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Rhodotorula septicemia: case report and minireview

2001; Elsevier BV; Volume: 7; Issue: 2 Linguagem: Inglês

10.1046/j.1469-0691.2001.00203.x

1469-0691

V. Petrocheilou-Paschou, Helen Prifti, Evangelos Kostis, Constantine S. Papadimitriou, Meletios Α. Dimopoulos, S. Stamatelopoulos,

Plant Pathogens and Fungal Diseases

Rhodotorula, a yeast member of the family Cryptococcaceae, was only recently recognized as a human pathogen especially affecting immunocompromised patients [1Vartivarian SE Annaissie EJ Bodey GP Emerging pathogens in immunocompromised patients: classification, diagnosis and management.Clin Infect Dis. 1993; 17: S487-S491Crossref PubMed Scopus (227) Google Scholar]. To our knowledge, over the last 40 years, no more than 40 cases of rhodotorula infections have been reported in patients with central indwelling vascular catheters. We isolated Rhodotorula rubra from both the catheter and the peripheral venous blood of a patient on azole prophylaxis. On this occasion, we reviewed the literature and the limited experience with rhodotorula hospital infections in Greece. A 21-year-old female patient, with non-Hodgkin's lymphoma in second remission, underwent autologous peripheral blood progenitor cell transplantation. A large peripheral double lumen catheter was placed in the subclavian vein for the collection and reinfusion of stem cells. The conditioning regimen was given on days −5 to −1. The patient received prophylactic oral ciprofloxacin 500 mg twice daily and fluconazole 200 mg/day. Because of severe vomiting and gastrointestinal mucositis, total parenteral nutrition was mandatory. One day after stem cell reinfusion (day 1), the patient developed grade 4 neutropenia on the WHO toxicity scale (PMN count 256, ketoconazole 0.25, 5-flucytosine 0.06, and itraconazole 1. Candida parapsilosis ATCC 90018 was also tested as a control, and MICs of the above antifungal agents (mg/L) were 0.25, 1, 0.016, 0.06 and 0.06, respectively. Fluconazole was discontinued and intravenous liposomal amphotericin B was started with a daily dose of 3 mg/kg of body weight. However, 3 days later, the patient remained febrile, and blood cultures were again positive for the same fungus, despite a PMN count of more than 1000/μL. Eventually, the central catheter was removed, and the following day the patient became afebrile. Rhodotorula was again isolated from the tip of the removed catheter. Following the removal of the catheter, treatment with liposomal amphotericin B was continued for a total of 7 days and the patient was discharged from the hospital, after complete hematologic recovery, without further complications. Rhodotorula was traditionally considered to be a contaminant, but within the last decade it has been progressively recognized that this yeast can cause infections, especially in immunocompromised patients with central venous catheters [1Vartivarian SE Annaissie EJ Bodey GP Emerging pathogens in immunocompromised patients: classification, diagnosis and management.Clin Infect Dis. 1993; 17: S487-S491Crossref PubMed Scopus (227) Google Scholar,2Kiehn TE Gorey E Brown AE Edwards FF Armstrong D Sepsis due to Rhodotorula related to use of indwelling central venous catheters.Clin Infect Dis. 1992; 14: 841-846Crossref PubMed Scopus (84) Google Scholar]. Rhodotorula rubra has been regarded as having lower virulence (about 15% mortality) in comparison with Candida spp. and Trichosporon spp., as has been reported by Krcmery et al in a recent review [3Krcmery V Krupova I Denning DW Invasive yeast infections other than Candida spp. in acute leukemia.J Hosp Infect. 1999; 41: 181-194Abstract Full Text PDF PubMed Scopus (93) Google Scholar]. It is thus an infrequent cause of infection, with only 12 culture-proven rhodotorula fungemia cases reported prior to 1984 [2Kiehn TE Gorey E Brown AE Edwards FF Armstrong D Sepsis due to Rhodotorula related to use of indwelling central venous catheters.Clin Infect Dis. 1992; 14: 841-846Crossref PubMed Scopus (84) Google Scholar]. More specifically, rhodotorula infection appears to represent a rare complication of bone marrow transplantation, with only one case reported in series of 1186 bone marrow recipients between 1974 and 1989 [4Morrison VA Haake RJ Weisdorf DJ The spectrum of noncandida fungal infections following bone marrow-transplantation.Medicine. 