- Email: [email protected]
Acquired Immunodeficiency Syndrome
CASE REPORT
Lung Scedosporiosis in Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome Siva T. Sarva, MD, PhD, Skantha K. Manjunath, MD, Heather S. Baldwin, MD, David B. Robins, MD and Amado X. Freire, MD, MPH
Abstract: A 31-year-old African American woman with human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/ AIDS) (recent CD4 count of 66/mm3) presented to the emergency room with a tension pneumothorax that required an emergent chest tube placement. Computed tomography scan showed fungus balls in multiple lung cavities and surrounding infiltrates. The patient showed remarkable improvement with voriconazole suggesting aspergillosis. However, the patient was serologically negative for Aspergillus and other common fungal infections. Because of a persistent air leak, surgical intervention was needed. The histological finding was consistent with invasive mycosis, and cultures were positive for Scedosporium apiospermum. Literature review showed that, among patients with HIV/AIDS, Scedosporium can present from focal localized to systemic disease, is resistant to traditional antifungal agents, and may respond to prompt management with voriconazole. Key Indexing Terms: Scedosporium; Pseudoallescheria; Systemic mycoses; HIV; Lung cavity. [Am J Med Sci 2010;339(3):300–303.]
S
cedosporium apiospermum and Pseudoallescheria boydii are filamentous fungi, which have been historically associated with white-grain mycetomas.1,2 The taxonomy of these fungi has evolved over the years leading to considerable variation in the name used to describe them in published reports.1 They were considered as 2 independent species until Emmons3 in 1944 showed them to be the asexual and sexual forms of the same species. These fungi are now being reported with increasing frequency as opportunistic pathogens in immunocompromised patients associated with infections of multiple sites including skin, lungs, sinuses, brain, and eyes.4 A large number of these patients have a history of hematological malignancy or were on posttransplant chronic immunosuppression.4 – 6 The clinical presentation, radiological features, and histological appearance of these cases have a marked resemblance to Aspergillus infections leading to frequent mischaracterization.7–9 Bronchopulmonary tree is one of the most common sites of isolation with clinical presentation varying from saprobic mycetomas, local invasive disease, to disseminated disease.4,7,10,11 Disseminated disease is often fatal with a high incidence of fungemia.6 Only a few cases have been reported in patients with immunosuppression secondary to HIV/AIDS. This case report and the accompanying literature review illustrate the clinical presentation, diagnosis, and management strategies in HIV/
From the Department of Medicine (STS) and Division of Pulmonary (SKM, AXF), Critical Care, and Sleep Medicine, University of Tennessee Health Science Center, College of Medicine, Memphis, Tennessee; and Department of Pathology (HSB, DBR), University of Tennessee College of Medicine, Memphis, Tennessee. Submitted September 23, 2009; accepted in revised form November 9, 2009. Correspondence: Amado X. Freire, MD, MPH, FACP, FCCP, FCCM, FAASM, University of Tennessee Heath Science Center, COM at Memphis, 956 Court Avenue, Room G-228, Memphis, TN 38163 (E-mail: [email protected]).
300
AIDS patients with this rare but potentially life-threatening fungal disease.
CASE REPORT A 31-year-old African American woman presented in a nonresponsive state, with clinical and radiological evidence of tension pneumothorax necessitating the placement of a chest tube to relieve her symptoms. Once stabilized, she was able to give a history of sudden discomfort in her left chest followed by severe shortness of breath and chest pain a few hours before presentation. Review of systems was positive for oral thrush and productive cough with yellowish sputum for 2 months and negative for fever, chills, hemoptysis, and weight loss. Her medical history was significant for HIV/AIDS, glucose-6-phosphate dehydrogenase deficiency, hepatitis C, hypertension, and disseminated Mycobacterium avium complex infection. She had been admitted 2 months before in a nearby hospital for Pneumocystis jirovecii pneumonia (PCP) and rightsided (contralateral) pneumothorax, with a CD4 count of 66/ mm3. She was a smoker, alcoholic, regular marijuana user, and had no past surgeries. Her clinic charts revealed she was noncompliant with highly active antiretroviral therapy, M avium complex therapy, and PCP prophylaxis. Her laboratory results were unremarkable except for marked eosinophilia (12%). A computed tomography scan of the chest showed multiple bilateral cavitary lesions with small dependent densities and mediastinal and left hilar lymphadenopathy (Figure 1). The patient was initially started on vancomycin, piperacillin/tazobactam, tobramycin, atovaquone, and methylprednisolone for presumed health care-associated pneumonia and PCP pneumonia. The patient continued to deteriorate with the
FIGURE 1. Chest computed tomography scan showing left lower lobe cavity with a mycetoma (arrow) and surrounding parenchymal infiltrate.
