Mycopathologia DOI 10.1007/s11046-015-9879-0
Meningitis Caused by Rhodotorula mucilaginosa in HIV-Infected Patient: A Case Report and Review of the Literature Fadzilah Mohd Nor • Lian Huat Tan Shi Ling Na • Kee Peng Ng
•
Received: 17 October 2014 / Accepted: 25 February 2015 Ó Springer Science+Business Media Dordrecht 2015
F. Mohd Nor (&) Drug Discovery and Health Community Research, Universiti Teknologi MARA, 40450 Shah Alam, Selangor, Malaysia e-mail: [email protected]
presented. High-grade fever and severe headaches were the complaints presented in three previous case reports. India ink and nigrosin stainings were performed in the two previous reports and both revealed positive results. R. mucilaginosa were isolated from the culture of the patient’s cerebrospinal fluid in all three previous reports. Predominant lymphocyte infiltration in the cerebrospinal fluid examination was documented in two reports. CD4 counts were above 100/ll in two previously published reports, while another report documented CD4 count as 56/ll. Amphotericin B and itraconazole are identified to be the first line of antifungal used and as the maintenance therapy, respectively. The possibility of relapse cannot be excluded as it was reported in the first report. It was also revealed that the current case has almost similar clinical presentation and therapeutic outcome as compared to the published reports, but some differences in diagnostic details were to be highlighted.
F. Mohd Nor Microbiology Unit, CPDRL, Faculty of Medicine, Universiti Teknologi MARA, Sg. Buloh Campus, Jalan Hospital, 47100 Sungai Buloh, Selangor, Malaysia
Keywords Meningitis Cerebrospinal fluid Rhodotorula mucilaginosa Human immunodeficiency virus infection
L. H. Tan Department of Infectious Diseases, Sunway Medical Centre, Jalan Lagoon Selatan, Bandar Sunway, 46150 Petaling Jaya, Selangor, Malaysia
Introduction
S. L. Na K. P. Ng Department of Medical Microbiology, Faculty of Medicine, University Malaya Medical Centre, 50603 Kuala Lumpur, Malaysia
Rhodotorula mucilaginosa (formerly known as Rhodotorula rubra) belongs to the Cryptococcaceae family. It is a basidiomycetous-encapsulated yeast,
Abstract Rhodotorula species are increasingly being identified as a cause of fungal infection in the central nervous system, especially in patients with compromised immunity. The diagnosis could easily be missed due to low index of suspicion, as cryptococcus meningitis and cerebral toxoplasmosis are more common amongst immunocompromised hosts. To date, there are six cases of Rhodotorula-related meningitis reported, and three are associated with human immunodeficiency virus infection. In this report, a case of a Malaysian male with underlying human immunodeficiency virus infection who developed Rhodotorula mucilaginosa meningitis is
123
Mycopathologia
characterized by the production of carotenoid pigments that give them their distinctive salmon pink to coral red appearance [1]. The fungus has inadvertently been isolated in human biological materials without pathological significance, as it has been found in urine and sputum, particularly in patients with severe debilitating diseases, blood from patients with permanent intravascular devices and saliva obtained from denture wearers [2]. Despite its ubiquitous nature, its potential to cause infection in the central nervous system (CNS), particularly in immunocompromised hosts, is being increasingly recognized in recent years. The omnipresent Rhodotorula as saprophytes, in association with Cryptococcus neoformans and Toxoplasma gondii, which are more frequent aetiological agents causing meningitis in human immunodeficiency virus (HIV)-infected patient, contributes to delay in making accurate diagnosis of Rhodotorula meningitis. To date, no known established scientific evidence is available explaining the pathogenic role of Rhodotorula in causing meningitis. This has created difficulties in making accurate diagnosis, which tends to lead to mismanagement of patient care. This case report will highlight a HIVpositive patient who developed meningitis caused by R. mucilaginosa and emphasize subtle differences that exist in our case in comparison with other reports.
