Blastoschizomyces capitatus pneumonia in an immunocompetent male.

Abstract: Blastoschizomyces capitatus is an emerging fungal pathogen. It has been well characterized as a cause of local and disseminated disease in immunocompromised hosts, especially in the setting of neutropenia. We describe a case of B capitatus pneumonia in an otherwise healthy man and review the clinical presentation, microbiologic characteristics, and treatment strategies for B capitatus infections.

Key Words: Blastoschizomyces capitatus, immunocompetent, pneumonia

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Blastoschizomyces capitatus is recognized as an emerging fungal pathogen in immunocompromised patients, especially those with underlying hematologic malignancies. Severe neutropenia, cytotoxic chemotherapy, prolonged antibiotic use, indwelling vascular devices, and corticosteroid use have all been linked to invasive disease. (1) Normally a colonizer of the skin and the respiratory and gastrointestinal tracts, the organism may cause disseminated disease in the setting of immune system compromise. Although local infections have been reported, these are often thought to be secondary to hematogenous spread. (2,3) We present a case of B capitatus pneumonia in an otherwise healthy patient, and postulate a novel route of infection.

Case Report

A 40-year-old male nonsmoker was admitted to the hospital with fever, cough, and shortness of breath. He was well until 1 week before admission, when he developed a cough, which was productive of minimal yellow to tan sputum for 3 days before admission. Subjective fever and chills were present for 2 days before admission, which correlated roughly with the onset of shortness of breath. He reported no headache, rhinorrhea, sneezing, or sore throat. His history was notable for the absence of recent travel or sick contacts.

Initial examination revealed a fever of 103.1[degrees]F, a pulse of 110 beats/min, a respiratory rate of 24 breaths/min, a blood pressure 135/89 mm Hg, and oxygen saturation by pulse oximetry of 91% on room air. His physical examination was notable for left lower lobe rhonchi and egophony. The remainder of his physical examination was unremarkable. Laboratory studies revealed a leukocyte count of 12,500 cells/mL and an absolute neutrophil count of 9,700 cells/mL. Room air arterial blood gas showed a Pa[O.sub.2] of 70 mm Hg. A chest radiograph revealed a dense left lower lobe consolidation.

The patient was treated with supplemental oxygen, intravenous vancomycin 1 g every 12 hours, and piperacillin-tazobactam 3.375 g every 6 hours. After 4 days of therapy, he remained febrile, with daily maximum temperatures greater than 102[degrees]F and no change in his oxygen requirement, clinical examination, or volume of sputum production. Radiographs demonstrated a slight increase in the size of the left-sided infiltrate. On day 5, fluconazole (400 mg intravenously every 24 hours) was added empirically with a slight decrease in his maximum temperature but no other significant clinical changes.

On hospital day 6, bronchoscopy was performed with protected brush sampling for culture from the left lower lobe. Gram stain demonstrated many polymorpho-nuclear leukocytes but no organisms, and stains for acid-fast bacilli, Nocardia species, and Pneumocystis carinii were negative. Cultures for viral respiratory pathogens were negative. Fungal elements were visible on periodic acid-Schiff stain. On hospital day 8, fungal culture demonstrated pure growth of B capitatus. Fluconazole was changed to amphotericin B lipid complex (ABLC) (5 mg/kg/d). By hospital day 10, fevers had resolved, he was weaned from oxygen, and all antimicrobials except ABLC were discontinued. He completed a 14-day course of ABLC therapy. At 6-week follow-up, he was clinically well and radiographs were clear. Workup for underlying occult malignancy or other source of immunosuppression including human immunodeficiency virus was unrevealing.

An intriguing component of the patient's history was a rather unusual means of using chewing tobacco. He reported that he often used the same ball of tobacco for days at a time, storing it uncovered on the seat of his truck between uses. The ball would often roll to the floor of his truck, but this did not preclude its use. Unfortunately, the collection of tobacco used before the onset of his illness was not available for microbiologic investigation after the finding of B capitatus from his bronchoscopy culture.