The American Journal of the Medical Sciences • Volume 339, Number 3, March 2010
Lung Scedosporiosis in HIV/AIDS
FIGURE 2. A 60 ⫻ (panel A) and 20⫻ (panel B) micrographs of the surgical sample showing hyphae with tissue invasion into adjacent lung parenchyma.
above therapy, and voriconazole was added for presumptive invasive aspergillosis. Within 24 hours of initiation of voriconazole, she showed remarkable improvement, and all other antibiotics were discontinued without any change in clinical condition. Despite the response to voriconazole therapy, the air leak failed to resolve completely. Sputum for acid-fast bacilli and serum galactomannan and fungal antigen tests were negative. Stain for Pneumocystis sp.; culture for bacteria, fungi, and viruses; and cytology for malignancy were all negative on the bronchoalveolar lavage fluid. Resection of the areas of involvement in the left lower lobe was planned for diagnosis of the causative agent and the management of unresolved air leak. A freely communicating large cavity with a fungus ball in it was visualized during thoracotomy and was resected. Histology of the resected samples showed nodular areas of fungal hyphae eliciting marked vascular granulation tissue response with tissue invasion into adjacent lung parenchyma (Figure 2). The fungal cultures of the samples were positive for S apiospermum. The air leak resolved after surgical intervention, and the patient was discharged.
TABLE 1.
DISCUSSION The summary of the literature review is provided in the Table 1. Four cases of pulmonary involvement with S apiospermum (P boydii) have been reported in HIV patients. Two of the 4 computed tomography scans of the chest showed cavities with mycetomas,12,13 whereas in the third case,14 there was extensive pneumonia. Histology was not performed in 1 case,13 whereas in the other 2 cases,12,14 there was evidence of mycetomas in lung cavities without tissue invasion. Histological finding in 1 case14 showed additional evidence of fungus-filled bronchiectasis. The fourth patient had disseminated disease with extensive lung involvement, and the autopsy showed mycelia in the bronchioles with necrosis in surrounding alveoli.15 Our patient, in contrast to the published cases, had histological evidence of lung parenchymal invasion in addition to lung mycetomas. CD4 count in 2 of the published cases with lung involvement was greater than 200/mm3, whereas it was not documented in the other 2. Our patient, unlike the cases with
HIV/AIDS patients with Scedosporium apiospermum (Pseudoallescheria boydii)
Author (Year) Present case Garci et al (2003)12 Zaas (2002)13 Rollot et al (2000)14 Scherr et al (1992)15 Montero et al (1998)16 Raffanti et al (1990)17 Yao (2001)18 Horton et al (1999)19 Slack et al (1999)20 Eckburg et al (1999)21 Busaba (1997)22 Meyer et al (1994)23
Condition
CD4
Dx
Management
Outcome
Mycetoma with tissue invasion Lung cavity with mycetoma Lung cavity with mycetoma Lung cavities with mycelia Lung and renal abscess Brain abscess Endocarditis, brain abscess Otits externa, mastoiditis Sinusitis Sinusitis, mastoiditis Mastoiditis Otitis externa, mastoiditis Sinusitis
66 NA 234 408 NA 37 NA 90 4 NA 60 10 ⬍50
Biopsy BAL BAL Biopsy BAL Autopsy Bl.culture Biopsy Biopsy Biopsy Biopsy Biopsy Aspiration
Voriconazole, surgery Voriconazole, lobectomy Voriconazole Itraconazole, pneumonectomy Rifampin, ethambutol, miconazole Antitoxoplasmosis drugs Ampicillin, gentamicin Miconazole, ampho B, mastoidectomy Ampho B, itraconazole, sphenoidotomy Ampho B, itraconazole Itraconazole, ketoconazole, antrectomy Itraconazole, radical masotidectomy Ketoconazole, sphenoidotomy
Nonfatal Nonfatal Nonfatal Nonfatal Fatal Fatal Fatal Fatal Fatal Nonfatal Fatal Nonfatal Fatal
CD4 indicates CD4 count/mm3; Dx, diagnostic modality; NA, not available; Bl.culture, blood culture; Ampho B, Amphotericin B.
