- Biomedical Research (2012) Volume 23, Issue 4
Foot bleb infection due to Rhodotorula mucilaginosa in a diabetic patient:Case report and review of the literature
Bhattacharyya S., Shivaprakash M.R., Chakrabarti A., Sharma N.*
Mycology Division, Department of Medical Microbiology, and *Department of Internal Medicine, Postgraduate Institute of Medical Education and Research, Chandigarh. India
Accepted date: July 21 2012
Abstract
Rhodotorula spp. are capsulated, pigmented, ubiquitous basidiomycetous yeasts causing different superficial and deep-seated opportunistic infections in the debilitated and immunocompromised patient. Earlier considered as saprophytes, fungi belonging to this genus are now considered as emerging pathogens. This is a report of foot bleb infection due to Rhodotorula mucilaginosa in a diabetic patient.
Keywords
Rhodotorula spp., basidiomycetous, Diabetes mellitus.
Introduction
Rhodotorula spp. are capsulated, basidiomycetous, round to oval, multilateral budding yeasts belonging to the family Cryptococcaceae, subfamily Rhodotoruloideae. They were previously considered as saprophytes and laboratory contaminants and have been recovered from environmental sources like soil, shower curtains, bathtub grout, and toothbrushes [1]. They are also found as commensal yeasts in skin, nails and mucous membranes [2]. However according to current scientific literature, they are considered important in the causation of sepsis and disseminated infection in the immunocompromised and debilitated host. Rhodotorula spp. have been implicated in the causation of meningitis, endocarditis, ventriculitis, peritonitis, fungemia, central venous catheter infection and keratitis in debilitated and immunocompromised patients. Rhodotorula spp. are usually resistant to triazoles and caspofungin and sensitive to amphotericin B. The genus Rhodotorula comprises several species, of which R. mucilaginosa has not yet been reported as a causative agent of sepsis in Diabetes mellitus.
Case Report
S, a 55 year-old female patient residing in Chandigarh, north India was admitted in the Emergency Ward of the Institute, on 13.08.2009 with the chief complaints of generalized swelling of the body since 15 days, shortness of breath since 7 days and cough since 5 days. She was a known hypertensive since 6 years and diabetic for the past 12 years, for which she was taking oral hypoglycemic agent. Clinical diagnosis of pneumonia and diabetic triopathy (nephropathy, neuropathy and retinopathy) with diabetic foot was made. The patient had also developed blebs in both feet. Initial laboratory investigations revealed a serum creatinine value of 4.8.mg/dl, total serum bilirubin of 0.6 mg/dl, hemoglobin of 8.9 gm% and total Leucocyte Count of 4200 cells/μl. Her Random Blood sugar value was 319 mg/dl preterminally. The patient was put on Injection Cloxacillin, Clindamycin, Piperacillin- Tazobactum and Insulin. She was not administered any antifungal agent. She died of cardiac asystole resulting from septic shock. Blood sample was sent before death for bacterial culture in Tryptone Soya Broth (TSB) and Bile broth, which showed no growth of any microroganisms after 5 days of incubation at 37°C aerobically. Bleb fluid from the foot lesions was aspirated and sent to the mycology laboratory. Microscopic examination of a 10% KOH Mount of the same showed polymorphonuclear leucocytes and oval budding yeasts of 4-5 μm size. The fluid was subjected to bacterial and fungal culture. Culture was done on 2 sets of Saboraud’s Dextrose Agar (SDA) at 37° C and 22° C respectively, and Brain Heart Infusion Agar (BHIA). Pink mucoid yeasts grew on all the tubes. Lactophenol Cotton Blue Mount showed oval budding yeasts. The yeast isolate was Urease positive, capsulated on India Ink staining, did not assimilate inositol (using Yeast Nitrogen Base) and did not form pseudohyphae on Corn Meal Agar at 22°C after 48 hours of incubation. Nitrate assimilation test using Yeast Carbon Base was negative. Based on these biochemical tests, it was identified as Rhodotorula spp. For species identification DNA was extracted by the method described [3]. DNA sequencing of D1 and D2 regions of rDNA by Sanger’s method revealed it to be Rhodotorula mucilaginosa. MIC values of Amphotericin B, Fluconazole, Voriconazole and Caspofungin against the isolate were 0.25 μg/ml, 16 μg/ml, 1 μg/ml and 2 μg/ml respectively by broth microdilution method. Thus the isolate was sensitive to Amphotericin B and Voriconazole but resistant to Fluconazole and Caspofungin.
