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Journal of Clinical Microbiology, October 2008, p. 3544-3545, Vol. 46, No. 10
0095-1137/08/$08.00+0 doi:10.1128/JCM.00873-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.
Femoral Prosthesis Infection by Rhodotorula mucilaginosa
Vincenzo Savini,1*
Federica Sozio,2
Chiara Catavitello,1
Marzia Talia,1
Assunta Manna,1
Fabio Febbo,1
Andrea Balbinot,1
Giovanni Di Bonaventura,3
Raffaele Piccolomini,3
Giustino Parruti,2 and
Domenico D'Antonio1
Clinical Microbiology and Virology Unit, Department of Transfusion Medicine, Spirito Santo Hospital, Pescara, Italy,1
Infectious Diseases Unit, Spirito Santo Hospital, Pescara, Italy,2
Clinical Microbiology, Aging Research Center (Ce.S.I.), and Department of Biomedical Sciences, Gabriele d'Annunzio University of Chieti-Pescara, Italy3
Received 6 May 2008/
Returned for modification 29 June 2008/
Accepted 16 August 2008

ABSTRACT
This case report is a case history of a femoral prosthesis infection
caused by
Rhodotorula mucilaginosa in a human immunodeficiency
virus patient. Though the pathogenicity of this organism for
bone tissue has been previously reported, this is the first
reported case of an orthopedic prosthesis infection by this
species of the genus
Rhodotorula.

CASE REPORT
A 41-year-old female human immunodeficiency virus patient sustained
a fracture of the left femoral epiphysis in a road traffic accident
in 1996. Surgical internal fixation was done but was followed
by an outbreak of chronic coxitis (confirmed by magnetic resonance)
until a femoral prosthesis was finally inserted in 2006. During
2007, an acute infection of the implanted prosthesis was diagnosed,
with the patient suffering from a fever (38.5°C), strong
local pain, and tumefaction. Furthermore, a fistula developed
from the internal site of the prosthetic infection as far as
the skin of the femoral region, with continuous pus discharge
from its external opening. No overt signs of septicemia were
observed, and mild leukocytosis was documented, whereas CD4
and CD8 levels were found to be normal. After receiving a 10-day
course of intramuscular piperacillin, empirically, followed
by no clinical improvement, the patient was admitted to the
hospital. Magnetic resonance and bone scintigraphy documented
the prosthesis infection. Also, drainage from the fistula was
cultured. Particularly, it was plated onto sheep blood agar,
mannitol salt agar, MacConkey agar, and Sabouraud dextrose agar
(plates were provided by bioMérieux, Marcy l'Etoile,
France). Blood culture plates were incubated at 36°C in
air, anaerobically, and under 5% CO
2-enriched atmosphere. Mannitol
and MacConkey media were processed at 36°C under aerobic
conditions. Finally, two Sabouraud plates were incubated at
36°C and 25°C, respectively, both in ambient air. After
24 h of incubation, neither bacterial nor fungal growth was
observed, whereas Sabouraud cultures processed at 25°C yielded
about 150 colonies of
Rhodotorula mucilaginosa, as a single
organism, after 48 h of incubation. Cultures from all of the
other mentioned media remained negative, so that no aerobic,
anaerobic, or microaerophilic organisms other than
Rhodotorula were observed. Identification of the isolate was suggested by
the phenotype of colonies, which were typically pink-red and
smooth, and by microscopic features (round-shaped yeast cells
without hyphae) and confirmed by the Vitek2 system (YST card;
bioMérieux) and by the mini API system (ID32C gallery;
bioMérieux). Gram staining of the secretion was carried
out and documented the presence of numerous images of phagocytosis
by polymorphonuclear leukocytes against yeast-like cells (the
yeast-like cells were mostly observed inside the cytoplasm of
granulocytes), indicating acute infection caused by yeast-like
organisms. Low MICs were observed for amphotericin B and flucytosine
against the isolate studied (MICs, 0.25 µg/ml and