© 2010 Lippincott Williams & Wilkins
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noninvasive disease, had a low CD4 count of 60/mm3, which could have contributed to the tissue invasion. Diagnosis was made by culture of bronchoalveolar lavage samples in 3 of the published cases. In 1 of the published cases, similar to our patient, diagnosis was made on culture of excised tissue as bronchoalveolar lavage cultures were negative. Two cases with evidence of mycetomas in lung cavities received voriconazole. One of them was managed with voriconazole alone,13 whereas another underwent additional lobectomy.12 One patient underwent pneumonectomy because of a nonfunctional lung,14 and itraconazole was started after the culture of the excised tissue was positive for S apiospermum. All the above 3 cases survived the infection. The patient with disseminated disease with extensive lung involvement15 presented initially with pulmonary problems and received miconazole and later ketoconazole. Despite institution of antifungal therapy, he failed to show any clinical improvement and finally succumbed to the infection. Our patient, despite having an invasive lung disease, improved remarkably after receiving voriconazole and survived the infection. Surgery had to be performed only to manage the air leak. This illustrates that initiation of voriconazole early may prevent extensive surgery, disseminated disease, and improve the clinical outcome. Two cases have been reported with brain abscesses. One of them did not have a proven source,16 whereas the other case had native mitral valve endocarditis with S apiospermum, which eventually led to brain dissemination.17 The CD4 count in one case was low (34/mm3), whereas it was not available in the other. Both patients did not receive antifungal therapy, and diagnosis was made postmortem. One patient was managed as presumptive toxoplasmosis and the other as bacterial endocarditis with septic emboli. Five adult cases and 1 pediatric case20 have been reported with maxillofacial involvement. One of the cases was diagnosed by aspiration of the sinuses,23 whereas the rest were diagnosed by biopsy. Unlike the patients with lung involvement, most of these patients had low CD4 counts (⬍200/mm3). Local invasion into the cranium was the most common lifethreatening complication and was seen in 3 patients. These patients were managed with various antifungal agents and surgery as noted in the Table 1. The efficacy of voriconazole in this patient group could not be commented on as none of the patients received it. High mortality was observed with only 2 of the 6 cases surviving hospitalization. In vitro susceptibility studies suggest that newer triazoles such as voriconazole, posaconazole, and ravuconazole have better activity than older antifungals such as amphotericin B, ketoconazole, and itraconazole against S apiospermum.24 –26 Similar to the clinical outcomes in patients with HIV/AIDS, clinical outcomes in posttransplant patients and patients with hematological malignancies have been better with the use of voriconazole.27–29 Surgical intervention improved survival in some cases.27 However, there are no large-scale studies to evaluate the optimal treatment strategy for these infections. Such studies are necessary in view of the increased frequency of Scedosporiosis in immunocompromised hosts.
CONCLUSIONS In HIV patients, lung cavities with mycetomas are not exclusively caused by Aspergillus. S apiospermum (P boydii) needs to be included in the differential diagnosis. All lung mycetomas are not saprobic, and there is a possibility of invasive lung disease especially in patients with low CD4
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counts. The fungus could cause not only local disease but also potentially life-threatening disseminated invasion in HIV patients. Prompt initiation of therapy with newer triazoles such as voriconazole and posaconazole may lead to better outcomes. REFERENCES 1. Cortez KJ, Roilides E, Quiroz-Telles F, et al. Infections caused by Scedosporium spp. Clin Microbiol Rev 2008;21:157–97. 2. McGinnis MR, Fader RC. Mycetoma: a contemporary concept. Infect Dis Clin North Am 1988;2:939 –54. 3. Emmons CW. Allescheria boydii and Monosporium apiospermum. Mycologia 1944;36:188 –93. 4. Castiglioni B, Sutton DA, Rinaldi MG, et al. Pseudallescheria boydii (Anamorph Scedosporium apiospermum). Infection in solid organ transplant recipients in a tertiary medical center and review of the literature. Medicine (Baltimore) 2002;81:333– 48. 