mycoses

Diagnosis,Therapy and Prophylaxis of Fungal Diseases

Case report

Rhodotorula glutinis meningitis: a case report and review of literature Sarala Menon,1 H. R. Gupta,2 R. Sequeira,2 Shazia Chavan,1 D. Gholape,2 S. Amandeep,1 N. Bhilave2 and A. S. Chowdhary1 1 Department of Microbiology, Grant Government Medical College and Sir J J Hospital, Mumbai, India and 2Department of General Medicine, Grant Government Medical College and Sir J J Hospital, Mumbai, India

Summary

Rhodotorula is ubiquitous saprophytic yeast belonging to phylum Basidiomycota. These encapsulated basidiomycetes are being increasingly recognised as important emerging human pathogens. There are scanty reports of meningitis caused by Rhodurorula spp in HIV infected patients. We present one such case of meningitis by Rhodutorula glutinis in HIV-infected patient. The patient also had a past history of abdominal tuberculosis. The diagnosis of Rhodotorula was confirmed by Gram staining and culture of the cerebrospinal fluid (CSF). Contamination was ruled out by repeated culturing of CSF from the same patient. Therapy with Amphotericin B showed good results. Patient was discharged from the hospital. However, in the seventh month of follow-up patient was readmitted with complaints of fever, breathlessness, altered sensorium, vomiting and succumbed to his illness. This time the CSF cultures remained negative for Rhodotorula, acid fast bacilli and other pyogenic organisms. Our last 11-year retrospective analysis of 8197 specimens received for mycological work-up showed that this is the first report of R. glutinis isolation from our institute.

Key words: Rhodotorula, yeast, meningitis, HIV infected, opportunistic infection.

Introduction Rhodotorula spp are ubiquitous saprophytic yeast that can be recovered from many environmental sources.1 Rhodotorula spp also exist as commensals on the skin, nails, and mucous membranes.2,3 While Rhodotorula strains appear to be less virulent than the more common yeast pathogens (Candida and Cryptococcus neoformans), during the last two decades, they have emerged as opportunistic pathogens particularly in immunocompromised patients.4,5 In the ARTEMIS surveillance project, Rhodotorula species were the fourth most Correspondence: Dr Sarala Menon, Associate Professor, Department of Microbiology, Grant Medical College and Sir J J Hospital, Mumbai 400008, India. Tel.: +91 98 6778 9568. Fax: +91 22 2371 2454. E-mail: [email protected] Submitted for publication 18 October 2013 Revised 21 January 2014 Accepted for publication 30 January 2014

doi:10.1111/myc.12180

common non-candidal yeast isolated from clinical specimens (4.2% of 8821 isolates).6 The genus Rhodotorula includes eight species, of which Rhodotorula mucilaginosa, Rhodutorula glutinis and Rhodotorula minuta are known to cause disease in humans.7 They have been implicated as causes of meningitis, endocarditis, ventriculitis, peritonitis, fungaemia, CVC-related infections and keratitis.4,8–13 Rhodotorula infections have been associated with a crude mortality rate of up to 15%.4 They can also cause sepsis and other lifethreatening complications.2,3 We present the first such case of R. glutinis meningitis from our institute.

Case report A 50-year-old male, a known case of retroviral disease with past history of abdominal tuberculosis, was admitted with low-grade fever (insidious, intermittent and associated with chills), severe headache and altered sensorium for 5 days. On physical examination he had a temperature of 100 °F. Central Nervous