Case Report A 35-year-old man with a history of unprotected homosexual activities was admitted with a 3-week history of high-grade fever associated with chills, loss of appetite and generalized weakness followed by 2 weeks of severe headache and non-productive cough. He denied any history of nausea, vomiting, upper and lower limb weakness, numbness, seizure, and change in mental state or vision. There were no joint pain, joint swelling and urinary and bowel symptoms. He also denied recent history of travelling or jungle trekking. He consulted several general practitioners and was given various medications including antibiotics, antipyretics and pain killers, but with no improvement. On physical examination, he was alert and conscious with full Glasgow coma scale. He was febrile with a temperature of 38 °C, blood pressure of 100/50 mmHg and pulse rate of 80 beats/min with
123
regular rhythm. Seborrhoeic dermatitis, angular cheilitis, oral thrush and cervical lymphadenopathy were present. A CNS examination and fundoscopy examination did not reveal any abnormality. Respiratory, abdominal and cardiovascular system examinations were unremarkable. A provisional diagnosis of chronic meningitis, specifically cryptococcus origin, was clinically suspected. Blood investigations were unremarkable except for mildly elevated transaminases and globulin. Contrasted computed tomography (CT) of the brain performed on day 1 after admission did not show any focal or diffuse brain lesion. Lumbar puncture was then performed and yielded clear cerebrospinal fluid (CSF) with opening pressure of ?15 cm H2O. The CSF biochemistry and microscopic analysis revealed a predominant neutrophil inflammatory response with normal glucose and elevated protein levels. Gram stain, Ziehl–Neelsen stain, India ink, cryptococcus latex antigen test, latex agglutination tests for Group B Streptococcus, Streptococcus pneumoniae, Haemophilus influenzae and Neisseria meningitidis were performed on the CSF but did not yield any positive findings. Blood was collected on day 3 of admission for bacterial and fungal culture, but both did not demonstrate any growth. Serum cryptococcus antigen, toxoplasma with cytomegalovirus (CMV) serology, rapid plasma reagin (RPR), hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibody and leptospira microscopic agglutination test (MAT) were all negative. Sputum examinations for acid-fast bacilli and mycobacterium culture were negative. However, HIV antibody testing was confirmed to be reactive by HIV Ag/Ab combo assay, chemiluminescent microparticle immunoassay, HIV 1/2 rapid test and particle agglutination test. Flow cytometry revealed that the CD4?T and CD8?T cell count and CD4/CD8 ratio were 313/ll (8 %), 3054 cells/ll (78 %) and 0.10, respectively. HIV viral load was performed and showed that 761 284 copies/ml of virion was detected based on real-time polymerase chain reaction. A positive growth of yeast was identified from CSF culture 48 h after lumbar puncture. A repeat lumbar puncture was carried out, and CSF analysis continued to show evidence of neutrophilic inflammatory response and elevated protein concentration. Empirical intravenous infusion of amphotericin B at 45 mg once daily (OD) (0.75 mg/kg body weight) was commenced
Mycopathologia
immediately while waiting for further identification of the organism. The CSF was inoculated on Sabouraud dextrose agar (SDA) and incubated at 35–37 °C. The growth of R. mucilaginosa was identified by its colonial morphology (salmon pink in colour and mucoid appearance). Multiple lateral budding yeast cells were seen on the Gram stain and were confirmed using API 32-C Bio-Merieux test kit. Antifungal susceptibility testing was performed. It was revealed that the minimum inhibitory concentration (MIC) of fluconazole and itraconazole against this isolate was [256 and 4 lg/ml, while MIC for amphotericin B, flucytosine and voriconazole was 0.064, 0.125 and 1.0 lg/ml, respectively. Diagnosis was revised to R. mucilaginosa meningitis, and intravenous amphotericin B 45 mg OD was continued. The dosage of amphotericin B was titrated to 35 mg OD (0.6 mg/kg body weight) on day 8 of the treatment as he began to develop drug-induced renal toxicity. He tolerated the lower dosage of amphotericin B with resolution of renal impairment. Headache was progressively reduced in severity, his fever and cough resolved following treatment, and his transaminases reduced. Repeat lumbar puncture and CSF analysis on day 11 of admission also showed remarkable improvement. Repeat CSF culture was negative for any growth. He was converted to itraconazole 200 mg twice a day (bid) after completing 14 days of amphotericin B and was discharged home well. Six weeks later, during his follow-up, it was noted that his headaches returned and he was readmitted for lumbar puncture to assess his CSF. At this time, he did not exhibit any neurological deficits and was still compliant to oral itraconazole 200 mg bid. After 48 h of his second admission, his CSF parameters returned to normal and there was no positive culture identified from the CSF. He was advised to continue oral itraconazole 200 mg bid while plans to institute highly active antiretroviral therapy (HAART) were in progress.
