JOURNAL OF CLINICAL MICROBIOLOGY , Feb. 2003, p. 857859 Vol. 41, No. 2 [601628]

JOURNAL OF CLINICAL MICROBIOLOGY , Feb. 2003, p. 857–859 Vol. 41, No. 2
0095-1137/03/$08.00 /H110010 DOI: 10.1128/JCM.41.2.857–859.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.
Catheter-Related Sepsis Due to Rhodotorula glutinis
Po-Ren Hsueh,1,2* Lee-Jene Teng,1,3Shen-Wu Ho,1,3
and Kwen-Tay Luh1,2
Departments of Laboratory Medicine1and Internal Medicine,2National Taiwan University
Hospital, and School of Medical Technology,3National Taiwan
University College of Medicine, Taipei, Taiwan
Received 8 July 2002/Returned for modification 3 October 2002/Accepted 21 October 2002
We describe a central venous catheter-related (Port-A-Cath; Smiths Industries Medical Systems [SIMS]
Deltec, Inc., St. Paul, Minn.) infection caused by Rhodotorula glutinis in a 51-year-old man with nasopharyngeal
carcinoma. He was treated with fluconazole for 8 weeks and had the catheter removed. Two isolates of R. glutinis
recovered from blood specimens (one obtained via peripheral veins and one via the catheter) before admin-
istration of fluconazole and one recovered from the removed catheter 17 days after initiation of fluconazole
therapy exhibited high-level resistance to fluconazole (MICs, >256 /H9262g/ml). These three isolates were found to
belong to a single clone on the basis of identical antibiotypes determined by the E test (PDM Epsilometer; ABBiodisk, Solna, Sweden) and biotypes determined by API ID32 C (bioMerieux, Marcy I’Etoile, France) andtheir identical random amplified polymorphic DNA patterns.
Species of the genus Rhodotorula are commensals in the
natural environment and in humans (1, 2, 4; M. Cowan and J.
Allen, Letter, J. Hosp. Infect. 19:293, 1991). Infections due to
Rhodotorula species have rarely been reported (1, 2, 5, 8–10,
12, 13). The majority of these infections are associated with theuse of indwelling venous catheters in patients with underlyingmalignancy (1, 2, 5, 10, 12, 13). Several Rhodotorula species
have been described as human pathogens, among which R.
rubra is the most common species (4, 8, 12). Although there
have been reports demonstrating three cases of culture-proven
R. glutinis fungemia in patients with intravenous catheters (12,
13), none of these have described the use of molecular typingmethods to demonstrate the genetic identity of multiple iso-lates of the organism from peripheral blood or from the cath-eter.
Case report. A 51-year-old man was found to have nasopha-
ryngeal carcinoma in May 1990 and received radiotherapy andintensive chemotherapy from June to August 1990. He washealthy for the following 7 years. Unfortunately, multiple bonemetastases were noticed in January 1998. He received localradiotherapy for bone lesions and eight courses of chemother-apy with various regimens from July 1998 to July 1999. APort-A-Cath catheter (Smiths Industries Medical Systems[SIMS] Deltec, Inc., St. Paul, Minn.) was implanted in June1999. From June 1999 to October 2000, he was admitted to thehospital three times due to facial cellulitis (caused by group GStreptococcus on one occasion and of unknown etiology on two
occasions) and was treated successfully with antibiotics. Thecatheter was flushed each time during his monthly visits to theoncology clinic.
On 18 November 2000, 1 day after the catheter was flushed,
he developed a fever and visited the emergency department.There were no obvious inflammatory signs over the cathetersite. His white blood count was 4,200/mm
3with 78% neutro-
phils. The fever disappeared spontaneously within 1 day. Cul-
ture of one blood specimen aspirated via the catheter duringthe febrile period was inoculated into one BACTEC Myco/FLytic bottle (Becton Dickinson, Sparks, Md.), which yielded ared yeast ( Rhodotorula species) (isolate A). Fever recurred 5
days later and again disappeared spontaneously. Blood cul-
tures collected from peripheral veins and from the catheter at
the emergency department also yielded red yeasts 5 days afterincubation (the isolates were not preserved). He returned tothe outpatient clinic on 29 November 2000 and remained afe-brile. Fluconazole (200 mg per day) was administered orallybeginning on 30 November. Unfortunately, fever up to 38.3°Coccurred on 3 December and he was admitted to the hospital.