Discussion
Rhodotorula spp. are ubiquitous yeasts and normal inhabitants of moist skin as well as the conjunctiva and respiratory, gastrointestinal and urinary tracts of humans [4]. Rhodotorula spp. have been recovered from faeces and cloacae of pigeons (Columbia livia) along with Cryptococcus spp., which highlights its widespread distribution [5]. Their physiologic and morphologic properties are similar to Cryptococcus spp except for red to pink carotenoid pigment production (Torulene, β-Carotene and Torularhodin) [6], inability to assimilate inositol and a smaller capsule [1]. Rhodotorula species, previously thought to be saprophytic yeasts and environmental contaminants, are being increasingly recognized as an emerging pathogen in the immunocompromised and debilitated host since the past decade, along with Trichosporon spp, and Geotrichum spp. [7]. The first case of Rhodotorula infection, a patient with endocarditis, was reported in 1960 by Louria and coworkers [8] An increase in the number of Rhodotorula infections has been reported, mainly in the last two decades. However, this increase could be a publication bias after the recognition of Rhodotorula as a pathogen. Other explanations are dramatic expansion in new modalities of treatment related to critical care medicine and transplantation, short and long term Central Venous Catheter usage with or without parenteral nutrition, broad spectrum antibiotics, hematologic neoplasms leading to neutropenia and chemotherapy with resultant immunosuppression [9]. Rhodotorula spp. have been implicated in the causation of meningitis, endocarditis, ventriculitis, peritonitis, fungaemia, central venous catheter infection and keratitis in debilitated and immunocompromised patients [10] In general, they seem to have lower virulence in comparison to other yeasts, with about 15% mortality overall [11]. However, infection can occasionally be life threatening , particularly in immunocompromised individuals. Resistance to azoles can favour its colonization on human skin when the growth of other fungi is inhibited or restricted [12]. Severeal virulence factors have been studied in the yeast, like extracellular phospholipases, but factors like reduced growth at 37°C and absence of dimorphism probably contribute to its reduced pathogenic potential [13].The genus Rhodotorula comprises about 34 species[14] which include R. glutinis, R. mucilaginosa (formerly known as R. rubra or R. pilimanae) [4] , R. minuta, R. himalayensis, R. gracilis, R. sloofiae and others. This was a case of foot bleb infection due to Rhodotorula mucilaginosa since blebs were present on both feet that yielded the pigmented yeast isolate on routine mycological media which did not assimilate inositol and nitrate. Many other cases of Rhodotorula infection are reported in the literature, mostly in HIVinfected patients. Though it is a saprophytic yeast, its isolation from blood cultures and other sterile body fluids such as Cerebrospinal Fluid (CSF) is of greater significance when contamination has been ruled out [15]. Among Rhodotorula species, R. mucilaginosa is the most frequently isolated one [16]. This species can be differentiated from other Rhodotorula species by positive assimilation of glucose, raffinose, sucrose, D-arabinose, trehalose and D-xylose and inability to assimilate galactose, maltose and Nitrate [17]. Sepsis due to Rhodotorula spp. has been reported in patients with malignancy. In diabetic patients, skin and superficial tissue infection by Rhodotorula spp. has been noted [18,19]. Rhodotorula mucilaginosa has been reported to be the causative agent of lymphadenitis in HIV-infected patients [4] . Chincholikar and Pal have reported R. mucilaginosa (R. rubra) in the causation of about 03.64 % cases of fungal diabetic foot infection [20] There is one reference of bloodstream infection due to R. mucilaginosa in neonatal Intensive Care Unit related to the use of indwelling vascular catheter [21]. Garcia-Suarez and coworkers have reported one case of catheter-related fungemia due to the same in a patient suffering from multiple myeloma [22]. This species has also been associated with femoral prosthesis infection [23]. All these reports can be attributed to the affinity of Rhodotorula spp. for synthetic biomaterials in general [22].This isolate was sensitive to Voriconazole and Amphotericin B and resistant to Fluconazole and Caspofungin. Diekema et al have studied the antifungal susceptibility pattern of 64 isolates of Rhodotorula spp., 24 of which were R. mucilagunosa, against Fluconazole, Echinocandins, Flucytosine and Amphotericin B [24]. They found that the most active agents were 5-flucytocine and Amphotericin B. All the isolates in their study were resistant to echinocandins and fluconazole, with ravuconazole showing some antifungal activity among the new azoles. These findings are concordant with other studies which report universal resistance of Rhodotorula spp. to azoles [25]. As far as our knowledge goes, this is the first report of isolation from foot bleb fluid of Rhodotorula mucilaginosa in a diabetic patient.
References
- Hazen KC, Howell SA: Candida, Cryptococcus, and other yeasts of medical importance. In: Murray PR, Baron EJ, Jorgensen JH, Landry ML, Pfaller MA. Manual of Clinical Microbiology. 9th ed 2007. ASM Press.pp 1768.
- Pfaller MA, Diekema DJ. Rare and Emerging Opportunistic Fungal Pathogens: Concern for Resistance beyond Candida albicans and Aspergillus fumigatus. J Clin Microbiol 2004; 42: 4419-4431.
- Amberg DC, Burke DJ, Strathern JN. Yeast DNA Isolations, Techniques and Protocols 3, in Methods in Yeast Genetics, 2005 edition. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY, USA, 2005.