Discussion The genus Rhodotorula includes three active species that are isolated most frequently from clinical materials: Rhodotorula glutinis, Rhodotorula minuta and R. mucilaginosa [1]. Colonial morphology of R.
mucilaginosa exhibits coral pink colonies with smooth surfaces and mucoid yeast-like in appearance, while microscopic appearance shows the presence of blastoconidia with the absence of pseudohyphae. Biochemically, Rhodotorula does not ferment carbohydrates, but produces urease enzyme [3]. Rhodotorula spp. and Cryptococcus spp. share many similar morphological and physiological properties that may lead to mistaken identities. Rhodotorula differs from Cryptococcus by its inability to assimilate inositol and from Candida by its pink to red colonies and also the lack of pseudohyphae. In 1976, Pore and Chen [4] reported the first case of Rhodotorula rubra meningitis in a 21-year-old male patient with acute lymphoblastic leukaemia. Twelve years later, Donald et al. [5] reported a second case of meningitis caused by similar organism in a postoperative ventriculitis patient who was immunocompetent. In 1996, Gyaurgieva et al. [6] first reported a meningitis case in an HIV-infected patient caused by Rhodotorula rubra. Later in 2001, Lanzafame et al. [2] described a case of meningitis caused by Rhodotorula glutinis in an old man with no predisposing condition. In 2007, Thakur et al. [7] from India reported a second case of meningitis caused by Rhodotorula rubra in an HIV-infected patient, followed by Baradkar and Kumar [8] in 2008, who reported R. mucilaginosa meningitis in HIV-seropositive patient. To the best of our knowledge, there have been a total of six cases of Rhodotorula spp.-related meningitis and this current case is the seventh reported in the world. It also represents as the fourth case of meningitis caused by Rhodotorula rubra/mucilaginosa occurring in an HIV-infected patient (Table 1). Rhodotorula has been attributed rarely as an aetiological agent, and in all reviewed cases, infection was clearly opportunistic. Immunosuppressive hosts, prolonged usage of steroids and chemotherapy agents, and an advent of AIDS are the contributing factors responsible for the rise in CNS fungal infections including R. mucilaginosa infection. In this case, HIV appeared to be a prominent risk factor for developing the infection, similar to the three previously reported cases. Interestingly, Rhodotorula glutinis was isolated from the CSF of an old man with no predisposing condition. Thus, Rhodotorula meningitis could have developed due to old age. This case is unique for several reasons. Firstly, microscopic findings of the CSF showed negative for
123
Mycopathologia Table 1 Summary of meningitis cases caused by Rhodotorula mucilaginosa in HIV-infected patient reported from 1996 to 2014 Year
Predisposing factor
India ink/nigrosin staining
CSF examination
CD4 cell count
Outcome
1996
HIV
Not documented
Not documented
259/ll
Recovered but relapse after 8 months
2007
HIV
Positive
Lymphocyte 55 %
56/ll
Succumbed after 23 days of hospitalization
196 cells/mm3
Recovered and no relapse observed until last follow-up
313/ll
Recovered and no relapse observed until last follow-up
Neutrophil 45 % 2008
HIV
Positive
Lymphocyte 60 % Neutrophil 40 %
2014
HIV
Negative
Lymphocyte 17 % Neutrophil 83 %
India ink with neutrophilic predominance. Secondly, the patient’s CD4 cell count at presentation was relatively higher and lastly, the patient had a good outcome with rapid resolution of symptoms compared to the other three previously reported cases. A possibility of contamination by Rhodotorula was suspected due to the ubiquitous existence in natural environment, and it has been known to cause nosocomial pseudoepidemics [9]. However, this can be excluded in this patient as CSF is a sterile fluid and it was collected and processed under aseptic conditions. Furthermore, headaches and other symptoms resolved completely a few days after treatment was instituted. The possible connections between Rhodotorula species and human pathology have been discussed in the past, with considerable difficulty in identifying lesions pathognomonic for the organisms, even in the case of post-mortem examinations [2]. The clinical picture with mycological findings and the prompt response to therapy fit well together in this case. Thus, it was considered to have pathogenic role in causing meningitis in the case. Therefore, it is a challenge in denying the pathological role of Rhodotorula in causing diseases particularly meningitis in immunocompromised patients. Acknowledgments We thank Jennifer Chong, Dr. Thuhairah Hasrah, Nurul Athirah and Prof. Dr. T.S. Soo-Hoo for their excellent contributions to the article.
