Le Infezioni in Medicina, n. 1, 108-112, 2023

doi: 10.53854/liim-3101-15


Aspergillus fumigatus causing vertebral osteomyelitis in an immunocompetent patient: a case report and literature review

Thomas A. N. Reed1,2, Anan Shtaya3,4, Kate Beard2, Kordo Saeed2,3, Sarah Glover2, Mark Fabian5, Mohammad Baraka4, Stephen McGillion4

1NIHR Southampton Clinical Research Facility, University Hospital Southampton NHS Foundation Trust, Southampton, UK;

2Department of Infection, University Hospital Southampton NHS Foundation Trust, Southampton, UK;

3University of Southampton, Clinical and Experimental Sciences, Southampton, UK;

4Wessex Spinal Unit, University Hospital Southampton NHS Foundation Trust, Southampton, UK;

5Cellular Pathology, University Hospital Southampton NHS Foundation Trust, Southampton, UK

Article received 13 December 2022, accepted 28 January 2023

Corresponding author

Thomas Reed

E-mail: thomas.reed@uhs.nhs.uk


Aspergillus vertebral osteomyelitis causing deformity in immunocompetent patients is uncommon. We describe a previously healthy 68-year-old male who was referred after 2 years of lower thoracic back pain and gibbus. His inflammatory markers and HIV test were normal. Imaging demonstrated bony destruction of T12/L1 and L2 with vertebral collapse. Following inconclusive CT-guided biopsy, he underwent reconstructive spinal surgery. Histopathology showed fungi and Aspergillus fumigatus was cultured. He was treated with isavuconazole 200 mg once daily for 12 months with a satisfactory clinical outcome. We present a summary of recently published cases of atraumatic Aspergillus vertebral osteomyelitis in immunocompetent patients without risk factors. Fungal infection should be considered in culture-negative spondylodiscitis, even in the absence of risk factors.

Keywords: Fungus, aspergillosis, vertebral osteomyelitis, Aspergillus.


Fungal infections of the spine are rare. Immunocompromised patients, such as those on immunosuppressive drugs, and those with acquired immunodeficiency syndrome are more prone to develop fungal infection of the spine than immunocompetent people [1-3]. Of the Aspergillus species, the most frequently isolated in human spine infection is Aspergillus fumigatus [4-6]. Invasive aspergillosis usually affects the lung, while spinal aspergillosis represents the most common type of osseous infection [7, 8]. The disease may result in neurological deficit [6]. Spinal deformity due to vertebral aspergillosis is uncommon and compromised approximately 7% of 112 cases of spinal aspergillosis in a recent systematic review [6]. In this report, we describe a case of an immunocompetent adult who presented with back pain and gibbus, and was found to have Aspergillus vertebral osteomyelitis (AVO).


A 68-year-old male gardener presented with worsening thoracolumbar back pain over a two-year period which had progressed to a kyphotic spinal deformity. He had no significant past medical history (including respiratory disease, malignancy, and frequent or recurrent infections) other than a traumatic subdural haematoma 20 years previously. He took no regular medications and had no history of exposure to systemic or inhaled glucocorticoids, and there was no history of injecting drug use. He denied fevers, night sweats, and weight loss. Neurological examination was normal, but he had a gibbous at the thoracolumbar junction, with some overlying skin changes. He had a white blood cell count of 9.0x109/L, a C-reactive protein of 1mg/L, and a negative HIV test. Magnetic resonance imaging of his spine demonstrated bony destruction of T12/L1 and L2 with vertebral collapse and abnormality of the adjacent disc spaces (Figure 1). On CT imaging of the chest, abdomen, and pelvis, there were no features of infection or malignancy, and no other significant findings reported. Cultures from a CT-guided biopsy did not isolate any bacteria (including mycobacteria), and, on this basis, no antimicrobial chemotherapy was commenced. There was insufficient biopsy sample for histopathological examination and no fungal cultures were performed. A subsequent whole spine CT noted an increase in size of a previously imaged, but unreported, soft tissue thickening at the apex of the right lung. Following multidisciplinary discussion, the patient underwent major reconstructive spinal surgery to correct his deformity and to send sufficient samples for microbiology and histopathology. He was discharged a week later.

Figure 1 - Pre-operative CT and MRI spine. A- Sagittal CT section demonstrates bony destruction of T12/L1 and L2 with vertebral collapse and abnormality of the adjacent disc spaces. B) T1 weighted MRI sagittal image shows low signal in the remaining parts of L2, L1 and T12. C) Sagittal STIR sequences image demonstrating high signal in L2-T1.

Direct culture from a surgical specimen did not grow any organism, however fastidious anaerobe broth culture isolated A. fumigatus. Because of concerns about environmental contamination the original specimen was re-cultured and again no growth was seen from direct culture, and broth culture isolated A. fumigatus. Histopathological examination of bone demonstrated extensive fibrosis with patchy acute and chronic inflammation. Septate, branching fungal hyphae with acute angles showing morphology highly suggestive of Aspergillus spp. were present within the tissue (Figure 2). An auramine stain did not show any acid-fast bacilli, there was no growth from mycobacterial culture, and Mycobacterium tuberculosis was not detected by PCR. Respiratory sampling was not performed, as respiratory pathology was not prospectively identified.