- Fung HB, Martyn CA, Shahidi A, Brown ST. Rhodotorula mucilaginosa lymphadenitis in an HIV-infected patient . Int J Inf Dis 2009.13:e27 – e29.
- Costa AK, Sidrim JJ, Cordeiro RA, Brilhante RS, Monteiro AJ, Rocha MF. Urban pigeons (Columba livia) as a potential source of pathogenic yeasts: a focus on antifungal susceptibility of Cryptococcus strains in Northeast Brazil. Mycopathologia 2010; 169: 207-213.
- Perrier V., Dubreucg E., and Gaizy E. Fatty acid and carotenoid composition of Rhodotorula strains. Arch Microbiol 1995; 164, 173-179.
- Lui AY, Turett GS, Karter DL, Bellman PC, Kislak JW. Amphotericin B lipid complex therapy in an AIDS patient with Rhodotorula rubra fungemia. Clin Inf Dis 1998; 27: 892-893.
- Louria DB, Greenberg SM, Molander DW. Fungemia caused by certain nonpathogenic strains of the family Cryptococcaceae. Report of two cases due to Rhodotorula and Torulopsis glabrata. New England J Med 1960; 263: 1281-1284.
- Tuon FF, Costa SF. Rhodotorula infection. A systematic review of 128 cases from literature. Rev Iberoam Micol 2008; 25: 135-140.
- Pamidimukkala U, Challa S, Lakshmi V, Tandon A, Kulkarni S, Raju SY. Sepsis and meningoencephalitis due to Rhodotorula glutinis in a patient with Systemic Lupus Erythmatosus, diagnosed at autopsy. Neurol Ind 2007; 55: 304-307.
- Lo Re V III, Fishman NO, Nachamkin I. Recurrent catheter-related Rhodotorula rubra infection. Clini Microbiol Inf 2003; 9: 897-900.
- Krzyściak P, Macura AB. Drug susceptibility of 64 strains of Rhodotorula sp.Wiadomooeci Parazytologiczne 2010; 56: 167-170.
- Mayser P, Laabs S, Heuer KU, Grunder K. Detection of extracellular phospholipase activity in Candida albicans and Rhodotorula rubra.Mycopathologia 1996; 135: 149-55.
- Kurtzman, CP, Fell, JW. The Yeasts: A Taxonomic Study. 4th edition. Amsterdam: Elsevier 1998.
- Rippon JW, Medical Mycology. The pathogenic actinomycetes. 3rd Edition. New York: W.B. Saunders Company; 1988. pp582-609.
- Kwon-Chung KJ, Bennett JE. Infections due to Trichosporon and other miscellaneous yeast-like fungi: In: Kwon-Chung KJ, Bennett JE, Editors. Medical Mycology. Philadelphia: Lee and Febiger, 1992. pp768-82.
- Kaur R, Wadhwa A, Agarwal SK. Rhodotorula mucilaginosa: an unusual cause of oral ulcers in AIDS patients. AIDS 2007; 21: 1068-1069.
- Mlinarić-Missoni E, Kalenić S, Vazić-Babić V. Species distribution and frequency of isolation of yeasts and dermatophytes from toe webs of diabetic patients.. Acta dermatovenerol Croat 2005;13: 85-92
- Chincholikar DA, Pal RB. Study of Bacterial and Fungal Infections of the Diabetic foot. Ind J Pathol Microbiol 2002; 45: 15-22.
- Perniola R, Faneschi ML, Manso E, Pizzolante M, Rizzo A, Sticchi Damiani A, Longo R. Rhodotorula mucilaginosa outbreak in neonatal intensive care unit: microbiological features, clinical presentation, and analysis of related variables. Eur J Clin Microbiol Inf Dis 2006; 25: 193-196.
- García-Suarez J, Gomez-Herruz P, Cuadros JA, Guillen H, Burgaleta C. Rhodotorula mucilaginosa catheterrelated fungaemia in a patient with multiple myeloma. Mycoses 2009 Dec 23. [Epub ahead of print] 23.
- Savini V, Sozio F, Catavitello C, Talia M, Manna A, Febbo F, Balbinot A, Di Bonaventura G, Piccolomini R, Parruti G, D’Antonio D. Femoral Prosthesis Infection by Rhodotorula mucilaginosa. J Clin Microbiol 2008; 46 (10): 3544-3545.
- Diekema DJ, Petroelje B, Messer SA, Hollis RJ, Pfaller MA. Activities of available and investigational antifungal agents against Rhodotorula species. J Clin Microbiol 2005; 43: 476-478.
- Gomez-Lopez A, Mellado E, Rodriguez-Tudela JL, Cuenca-Estrella M. Susceptibility profile of 29 clinical isolates of Rhodotorula spp.and literature review. J Antimicrob Chemother 2005; 55: 312-316.