Systemic Cryptococcus Albidus Infection in a Doberman Pinscher

598 Brief Communications J Vet Diagn Invest 17:598–600 (2005) Systemic Cryptococcus albidus infection in a Doberman Pinscher Olivia Labrecque,1 Doris Sylvestre, Serge Messier Abstract. Cryptococcus albidus is a saprophytic, encapsulated yeast usually found in air, both outdoor and indoor, and sometimes on human skin. It is not usually considered to be a primary pathogen. Most cryptococcal infections of humans and animals are caused by Cryptococcus neoformans. Several cases of C. albidus infection have been reported in humans over the past 20 years. In the veterinary literature, 2 equine cases have been described: genital infection and mycotic keratitis. The present report is the first documented case of C. albidus systemic infection in a dog. Veterinarians and diagnosticians should be aware that C. albidus may be a potential canine pathogen. Key words: Cryptococcus albidus; dogs; systemic infection. A 5-year-old female Doberman Pinscher weighing 23.2 kg was presented to a veterinarian for surgery to remove masses on its left forelimb. At the time of surgery, the dog received 450,000 U of long-acting penicillin G benzathinea intramuscularly. Three days postoperatively, the animal removed its stitches and the wound became infected. The veterinarian cleaned the wound and gave the dog 225,000 U of longacting penicillin G benzathine intramuscularly. Five days after surgery, the dog presented with an acute mastitis. After emptying the mammary gland, the animal was placed on enrofloxacinb (13 mg/kg once a day PO) for 10 days. Two weeks after surgery, the owner noted signs of blindness in the dog and the appearance of 2 masses on its back. The following week, the animal became incontinent, exhibited polydipsia, and had difficulty walking. Blood tests performed at the veterinary clinic revealed no abnormalities on the routine hemogram; however, below normal values were noted for albumin, sodium, and chloride. The same day, 18 days after surgery, the dog died and was submitted for necropsy at the Faculté de médecine vétérinaire, Université de Montréal. Grossly, there was hyperemia of the right sclera and ulcerations on the vulva and left forelimb. Three nodules were present in the subcutaneous tissues of the thorax. There was tumefaction of the mammary gland. The lungs were edematous and consolidated. Retropharyngeal and popliteal lymph nodes were enlarged. On cut surface, white nodules of variable diameter (3 to 7 mm) were found within the lymph nodes. Similar nodules were also found in the lungs, myocardium, and tracheobronchial lymph nodes. There was a greenish exudate in the ventral portion of the brain. Histopathology revealed granulomatous lesions in the lungs, lymph nodes, skin, mammary gland, eyes, brain, myocardium, hypophysis, and thyroid. Numerous yeast-like cells From the Département de Pathologie et Microbiologie, Faculté de médecine vétérinaire, Université de Montréal, C.P. 5000, Saint-Hyacinthe J2S7C6, Québec, Canada (Labrecque, Messier), and Laboratoire d’expertises et d’analyses du Québec, C.P. 3500, Saint-Hyacinthe J2S7X9, Québec, Canada (Sylvestre). 1 Corresponding Author: Olivia Labrecque, Laboratoire de bactériologie clinique, Faculté de médecine vétérinaire, 1425 des Vétérinaires, Saint-Hyacinthe J2S8H5, Québec, Canada. were found within the granulomas. The fungal cells were ovoid, possessed a thick capsule, were 7 to 15 mm in diameter, and reproduced by narrow-based budding (Fig. 1). The presence of the same fungus was noted in the eyes and blood vessels. From routine aerobic cultures, Streptococcus equi subspecies zooepidemicus was isolated from the spleen, mammary gland, and lymph nodes. An alpha-hemolytic Streptococcus was also isolated from the lymph nodes. No bacterial growth was obtained from the lungs, kidneys, or meninges. A yeastlike organism was isolated from the lymph nodes and sent to the Laboratoire de santé publique du Québecc for identification. Primary tests for yeast identification included morphologic exam by Dalmau’s technique, urease production, glucose fermentation, growth on medium containing cycloheximide, and a commercial yeast identification test system.d The yeast was identified as Cryptococcus albidus. The final diagnosis for this case was systemic cryptococcosis caused by C. albidus. Several cases of C. albidus infection have been reported in human medicine over the past 20 years. In the veterinary literature, 2 equine cases have been described. The present report appears to be the first documented case of C. albidus systemic infection in a dog. Only 2 other cases of C. albidus have been described in animals. Genital infection in a stallion was reported from Italy in 1973.2 In a French report from 1990, the yeast was also isolated from a horse with mycotic keratitis.4 In the latter