0.03
µg/ml, respectively), whereas higher values were documented
for fluconazole (MIC, >256 µg/ml), itraconazole (MIC,
>16 µg/ml), and voriconazole (MIC, 8 µg/ml).
MICs were obtained by performing a Sensititre YeastOne test
(Trek Diagnostic Systems Ltd., Imberhome Lane, East Grinstead,
West Sussex, England). Particularly, the Sensititre plate was
incubated for 48 h, at no more than 30°C. Liposomal amphotericin
B treatment was started, thus leading to rapid resolution of
fever, reduction of tumefaction and pain, and gradual disappearing
of fistula drainage within 10 days. The fistula finally disappeared,
too, within 2 weeks. Also, clinical improvement was documented
by magnetic resonance and scintigraphy. The patient is currently
waiting for surgical replacement of the femoral prosthesis.
Rhodotorula is a common airborne ubiquitous fungus (with a terrestrial and marine worldwide distribution), which has been known to cause fungemia, meningitis, ventriculitis, peritonitis, endocarditis, and infections of devices such as catheters and contact lenses (1, 2, 7, 10, 11). Furthermore, Rhodotorula has been collected as a saprophyte from skin, vaginal, and respiratory specimens, as well as a colonizing organism on hemodialysis machines and fiber-optic bronchoscopes, (6, 7). Most Rhodotorula isolates commonly show resistance to fluconazole, itraconazole, and voriconazole, while ravuconazole, amphotericin B, and flucytosine generally exert good in vitro activity (5, 8, 9, 12). Particularly, the Sensititre YeastOne technique (a colorimetric microdilution test) has shown its value for antifungal susceptibility testing of yeast-like fungi, given its correlation with reference procedures (4, 5), but 25°C to 30°C temperatures and at least 48-h incubations are needed (4, 6). The main species of the genus, R. mucilaginosa (formerly both Rhodotorula rubra and Rhodotorula pilimanae) and Rhodotorula glutinis, were previously labeled as nonpathogenic, contaminant yeasts but emerged as opportunistic agents of infections in the last two decades. While a prosthetic joint infection by Rhodotorula minuta (3) as well as an R. mucilaginosa osteomyelitis after traumatic bone fracture have been reported previously (7), the case we describe represents, to our knowledge, the first report of a prosthetic bone infection due to R. mucilaginosa. Given the ubiquitous distribution of this fungus, the contamination of cultures was also suspected. Anyway, this was unlikely, as drainage from fistula was obtained by means of sterile techniques and immediately subjected to culture. Furthermore, profuse pure growth of typical colonies was observed. In addition, Gram staining emphasized the role of the observed yeasts as pathogens, given the numerous images of phagocytosis observed. Finally, prompt response to antifungal treatment corroborated our findings.
In the case we described, the role of the underlying human immunodeficiency virus infection as a risk factor for acquiring such a fungal complication remained unclear, whereas we considered the femoral prosthesis as the major predisposing factor. Especially, this report first noted the affinity of R. mucilaginosa for orthopedic devices, besides further emphasizing the affinity of all members of the Rhodotorula genus for synthetic materials in general, such as intravenous catheters, contact lenses, plastic materials of fiber-optic bronchoscopes, and hemodialysis machines (3, 7). This is remarkable, as osteomyelitis by this fungus may represent a life-threatening disease if complicated by fungemia; in fact, fungemia would appear to be a difficult-to-treat infection, leaving few therapeutic alternatives and making the removal of the catheter a needed step for treatment, given the strong adherence of this yeast to the device surface. Finally, we would emphasize the widespread antifungal resistance among organisms of the Rhodotorula genus. This mainly appears to be an azole resistance, so that amphotericin B still remains a great weapon against serious infections by this yeast.

ACKNOWLEDGMENTS
We thank Annarita Perfetti for her collaboration.

FOOTNOTES
* Corresponding author. Mailing address: Clinical Microbiology and Virology Unit, Department of Transfusion Medicine, Spirito Santo Hospital, via Fonte Romana 8, 65100 Pescara, Italy. Phone: 320-6265740. Fax: 085-4252607. E-mail:
vincsavi{at}yahoo.it 
Published ahead of print on 27 August 2008. 