After admission, Port-A-Cath-related fungemia was sus-
pected. Removal of the vascular catheter and treatment withamphotericin B were recommended, but the patient insisted onkeeping the catheter and remaining on fluconazole therapybecause of fear of the informed side effects of amphotericin B.Intravenous fluconazole (400 mg per day) was given immedi-ately after blood cultures were performed. His fever subsided2 days later. Five days after the patient’s fever had subsided,cultures from the blood also yielded a red yeast, which wasidentified as R. glutinis (isolate B) (see below). Two blood
cultures performed on the 7th and 12th days after initiation ofintravenous fluconazole did not disclose the presence of thered yeast. The catheter was subsequently removed on the 17thday of hospitalization, and cultures of blood drawn from pe-ripheral veins and the catheter and of blood-like material be-tween the disk and metal portions of the catheter were alsodone. A Gram stain of the blood-like material disclosed manyyeast-like organisms, which were later found to be red yeasts(isolate C). The culture of blood drawn from the catheter andperipheral veins did not yield the organism. The patient re-mained afebrile after initiation of fluconazole therapy, and thedrug treatment was continued for about 4 weeks. He was dis-charged on 29 December 2000, and oral fluconazole (600 mgper day) was administrated for an additional 4 weeks. Two sets
* Corresponding author. Mailing address: Department of Labora-
tory Medicine, National Taiwan University Hospital, No. 7 Chung-
Shan South Rd., Taipei, Taiwan. Phone: 886-2-23123456, ext. 5363.Fax: 886-2-23224263. E-mail: hsporen@ha.mc.ntu.edu.tw.
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of blood cultures were collected 1 month after discontinuation
offluconazole therapy and were negative for the organism. At
the 3-month follow-up, there was no evidence of recurrence.
Microbiology. All isolates (A, B, and C) were identi fied as R.
glutinis by use of conventional methods (orange colonies on
Sabouraud dextrose agar at 25 °C and oval budding cells with-
out pseudohyphae on cornmeal-Tween 80 agar [Difco Labo-
ratories, Detroit, Mich.]) and API ID32 C (code number5475750313; probability of species identi fication, 99.7%; typi-
cality index, 99.6%) (bioMerieux, Marcy I ’Etoile, France). For
comparison, two isolates of R. glutinis (one blood isolate [D]
and one isolate from pus [E] recovered from two patients seenat the National Taiwan University Hospital in 1999 and 2000,respectively) were also included in the study as control strains.
The MICs for these isolates, determined by the E test (PDM
Epsilometer; AB Biodisk, Solna, Sweden), were measured onRPMI 1640 –2% glucose agar medium supplemented with mor-
pholinepropanesulfonic acid (MOPS) as previously described(6). The MICs were read after 2 days of incubation at 37 °C.
Measurement of the MICs of fluconazole for these isolates was
also performed using the methods recommended by the Na-tional Committee for Clinical Laboratory Standards (11). Ran-dom ampli fied polymorphic DNA (RAPD) patterns of these
isolates were determined by arbitrarily primed PCR as de-scribed previously (6). The three oligonucleotide primers used,M13 (5 /H11032-GAGGGTGGCGGTTCT-3 /H11032), OPH-15 (5 /H11032-AATGG
CGCAG-3 /H11032), and OPH-19 (5 /H11032-CTGACCAGCC-3 /H11032) were cho-
sen from 20 primers in a kit (OPH-1 to OPH-20) purchased
from Operon Technologies, Inc. (Alameda, Calif.).
