Epidemiology and Outcome of Rhodotorula Fungemia in a Tertiary Care Hospital
- Section of Infectious Diseases and Microbiology, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil
- Reprints or correspondence: Dr. Luciano Z. Goldani, Unidade de Infectologia, Hospital de Clínicas de Porto Alegre, Rua Ramiro Barcelos 2350, 90035-003 Porto Alegre, RS, Brazil (Lgodani{at}ufrgs.br).
Abstract
We reviewed demographic data, risk factors, treatment, and outcomes associated with Rhodotorula fungemia in a tertiary care hospital during 2002–2005. Rhodotorula species caused fungemic episodes in 7 patients during the 4-year period that we studied. The most common predisposing factors were patients with hematological and solid malignancy receiving corticosteroids and cytotoxic drugs, the presence of central venous catheters, and the use of broad-spectrum antibiotics. Because of Rhodotorula species's intrinsic resistance to triazole and echinocandin antifungal agents, patients receiving fluconazole and caspofungin might be susceptible to the development of breakthrough Rhodotorula fungemia.
Rhodotorula is a genus of pink-colored yeasts classified in the family Cryptococcaceae [1]. Rhodotorula species are common airborne organisms that may be present on the skin and in sputum, urine, and feces. Rhodotorula species have been implicated as an infrequent cause of infections, such as septicemia, endocarditis, meningitis, and peritonitis [2]. To date, most infections caused by Rhodotorula species have been associated with intravenous catheters and with patients who have solid tumors, lymphoproliferative diseases, chronic renal failure, diabetes, endocarditis, pulmonary diseases, and AIDS [3–26].
Recent reports of Rhodotorula fungemia have been limited by a relatively small number of subjects. Therefore, we conducted this retrospective study at a tertiary care hospital that covered a 4-year period, to identify the risk factors, treatment, outcome, and other relevant prognostic data associated with Rhodotorula fungemia.
Methods. The records of the microbiology laboratory at Hospital de Clínicas de Porto Alegre, a 749-bed tertiary care hospital in southern Brazil, were reviewed for the period 1 January 2000 through 31 December 2005 to identify all cases of Rhodotorula fungemia. The medical records of all patients with Rhodotorula fungemia were available for review. The following information was collected for all patients who had Rhodotorula fungemia during this period: age, sex, underlying malignancy, presence of a central venous catheter, administration of antibiotics, treatment, and outcome. These data reflect each patient's status during the 30 days before the collection of the first blood samples that yielded positive results on culture, and they reflect the subsequent course of infection. Blood cultures were performed using the continuously monitored noninvasive system BACTEC 9240 (Becton and Dickenson Medical Systems). Rhodotorula species isolates were identified using broad-range primer pairs ITS5 (5′ GGA AGT AAA AGT CGT AAC AAG G) and ITS2 (5′ GCT GCG TTC TTC ATC GAT GC) or ITS3 (5′ GCA TCG ATG AAG AAC GCA GC) and ITS4 (5′ TCC TCC GCT TAT TGA TAT GC), which amplify ribosomal internal transcribed spacer regions 1 and 2, respectively, as previously described [27]. Species identifications were made by comparative sequence analysis and by GenBank searches. Rhodotorula fungemia is defined as the isolation of the organism from ⩾1 culture of a blood sample and associated fever or other signs of infection (e.g., chills, hypothermia, or hypotension). Associated mortality is defined as death attributed to Rhodotorula infection, with or without therapy.
Results. Of the 76,454 blood cultures performed, 10 cultures of blood samples obtained from 7 patients grew Rhodotorula species (table 1); the overall incidence was 0.056 episodes per 1000 hospital admissions. Sequencing of internal transcribed spacers 1 and 2 of Rhodotorula species isolates revealed that all isolates were Rhodotorula mucilaginosa. Cultures of samples obtained from the central venous catheter tip from 1 patient grew R. mucilaginosa.
Table 1
Microbiological characteristics of 7 patients with Rhodotorula fungemia.