Discussion

Invasive fungal infections are increasingly important as causes of morbidity and mortality, especially among immunocompromised patients. The clinical importance of Candida species, Aspergillus species, and Zygomycetes is well recognized. (4) B capitatus has been noted as playing an increasingly important role in local and systemic infections in immunocompromised patients, especially those with hematologic malignancy and neutropenia. (1) Among these patients, the clinical presentation of B capitatus does not differ from other fungal infections, with the hallmark of infection being fever refractory to antimicrobials. (4)

Disseminated infection is the most widely reported of B capitatus clinical entities. (1,5-7) Other reports have described endocarditis, (8,9) meningitis, (10) osteomyelitis, (2) and gastrointestinal tract (11) and hepatosplenic disease. (12) Such cases were invariably among patients with well-characterized immune suppression and primarily among patients with severe neutropenia. Systemic infections occur with markedly increased frequency in Europe when compared with North America (85% versus 10%) for reasons yet to be elucidated. (13) Onychomycosis without systemic illness caused by B capitatus has been described in a patient without evidence of immunosuppression. (14)

B capitatus is a soil saprophyte that is also a colonizer of the skin and normal gastrointestinal and respiratory tracts. (1) The organism was originally known as Trichosporon capitatum and then Geotrichum capitatum, but has been reclassified to the genus Blastoschizomyces. (13)

B capitatus grows as cream-colored round to oval colonies on both blood agar and Sabouraud glucose agar. Morphologically similar molds include Geotrichum candidum and Trichosporon beigelii. Distinguishing morphologic characteristics of B capitatus include septate hyphae with narrow angle branching and the presence of conidia with tapered ends at the tip of proliferating cells--these are termed annelloconidia. (2,13) Biochemical characteristics that help to further differentiate B capitatus include the inability to use potassium nitrate as a sole nitrogen source, the inability to hydrolyze urea, and resistance to cycloheximide. (2,8,13)

The most appropriate antifungal agent for B capitatus infections is yet to be determined. Studies that have included antifungal susceptibility testing have demonstrated that B capitatus is usually sensitive to the polyene amphotericin B (minimum inhibitory concentration [MIC], 0.15-0.62 [micro]g/mL) and relatively resistant to 5-fluorocytosine (MIC, 0.04 to >100 [micro]g/mL). (8) Among triazoles, itraconazole and ketoconazole have shown favorable MICs (0.2 and 1.5 mg/mL, respectively). (2) Earlier studies demonstrated fluconazole activity versus B capitatus four to eight times greater than that of amphotericin B. (15) Recent studies, however, have documented the emergence of fluconazole resistance in cancer patients with invasive B capitatus. (7) Studies investigating the efficacy of newer antifungals such as voriconazole and capsofungin may help delineate additional therapeutic options.

Conclusion

This case is unique because it represents clinical disease caused by B capitatus in a patient without underlying immunosuppression. Several components of the case point to B capitatus as being either the sole infectious agent causing disease or at least a significant contributor. Of significant importance is the isolation of the organism from a protected brush sample. Although B capitatus is a colonizer of the normal respiratory tract, protected brush sampling should decrease the isolation of respiratory colonizers from clinical isolates. (16) The isolation of a pure culture of the organism also suggests a role in the patient's clinical presentation. The most likely alternative diagnosis on this case would be a slowly resolving bacterial pneumonia. Historical factors making this alternative less likely include a lack of clinical response to antibacterial therapy and persistent fevers--hallmarks of untreated fungal infection. In addition, clinical resolution after a course of antifungal therapy suggests a significant, if not primary, role for B capitatus in this respiratory infection.

Without the isolation of B capitatus from the patient's chewing tobacco, this site can never be proven as the initial source of the patient's infection. It is reasonable to assume that a large inoculum of B capitatus would be necessary to cause clinically significant disease in an otherwise immunocompetent individual, and the possibility of frequent reexposure to the organism through chewing-tobacco habituation provides a plausible explanation.