123
Conflict of interest The authors declare that they have no conflicts of interest concerning this article.
References 1. Anaissie EJ, McGinnis MR, Pfaller MA. Opportunistic Mycoses. In: Murray PR, Rosenthal KS, Pfaller MA, editors. Medical microbiology. Pennsylvania: Elsevier Mosby; 2005. p. 779–800. 2. Lanzafame M, De Checchi G, Parinello A, Catlelan AM, Trevenzoli M. Rhodotorula glutinis-related meningitis. J Clin Microbiol. 2001;39:410. 3. Ellis D. Rhodotorula. Fungal descriptions; yeast. University of Adelaide, Australia. http://www.mycology.adelaide.edu. au (2014). Accessed 17 Jul 2014. 4. Pore RS, Chen J. Meningitis caused by Rhodotorula. Saboraudia. 1976;14:331–5. 5. Donald FE, Sharp JF, Firth JL, Crowley JL, Ispahani P. Rhodotorula rubra ventriculitis. J Infect. 1988;16:187–91. 6. Gyaurgieva OH, Bogomolova TS, Gorshkova GI. Meningitis caused by Rhodotorula rubra in an HIV-infected patient. J Med Vet Mycol. 1996;34:357–9. 7. Thakur K, Singh G, Agarwal S, Rani L. Meningitis caused by Rhodotorula rubra in an human immunodeficiency virus infected patient. Indian J of Med Microbiol. 2007;25:166–8. 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. Braun DK, Kauffman CA. Rhodotorula fungaemia: a life threatening complication of indwelling central venous catheters. Mycoses. 1992;35:305–8.
Meningitis Caused by Rhodotorula mucilaginosa in HIV-Infected Patient: A Case Report and Review of the Literature Fadzilah Mohd Nor • Lian Huat Tan Shi Ling Na • Kee Peng Ng
•
Received: 17 October 2014 / Accepted: 25 February 2015 Ó Springer Science+Business Media Dordrecht 2015
F. Mohd Nor (&) Drug Discovery and Health Community Research, Universiti Teknologi MARA, 40450 Shah Alam, Selangor, Malaysia e-mail: [email protected]
presented. High-grade fever and severe headaches were the complaints presented in three previous case reports. India ink and nigrosin stainings were performed in the two previous reports and both revealed positive results. R. mucilaginosa were isolated from the culture of the patient’s cerebrospinal fluid in all three previous reports. Predominant lymphocyte infiltration in the cerebrospinal fluid examination was documented in two reports. CD4 counts were above 100/ll in two previously published reports, while another report documented CD4 count as 56/ll. Amphotericin B and itraconazole are identified to be the first line of antifungal used and as the maintenance therapy, respectively. The possibility of relapse cannot be excluded as it was reported in the first report. It was also revealed that the current case has almost similar clinical presentation and therapeutic outcome as compared to the published reports, but some differences in diagnostic details were to be highlighted.