As shown in table 2, 4 patients (57%) had solid tumors and exposure to cytotoxic drugs; 1 of these underwent major surgery at the tumor site and was receiving total parenteral nutrition. Three patients (43%) had leukemia and exposure to corticosteroids and cytotoxic drugs. Six patients (86%) were neutropenic and were exposed to broad-spectrum antibiotics for 12–26 days. Two patients (28%) were taking prophylatic fluconazole when they developed Rhodotorula fungemia. Six patients (75%) were neutropenic (table 1). All 7 patients who were determined to have Rhodotorula fungemia had a central venous catheter. Of these 7 episodes, 5 were treated with antifungal agents and removal of the catheter, and 2 were treated only with removal of the catheter (table 2). Antifungal therapy included amphotericin B plus 5-flucytosine (2 patients), amphotericin B (2 patients), fluconazole (1 patient), and voriconazole following amphotericin B (1 patient). The overall rate of mortality was 42% (3 of 7 patients). All 3 patients died within 10 days of the incident sample culture. The outcome was favorable for the 2 patients that were treated only by removal of the catheter.
Table 2
Characteristics of patients with Rhodotorula fungemia.
Discussion. A review of English language literature on Rhodotorula bloodstream infections revealed 59 cases during the period of 1960–2003 (table 3) [3–26]. Among Rhodotorula species that have been identified, R. mucilaginosa (previously named Rhodotorula rubra) is the most prevalent. The major risk factor for Rhodotorula fungemia has been prolonged use of indwelling intravenous catheters in patients with hematological and solid malignancies who are taking corticosteroids and cytotoxic drugs. In addition, administration of broad-spectrum antibiotics has been consistently reported in patients who developed Rhodotorula fungemia.
Table 3
Summary of characteristics of 59 patients with proven cases of Rhodotorula fungemia described in the literature.
Rhodotorula fungemia has been described in patients for whom samples taken from central venous catheters did not grow Rhodototorula species on culture, or who did not have central venous catheters [18, 23, 25]. Considering that samples taken from the central venous catheters in our patients did not grow Rhodotorula species on culture, it seems possible that the fungus could have intruded in the bloodstream through disruption of gastrointestinal mucosa by cytotoxic drugs. Rhodotorula species are present in the normal gastrointestinal flora, and broad-spectrum antibiotics could contribute to its overgrowth in the gastrointestinal tract.
The need for antifungal therapy for Rhodotorula fungemia is currently uncertain. As reported in our study and in previous case reports, a substantial number of survivors of Rhodotorula fungemia did not receive antifungal therapy [10, 23, 25, 26] and appeared to respond to a simple removal of the indwelling intravenous catheters. Occasionally, patients with Rhodotorula fungemia have been successfully treated with antifungal agents without the removal of the central venous catheter [9, 10]. Although 3 of the 7 patients in our study died, the overall mortality rate of Rhodotorula fungemia of reported cases in the literature is 20% (table 3).
In vitro susceptibility tests of Rhodotorula species in previous studies revealed low MICs to amphotericin B (0.25–1.2 µg/mL), and higher MICs to fluconazole (6.4 to >100 µg/mL) [9, 10, 22, 26]. Diekema et al. [28] reported the in vitro activities of 8 antifungals against 64 Rhodotorula isolates. Rhodotorula strains were resistant in vitro to fluconazole (MIC50, >128 µg/mL) and caspofungin (MIC50, >8 µg/mL). Amphotericin B (MIC50, 1 µg/mL) and flucytosine (MIC50, 0.12 µg/mL) were both active in vitro, and the new and investigational triazoles have all displayed some in vitro activity, ravuconazole being the most active (MIC50, 0.25 µg/mL). In fact, patients described in previous case reports and 2 patients from our study developed Rhodotorula fungemia while receiving prophylaxis with fluconazole [9, 19]. Although it provides protection against drug-susceptible organisms, widespread antifungal prophylaxis with triazole antifungal agents in immunocompromised patients may also allow the emergence of more resistant fungi, such as Rhodotorula species.
In summary, immunocompromised patients—especially those with hematological and solid malignancies who are receiving broad-spectrum antibiotics, corticosteroids, and cytotoxic drugs and who have permanent indwelling intravenous catheters—are susceptible to Rhodotorula fungemia. Because of the intrinsic resistance of Rhodotorula species to triazoles and echinocandins, patients receiving fluconazole and caspofungin are susceptible to develop breakthrough Rhodotorula fungemia. Additional investigations, such as case-control studies to examine risk factors for Rhodotorula fungemia or sample culture surveys to determine the frequency of gastrointestinal tract or skin carriage, will be important to better understand the epidemiology of this rare fungal infection.
Acknowledgments
Financial support. CNPq (Brazilian National Agency for Research and Technology Development).
Potential conflicts of interest. All authors: no conflicts
- Received March 7, 2006.
- Accepted June 1, 2006.
- © 2006 by the Infectious Diseases Society of America
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