Infectious Diseases in Clinical Practice:
Aspergillus Vertebral Osteomyelitis in an Immunocompetent Host Treated With Voriconazole
Nusair, Ahmad MD*; Smith, Philip W. MD†
*Infectious Diseases Department, Creighton University Medical Center and †Infectious Diseases Department, University of Nebraska MedicalCenter, Omaha, Nebraska.
Address correspondence and reprint requests to Ahmad Nusair, MD, Infectious Diseases Department, 985400 Nebraska Medical Center, Omaha, NE 68198-5400. E-mail: firstname.lastname@example.org.
Aspergillus osteomylyelitis in immunocompetent hosts is a rare disease. In this article, we report a case of Aspergillus vertebral osteomyelitis in an immunocompetent woman who presented with pathological fractures of the thoracic vertebrae. We reviewed medical literature to find the optimal regimen, and in our case, we elected to start the patient on voriconazole and intended to treat for a minimum of 6 months. Our patient responded nicely to voriconazole and showed clinical and radiological resolution of osteomyelitis after 6 weeks of therapy.
A 49-year-old woman with medical history of hepatitis C infection secondary to injection drug use presented in October 2005 with history of progressively worsening back pain. Pain was first reported in February 2005. It was described as sharp and radiating around the left flank.
Physical examination was unremarkable except for kyphosis and spasm of the paraspinous musculature in the left side of the thoracic spine. Initial blood work showed a white blood cell count of 8500 cells/mL without bands, creatinine of 0.7 mg/dL, sedimentation rate of 29 mm/h (<20 mm/h), and C-reactive protein of 0.3 mg/dL (<0.7 mg/dL). Magnetic resonance imaging (MRI) of the spine showed T8 and T9 vertebral bodies compression fractures with increased signal within the disk space on T2-weighted images most consistent with osteomyelitis and discitis (Fig. 1).
On October 21, 2005, percutaneous needle biopsy of the right side of the T8 vertebral body and posterior portion of the T8-T9 intervertebral disk was performed under computed tomography guidance. Pathology revealed a fibrotic process without evidence of infectious process or malignancy. After thorough workup to rule out a metastatic process, a bacterial etiology was presumed, and she was started on oral moxifloxacin and rifampin.
In November 2005, after completing 6 weeks of antibiotics, she continued to complain of progressive pain, and a repeat MRI showed T8 and T9 vertebral body compression fractures with possible discitis and perivertebral abscess formation. In the light of this deterioration, it was decided to continue with antibiotics and arrange for a surgical biopsy. On December 14, 2005, she was admitted for surgical debridement and left transthoracic transpleural T8 and T9 corpectomies; T7-T8 and T9-T10 discectomies; T7-T8, T8-T9, and T9-10 arthrodesis with Pyramesh cage filled with autograft (harvest of the eighth rib); and T7-T10 anterior Vantage plate. Samples obtained were examined histopathologically and cultured. The cultures from T8-T9 disk grew Aspergillus fumigatus. Fungal hyphae were identified in the tissue samples obtained from T8-T9 disk space and vertebrae.
The patient was started on intravenous voriconazole and received this for a total of 9 days. She was discharged on oral voriconazole 200 mg BID, with intention to treat for 6 months. The patient was seen in a follow-up visit in February 2006. She was doing fairly well. She denied any fever; she complained of mild back pain mainly on exertion but not at rest as she had before surgery. Physical examination showed persistence of the kyphotic deformity of the back, but there was no tenderness over the vertebrae. There were no neurological deficits. The repeat MRI showed the same kyphotic deformity and most importantly resolution of edema and signs of inflammation consistent with resolving vertebral osteomyelitis (see Fig. 2).
Aspergillus species are ubiquitous fungi; of those recognized as human pathogens, A. fumigatus and Aspergillus niger are the most common.1,2 Exposure to Aspergillus is usually by inhalation of the spores. Lungs are the primary target and the entry point for more aggressive and invasive disease, which develops in the immunocompromised host.
Aspergillus can result in several clinical syndromes depending on the target organ and the degree of dissemination, which is primarily dictated by the degree and duration of immune suppression. Several forms of Aspergillus infections have been reported in this population, ranging from rib and vertebral osteomyelitis to endocarditis.3-5 Invasive aspergillosis has a predilection for severely neutropenic patients, solid organ transplants recipients, and bone marrow transplant recipients. It is also not uncommonly seen in patients with acquired immunodeficiency syndrome and with chronic granulomatous disease.1,2
Among all different etiologies of vertebral osteomyelitis, Aspergillus remains extremely rare in immunocompetent hosts. In 1987, Brown et al6 reported 2 cases of seemingly immunocompetent adults who used intravenous drugs. Tuazon et al7 in 1974 reported the presence of Aspergillus in one fourth of street heroin samples. They also reviewed other reported cases, among which were 5 who were on immunosuppressive therapy. One patient had cirrhosis and history of intravenous drug use, and the other had glucose-6-phosphate dehydrogenase deficiency.6 In 2004, Vaishya and Sharma8 reported a case of vertebral osteomyelitis in an immunocompetent adult, noting that only 4 other cases have been reported previously. In 2005, Mouas et al9 discussed 20 cases of osteomyelitis, 6 of which were immunocompetent, and only 2 of these immunocompetent patients had vertebral osteomyelitis.
The use of amphotericin B has been the standard of care. Surgical intervention is nevertheless a major determinant of good outcome.10,11 With the introduction of new antifungals, there are new agents available with potentially better outcome than conventional therapy. The paucity of cases makes drawing conclusions from case reports rather impractical.
