a wide MIC range for flucytosine (0.06->64 [micro]g/mL) and amphotericin B (0.06-8 [micro]g/mL) (Table). (22) Treatment of R mucilaginosa fungemia with antifungal agents alone, catheter removal alone, or a combination of both, have all been suggested. (5,10,23) The patient presented refused port removal, and was treated with voriconazole based on susceptibility testing and ease of oral administration. Fungemia persisted despite antifungal treatment, suggesting that removal of the central venous catheter is pertinent for clearance of the infection. Based on our experience, we believe that catheter removal should be the recommended approach in patients who present with R mucilaginosa catheter-related fungemia, combined with appropriate antifungal therapy. Susceptibilities to different antifungal agents should be obtained. For severely immunosuppressed Immunosuppressed A state in which the immune system is suppressed by medications during the treatment of other disorders, like cancer, or following an organ transplantation. Mentioned in: Fifth Disease patients who present with septicemia septicemia (sĕptĭsē`mēə), invasion of the bloodstream by virulent bacteria that multiply and discharge their toxic products. The disorder, which is serious and sometimes fatal, is commonly known as blood poisoning. attributed to R mucilaginosa, amphotericin B may be the optimal antifungal treatment. The new, broad-spectrum azoles (eg, voriconazole) could possibly be prescribed, if susceptibility data is available to support their use. One to two weeks of antifungals have been used in the past with successful outcomes. (5,6) It would be prudent to tailor the length of the treatment based on the severity of the disease, the host's immune status, and clinical response to therapy. Conclusion The increasing population of immunocompromised patients with chronic indwelling catheters has led to infections with less common organisms. The isolation of R mucilaginosa in blood cultures should alert physicians to promptly initiate an appropriate therapeutic regimen. If a central venous catheter is present, recommendations for catheter removal should be made for definitive treatment. Because of the limited number of reported cases of R mucilaginosa fungemia, treatment guidelines have not been clearly established. When infection with R mucilaginosa occurs, prompt antifungal therapy should be instituted. Acknowledgments The authors thank Ms. Mindy Tokarczyk, from the Department of Microbiology, Thomas Jefferson University It began as Jefferson Medical College in 1824. On July 1, 1969 the institution officially became Thomas Jefferson University. The university is made up of three colleges:
References 1. Larone DH. Medically Important Fungi: A Guide to Identification. Fourth ed. Vol 1. Washington, DC, American Society of Microbiology Press, 2002. 2. Anaissie EJ, McGinnis MR, Pfaller MA. Clinical Mycology mycology Study of fungi (see fungus), including mushrooms and yeasts. Many fungi are useful in medicine and industry. Mycological research has led to the development of such antibiotic drugs as penicillin, streptomycin, and tetracycline. . First ed. Vol 1. Philadelphia, Churchill Livingstone, The Curtis Center, 2003. 3. Samonis G, Anatoliotaki M, Apostolakou H, et al. Transient fungemia due to Rhodotorula rubra in a cancer patient: case report and review of the literature. Infection 2001;29:173-176. 4. Chung JW, Kim BN, Kim YS. Central venous catheter-related Rhodotorula rubra fungemia. J Infect Chemother 2002;8:109-110. 5. Kiehn TE, Gorey E, Brown AE, et al. Sepsis due to Rhodotorula related to use of indwelling indwelling /in·dwell·ing/ (in´dwel-ing) pertaining to a catheter or other tube left within an organ or body passage for drainage, to maintain patency, or for the administration of drugs or nutrients. central venous catheters. Clin Infect Dis 1992;14:841-846. 6. Lo Re V, Fishman NO, Nachamkin I. Recurrent catheter-related Rhodotorula rubra infection. Clin Microbiol Infect 2003;9:897-900. 7. Lifshitz T, Levy J. Rhodotorula rubra keratitis and melting after repeated penetrating keratoplasty keratoplasty /ker·a·to·plas·ty/ (ker´ah-to-plas?te) plastic surgery of the cornea; corneal transplantation. optic keratoplasty . Eur J Ophthalmol 2005;15:135-137. 8. Eisenberg ES, Alpert BE, Weiss RA, et al. Rhodotorula rubra peritonitis in patients undergoing continuous ambulatory peritoneal dialysis continuous ambulatory peritoneal dialysis See Peritoneal dialysis. . Am J Med 1983;75:349-352. 