case, other bacterial agents such as Moraxella, Streptococcus equinus, and Aerococcus viridans were also recovered, and the role of C. albidus was not well established.4 In humans, C. albidus has been associated with meningitis11, skin infection12, pulmonary infection17, mucormycosis empyema, osteomyelitis, and septicemia.5–10 In each case, patients were immunocompromised by other diseases such as HIV. Cryptococcus albidus is an ubiquitous saprophytic encapsulated yeast occasionally found on human skin.7 One study reported different sources of C. albidus to be air, nails, lungs, sputum, a beer bottle, bone, blood, chronic balanoposthisis, pigeon excreta, and soil.16 In another report, C. albidus was isolated from the skin and hair of dog, as well as horse urine samples.1 In humans and animals, cryptococcal infections are usu- Downloaded from vdi.sagepub.com by guest on February 15, 2016 Brief Communications 599 Figure 1. The black arrow shows Cryptococcus albidus narrow-based budding cell in ocular tissue. The white arrow shows a (Cryptococcus albidus) cell. Magnification, 403. ally caused by Cryptococcus neoformans. Over the past 30 years, the emergence of cryptococcal infections in humans has been noted. The same is not true regarding animals. Because C. albidus is a saprophytic microorganism and is seldom encountered in clinical cases, there is no information on how humans and animals become infected. It is possible that the pathogenesis is similar to that of C. neoformans. In the environment, Cryptococcus cells are nonencapsulated and can easily penetrate the airways.7 They can infect either the upper or the lower respiratory tract.7 Once in the tissues, they regenerate their thick capsule, which is an important virulence factor.7 Cryptococcus species can cause both local and systemic infections.7 In veterinary medicine, C. neoformans affects cats more frequently than dogs.7 Unlike cats, dogs often develop systemic infection.7 In dogs, the fungus has a tropism for the central nervous and ocular systems, but in systemic cryptococcosis, lesions are present in the lungs, kidneys, lymph nodes, spleen, and liver.7 Laboratory identification of C. albidus includes examination of colonial and microscopic morphology and detection of a capsule.12 On Sabouraud dextrose agar, C. albidus colonies are creamy, smooth, mucoid, and yeast-like in appearance.9 By use of India ink staining, distinct capsules can be seen surrounding the yeast cells. These capsules are unique to Cryptococcus species.9 There are 2 subspecies of C. albidus: albidus and diffluens.9 Biochemical tests allow differentiation of C. neoformans from the C. albidus subspecies.9 Cryptococcus neoformans is galactose positive. Cryptococcus albidus subsp. albidus is lactose positive, and C. albidus subsp. diffluens is melibiose positive.9 All species of Cryptococcus are urease positive.9 The appearance of the colonies on Niger or birdseed agar can be used to differentiate these species, as C. neoformans is usually brown and the others are creamcolored.15 The brown pigment from C. neoformans is owing to the production of melanin, which may be an important virulence factor.6 Some strains of C. albidus have shown melanin production in smaller amounts, with colonies appearing as light brown.6 Commercial yeast identification systems may be used to identify these organisms.15 The clinical diagnosis of cryptococcal infection generally relies on a serological test that uses an antigen latex agglutination assay.11 By this method, there is no evidence of cross-reaction between C. neoformans and C. albidus. Isolation of C. albidus from clinical specimens is the sole means of diagnosis. There are several factors that may have led to infection with Downloaded from vdi.sagepub.com by guest on February 15, 2016 600 Brief Communications C. albidus in this animal. In all reported human cases of C. albidus infection, immunodeficiency seems to play a role in the disease process. Although there is no direct evidence of this occurring in animals, one reference suggests immunodeficiency in the pathogenesis of animal cryptococcosis.3 In the case presented, the routine hemogram did not reveal any abnormalities. Although the left forelimb masses have not been analyzed, they may have been neoplastic. Neoplasia may have compromised this animal’s immune function and predisposed it to infection with C. albidus. Another factor in fungal overgrowth is prolonged administration of broad spectrum antibiotics, which destroys normal microbial flora and facilitates invasion. This dog received the recommended dose of enrofloxacin for 10 days.b In addition, the presence of concomitant mastitis may have allowed colonization of C. albidus. The possibility that C. albidus was the etiologic agent of the mastitis, which led to systemic infection, cannot be ruled out. The dog may also have