1993; 72: 78-89Crossref PubMed Scopus (173) Google Scholar]. In 1992, 23 catheter-related cases of sepsis caused by this yeast were described in cancer patients from one center [2Kiehn TE Gorey E Brown AE Edwards FF Armstrong D Sepsis due to Rhodotorula related to use of indwelling central venous catheters.Clin Infect Dis. 1992; 14: 841-846Crossref PubMed Scopus (84) Google Scholar], and since then another five patients with fungemia have been reported in the English-language literature [5Sheu MJ Wang CC Wang CC Shi WJ Chu ML Rhodotorula septicemia: report of a case.J Formos Med Assoc. 1994; 93: 645-647PubMed Google Scholar, 6Goldani LZ Craven DE Sugar AM Central venous catheter infection with Rhodotorula minuta in a patient with AIDS taking suppressive doses of fluconazole.J Med Vet Mycol. 1995; 33: 267-270Crossref PubMed Scopus (37) Google Scholar, 7Fanci R Pecile P Martinez RL Fabbri A Nicoletti P Amphotericin B treatment of fungemia due to unusual pathogens in neutropenic patients: report of two cases.J Chemother. 1997; 9: 427-430Crossref PubMed Scopus (18) Google Scholar, 8Marinova I Szabadosova V Brandeburova O Krcmery VJ Rhodotorula spp fungemia in an immunocompromised boy after neurosurgery successfully treated with miconazole and 5-flucytosine: case report and review of the literature.Chemotherapy. 1994; 40: 287-289Crossref PubMed Scopus (22) Google Scholar, 9Lui AY Turett GS Karter DL Bellman PC Kislak JW Amphotericin B lipid complexin an AIDS patient with Rhodotorula rubra fungemia.Clin Infect Dis. 1998; 27: 892-893Crossref PubMed Scopus (24) Google Scholar]. In our country, cases of sepsis due to Rhodotorula are even rarer. This is the only case documented in our hospital in the last 15 years. A case of fungemia following surgery for colon carcinoma was recently reported from Greece [10Papadogeorgakis H Frangoulis E Papaefstathiou C Katsambas A Rhodotorula rubra fungemia in an immunosuppressed patient.J Eur Acad Dermatol Venereol. 1999; 12: 169-170Crossref PubMed Google Scholar], and another one was included in a surveillance study conducted among several hospitals in Athens during the last 2 years [11Paniara O Frangoulis E Stylianea-Foundoulaki A Danielidis V Velegraki A the Hellenic group for the study of fungal infections Epidemiological survey on fungal infection in Europe.Acta Microb Hell. 1999; 44: 573-581Google Scholar]. In the latter study, Rhodotorula was isolated from a quadriplegic child. Most of the reported infections were documented in cancer patients with indwelling vascular catheters [2Kiehn TE Gorey E Brown AE Edwards FF Armstrong D Sepsis due to Rhodotorula related to use of indwelling central venous catheters.Clin Infect Dis. 1992; 14: 841-846Crossref PubMed Scopus (84) Google Scholar,5Sheu MJ Wang CC Wang CC Shi WJ Chu ML Rhodotorula septicemia: report of a case.J Formos Med Assoc. 1994; 93: 645-647PubMed Google Scholar]; four of them were neutropenic [2Kiehn TE Gorey E Brown AE Edwards FF Armstrong D Sepsis due to Rhodotorula related to use of indwelling central venous catheters.Clin Infect Dis. 1992; 14: 841-846Crossref PubMed Scopus (84) Google Scholar,5Sheu MJ Wang CC Wang CC Shi WJ Chu ML Rhodotorula septicemia: report of a case.J Formos Med Assoc. 1994; 93: 645-647PubMed Google Scholar,9Lui AY Turett GS Karter DL Bellman PC Kislak JW Amphotericin B lipid complexin an AIDS patient with Rhodotorula rubra fungemia.Clin Infect Dis. 1998; 27: 892-893Crossref PubMed Scopus (24) Google Scholar] and only two had positive blood cultures from both catheter and peripheral vein [2Kiehn TE Gorey E Brown AE Edwards FF Armstrong D Sepsis due to Rhodotorula related to use of indwelling central venous catheters.Clin Infect Dis. 1992; 14: 841-846Crossref PubMed Scopus (84) Google Scholar,8Marinova I Szabadosova V Brandeburova O Krcmery VJ Rhodotorula spp fungemia in an immunocompromised boy after neurosurgery successfully treated with miconazole and 5-flucytosine: case report and review of the literature.Chemotherapy. 