© 2014 Blackwell Verlag GmbH Mycoses, 2014, 57, 448–452

Rhodotorula glutinis meningitis

System examination revealed disorientation and altered sensorium with signs of neck stiffness and increased planter reflexes. Cardiovascular and respiratory system were normal. Per-abdominal examination showed abdomen to be soft with no hepato-splenomegaly. X-ray of the chest was normal. Cerebral NECT scan showed mild cerebral atrophy and bilateral maxillary and left ethmoid sinusitis. MRI showed generalised cerebral atrophy fluid in mastoid air cells bilaterally and inflammatory thickening in both maxillary and ethmoid sinuses. Serological test for HIV was reactive for HIV-1 antibodies by COMB AIDS (first test), Pareekshak Triline (second test), Pareekshak Trispot (third test). CD4+T cells absolute – 119 cells ll 1 and CD4+T cells percentage – 5%. Rapid test for Malaria antigen was negative. NS1 antigen, IgG and IgM antibodies for dengue were negative. Antigen detection for C. neoformans was done by Latex Agglutination Test (LAT) and was found to be negative. IgM for Toxoplasma gondii done by solid phase capture enzyme immunoassay was also negative. Lumber puncture yielded slightly hazy cerebrospinal fluid (CSF) in appearance with colourless supernatant and deposit present but cobweb coagulum was absent. The CSF was then sent to our laboratory for mycological work-up.

Figure 1 Gram staining of cerebrospinal fluid (CSF) showing

Gram positive, 4–6 lm in diameter narrow-based budding yeast cells (91000).

Mycological investigations Our laboratory received CSF for microscopy and culture. Initially Gram stain and India ink preparation was performed on CSF.7,14,15 Both revealed no organisms. Ziehl Neelsen stain was negative for acid fast bacilli. No organisms grew on bacteriological culture of CSF. However, CSF culture on Sabouraud’s dextrose agar with antibiotics (chloramphenicol – 0.05 mg l 1 and cycloheximide – 0.5 mg l 1) and without antibiotics at 30 °C and 37 °C revealed the coral red coloured, pasty and mucoid growth after 4–5 days of incubation. Similar growth was also observed on Lowenstein-Jensen media which was inoculated for acid fast organisms. Gram staining of the colony showed presence of yeast. Although the colony morphology & Gram stain was suggestive of the organism as Rhodotorula spp, our reluctance to identify it as causative agent of the disease was due to the saprophytic nature of the organism. However, the findings were communicated to the clinician with a note of possibility of contaminants. Because of the persisting symptoms, on day 7 repeat CSF was sent from the same patient. This time Gram stain of CSF showed presence of Gram-positive yeast (4–6 l in diameter)

© 2014 Blackwell Verlag GmbH Mycoses, 2014, 57, 448–452

Figure 2 Gram staining of colony showing Gram positive,

4–6 lm in diameter budding yeast cells (91000).

with narrow-based budding (Fig. 1). India ink preparation also revealed the presence of small halos around the yeast. Similar growth was observed on Sabouraud’s medium with and without antibiotics. Repeated isolation of the same organism made us label this organism as the causative agent. The organism was presumptively identified as Rhodotorula by coral red pasty mucoid growth after Gram stain of colony (Fig. 2). Ballistospore test was set up to rule out another coral red fungus, Sporobolomyces. As this yeast was from CSF and was urease positive, we performed inositol and nitrate assimilation tests using modified Wickerham medium to rule out Cryptococcus.

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Tubes of yeast nitrogen base without inositol and yeast carbon base without potassium nitrate served as controls. Test yeast strain was found to be negative for inositol assimilation and was able to assimilate nitrate hence was confirmed as R. glutinis. However, blood cultures showed no growth on culture. After Microbiology culture reports, the patient was put on Amphotericin B (lyophilised, 1 gm given in 14 days) along with antiretroviral therapy. CSF examined 10 days after the beginning of the antifungal treatment showed no growth. However, in the seventh month of followup patient was readmitted with complaints of fever, breathlessness for 3 days and altered sensorium and vomiting. This time the CSF cultures remained negative for Rhodotorula, acid fast bacilli and other pyogenic organisms. The patient’s condition deteriorated after 7 days of admission and he succumbed to his illness.