acquired a nosocomial yeast infection during surgery. This is known to occur in humans. Because the clinical signs appeared several days after the surgery, this hypothesis is less probable. Cryptococcus albidus has been isolated from the skin and hair of dogs and may be normal canine skin flora. This animal’s wound may have become contaminated during removal of its sutures. The organism could possibly have disseminated hematogenously. A case of skin infection attributed to C. albidus has been reported in a man affected with Sézary syndrome; however, there was no mention of systemic illness.5 In one report of canine infection with C. neoformans, there was a history of urinary tract infection and it was presumed to be the portal of entry for the yeast.13 As there were no kidney lesions in this dog, that route of infection can be eliminated. There is no established medical treatment for C. albidus in animals. The equine ocular infection was treated successfully with topical amphotericin B administered for 1.5 months.4 In human medicine, amphotericin B and flucytosine are given for up to 8 weeks. The use of flucytosine in monotherapy leads to antimicrobial resistance after 7 to 8 weeks of use.14 In all human cases of C. albidus infection, the prognosis was poor.7 In conclusion, this appears to be the first documented case of systemic infection owing to C. albidus in a dog. Unlike most human cases, immunodeficiency appears not to have been a factor in the present case; however, further diagnostic tests should be performed to address this issue. Veterinarians and diagnosticians should be aware that C. albidus may be a potential canine pathogen. Acknowledgements. We wish to thank the staff of the veterinary clinic and Nancy Beaudry, the owner of Daisy. Sources and manufacturers a. P.V.U. division of Vétoquinol, Lavaltrie, Québec, Canada. b. Bayer, Bayer Inc., Division agricole santé animale, Toronto, Ontario, Canada. c. Laboratoire de santé publique du Québec, Sainte-Anne-de-Bellevue, Québec, Canada. d. BioMérieux Canada, Inc., St. Laurent, Québec, Canada. References 1. Chengappa MM, Maddux RL, Greer SC, et al.: 1984, Isolation and identification of yeasts and yeastlike organisms from clinical veterinary sources. J Clin Microbiol 19:427–428. 2. Codazza D, Bertoldini G, Sampieri G: 1973, Genital infection caused by Cryptococcus albidus in the horse. Folia Vet Lat 3: 339–42. 3. Cutsem JV, Rochette F: 1992, Chien et chat. In: J Van Cutsem and F Rochette, eds. Mycoses des animaux domestiques, pp. 87–107. Beerse, Belgium. 4. Desbrosse AM: 1996, Cryptococcus mycotic keratitis in a horse. Pratique Vétérinaire Equine 28:147–148. 5. Gluck JL, Myers JP, Pass LM: 1987, Cryptococcemia due to Cryptococcus albidus. South Med J 80:511–513. 6. Ikeda R, Sugita T, Jacobson ES, Shinoda T: 2002, Laccase and melanization in clinically important Cryptococcus species other than Cryptococcus neoformans. J Clin Microbiol 40:1214–1218. 7. Jacobs GJ, Medleau L: 1995, Cryptococcosis. In: Craig E Greene, ed. 1998. Infectious diseases of the dog and cat, 2nd ed., pp. 383–390. WB Saunders, Philadelphia, PA. 8. Kordossis T, Avlami A, Velegraki A, et al.: 1998, First report of Cryptococcus laurentii meningitis and a fatal case of Cryptococcus albidus cryptococcaemia in AIDS patients. Med Mycol 36:335–339. 9. Larone DH: 1987, Yeasts and yeastlike organisms. In: David H Larone, ed. Medically important fungi A guide to identification, 2nd ed., pp. 53–75, Elsevier Science Publishing Co., New York, NY. 10. Loison J, Bouchara JP, Gueho E, et al.: 1996, First report of Cryptococcus albidus septicaemia in an HIV patient. J Infect 33:139–140. 11. Melo JC, Srinivasan S, Scott ML, Raff MJ: 1980, Cryptococcus albidus meningitis. J Infect 2:79–82. 12. Narayan S, Batta K, Colloby P, Tan CY: 2000, Cutaneous cryptococcus infection due to C. albidus associated with Sezary syndrome. Br J Dermatol 143:632–634. 13. Newman SJ, Langston CE, Scase TJ: 2003, Cryptococcal pyelonephritis in a dog. J Am Vet Med Assoc 222:180–183. 14. Prescott JF: 2000, Antifungal Chemotherapy. In: Antimicrobial therapy in veterinary medicine, ed. Prescott JF, Baggot JD, Walker RD, 3rd ed., pp. 367–395. Iowa State University Press, Ames, IA. 15. Quinn PJ, Carter ME, Marker B, Carter GR: 1994, The pathogenic yeasts. In: PJ Quinn and BK Markley, eds. Clinical veterinary microbiology, pp. 395–401. Mosby, London, England. 16. Sugita T, Takashima M, Ikeda R, et al.: 2001, Intraspecies diversity of Cryptococcus albidus isolated from humans as revealed by sequences of the internal transcribed spacer regions. Microbiol Immunol 45:291–297. 17. Wells GM, Gajjar A, Pearson TA, et al.: 1998, Pulmonary cryptosporidiosis and Cryptococcus albidus fungemia in a child with acute lymphocytic leukemia. Med Pediatr Oncol 31:544–546. Downloaded from vdi.sagepub.com by guest on February 15, 2016