REFERENCES
1 - Anatoliotaki, M., E. Mantadakis, E. Galanakis, and G. Samonis. 2003. Rhodotorula species fungemia: a threat to the immunocompromised host. Clin. Lab. 49:49-55.[Medline]
2 - Braun, D. K., and C. A. Kauffman. 1992. Rhodotorula fungemia: a life-threatening complication of indwelling central venous catheters. Mycoses 35:305-308.[Medline]
3 - Cutrona, A. F., M. Shah, M. S. Himes, and M. A. Miladore. 2002. Rhodotorula minuta: an unusual fungal infection in hip joint prosthesis. Am. J. Orthop. 31:137-140.[Medline]
4 - Espinel-Ingroff, A., M. Pfaller, S. A. Messer, C. C. Knapp, N. Holliday, and S. B. Killian. 1999. Multicenter comparison of the Sensititre YeastOne Colorimetric Antifungal Panel with the National Committee for Clinical Laboratory Standards M27-A reference method for testing clinical isolates of common and emerging Candida spp., Cryptococcus spp., and other yeasts and yeast-like organisms. J. Clin. Microbiol. 37:591-595.[Abstract/Free Full Text]
5 - Galan-Sanchez, F., P. Garcia-Martos, C. Rodriguez-Ramos, P. Marin-Casanova, and J. Mira-Gutiérrez. 1999. Microbiological characteristics and susceptibility patterns of strains of Rhodotorula isolated from clinical samples. Mycopathologia 145:109-112.[CrossRef][Medline]
6 - Gomez-Lopez, A., E. Mellado, J. L. Rodriguez-Tudela, and M. Cuenca-Estrella. 2005. Susceptibility profile of 29 clinical isolates of Rhodotorula spp., and literature review. J. Antimicrob. Chemother. 55:312-316.[Abstract/Free Full Text]
7 - Goyal, R., S. Das, A. Arora, and A. Aggarwal. 2008. Rhodotorula mucilaginosa as a cause of persistent femoral nonunion. J. Postgrad. Med. 54:25-27.[Medline]
8 - Pfaller, M. A., D. J. Diekema, D. L. Gibbs, V. A. Newell, J. F. Meis, I. M Gould, W. Fu, A. L. Colombo, E. Rodriguez-Noriega, and the Global Antifungal Surveillance Study. 2007. Results from the ARTEMIS DISK Global Antifungal Surveillance study, 1997 to 2005: an 8.5-year analysis of susceptibilities of Candida species and other yeast species to fluconazole and voriconazole determined by CLSI standardized disk diffusion testing. J. Clin. Microbiol. 45:1735-1745.[Abstract/Free Full Text]
9 - Preney, L., M. Theraud, C. Guiguen, and J. P. Cangneux. 2003. Experimental evaluation of antifungal and antiseptic agents against Rhodotorula spp. Mycoses 56:492-495.
10 - Samonis, G., M. Anatoliaki, H. Apostolakou, S. Maraki, D. Mavroudis, and V. Georgoulias. 2001. Transient fungemia due to Rhodotorula rubra in a cancer patient: case report and review of the literature. Infection 29:173-176.[CrossRef][Medline]
11 - Tuon, F. F., G. M. de Almeida, and S. F. Costa. 2007. Central venous catheter-associated fungemia due to Rhodotorula spp.—a systematic review. Med. Mycol. 45:441-447.[CrossRef][Medline]
12 - Zaas, A. K., M. Boyce, W. Schell, B. A. Lodge, J. L. Miller, and J. R. Perfect. 2003. Risk of fungemia due to Rhodotorula and antifungal susceptibility testing of Rhodotorula isolates. J. Clin. Microbiol. 41:5233-5235.[Abstract/Free Full Text]
Journal of Clinical Microbiology, October 2008, p. 3544-3545, Vol. 46, No. 10
0095-1137/08/$08.00+0 doi:10.1128/JCM.00873-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.