Discussion Rhodotorula is a basidiomycetous yeast genus that produces carotenoid pigments (yellowish to red), multilateral budding cells, rudimentary pseudohyphae and occasionally a faint capsule. Individual colonies are usually pink or coral in colour, yeast-like, smooth and sometimes mucoid in appearance.16 Rhodotorula is common environmental yeast that is found in air, soil, lakes, ocean water, milk, fruit juices. Previously regarded as non-pathogenic, Rhodotorula spp have emerged as opportunistic pathogens with the ability to colonise and infect susceptible patients.1 Rhodotorula infections occur worldwide but are most frequently isolated in the Asia–Pacific region (48.8%).16 However, our retrospective analysis of 11-year data (2002–2012) showed that this is the first isolation of Rhodotorula spp from this institute. A total of 8197 specimens were received for mycology work-up during this period. Of the 8197, 4378 were CSF specimens. One hundred and eighty-one (4.13%) CSF specimens were culture positive which constituted, C. neoformans (n = 179), Trichosporon asahii (n = 1) and R. glutinis (n = 1). Rhodotorula spp. are being now increasingly reported as important human pathogens.4,8–13 Rhodotorula is mostly seen associated with immunosuppressed individuals, especially undergoing invasive procedures.17 Most cases of Rhodotorula infection are fungaemia associated with catheters, endocarditis and meningitis.18 Immunocompetent individuals are also at the risk of infection by this fungus, but with low prevalence.19

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Meningitis caused by Rhodotorula species is still rare. Tuon and Costa [18] have taken a systematic review of 128 cases of Rhodotorula infections. From 128 cases, five cases were of meningitis and one of ventriculitis. Few of the available complete reports along with these five cases are compiled in Table 1. Table 1 shows that in most of the patients the underlying condition reported is HIV-1 infection which is leading to low CD4 count with the exception of Khanna et al [27] report where the patient was HIV 2 infected. The commonest species causing meningitis seems to be Rhodotorula muciliginosa. R. glutinis seems to be rare species associated with meningitis with only few cases reported in literature.9,25 It appears that Rhodotorula meningitis should be considered a hospital infection, although there is one case of community acquired infection was reported.19 In our case, it is very difficult to hypothesise the pathogenesis of meningitis. Our patient was a known case of abdominal Koch’s with retroviral disease. So, initially the diagnosis was tuberculous meningitis looking in to history, clinical and biochemical parameters of CSF analysis. However, CSF culture repeatedly showed growth of Rhodotorula and remained negative for tubercle as well as pyogenic organisms. After the Rhodotorula report, he was administered with antifungal therapy with Amphotericin B (lyophilised, 1 gm given in 14 days). Patient responded well to Amphotericin B. CSF also was showing no growth of any organism including Rhodotorula. Our patient was on fluconozole (preventive) therapy. In spite of this preventive therapy, he developed meningitis. Literature survey does mention that Rhodotorula species are susceptible to amphotericin and flucytosine in vitro, but not to fluconazole or caspofungin; susceptibility to triazoles such as voriconazole is variable.13,28 Amphotericin is the antifungal agent of choice for treatment of Rhodotorula infections.6. Neither fluconazole nor the echinocandins should be used to treat infections due to Rhodotorula species, and the role of the extended-spectrum triazoles is uncertain. Of the extended-spectrum triazoles, ravuconazole is the most potent.6 No secondary prophylaxis was given in the present case as CSF culture was negative on readmission. Gyaurgieva et al. [22] have reported relapse of Rhodotorula meningitis. The infection in this case was then eradicated with suppressive and maintenance therapy of itraconazole. However, in the present case, the patient was presented with fever, breathlessness, altered sensorium, vomiting after 7 months. CSF remained negative for Rhodotorula, tubercle bacilli as well as pyogenic organisms. The major factors which were found to be associated with

© 2014 Blackwell Verlag GmbH Mycoses, 2014, 57, 448–452

Rhodotorula glutinis meningitis

Table 1 Rhodotorula meningitis cases reported in the literature. Author

Age/sex

Previous disease

Diagnosis

Rhodotorula spp

Treatment

Outcome

Pore & Chen [20]

14/M

Meningitis

R. mucilaginosa

AMB

Death

Donald [21] Gyaurgieva [22]

32/F 39/M

Acute lymphocytic leukaemia Meningioma AIDS

Ventriculitis Meningitis

R. mucilaginosa R. mucilaginosa

5FC 5FC, itraconazole

Huttova [23] Ahmed [24] Lanzafame et al. [25] Thakur et al. [26] Baradkar & Kumar [8]

