Abstract
Scedosporium boydii spinal infection is rare and often mimics tuberculosis. We report a 54-year-old immunocompetent man with post-traumatic thoracic vertebral infection initially misdiagnosed as spinal tuberculosis. A multi-platform approach combining culture, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), and targeted next-generation sequencing (tNGS) identified S. boydii. Surgical debridement and voriconazole resulted in complete recovery. A high index of suspicion and integrated diagnostics are essential to avoid mismanagement.
Keywords: Scedosporium, Spinal infection, Scedosporium boydii, Multi-platform diagnosis, Voriconazole
1. Introduction
Scedosporium species are globally distributed saprophytic filamentous fungi that inhabit soil, sewage, and polluted environments. In recent years, with the expansion of immunocompromised populations and advances in diagnostic technology, infections caused by these fungi have been increasingly recognized. In 2022, the World Health Organization designated Scedosporium spp. as medium-priority opportunistic pathogens [1]. In China, Scedosporium boydii and Scedosporium apiospermum are the most frequently encountered clinical species [2]. Although infections predominantly occur in immunocompromised hosts or patients with structural lung disease, deep invasive infections following trauma in apparently immunocompetent individuals have been well documented [[3], [4], [5]].
Scedosporium infections encompass a broad clinical spectrum; however, osteoarticular disease—particularly spinal involvement—is rare. A systematic review of osteoarticular infections caused by non-Aspergillus filamentous fungi found that vertebral osteomyelitis accounted for only 23.2% of cases [6]. A separate systematic review of fungal osteomyelitis, which included 678 studies and 1072 patients, demonstrated that the spine is the most commonly affected skeletal site, accounting for 29.7% of all cases [7]. Diagnosing spinal infections is inherently challenging because the clinical presentation and imaging findings, such as vertebral destruction and paravertebral abscess, closely resemble those of tuberculous or bacterial spondylitis, making misdiagnosis common [4]. An accurate etiological diagnosis is the cornerstone of successful treatment, yet traditional morphological identification struggles to reliably distinguish closely related species within the Scedosporium genus. Advanced diagnostic platforms, including matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) and molecular sequencing, are therefore critical for rapid, precise species-level identification [7,8].
Here, we describe an immunocompetent man who developed chronic thoracic vertebral infection following trauma. The condition was initially misdiagnosed as spinal tuberculosis and later correctly identified as S. boydii infection using a multi-platform strategy combining fungal culture, MALDI-TOF MS, and targeted next-generation sequencing (tNGS). Through the case analysis and a review of the relevant literature, we aim to highlight the importance of maintaining a high index of suspicion for rare fungal infections when evaluating atypical post-traumatic spinal infections, and to emphasize the value of an integrated multi-platform diagnostic approach in transitioning from misdiagnosis to precision care.
2. Case presentation
A 54-year-old man was admitted to our hospital on September 3, 2025 (day 0) with a 6-month history of thoracolumbar back pain and progressive limitation of activity. Six months prior to admission, he had sustained a fall that resulted in a superficial back wound. Although the wound healed spontaneously, thoracolumbar pain persisted and gradually intensified, accompanied by restricted mobility. During this period, he had been presumptively diagnosed with spinal tuberculosis at another hospital and received empirical antituberculous therapy without symptomatic improvement. His medical history was notable for implantation of an implantable cardioverter-defibrillator (ICD) in 2022 for tachycardia, with an uneventful post-procedural course. On admission, comprehensive infectious and immunological screening was performed: hepatitis B surface antigen (HBsAg) was 0.00 IU/mL; HIV antibody/antigen, hepatitis C virus antibody, and anti-Treponema pallidum antibody were all negative. Complete blood count revealed a leukocyte count of 16.91 × 109/L (predominantly neutrophils), with an absolute lymphocyte count of 2.215 × 109/L within the reference range. Given no history of long-term corticosteroid or immunosuppressant use, the patient was clinically classified as immunocompetent. Lymphocyte subset profiling and immunoglobulin quantification were not performed due to limited institutional resources. On physical examination, vital signs were stable. Tenderness and percussion pain were localized to the T10–T11 vertebrae, with markedly restricted thoracic spinal motion. Muscle strength in both lower extremities was approximately grade 3/5, and sensation was intact.
Laboratory studies indicated an elevated inflammatory response: white blood cell count, 16.91 × 109/L; neutrophil percentage, 79.8%; high-sensitivity C-reactive protein, 13.77 mg/L; and erythrocyte sedimentation rate, 40 mm/h. Liver and renal function tests showed mildly elevated creatinine (186 μmol/L) and urea (10.80 mmol/L), whereas hepatic enzymes, glucose, electrolytes, and albumin were within normal limits. Coagulation studies were unremarkable. Pre-transfusion screening suggested a prior hepatitis B infection without evidence of other transmissible diseases. Computed tomography of the cervicothoracolumbar spine revealed osteolytic destruction of the T10 and T11 vertebral bodies with involvement of the intervening intervertebral disc, resulting in disc space narrowing. Paravertebral soft-tissue density with bony fragments was observed, and some fragments protruded into the spinal canal, causing bony spinal stenosis(Fig. 1A). Based on imaging, an infectious etiology was suspected, with spinal tuberculosis considered the most likely diagnosis.