5. Guarro J, Kantarcioglu AS, Horre R, et al. Scedosporium apiospermum: changing clinical spectrum of a therapy-refractory opportunist. Med Mycol 2006;44:295–327. 6. Lamaris GA, Chamilos G, Lewis RE, et al. Scedosporium infection in a tertiary care cancer center: a review of 25 cases from 1989 –2006. Clin Infect Dis 2006;43:1580 – 4. 7. Al Refai M, Duhamel C, Le Rochais JP, et al. Lung scedosporiosis: a differential diagnosis of aspergillosis. Eur J Cardiothorac Surg 2002; 21:938 –9. 8. Sheu R, Bricker AO, Sahi H, et al. Pseudallescheria boydii (Scedosporium species) in 3 lung transplant recipients: computed tomography findings and literature review. J Comput Assist Tomogr 2009;33:247–52. 9. Tadros TS, Workowski KA, Siegel RJ, et al. Pathology of hyalohyphomycosis caused by Scedosporium apiospermum (Pseudallescheria boydii): an emerging mycosis. Hum Pathol 1998;29:1266 –72. 10. Travis LB, Roberts GD, Wilson WR. Clinical significance of Pseudallescheria boydii: a review of 10 years’ experience. Mayo Clin Proc 1985;60:531–7. 11. Reddy PC, Christianson CS, Gorelick DF, et al. Pulmonary monosporosis: an uncommon pulmonary mycotic infection. Thorax 1969;24: 722– 8. 12. Garci J, Perkins A, Garau M, et al. Successful treatment with voriconazol of a Pseudallescheria boydii fungus ball in a HIV positive patient and previous tuberculosis. Rev Iberoam Micol 2003;20:64 –7. 13. Zaas D. Cases from the Osler Medical Service at Johns Hopkins University. Scedosporium apiospermum mycetoma of the lung. Am J Med 2002;113:760 –2. 14. Rollot F, Blanche P, Richaud-Thiriez B, et al. Pneumonia due to Scedosporium apiospermum in a patient with HIV infection. Scand J Infect Dis 2000;32:439. 15. Scherr GR, Evans SG, Kiyabu MT, et al. Pseudallescheria boydii infection in the acquired immunodeficiency syndrome. Arch Pathol Lab Med 1992;116:535– 6. 16. Montero A, Cohen JE, Fernandez MA, et al. Cerebral pseudallescheriasis due to Pseudallescheria boydii as the first manifestation of AIDS. Clin Infect Dis 1998;26:1476 –7. 17. Raffanti SP, Fyfe B, Carreiro S, et al. Native valve endocarditis due to Pseudallescheria boydii in a patient with AIDS: case report and review. Rev Infect Dis 1990;12:993– 6. 18. Yao M, Messner AH. Fungal malignant otitis externa due to Scedosporium apiospermum. Ann Otol Rhinol Laryngol 2001;110:377– 80. 19. Horton CK, Huang L, Gooze L. Pseudallescheria boydii infection in AIDS. J Acquir Immune Defic Syndr Hum Retrovirol 1999;20:209 –11. 20. Slack CL, Watson DW, Abzug MJ, et al. Fungal mastoiditis in
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immunocompromised children. Arch Otolaryngol Head Neck Surg 1999;125:73–5. 21. Eckburg PB, Zolopa AR, Montoya JG. Invasive fungal sinusitis due to Scedosporium apiospermum in a patient with AIDS. Clin Infect Dis 1999;29:212–3. 22. Busaba NY, Poulin M. Invasive Pseudallescheria boydii fungal infection of the temporal bone. Otolaryngol Head Neck Surg 1997;117:S91–94. 23. Meyer RD, Gaultier CR, Yamashita JT, et al. Fungal sinusitis in patients with AIDS: report of 4 cases and review of the literature. Medicine (Baltimore) 1994;73:69 –78. 24. Cuenca-Estrella M, Ruiz-Diez B, Martinez-Suarez JV, et al. Comparative in-vitro activity of voriconazole (UK-109,496) and six other antifungal agents against clinical isolates of Scedosporium prolificans and Scedosporium apiospermum. J Antimicrob Chemother 1999;43: 149 –51.
© 2010 Lippincott Williams & Wilkins
25. Meletiadis J, Meis JF, Mouton JW, et al. In vitro activities of new and conventional antifungal agents against clinical Scedosporium isolates. Antimicrob Agents Chemother 2002;46:62– 8. 26. Carrillo AJ, Guarro J. In vitro activities of four novel triazoles against Scedosporium spp. Antimicrob Agents Chemother 2001;45:2151–3. 27. Husain S, Munoz P, Forrest G, et al. Infections due to Scedosporium apiospermum and Scedosporium prolificans in transplant recipients: clinical characteristics and impact of antifungal agent therapy on outcome. Clin Infect Dis Jan 1 2005;40(1):89 –99. 28. Sahi H, Avery RK, Minai OA, et al. Scedosporium apiospermum (Pseudoallescheria boydii) infection in lung transplant recipients. J Heart Lung Transplant 2007;26:350 – 6. 29. Troke P, Aguirrebengoa K, Arteaga C, et al. Treatment of scedosporiosis with voriconazole: clinical experience with 107 patients. Antimicrob Agents Chemother. 2008;52:1743–50.