13/M 65/M 69/M 30/M 36/M

Neuroblastoma AIDS Immunocompetent HIV-1 infected HIV-1 infected

Meningitis Meningitis Meningitis Meningitis Meningitis

R. mucilaginosa R. mucilaginosa Rhodotorula glutinis R. mucilaginosa R. mucilaginosa

Shinde et al. [9] Loss et al. [19]

36/M 58/M

HIV-1 infected Immunocompetent

R. glutinis R. mucilaginosa

Khanna [27] Present study 2012

45/F 50 years/M

HIV-2 infected HIV-1 infected

Meningitis Meningitis & infective endocarditis Meningitis H/O Abdominal Kochs Meningitis

Miconazole Miconazole AMB AMB+ 5FC AMB+ itraconazole AMB AMB

Cure Relapse after 6 months, Suppressive therapy with itraconazole eradicated the infection Cure Death Cure Death Cure

R. mucilaginosa R. glutinis

AMB AMB

Cure Cure Cure Patient responded to AMB, discharged from hospital, however, death after 7 months after initial discharge.

AMB, Amphotericin B; 5FC, 5 Flurocytosine.

his death are the patient’s compromised immune status (low CD4 count), HIV status as well as history of tuberculosis. The patient did not have any response to antiretroviral therapy and remained severely lymphopenic during the entire treatment course and readmission. Although Rhodotorula does not seem to be the cause of the death in this particular case, one definitely needs to look for fungal causes especially in immunocompromised patients. This may lead to early and targeted therapy towards this fungi and longer life expectancy. In spite of the increased number of invasive infections due to Rhodotorula spp., limited data on antifungal susceptibility are available.5 The list of documented fungal pathogens is extensive, and one can no longer ignore fungi as contaminants or clinically insignificant when they are isolated from sterile body fluids. It is also apparent that the prognosis and response to therapy may vary with the type of fungus as well as with the immune status of the host. Both clinicians and microbiologists should make a joint effort to identify these newer agents associated with various clinical conditions and also generate data on susceptibility patterns.

© 2014 Blackwell Verlag GmbH Mycoses, 2014, 57, 448–452

Acknowledgements Authors would like to acknowledge help of various departments (such as Radiology, Medicine, Biochemistry, Pathology laboratories) as their findings are used to discuss this case in this report.

References 1 2

3 4

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Wirth F, Goldani LZ. Epidemiology of Rhodotorula: an emerging pathogen. Interdiscip Perspect Infect Dis 2012; 465717: 7. Pfaller MA, Diekema DJ. Rare and emerging opportunistic fungal pathogens: concern for resistance beyond Candida albicans and Aspergillus fumigatus. J Clin Microbiol 2004a; 42: 4419–31. Richardson M, Lass-Florl C. Changing epidemiology of systemic fungal infections. Clin Microbiol Infect 2008; 14(Suppl. 4): 5–24. De Almeida GMD, Costa SF, Melhem M et al. Rhodotorula spp. isolated from blood cultures: clinical and microbiological aspects. Med Mycol 2008; 46: 547–56. Lopez AG, Mellado E, Tudela JLR, Estrella MC. Susceptibility profile of 29 clinical isolates of Rhodotorula spp. and literature review. J Antimicrob Chemother 2005; 55: 312–6. Pfaller MA, Diekema DJ, Gibbs DL et al. 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 fl uconazole and voriconazole determined by CLSI standardized diffusion testing. J Clin Microbiol 2007; 45: 1735–45.