You know more of a road by having traveled it than by all the
conjectures and descriptions in the world.
--William Hazlitt

Accepted December 8, 2003.

Copyright [c] 2004 by The Southern Medical Association

0038-4348/04/9707-0702

References

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2. D'Antonio D, Piccolomini R, Fioritoni G, et al. Osteomyelitis and intervertebral discitis caused by Blastoschizomyces capitatus in a patient with acute leukemia. J Clin Microbiol 1994; 32:224-227.

3. Ortiz AM, Sanz-Rodriguez C, Culebras J, et al. Multiple spondylodiscitis caused by Blastoschizomyces capitatus in an allogeneic bone marrow transplantation recipient. J Rheumatol 1998; 25:2276-2278.

4. Chmel F. Fungal infections in the immunocompromised host: clinical syndromes and diagnosis, in Murphy JW, Friedman H, Bendinelli M (eds): Fungal Infections and Immune Responses. New York, Plenum Press, 1993, pp 405-423.

5. Liu KL, Herbrecht R, Bergerat JP, et al. Disseminated Trichosporon capitatum infection in a patient with acute leukemia undergoing bone marrow transplantation. Bone Marrow Transplant 1990;6:219-221.

6. Herbrecht R, Liu KL, Koenig H, et al. Trichosporon capitatum septicemia in immunocompromised patients. Pathol Biol 1990;38:585-588.

7. D'Antonio D, Mazzoni A, Iocone A, et al. Emergence of fluconazole-resistant strains of Blastoschizomyces capitatus causing nosocomial infections in cancer patients. J Clin Microbiol 1996;34:753-755.

8. Polacheck 1, Salkin IF, Kitzes-Cohen R, et al. Endocarditis caused by Blastoschizomyces capitatus and taxonomic review of the genus. J Clin Microbiol 1992;30:2318-2322.

9. Arnold AG, Gribbin B, De Leval M, et al. Trichosporon capitatum causing recurrent fungal endocarditis. Thorax 1981;36:478-480.

10. Naficy AB, Murray HW. Isolated meningitis caused by Blastoschizomyces capitatus. J Infect Dis 1990;161:1041-1042.

11. Ito T, Ishikawa R, Fujii R, et al. Disseminated Trichosporon capitatum infection in a patient with acute leukemia. Cancer 1988;61:585-588.

12. DeMaio J, Coleman L. The use of adjuvant interferon-gamma therapy for hepatosplenic Blastoschizomyces capitatus infection in a patient with leukemia. Clin Infect Dis 2000;31:822-824.

13. Salkin IF, Gordon MA, Samsonoff WA, et al. Blastoschizomyces capitatus, a new combination. Mycotaxon 1985;22:375-380.

14. D'Antonio D, Romano F, Iacone A, et al. Onychomycosis caused by Blastoschizomyces capitatus. J Clin Microbiol 1999;37:2927-2930.

15. Venditti M, Posteraro B, Morace G, et al. In-vitro comparative activity of fluconazole and other antifungal agents against Blastoschizomyces capitatus. J Chemother 1991;3:13-15.

16. Meduri GU, Beals DH, Maijub AG, et al. Protected bronchoalveolar lavage: a new bronchoscopic technique to retrieve uncontaminated distal airway secretions. Am Rev Respir Dis 1991;143:855-864.

RELATED ARTICLE: Key Points

* Blastoschizomyces capitatus is recognized as an emerging fungal pathogen able to cause disseminated disease.

* B capitatus infections are usually seen in patients with underlying immunosuppression.

* This report describes a case of B capitatus pneumonia in an immunocompetent patient.

Todd S. Wills, MD, Amber Degryse, BS, Jenna Lavina, BS, and John T. Sinnott, MD

From the Department of Internal Medicine, Division of Infectious Diseases, University of South Florida College of Medicine, Tampa, FL.

Reprint requests to Todd S. Wills, MD, Department of Internal Medicine, Division of Infectious Diseases, University of South Florida College of Medicine, Tampa General Healthcare, P.O. Box 1289, Tampa, FL 33601.