9. Gyaurgieva OH, Bogomolova TS, Gorshkova GI. Meningitis caused by Rhodotorula rubra in an HIV-infected patient. J Med Vet Mycol 1996;34:357-359. 10. Goldani LZ, Craven DE, Sugar AM. Central venous catheter infection with Rhodotorula minuta in a patient with AIDS taking suppressive sup·pres·sive adj. Tending or serving to suppress. Adj. 1. suppressive - tending to suppress; "the government used suppressive measures to control the protest" doses of fluconazole. J Med Vet Mycol 1995;33:267-270. 11. Diekema DJ, Petroelje B, Messer SA, et al. Activities of available and investigational antifungal agents against Rhodotorula species. J Clin Microbiol 2005;43:476-478. 12. Naveh Y, Friedman A, Merzbach D, et al. Endocarditis caused by Rhodotorula successfully treated with 5-fluorocytosine. Br Heart J 1975;37:101-104. 13. Louria DB, Greenberg SM, Molander DW. Fungemia caused by certain nonpathogenic strains of the family Cryptococcaceae: report of two cases due to Rhodotorula and Torulopsis glabrata. N Engl J Med 1960;263:1281-1284. 14. Maeder M, Vogt PR, Schaer G, et al. Aortic aortic pertaining to or emanating from the aorta. See also aortic arch. aortic aneurysm occurs most often in dogs, where it is caused by Spirocerca lupi larvae, turkeys and primates, causing dyspnea, cyanosis and coughing. homograft homograft: see transplantation, medical. endocarditis caused by Rhodotorula mucilaginosa. Infection 2003;31:181-183. 15. Pore RS, Chen J. Meningitis caused by Rhodotorula. Sabouraudia 1976;14:331-335. 16. Donald FE, Sharp JF, Firth JL, et al. Rhodotorula rubra ventriculitis. J Infect 1988;16:187-191. 17. Gregory JK, Haller JA. Chronic postoperative Rhodotorula endophthalmitis. Arch Ophthalmol 1992;110:1686-1687. 18. Hagan ME, Klotz SA, Bartholomew W, et al. A pseudoepidemic of Rhodotorula rubra: a marker for microbial microbial pertaining to or emanating from a microbe. microbial digestion the breakdown of organic material, especially feedstuffs, by microbial organisms. contamination of the bronchoscope. Infect Control Hosp Epidemiol 1995;16:727-728. 19. Leeber DA, Scher I. Rhodotorula fungemia presenting as 'endotoxic' shock. Arch Intern Med 1969;123:78-81. 20. Pien FD, Thompson RL, Deye D, et al. Rhodotorula septicemia: two cases and a review of the literature. Mayo Clin Proc 1980;55:258-260. 21. Braun DK, Kauffman CA. Rhodotorula fungaemia: a life-threatening complication of indwelling central venous catheters. Mvcoses 1992;35:305-308. 22. Gomez-Lopez A, Mellado E, Rodriguez-Tudela JL, et al. Susceptibility profile of 29 clinical isolates of Rhodotorula spp. and literature review. J Antimicrob Chemother 2005;55:312-316. 23. Rusthoven JJ, Feld R, Tuffnell PG. Systemic infection by Rhodotorula spp in the immunocompromised host. J Infect 1984;8:241-246. Dionissios Neofytos, MD, David Horn, MD, FACP FACP Fellow of the American College of Physicians. FACP abbr. 1. Fellow of the American College of Physicians 2. Fellow of the American College of Prosthodontists , and Joseph A. De Simone, Jr, MD From the Division of Infectious Diseases and Environmental Medicine, Thomas Jefferson University, Philadelphia, PA. Reprint requests to Dionissios Neofytos, Division of Infectious Diseases and Environmental Medicine, Thomas Jefferson University Hospital, 125 South 9th Street, Suite 403, Philadelphia, PA 19107. Email: dionissios.neofytos@mail.tju.edu Accepted August 23, 2006. RELATED ARTICLE: Key Points * Rhodotorula mucilaginosa can be a significant, recalcitrant pathogen in immunocompromised patients. * Susceptibilities to different antifungal agents should be obtained and administration of antifungal therapy combined with catheter removal is the recommended approach in patients who present with R mucilaginosa catheter-related fungemia.
Table. Literature review of MICs for Rhodotorula mucilaginosa
Diekema et al
Antifungal MIC (mcg/mL)
agent (24 isolates)
5-FC 0.06-[less than or equal to]0.5
Amphotericin B 0.25-[less than or equal to]1.0
Caspofungin [greater than or equal to]16
Fluconazole [greater than or equal to]16
Voriconazole 0.25-8
Gomez-Lopez et al
Antifungal MIC (mcg/mL)
agent (25 isolates)
5-FC 0.06->64
Amphotericin B 0.06-8
Caspofungin Not done
Fluconazole 8-[greater than or equal to]64
Voriconazole 0.5-8
Case patient
Antifungal MIC (mcg/mL)
agent (1 isolate)
5-FC Not done
Amphotericin B [less than or equal to]0.5
Caspofungin [greater than or equal to]16
Fluconazole [greater than or equal to]64
Voriconazole [less than or equal to]2
MIC, minimal inhibitory concentration; 5-FC, 5-flucytosine.
|
|
||||||||||||||||||||
Printer friendly
Cite/link
Email
Feedback
Reader Opinion