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Larone DH. Medically Important Fungi-A Guide to Identification, 4th edn. Washington DC: ASM Press, 2002: 131–2, 328–9. 8 Baradkar VP, Kumar S. Meningitis caused by Rhodotorula mucilaginosa in human immunodeficiency virus seropositive patient. Ann Indian Acad Neurol 2008; 11: 245–7. 9 Shinde RS, Mantur BG, Patil G, Parande MV, Parande AM. Meningitis due to Rhodotorula glutinis in an HIV infected patients. Indian J Med Microbiol 2008; 26: 375–7. 10 Hsueh P-R, Teng L-J, Ho S-W, Luh K-T. Catheter- related sepsis due to Rhodotorula glutinis. J Clin Microbiol 2003; 41: 857–9. 11 Fung HB, Martyn CA, Shahidi A, Brown ST. Rhodotorula mucilaginosa lymphadenitis in an HIV- infected patient. Inter J Infect Dis 2008; 13: e27–e29. 12 Riedel DJ, Johnson JK, Forrest GN. Rhodotorula glutinis fungemia in a liver-kidney transplant patient. Transpl Infect Dis 2007; 10: 197–200. 13 Zaas AK, Boyce M, Schell W, Alexander lodge B, Miller JL, Perfect JR. Risk of fungemia due to Rhodotorula and antifungal susceptibility testing of Rhodotorula isolates. J Clin Microbiol 2003; 41: 5233–5. 14 Colle JG, Fraser AG, Marmion BP, Simmon A. Mackie and McCartney Practical Medical Microbiology. 14th edn. Edinburgh: Churchill Livingstone, 1996: 695–717. 15 Rippon JW, Medical Mycology. The Pathogenic Actinomycetes. 3rd edn. New York: WB Saunders Company, 1988: 582–609. 16 Miceli MH, Diaz JA, Lee SA. Emerging opportunistic infections. Lancet Infect Dis 2011; 11: 142–51. 17 Lo RV III, Fishman NO, Nachamkin I. Recurrent catheter - related Rhodotorula rubra infection. Clin Microbiol Infect 2003; 9: 897–900. 18 Tuon F, Costa S. Rhodotorula infection. A systematic review of 128 cases from literature. Rev Iberoam Micol 2008; 25: 135–40. 7

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25

26

27

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Loss SH, Antonio CP, Roehrig C, Castro PS, Maccari JG. Meningitis and infective endocarditis caused by Rhodotorula mucilaginosa in an immunocompetent patient. Rev Bras Ter Intensiva 2011; 23: 507–9. Pore RS, Chen J. Meningitis caused by Rhodotorula. Sabouraudia 1976; 14: 331–5. Donald FE, Sharp JF, Firth JL, Crowley JL, Ispahani P. Rhodotorula rubra ventriculitis. J Infect 1988; 16: 187–91. Gyaurgieva OH, Bogomolova TS, Gorshkova GI. Meningitis caused by Rhodotorula rubra in an HIV - infected patient. J Med Vet Mycol 1996; 34: 357–9. Huttova M, Kralinsky K, Horn J et al. Prospective study of nosocomial fungal Meningitis in children – Report of 10 Cases. Scand J Infect Dis 1998; 30: 485–7. Ahmed A, Aggarwal M, Chiu R, Ramratnam B, Rinaldi M, Flanigan TP. A fatal case of Rhodotorula meningitis in AIDS. Med Health R I 1998; 81: 22–23. Lanzafame M, De Checchi G, Parinello A, Trevenzoli M, Cattelan AM. Rhodotorula glutinis related meningitis. J Clin Microbiol 2001; 39: 410. Thakur K, Singh G, Agrawal S, Rani L. Meningitis caused by Rhodotorula rubra in an human immunodefi ciency virus infected patient. Indian J Med Microbiol 2007; 25: 166–8. Khannna A, Khanna M, Aggarwal A. Rhodotorula meningitis in a HIV-2 seropositive patient: a case report. J Clin Diagn Res 2012; 6: 123–6. Diekema DJ, Petroelje B, Messer SA, Hollis RJ, Pfaller MA. Activities available and investigational antifungal agents against Rhodotorula species. J Clin Microbiol 2005; 43: 476–8.

© 2014 Blackwell Verlag GmbH Mycoses, 2014, 57, 448–452

Rhodotorula glutinis meningitis: a case report and review of literature.

Rhodotorula is ubiquitous saprophytic yeast belonging to phylum Basidiomycota. These encapsulated basidiomycetes are being increasingly recognised as ...
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