Isolates A, B, and C had identical antibiotypes: amphoteri-
cin B MICs of 0.125 /H9262g/ml, fluconazole MICs of /H11022256/H9262g/ml
(the MICs determined by the E test and the NCCLS methodwere identical), ketoconazole MICs of 0.25 /H9262g/ml, itraconazole
MICs of 8 /H9262g/ml, and flucytosine MICs of 0.06 /H9262g/ml. How-
ever, for isolates D and E, the itraconazole MICs were 0.5 and1/H9262g/ml, respectively, while the MICs of the other four agents
were within one to two twofold dilutions of those for isolatesA, B, and C. Isolates A, B, and C had identical RAPD patterns(they shared every band), and these patterns were different
from those of the three control isolates (Fig. 1).Discussion. Our findings are unique for three reasons. First,
although catheter-related R. glutinis infection has been previ-
ously described, our report using phenotypic and genotypic
typing methods clearly demonstrates that R. glutinis caused
catheter-related infection (isolates recovered from peripheralblood and the inner part of the catheter had identical pheno-types and genotypes). The recurrent nature of infection wasdue to the persistence of this organism in the catheter for aperiod of at least 1 month. Second, strains of R. glutinis are
intrinsically highly resistant to fluconazole, and amphotericin B
is the drug of choice for treating infections caused by thisorganism. Fluconazole at a dosage of 400 mg per day admin-istered intravenously seemed to improve our patient ’s clinical
condition and remove the yeasts from his bloodstream. Obvi-
ously, after 17 days of treatment, this agent failed to clear thisorganism from the inside of the catheter. The reason why theorganism was cleared from the bloodstream but not from theinner part of the catheter (the concentrations of fluconazole
running through the catheter would be theoretically highest)before the removal of the catheter is not fully understood. Theprobable immunocompetent status of the patient and the highfungal burden within the inner part of the catheter mightcontribute in part to this phenomenon. Moreover, bio film for-
mation by organisms such as Candida albicans has been dem-
onstrated to contribute to the persistence of the organism anddrug resistance (3). Determining whether this is also true of R.
glutinis requires further investigation. Finally, our study clearly
demonstrated that RAPD patterns generated by arbitrarily
primed PCR were acceptable as a typing method for a variety
of fungi, including R. glutinis isolates (6, 7).
Previous susceptibility studies of Rhodotorula species have
shown that all tested isolates were susceptible to amphotericinB (MICs ranged from 0.125 to 1.6 /H9262g/ml), ketoconazole (MICs
of/H113490.25/H9262g/ml), itraconazole (MICs ranged from 0.25 to 12.8
/H9262g/ml), and flucytosine (MICs of /H113490.25/H9262g/ml) and resistant to
fluconazole (MICs of /H1135032/H9262g/ml) (4). Among the 13 R. glutinis
isolates tested by Galan-Sanchez et al. (4), 92.3% were highlyresistant to fluconazole (MICs of /H11350256/H9262g/ml). The suscepti-
bility results for our isolates, i.e., high-level resistance to flu-
conazole and high MICs of itraconazole, were consistent withthese previous findings (4). Fluconazole is not recommended
as the drug of choice for the treatment of infections due toRhodotorula species (2, 4, 9, 13). In one previous report, flu-
conazole failed to clear R.glutinis within a central venous
catheter, which led to recurrent sepsis 5 days after the initia-tion of fluconazole treatment, necessitating subsequent am-
photericin B treatment in a nonneutropenic patient with acuteleukemia (13). The initial satisfactory improvement of ourpatient ’s clinical condition was the reason why we continued
fluconazole therapy for him.
Although strains of Rhodotorula species have been shown to
cause a variety of severe infections in humans, these organismshave frequently been reported as contaminants in cultureplates or medical equipment because of their ubiquitous exis-tence in the natural environment and have been known tocause nosocomial pseudoepidemics (1, 2, 4, 7, 14; Cowan andAllen, letter). In our patient, R. glutinis might have entered
into the bloodstream via repeated flushing with contaminated
normal saline or via an inadequately disinfected skin surfaceand then further multiplied and persisted within the catheter.
FIG. 1. RAPD patterns of the five isolates of R. glutinis obtained
with three primers: M13, OPH-15, and OPH-19. Lanes M, molecular
size markers (1-kb ladder; Gibco BRL, Gaithersburg, Md.); lanes A toE, patterns for isolates A to E, respectively. See the text for thedesignation of these isolates.858 NOTES J. C
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In conclusion, we report a microbiologically documented
central venous catheter-related infection caused by R. glutinis
in a nonneutropenic cancer patient. Although the isolate was
highly resistant to fluconazole in vitro, this agent (high dose)
was able to clear the organism from the bloodstream and thepatient received fluconazole treatment for 8 weeks and had the
catheter removed. Amphotericin B remains the most active
agent against this organism and should be used as the treat-
ment of choice.
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