Figure 2 - A) Areas of fibrosis adjacent to the trabecular bone, containing foci of acute inflammation and septate fungal hyphae (examples highlighted by arrows) (H&E, 25x). B) The organisms are highlighted by Grocott Methenamine Silver (GMS) staining which demonstrates acute angle branching (25x).

Six weeks after surgery, serum galactomannan and b-D-glucan were tested and were normal (index value 0.30) and raised respectively (139 pg/ml). Two months after surgery, repeat CT imaging demonstrated stable appearances of the right apical lung lesion, which was reported as likely rounded atelectasis. At this point he commenced oral voriconazole 200 mg twice daily (after initial loading doses), which was shortly increased to 300 mg twice daily, guided by blood voriconazole levels. After eight weeks of treatment, he was noted to have deranged liver function tests, and the voriconazole dose was reduced to 200 mg twice daily. His blood voriconazole levels became low again, and after 10 weeks of treatment this was changed to isavuconazole 200 mg once daily (after initial loading doses).

Six months after surgery his serum galactomannan and b-D-glucan were both normal. He completed 12 months of antifungal treatment, with a satisfactory clinical and radiological response. Investigations did not reveal any underlying primary or secondary immunodeficiency.


Although AVO is most seen in patients with co-morbidities that include primary immunodeficiency, solid organ transplant, IV drug use, COPD, and diabetes mellitus, 24-34% of patients may have no predisposing risk factors or immunosuppression [4, 7]. The extent of immunosuppression required to increase the risk of AVO is not clear, but may be minimal, for example use of steroid inhalers, or infrequent short courses of corticosteroids [7].

Diagnosis of AVO maybe challenging, especially in immunocompetent patients when it may be low on the list of differential diagnoses. Forty-one-percent of all patients may have contiguous spread from a pulmonary source which could be diagnosed radiologically in combination with respiratory sampling, but contiguous spread is less common among immunocompetent patients (10%) [7, 9]. In this patient group acquisition by haematogenous spread (52%), and direct inoculation through trauma or surgery (29%) is more common [9]. It is plausible that the primary area of infection was in the apex of the right lung, evidenced by the changes seen on CT, and spread haematogenously. Even in the presence of proven pulmonary disease, direct sampling is required. Diagnosis of Aspergillus osteomyelitis is made most frequently by open biopsy (55%) or percutaneous biopsy (36%) [7]. Since direct culture methods may yield the diagnosis in only 74% of confirmed cases, a diagnostic approach that combines culture, histopathology, and molecular methods may need to be taken [4]. The European Organization for Research and Treatment of Cancer and the Mycoses Study Group Education and Research Consortium (EORTC/MSGERC) have produced consensus definitions of invasive fungal disease [10]. Culture of Aspergillus spp. from a normally sterile site or demonstration of hyphae compatible with Aspergillus spp. on histopathologic examination are required to fulfil the current EORTC/MSGERC definition of proven invasive aspergillosis.

Using the EORTC/MSGERC criteria, a diagnosis of probable invasive aspergillosis can be made in the combined presence of specified host factors (e.g., haematologic malignancy), clinical features, and mycologic evidence, including molecular diagnostic results which are becoming more routinely available. Raised serum galactomannan may indicate probable or possible invasive aspergillosis, with a sensitivity and specificity of 82% and 81% respectively, and can be a useful biomarker to monitor response to therapy [11]. Beta-D-glucan testing may be used in a similar way, but lacks specificity, and the EORTC/MSGERC do not support its use for diagnosis of invasive aspergillosis [10]. Use of polymerase-chain-reaction assays for Aspergillus spp. are usually restricted to reference laboratories, and current Infectious Diseases Society of America (IDSA) guidelines recommend their judicious use only in conjunction with other diagnostic tests [12].

To provide context to our case, we performed a review of literature available on PubMed, to identify published cases of proven atraumatic AVO in immunwocompetent patients without identifiable patient or lifestyle risk. We were able to retrieve details of eight such patients published from 2010 to 2023 (Table 1). Four of these patients had a diagnosis proven by mycological culture, with two yielding A. fumigatus. Three patients had a likely or possible iatrogenic source of infection.

Surgical management of Aspergillus osteomyelitis is generally favoured in addition to at least 8 weeks of antifungal therapy and is recommended for cases with spinal instability or features of spinal cord or radicular compression [9, 12]. In our review of similar cases, the one patient who did not receive surgical management died after two months of antifungal chemotherapy. The efficacy of voriconazole over amphotericin B for treatment of invasive aspergillosis has been established, and IDSA guidelines recommend voriconazole as the initial antifungal agent of choice [12. 13]. However, multiple drug interactions, toxicity, and the need for therapeutic drug monitoring can be problematic [11]. Isavuconazole has been shown to be non-inferior to voriconazole for treatment of invasive aspergillosis, with a favourable side effect profile and no requirement for therapeutic drug monitoring [14]. Further data may see isavuconazole recommended as first line treatment of choice for invasive aspergillosis [11].


AVO is an uncommon but treatable disease, but diagnosis is often challenging. Early recognition of the disease requires a high index of suspicion and appropriate investigation. AVO should be considered in culture-negative spondylodiscitis. Delayed diagnosis may result in development of spinal deformity, requiring surgical correction in addition to prolonged antifungal treatment.

Conflict of interest



No dedicated funds for this study.


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