F. Mohd Nor Microbiology Unit, CPDRL, Faculty of Medicine, Universiti Teknologi MARA, Sg. Buloh Campus, Jalan Hospital, 47100 Sungai Buloh, Selangor, Malaysia
Keywords Meningitis Cerebrospinal fluid Rhodotorula mucilaginosa Human immunodeficiency virus infection
L. H. Tan Department of Infectious Diseases, Sunway Medical Centre, Jalan Lagoon Selatan, Bandar Sunway, 46150 Petaling Jaya, Selangor, Malaysia
Introduction
S. L. Na K. P. Ng Department of Medical Microbiology, Faculty of Medicine, University Malaya Medical Centre, 50603 Kuala Lumpur, Malaysia
Rhodotorula mucilaginosa (formerly known as Rhodotorula rubra) belongs to the Cryptococcaceae family. It is a basidiomycetous-encapsulated yeast,
Abstract Rhodotorula species are increasingly being identified as a cause of fungal infection in the central nervous system, especially in patients with compromised immunity. The diagnosis could easily be missed due to low index of suspicion, as cryptococcus meningitis and cerebral toxoplasmosis are more common amongst immunocompromised hosts. To date, there are six cases of Rhodotorula-related meningitis reported, and three are associated with human immunodeficiency virus infection. In this report, a case of a Malaysian male with underlying human immunodeficiency virus infection who developed Rhodotorula mucilaginosa meningitis is
123
Mycopathologia
characterized by the production of carotenoid pigments that give them their distinctive salmon pink to coral red appearance [1]. The fungus has inadvertently been isolated in human biological materials without pathological significance, as it has been found in urine and sputum, particularly in patients with severe debilitating diseases, blood from patients with permanent intravascular devices and saliva obtained from denture wearers [2]. Despite its ubiquitous nature, its potential to cause infection in the central nervous system (CNS), particularly in immunocompromised hosts, is being increasingly recognized in recent years. The omnipresent Rhodotorula as saprophytes, in association with Cryptococcus neoformans and Toxoplasma gondii, which are more frequent aetiological agents causing meningitis in human immunodeficiency virus (HIV)-infected patient, contributes to delay in making accurate diagnosis of Rhodotorula meningitis. To date, no known established scientific evidence is available explaining the pathogenic role of Rhodotorula in causing meningitis. This has created difficulties in making accurate diagnosis, which tends to lead to mismanagement of patient care. This case report will highlight a HIVpositive patient who developed meningitis caused by R. mucilaginosa and emphasize subtle differences that exist in our case in comparison with other reports.
Case Report A 35-year-old man with a history of unprotected homosexual activities was admitted with a 3-week history of high-grade fever associated with chills, loss of appetite and generalized weakness followed by 2 weeks of severe headache and non-productive cough. He denied any history of nausea, vomiting, upper and lower limb weakness, numbness, seizure, and change in mental state or vision. There were no joint pain, joint swelling and urinary and bowel symptoms. He also denied recent history of travelling or jungle trekking. He consulted several general practitioners and was given various medications including antibiotics, antipyretics and pain killers, but with no improvement. On physical examination, he was alert and conscious with full Glasgow coma scale. He was febrile with a temperature of 38 °C, blood pressure of 100/50 mmHg and pulse rate of 80 beats/min with
123
regular rhythm. Seborrhoeic dermatitis, angular cheilitis, oral thrush and cervical lymphadenopathy were present. A CNS examination and fundoscopy examination did not reveal any abnormality. Respiratory, abdominal and cardiovascular system examinations were unremarkable. A provisional diagnosis of chronic meningitis, specifically cryptococcus origin, was clinically suspected. Blood investigations were unremarkable except for mildly elevated transaminases and globulin. Contrasted computed tomography (CT) of the brain performed on day 1 after admission did not show any focal or diffuse brain lesion. Lumbar puncture was then performed and yielded clear cerebrospinal fluid (CSF) with opening pressure of ?15 cm H2O. The CSF biochemistry and microscopic analysis revealed a predominant neutrophil inflammatory response with normal glucose and elevated protein levels. Gram stain, Ziehl–Neelsen stain, India ink, cryptococcus latex antigen test, latex agglutination tests for Group B Streptococcus, Streptococcus pneumoniae, Haemophilus influenzae and Neisseria