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Lung Scedosporiosis in Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome Siva T. Sarva, MD, PhD, Skantha K. Manjunath, MD, Heather S. Baldwin, MD, David B. Robins, MD and Amado X. Freire, MD, MPH
Abstract: A 31-year-old African American woman with human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/ AIDS) (recent CD4 count of 66/mm3) presented to the emergency room with a tension pneumothorax that required an emergent chest tube placement. Computed tomography scan showed fungus balls in multiple lung cavities and surrounding infiltrates. The patient showed remarkable improvement with voriconazole suggesting aspergillosis. However, the patient was serologically negative for Aspergillus and other common fungal infections. Because of a persistent air leak, surgical intervention was needed. The histological finding was consistent with invasive mycosis, and cultures were positive for Scedosporium apiospermum. Literature review showed that, among patients with HIV/AIDS, Scedosporium can present from focal localized to systemic disease, is resistant to traditional antifungal agents, and may respond to prompt management with voriconazole. Key Indexing Terms: Scedosporium; Pseudoallescheria; Systemic mycoses; HIV; Lung cavity. [Am J Med Sci 2010;339(3):300–303.]
S
cedosporium apiospermum and Pseudoallescheria boydii are filamentous fungi, which have been historically associated with white-grain mycetomas.1,2 The taxonomy of these fungi has evolved over the years leading to considerable variation in the name used to describe them in published reports.1 They were considered as 2 independent species until Emmons3 in 1944 showed them to be the asexual and sexual forms of the same species. These fungi are now being reported with increasing frequency as opportunistic pathogens in immunocompromised patients associated with infections of multiple sites including skin, lungs, sinuses, brain, and eyes.4 A large number of these patients have a history of hematological malignancy or were on posttransplant chronic immunosuppression.4 – 6 The clinical presentation, radiological features, and histological appearance of these cases have a marked resemblance to Aspergillus infections leading to frequent mischaracterization.7–9 Bronchopulmonary tree is one of the most common sites of isolation with clinical presentation varying from saprobic mycetomas, local invasive disease, to disseminated disease.4,7,10,11 Disseminated disease is often fatal with a high incidence of fungemia.6 Only a few cases have been reported in patients with immunosuppression secondary to HIV/AIDS. This case report and the accompanying literature review illustrate the clinical presentation, diagnosis, and management strategies in HIV/
From the Department of Medicine (STS) and Division of Pulmonary (SKM, AXF), Critical Care, and Sleep Medicine, University of Tennessee Health Science Center, College of Medicine, Memphis, Tennessee; and Department of Pathology (HSB, DBR), University of Tennessee College of Medicine, Memphis, Tennessee. Submitted September 23, 2009; accepted in revised form November 9, 2009. Correspondence: Amado X. Freire, MD, MPH, FACP, FCCP, FCCM, FAASM, University of Tennessee Heath Science Center, COM at Memphis, 956 Court Avenue, Room G-228, Memphis, TN 38163 (E-mail: [email protected]).
300
AIDS patients with this rare but potentially life-threatening fungal disease.