1994; 40: 287-289Crossref PubMed Scopus (22) Google Scholar]. Our patient had a lymphoma, was severely neutropenic and had a central venous catheter placed for stem cell collection and reinfusion, as well as for total parenteral nutrition. Our patient also had positive blood cultures obtained from the catheter, as well as from a peripheral vein. As has been stressed by Kiehn et al [2Kiehn TE Gorey E Brown AE Edwards FF Armstrong D Sepsis due to Rhodotorula related to use of indwelling central venous catheters.Clin Infect Dis. 1992; 14: 841-846Crossref PubMed Scopus (84) Google Scholar], Rhodotorula usually remains in the lumen of the catheter, and blood cultures from peripheral veins are usually negative. Severe neutropenia is the most likely cause of this dissemination, as Fanci et al [7Fanci R Pecile P Martinez RL Fabbri A Nicoletti P Amphotericin B treatment of fungemia due to unusual pathogens in neutropenic patients: report of two cases.J Chemother. 1997; 9: 427-430Crossref PubMed Scopus (18) Google Scholar] suggested in their case report. Central vein catheter has been recognized as a major risk factor for rhodotorula fungemia. In the majority of the reported cases, indwelling catheters had been placed 1–22 months prior to fungemia. Our patient developed rhodotorula sepsis very early, only 9 days after the catheter insertion. Although catheter insertion is a specific risk factor for Rhodotorula fungemia, severe neutropenia and total parenteral nutrition combined possibly played a supplementary role in the development of the septicemia [3Krcmery V Krupova I Denning DW Invasive yeast infections other than Candida spp. in acute leukemia.J Hosp Infect. 1999; 41: 181-194Abstract Full Text PDF PubMed Scopus (93) Google Scholar]. The treatment of catheter-related Rhodotorula fungemia remains controversial. Some authors believe that catheter removal is not necessary for cure [1Vartivarian SE Annaissie EJ Bodey GP Emerging pathogens in immunocompromised patients: classification, diagnosis and management.Clin Infect Dis. 1993; 17: S487-S491Crossref PubMed Scopus (227) Google Scholar,2Kiehn TE Gorey E Brown AE Edwards FF Armstrong D Sepsis due to Rhodotorula related to use of indwelling central venous catheters.Clin Infect Dis. 1992; 14: 841-846Crossref PubMed Scopus (84) Google Scholar]. On the other hand, in a small number of cases, catheter removal without antifungal therapy was also curative. Our patient was febrile, and the cultures still yielded Rhodotorula, 3 days after amphotericin B introduction, while she became afebrile 1 day after removal of the catheter. Treatment with amphotericin B was continued for a further 7-day course, as Kiehn et al [2Kiehn TE Gorey E Brown AE Edwards FF Armstrong D Sepsis due to Rhodotorula related to use of indwelling central venous catheters.Clin Infect Dis. 1992; 14: 841-846Crossref PubMed Scopus (84) Google Scholar] recommended in their report. Our case strengthens the point of view that catheter removal and administration of antifungal therapy appears to be the optimal treatment. Liposomal amphotericin B was chosen, because it is generally better tolerated than the amphotericin B deoxycholate. Our patient became fungemic despite fluconazole prophylaxis, and in vitro susceptibility testing performed with antifungal drugs revealed that the Rhodotorula isolate was highly resistant to fluconazole, as has also been reported by others [10Papadogeorgakis H Frangoulis E Papaefstathiou C Katsambas A Rhodotorula rubra fungemia in an immunosuppressed patient.J Eur Acad Dermatol Venereol. 1999; 12: 169-170Crossref PubMed Google Scholar,12Galan-Sanchez F Garcia-Martos P Rodriguez-Ramos C Marin-Casanova P Mira-Gutierrez J Microbiological characteristics and susceptibility patterns of strains of Rhodotorula isolated from clinical samples.Mycopathologia. 1999; 145: 109-112Crossref PubMed Scopus (49) Google Scholar]. Regarding prophylactic treatment of immunocompromised patients with fluconazole, it should be remembered that widespread antifungal prophylaxis, although providing protection against sensitive organisms, also may allow the emergence of more resistant isolates such as Rhodotorula spp.