meningitidis were performed on the CSF but did not yield any positive findings. Blood was collected on day 3 of admission for bacterial and fungal culture, but both did not demonstrate any growth. Serum cryptococcus antigen, toxoplasma with cytomegalovirus (CMV) serology, rapid plasma reagin (RPR), hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibody and leptospira microscopic agglutination test (MAT) were all negative. Sputum examinations for acid-fast bacilli and mycobacterium culture were negative. However, HIV antibody testing was confirmed to be reactive by HIV Ag/Ab combo assay, chemiluminescent microparticle immunoassay, HIV 1/2 rapid test and particle agglutination test. Flow cytometry revealed that the CD4?T and CD8?T cell count and CD4/CD8 ratio were 313/ll (8 %), 3054 cells/ll (78 %) and 0.10, respectively. HIV viral load was performed and showed that 761 284 copies/ml of virion was detected based on real-time polymerase chain reaction. A positive growth of yeast was identified from CSF culture 48 h after lumbar puncture. A repeat lumbar puncture was carried out, and CSF analysis continued to show evidence of neutrophilic inflammatory response and elevated protein concentration. Empirical intravenous infusion of amphotericin B at 45 mg once daily (OD) (0.75 mg/kg body weight) was commenced
Mycopathologia
immediately while waiting for further identification of the organism. The CSF was inoculated on Sabouraud dextrose agar (SDA) and incubated at 35–37 °C. The growth of R. mucilaginosa was identified by its colonial morphology (salmon pink in colour and mucoid appearance). Multiple lateral budding yeast cells were seen on the Gram stain and were confirmed using API 32-C Bio-Merieux test kit. Antifungal susceptibility testing was performed. It was revealed that the minimum inhibitory concentration (MIC) of fluconazole and itraconazole against this isolate was [256 and 4 lg/ml, while MIC for amphotericin B, flucytosine and voriconazole was 0.064, 0.125 and 1.0 lg/ml, respectively. Diagnosis was revised to R. mucilaginosa meningitis, and intravenous amphotericin B 45 mg OD was continued. The dosage of amphotericin B was titrated to 35 mg OD (0.6 mg/kg body weight) on day 8 of the treatment as he began to develop drug-induced renal toxicity. He tolerated the lower dosage of amphotericin B with resolution of renal impairment. Headache was progressively reduced in severity, his fever and cough resolved following treatment, and his transaminases reduced. Repeat lumbar puncture and CSF analysis on day 11 of admission also showed remarkable improvement. Repeat CSF culture was negative for any growth. He was converted to itraconazole 200 mg twice a day (bid) after completing 14 days of amphotericin B and was discharged home well. Six weeks later, during his follow-up, it was noted that his headaches returned and he was readmitted for lumbar puncture to assess his CSF. At this time, he did not exhibit any neurological deficits and was still compliant to oral itraconazole 200 mg bid. After 48 h of his second admission, his CSF parameters returned to normal and there was no positive culture identified from the CSF. He was advised to continue oral itraconazole 200 mg bid while plans to institute highly active antiretroviral therapy (HAART) were in progress.
Discussion The genus Rhodotorula includes three active species that are isolated most frequently from clinical materials: Rhodotorula glutinis, Rhodotorula minuta and R. mucilaginosa [1]. Colonial morphology of R.
mucilaginosa exhibits coral pink colonies with smooth surfaces and mucoid yeast-like in appearance, while microscopic appearance shows the presence of blastoconidia with the absence of pseudohyphae. Biochemically, Rhodotorula does not ferment carbohydrates, but produces urease enzyme [3]. Rhodotorula spp. and Cryptococcus spp. share many similar morphological and physiological properties that may lead to mistaken identities. Rhodotorula differs from Cryptococcus by its inability to assimilate inositol and from Candida by its pink to red colonies and also the lack of pseudohyphae. In 1976, Pore and Chen [4] reported the first case of Rhodotorula rubra meningitis in a 21-year-old male patient with acute lymphoblastic leukaemia. Twelve years later, Donald et al. [5] reported a second case of meningitis caused by similar organism in a postoperative ventriculitis patient who was immunocompetent. In 1996, Gyaurgieva et al. [6] first reported a meningitis case in an HIV-infected patient caused by Rhodotorula rubra. Later in 2001, Lanzafame et al. [2] described a case of meningitis caused by Rhodotorula glutinis in an old man with no predisposing condition. In 2007, Thakur et al. [7] from India reported a second case of meningitis caused by Rhodotorula rubra in an HIV-infected patient, followed by Baradkar and Kumar [8] in 2008, who reported R. mucilaginosa meningitis in HIV-seropositive patient. To the best of our knowledge, there have been a total of six cases of Rhodotorula spp.