Amphotericin B has poor bone penetration and significant toxicity. Amphotericin B lipid complex, the lipid or liposomal formulations of amphotericin, are associated with fewer toxicities, but they do not have additional benefits in terms of fungicidal activity.9,12 Itraconazole and 5-fluorocytosine have been used in combination with amphotericin B in osteomyelitis.13 Voriconazole is an excellent anti-Aspergillus agent with fungicidal activity better than amphotericin B, at least in vitro; unfortunately, there is limited information about voriconazole bone penetration.9,14 The largest series of voriconazole treated patients for invasive bone aspergillus was published by Mouas et al.9 In that review, one patient had a similar profile to our patient with history of alcohol abuse and intravenous drug use and did not receive antifungal therapy before voriconazole. The patient received 127 days of voriconazole and failed therapy. Two immunocompetent patients in that series had isolated spondylodiskitis. They received initial antifungal regimen that included amphotericin B, then were switched to voriconazole. One of them received more than 12 months of voriconazole and had complete resolution. The other received less than 12 weeks of voriconazole and responded partially. In the group of patients with "satisfactory response" regardless of their immune status, the median treatment duration was 180 days.
For invasive aspergillosis, the recommended voriconazole regimen is 6 mg/kg IV BID on day 1, followed by 4 mg/kg IV BID. After 7 days, one may consider switching to 200 mg PO BID; the dose may be increased to 300 mg PO BID if the response is inadequate.15 In the face of paucity of information about Aspergillus vertebral osteomyelitis, the duration of therapy remains ambiguous. One could consider the treatment duration recommendation for Candida bone infection of 6 to 12 months as appropriate for Aspergillus bone infection.16-19 Clinical parameters, inflammatory markers, imaging studies, and serum galactomannan may be all considered when deciding the duration of therapy, but the length of therapy remains empirical.20
2. Maertens J, Van Eldere J, Verhaegen J, et al. Use of circulating galactomannan screening for early diagnosis of invasive aspergillosis in allogeneic stem cell transplant recipients. J Infect Dis. 2002;186(9):1297-1306.
3. Salloum A, Rao S, Havasi A, et al. Aspergillus rib and vertebral osteomyelitis in a former intravenous drug user. Am J Med. 2004;116(3):208-209.
4. Petrosillo N, Pellicelli AM, Cicalini S, et al. Endocarditis caused by Aspergillus species in injection drug users. Clin Infect Dis. 2001;33(8):e97-e99.
5. Santos AB, Llamas P, Gadea I, et al. Aspergillus fumigatus: a rare cause of vertebral osteomyelitis. Haematologica. 2004;89(3):ECR10.
6. Brown DL, Musher DM, Taffet GE. Hematogenously acquired Aspergillus vertebral osteomyelitis in seemingly immunocompetent drug addicts. West J Med. 1987;147(1):84-85.
7. Tuazon CU, Hill R, Sheagren JN. Microbiologic study of street heroin and injection paraphernalia. J Infect Dis. 1974;129:327-329.
8. Vaishya S, Sharma MS. Spinal Aspergillus vertebral osteomyelitis with extradural abscess: case report and review of literature. Surg Neurol. 2004;61(6):551-555.
9. Mouas H, Lutsar I, Dupont B, et al. Voriconazole/Bone Invasive Aspergillosis Study Group: Voriconazole for invasive bone aspergillosis: a worldwide experience of 20 cases. Clin Infect Dis. 2005;40(8):1141-1147.
10. Stratov I, Korman TM, Johnson PD. Management of Aspergillus osteomyelitis: report of failure of liposomal amphotericin B and response to voriconazole in an immunocompetent host and literature review. Eur J Clin Microbiol Infect Dis. 2003;22(5):277-283.
11. Stevens DA, Kan VL, Judson MA, et al. Practice guidelines for diseases caused by Aspergillus. Clin Infect Dis. 2000;30(4):696-709.
12. Lodge BA, Ashley ED, Steele MP, et al. Aspergillus fumigatus empyema, arthritis, and calcaneal osteomyelitis in a lung transplant patient successfully treated with posaconazole. J Clin Microbiol. 2004;42(3):1376-1378.
13. Kirby A, Hassan I, Burnie J. Recommendations for managing Aspergillus osteomyelitis and joint infections based on a review of the literature J Infect. 2006;52(6):405-414.
14. Krishnan S, Manavathu EK, Chandrasekar PH. A comparative study of fungicidal activities of voriconazole and amphotericin B against hyphae of Aspergillus fumigatus. J Antimicrob Chemother. 2005;55(6):914-920.
15. Sugar AM. Treatment of invasive aspergillosis. 2006. Available at: http://Uptodate.com
. Accessed March 2006.
16. Pappas PG, Rex JH, Sobel JD, et al. Guidelines for the treatment of candidiasis. Clin Infect Dis. 2004;38(2):161-189.
17. Bisbe J, Miro JM, Latorre X, et al. Disseminated candidiasis in addicts who use brown heroin: report of 83 cases and review. Clin Infect Dis. 1992;15(6):910-923.
18. Gathe JC Jr, Harris RL, Garland B, et al. Candida osteomyelitis. Report of five cases and review of the literature. Am J Med. 1987;82(5):927-937.
19. Sexton DJ and McDonald M. Vertebral osteomyelitis. 2006. Available at: http://Uptodate.com
. Accessed March 2006.
20. Miller DJ, Mejicano GC. Vertebral osteomyelitis due to Candida species: case report and literature review. Clin Infect Dis. 2001;33(4):523-530.
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