CASE REPORT A 31-year-old African American woman presented in a nonresponsive state, with clinical and radiological evidence of tension pneumothorax necessitating the placement of a chest tube to relieve her symptoms. Once stabilized, she was able to give a history of sudden discomfort in her left chest followed by severe shortness of breath and chest pain a few hours before presentation. Review of systems was positive for oral thrush and productive cough with yellowish sputum for 2 months and negative for fever, chills, hemoptysis, and weight loss. Her medical history was significant for HIV/AIDS, glucose-6-phosphate dehydrogenase deficiency, hepatitis C, hypertension, and disseminated Mycobacterium avium complex infection. She had been admitted 2 months before in a nearby hospital for Pneumocystis jirovecii pneumonia (PCP) and rightsided (contralateral) pneumothorax, with a CD4 count of 66/ mm3. She was a smoker, alcoholic, regular marijuana user, and had no past surgeries. Her clinic charts revealed she was noncompliant with highly active antiretroviral therapy, M avium complex therapy, and PCP prophylaxis. Her laboratory results were unremarkable except for marked eosinophilia (12%). A computed tomography scan of the chest showed multiple bilateral cavitary lesions with small dependent densities and mediastinal and left hilar lymphadenopathy (Figure 1). The patient was initially started on vancomycin, piperacillin/tazobactam, tobramycin, atovaquone, and methylprednisolone for presumed health care-associated pneumonia and PCP pneumonia. The patient continued to deteriorate with the
FIGURE 1. Chest computed tomography scan showing left lower lobe cavity with a mycetoma (arrow) and surrounding parenchymal infiltrate.
The American Journal of the Medical Sciences • Volume 339, Number 3, March 2010
Lung Scedosporiosis in HIV/AIDS
FIGURE 2. A 60 ⫻ (panel A) and 20⫻ (panel B) micrographs of the surgical sample showing hyphae with tissue invasion into adjacent lung parenchyma.
above therapy, and voriconazole was added for presumptive invasive aspergillosis. Within 24 hours of initiation of voriconazole, she showed remarkable improvement, and all other antibiotics were discontinued without any change in clinical condition. Despite the response to voriconazole therapy, the air leak failed to resolve completely. Sputum for acid-fast bacilli and serum galactomannan and fungal antigen tests were negative. Stain for Pneumocystis sp.; culture for bacteria, fungi, and viruses; and cytology for malignancy were all negative on the bronchoalveolar lavage fluid. Resection of the areas of involvement in the left lower lobe was planned for diagnosis of the causative agent and the management of unresolved air leak. A freely communicating large cavity with a fungus ball in it was visualized during thoracotomy and was resected. Histology of the resected samples showed nodular areas of fungal hyphae eliciting marked vascular granulation tissue response with tissue invasion into adjacent lung parenchyma (Figure 2). The fungal cultures of the samples were positive for S apiospermum. The air leak resolved after surgical intervention, and the patient was discharged.
TABLE 1.
DISCUSSION The summary of the literature review is provided in the Table 1. Four cases of pulmonary involvement with S apiospermum (P boydii) have been reported in HIV patients. Two of the 4 computed tomography scans of the chest showed cavities with mycetomas,12,13 whereas in the third case,14 there was extensive pneumonia. Histology was not performed in 1 case,13 whereas in the other 2 cases,12,14 there was evidence of mycetomas in lung cavities without tissue invasion. Histological finding in 1 case14 showed additional evidence of fungus-filled bronchiectasis. The fourth patient had disseminated disease with extensive lung involvement, and the autopsy showed mycelia in the bronchioles with necrosis in surrounding alveoli.15 Our patient, in contrast to the published cases, had histological evidence of lung parenchymal invasion in addition to lung mycetomas. CD4 count in 2 of the published cases with lung involvement was greater than 200/mm3, whereas it was not documented in the other 2. Our patient, unlike the cases with
HIV/AIDS patients with Scedosporium apiospermum (Pseudoallescheria boydii)
Author (Year) Present case Garci et al (2003)12 Zaas (2002)13 Rollot et al (2000)14 Scherr et al (1992)15 Montero et al (1998)16 Raffanti et al (1990)17 Yao (2001)18 Horton et al (1999)19 Slack et al (1999)20 Eckburg et al (1999)21 Busaba (1997)22 Meyer et al (1994)23
Condition
CD4
Dx
Management
Outcome
Mycetoma with tissue invasion Lung cavity with mycetoma Lung cavity with mycetoma Lung cavities with mycelia Lung and renal abscess Brain abscess Endocarditis, brain abscess Otits externa, mastoiditis Sinusitis Sinusitis, mastoiditis Mastoiditis Otitis externa, mastoiditis Sinusitis
66 NA 234 408 NA 37 NA 90 4 NA 60 10 ⬍50
Biopsy BAL BAL Biopsy BAL Autopsy Bl.culture Biopsy Biopsy Biopsy Biopsy Biopsy Aspiration
Voriconazole, surgery Voriconazole, lobectomy Voriconazole Itraconazole, pneumonectomy Rifampin, ethambutol, miconazole Antitoxoplasmosis drugs Ampicillin, gentamicin Miconazole, ampho B, mastoidectomy Ampho B, itraconazole, sphenoidotomy Ampho B, itraconazole Itraconazole, ketoconazole, antrectomy Itraconazole, radical masotidectomy Ketoconazole, sphenoidotomy
Nonfatal Nonfatal Nonfatal Nonfatal Fatal Fatal Fatal Fatal Fatal Nonfatal Fatal Nonfatal Fatal
CD4 indicates CD4 count/mm3; Dx, diagnostic modality; NA, not available; Bl.culture, blood culture; Ampho B, Amphotericin B.