-related meningitis and this current case is the seventh reported in the world. It also represents as the fourth case of meningitis caused by Rhodotorula rubra/mucilaginosa occurring in an HIV-infected patient (Table 1). Rhodotorula has been attributed rarely as an aetiological agent, and in all reviewed cases, infection was clearly opportunistic. Immunosuppressive hosts, prolonged usage of steroids and chemotherapy agents, and an advent of AIDS are the contributing factors responsible for the rise in CNS fungal infections including R. mucilaginosa infection. In this case, HIV appeared to be a prominent risk factor for developing the infection, similar to the three previously reported cases. Interestingly, Rhodotorula glutinis was isolated from the CSF of an old man with no predisposing condition. Thus, Rhodotorula meningitis could have developed due to old age. This case is unique for several reasons. Firstly, microscopic findings of the CSF showed negative for
123
Mycopathologia Table 1 Summary of meningitis cases caused by Rhodotorula mucilaginosa in HIV-infected patient reported from 1996 to 2014 Year
Predisposing factor
India ink/nigrosin staining
CSF examination
CD4 cell count
Outcome
1996
HIV
Not documented
Not documented
259/ll
Recovered but relapse after 8 months
2007
HIV
Positive
Lymphocyte 55 %
56/ll
Succumbed after 23 days of hospitalization
196 cells/mm3
Recovered and no relapse observed until last follow-up
313/ll
Recovered and no relapse observed until last follow-up
Neutrophil 45 % 2008
HIV
Positive
Lymphocyte 60 % Neutrophil 40 %
2014
HIV
Negative
Lymphocyte 17 % Neutrophil 83 %
India ink with neutrophilic predominance. Secondly, the patient’s CD4 cell count at presentation was relatively higher and lastly, the patient had a good outcome with rapid resolution of symptoms compared to the other three previously reported cases. A possibility of contamination by Rhodotorula was suspected due to the ubiquitous existence in natural environment, and it has been known to cause nosocomial pseudoepidemics [9]. However, this can be excluded in this patient as CSF is a sterile fluid and it was collected and processed under aseptic conditions. Furthermore, headaches and other symptoms resolved completely a few days after treatment was instituted. The possible connections between Rhodotorula species and human pathology have been discussed in the past, with considerable difficulty in identifying lesions pathognomonic for the organisms, even in the case of post-mortem examinations [2]. The clinical picture with mycological findings and the prompt response to therapy fit well together in this case. Thus, it was considered to have pathogenic role in causing meningitis in the case. Therefore, it is a challenge in denying the pathological role of Rhodotorula in causing diseases particularly meningitis in immunocompromised patients. Acknowledgments We thank Jennifer Chong, Dr. Thuhairah Hasrah, Nurul Athirah and Prof. Dr. T.S. Soo-Hoo for their excellent contributions to the article.
123
Conflict of interest The authors declare that they have no conflicts of interest concerning this article.
References 1. Anaissie EJ, McGinnis MR, Pfaller MA. Opportunistic Mycoses. In: Murray PR, Rosenthal KS, Pfaller MA, editors. Medical microbiology. Pennsylvania: Elsevier Mosby; 2005. p. 779–800. 2. Lanzafame M, De Checchi G, Parinello A, Catlelan AM, Trevenzoli M. Rhodotorula glutinis-related meningitis. J Clin Microbiol. 2001;39:410. 3. Ellis D. Rhodotorula. Fungal descriptions; yeast. University of Adelaide, Australia. http://www.mycology.adelaide.edu. au (2014). Accessed 17 Jul 2014. 4. Pore RS, Chen J. Meningitis caused by Rhodotorula. Saboraudia. 1976;14:331–5. 5. Donald FE, Sharp JF, Firth JL, Crowley JL, Ispahani P. Rhodotorula rubra ventriculitis. J Infect. 1988;16:187–91. 6. Gyaurgieva OH, Bogomolova TS, Gorshkova GI. Meningitis caused by Rhodotorula rubra in an HIV-infected patient. J Med Vet Mycol. 1996;34:357–9. 7. Thakur K, Singh G, Agarwal S, Rani L. Meningitis caused by Rhodotorula rubra in an human immunodeficiency virus infected patient. Indian J of Med Microbiol. 2007;25:166–8. 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. Braun DK, Kauffman CA. Rhodotorula fungaemia: a life threatening complication of indwelling central venous catheters. Mycoses. 1992;35:305–8.