© 2010 Lippincott Williams & Wilkins
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Sarva et al
noninvasive disease, had a low CD4 count of 60/mm3, which could have contributed to the tissue invasion. Diagnosis was made by culture of bronchoalveolar lavage samples in 3 of the published cases. In 1 of the published cases, similar to our patient, diagnosis was made on culture of excised tissue as bronchoalveolar lavage cultures were negative. Two cases with evidence of mycetomas in lung cavities received voriconazole. One of them was managed with voriconazole alone,13 whereas another underwent additional lobectomy.12 One patient underwent pneumonectomy because of a nonfunctional lung,14 and itraconazole was started after the culture of the excised tissue was positive for S apiospermum. All the above 3 cases survived the infection. The patient with disseminated disease with extensive lung involvement15 presented initially with pulmonary problems and received miconazole and later ketoconazole. Despite institution of antifungal therapy, he failed to show any clinical improvement and finally succumbed to the infection. Our patient, despite having an invasive lung disease, improved remarkably after receiving voriconazole and survived the infection. Surgery had to be performed only to manage the air leak. This illustrates that initiation of voriconazole early may prevent extensive surgery, disseminated disease, and improve the clinical outcome. Two cases have been reported with brain abscesses. One of them did not have a proven source,16 whereas the other case had native mitral valve endocarditis with S apiospermum, which eventually led to brain dissemination.17 The CD4 count in one case was low (34/mm3), whereas it was not available in the other. Both patients did not receive antifungal therapy, and diagnosis was made postmortem. One patient was managed as presumptive toxoplasmosis and the other as bacterial endocarditis with septic emboli. Five adult cases and 1 pediatric case20 have been reported with maxillofacial involvement. One of the cases was diagnosed by aspiration of the sinuses,23 whereas the rest were diagnosed by biopsy. Unlike the patients with lung involvement, most of these patients had low CD4 counts (⬍200/mm3). Local invasion into the cranium was the most common lifethreatening complication and was seen in 3 patients. These patients were managed with various antifungal agents and surgery as noted in the Table 1. The efficacy of voriconazole in this patient group could not be commented on as none of the patients received it. High mortality was observed with only 2 of the 6 cases surviving hospitalization. In vitro susceptibility studies suggest that newer triazoles such as voriconazole, posaconazole, and ravuconazole have better activity than older antifungals such as amphotericin B, ketoconazole, and itraconazole against S apiospermum.24 –26 Similar to the clinical outcomes in patients with HIV/AIDS, clinical outcomes in posttransplant patients and patients with hematological malignancies have been better with the use of voriconazole.27–29 Surgical intervention improved survival in some cases.27 However, there are no large-scale studies to evaluate the optimal treatment strategy for these infections. Such studies are necessary in view of the increased frequency of Scedosporiosis in immunocompromised hosts.
CONCLUSIONS In HIV patients, lung cavities with mycetomas are not exclusively caused by Aspergillus. S apiospermum (P boydii) needs to be included in the differential diagnosis. All lung mycetomas are not saprobic, and there is a possibility of invasive lung disease especially in patients with low CD4
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counts. The fungus could cause not only local disease but also potentially life-threatening disseminated invasion in HIV patients. Prompt initiation of therapy with newer triazoles such as voriconazole and posaconazole may lead to better outcomes. REFERENCES 1. Cortez KJ, Roilides E, Quiroz-Telles F, et al. Infections caused by Scedosporium spp. Clin Microbiol Rev 2008;21:157–97. 2. McGinnis MR, Fader RC. Mycetoma: a contemporary concept. Infect Dis Clin North Am 1988;2:939 –54. 3. Emmons CW. Allescheria boydii and Monosporium apiospermum. Mycologia 1944;36:188 –93. 4. Castiglioni B, Sutton DA, Rinaldi MG, et al. Pseudallescheria boydii (Anamorph Scedosporium apiospermum). Infection in solid organ transplant recipients in a tertiary medical center and review of the literature. Medicine (Baltimore) 2002;81:333– 48. 5. Guarro J, Kantarcioglu AS, Horre R, et al. Scedosporium apiospermum: changing clinical spectrum of a therapy-refractory opportunist. Med Mycol 2006;44:295–327. 6. Lamaris GA, Chamilos G, Lewis RE, et al. Scedosporium infection in a tertiary care cancer center: a review of 25 cases from 1989 –2006. Clin Infect Dis 2006;43:1580 – 4. 7. Al Refai M, Duhamel C, Le Rochais JP, et al. Lung scedosporiosis: a differential diagnosis of aspergillosis. Eur J Cardiothorac Surg 2002; 21:938 –9. 8. Sheu R, Bricker AO, Sahi H, et al. Pseudallescheria boydii (Scedosporium species) in 3 lung transplant recipients: computed tomography findings and literature review. J Comput Assist Tomogr 2009;33:247–52. 9. Tadros TS, Workowski KA, Siegel RJ, et al. Pathology of hyalohyphomycosis caused by Scedosporium apiospermum (Pseudallescheria boydii): an emerging mycosis. Hum Pathol 1998;29:1266 –72. 10. Travis LB, Roberts GD, Wilson WR. Clinical significance of Pseudallescheria boydii: a review of 10 years’ experience. Mayo Clin Proc 1985;60:531–7. 11. Reddy PC, Christianson CS, Gorelick DF, et al. Pulmonary monosporosis: an uncommon pulmonary mycotic infection. Thorax 1969;24: 722– 8. 12. Garci J, Perkins A, Garau M, et al. Successful treatment with voriconazol of a Pseudallescheria boydii fungus ball in a HIV positive patient and previous tuberculosis. Rev Iberoam Micol 2003;20:64 –7. 13. Zaas D. Cases from the Osler Medical Service at Johns Hopkins University. Scedosporium apiospermum mycetoma of the lung. Am J Med 2002;113:760 –2. 14. Rollot F, Blanche P, Richaud-Thiriez B, et al. Pneumonia due to Scedosporium apiospermum in a patient with HIV infection. Scand J Infect Dis 2000;32:439. 15. Scherr GR, Evans SG, Kiyabu MT, et al. Pseudallescheria boydii infection in the acquired immunodeficiency syndrome. Arch Pathol Lab Med 1992;116:535– 6. 16. Montero A, Cohen JE, Fernandez MA, et al. Cerebral pseudallescheriasis due to Pseudallescheria boydii as the first manifestation of AIDS. Clin Infect Dis 1998;26:1476 –7. 17. Raffanti SP, Fyfe B, Carreiro S, et al. Native valve endocarditis due to Pseudallescheria boydii in a patient with AIDS: case report and review. Rev Infect Dis 1990;12:993– 6. 18. Yao M, Messner AH. Fungal malignant otitis externa due to Scedosporium apiospermum. Ann Otol Rhinol Laryngol 2001;110:377– 80. 19. Horton CK, Huang L, Gooze L. Pseudallescheria boydii infection in AIDS. J Acquir Immune Defic Syndr Hum Retrovirol 1999;20:209 –11. 20. Slack CL, Watson DW, Abzug MJ, et al. Fungal mastoiditis in
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25. Meletiadis J, Meis JF, Mouton JW, et al. In vitro activities of new and conventional antifungal agents against clinical Scedosporium isolates. Antimicrob Agents Chemother 2002;46:62– 8. 26. Carrillo AJ, Guarro J. In vitro activities of four novel triazoles against Scedosporium spp. Antimicrob Agents Chemother 2001;45:2151–3. 27. Husain S, Munoz P, Forrest G, et al. Infections due to Scedosporium apiospermum and Scedosporium prolificans in transplant recipients: clinical characteristics and impact of antifungal agent therapy on outcome. Clin Infect Dis Jan 1 2005;40(1):89 –99. 28. Sahi H, Avery RK, Minai OA, et al. Scedosporium apiospermum (Pseudoallescheria boydii) infection in lung transplant recipients. J Heart Lung Transplant 2007;26:350 – 6. 29. Troke P, Aguirrebengoa K, Arteaga C, et al. Treatment of scedosporiosis with voriconazole: clinical experience with 107 patients. Antimicrob Agents Chemother. 2008;52:1743–50.
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