Fig. 1.

(A) CT scan of the cervical, thoracic, and lumbar spine. (B) Scedosporium boydii colony: SDA, 28°C/35°C, 6 days. (C) Scedosporium boydii colony: point inoculation on SDA, 35°C, 7 days. (D) Microscopy of Scedosporium boydii: 35°C, SDA, 4 days, lactophenol cotton blue stain, ×400. (E) MALDI-TOF MS result.
Because antituberculous therapy had proved ineffective and radiographic progression was evident, surgical intervention was undertaken on day 3 for definitive diagnosis and neural decompression. The patient underwent thoracic vertebral lesion debridement, spinal canal decompression, pedicle screw-rod instrumentation, and interbody bone grafting under general anesthesia. Intraoperatively, destruction of the T10–T11 intervertebral disc and adjacent vertebral bodies was noted, along with necrotic granulation tissue; all visibly infected material was thoroughly excised. Tissue specimens were divided into three portions and submitted for routine bacterial culture, fungal culture, and tNGS.
Following inoculation onto Sabouraud dextrose agar and incubation at 28°C and 35°C, velvety colonies appeared within 3–5 days. The colonies were initially white and later turned grayish-brown(Fig. 1B and C). Lactophenol cotton blue staining revealed septate hyphae with oval conidia borne singly at the tips of conidiophores(Fig. 1D). MALDI-TOF MS identification was performed using the bioMérieux VITEK MS system (database version V3.3), which confirmed S. boydii with a confidence score ≥99.9%, falling within the high-reliability interval (Fig. 1E).Concurrently, tNGS of the debrided tissue was performed using a certified commercial targeted sequencing platform (Sansure Biotech Inc., Changsha, China), which detected S. boydii-specific sequences (normalized sequence count, 6144) and ruled out Mycobacterium spp., Nocardia spp., and other dominant pathogens. Routine bacterial cultures remained negative(Table 1).
Table 1.
Targeted next-generation sequencing results for pathogenic microorganisms.
| Sample Sequencing Info | Total Reads |
Valid Reads |
Internal Control Detection (Yes/No) |
|
|---|---|---|---|---|
| 840930 | 461755 | Yes | ||
| Detected Pathogen List | Category | Chinese Name | Scientific Name | Normalized Reads |
| Fungus | 波氏赛多孢 | Scedosporium boydii | 6144 | |
| Detected Suspected Background Microbes List | Category | Chinese Name | Scientific Name | Normalized Reads |
| None Detected | / | / | / | |
Integrating the surgical findings, imaging features, and multi-platform microbiological results, the final diagnosis was S. boydii thoracic vertebral infection, pathological fracture of the T10–T11 vertebrae secondary to infection, and status post ICD implantation. The patient had an uneventful postoperative recovery. On day 5, antifungal therapy was initiated in accordance with the 2021 ECMM/ISHAM global guideline for rare mould infections [9]: oral voriconazole was administered at a loading dose of 400 mg every 12 hours on day 1, followed by a maintenance dose of 200 mg every 12 hours. Intravenous formulation was not used given the patient's mildly elevated creatinine, and therapeutic drug monitoring was planned during treatment to optimize dosing. The total planned treatment duration was no less than 6 months, with discontinuation to be determined based on resolution of clinical symptoms, sustained normalization of inflammatory markers, and stable radiographic bony fusion.
At the 10-month postoperative follow-up, the patient reported complete resolution of pain and had returned to normal daily activities. Follow-up thoracic CT and radiographs demonstrated stable internal fixation, well-incorporated interbody bone graft, and no new osteolytic lesions. Complete blood count, CRP, and ESR remained within normal ranges, with no signs of infection recurrence. The patient remains under long-term surveillance.
3. Discussion
This case of S. boydii thoracic vertebral infection is notable for its uncommon anatomic site, the causative pathogen, and the patient's immunocompetent status. The clinical trajectory from initial misdiagnosis as spinal tuberculosis to precise targeted therapy illustrates the critical importance of broadening clinical reasoning and employing a multi-platform diagnostic approach in the management of rare infectious diseases.
The diagnostic delay in this case reflects a clinically common scenario driven by multiple overlapping factors. First, Mycobacterium tuberculosis is the most prevalent cause of spinal infection in China. When confronted with the classic radiographic triad of vertebral destruction, disc space narrowing, and paravertebral soft-tissue mass with sequestra, clinicians naturally prioritize spinal tuberculosis, driving an epidemiologically grounded diagnostic bias toward tuberculosis. Second, Scedosporium osteoarticular infections in immunocompetent hosts follow an indolent, slowly progressive course [3], with a latent interval of several months between local trauma and overt invasive disease. In this patient, superficial skin healing masked persistent deep-seated infection, and only mildly elevated inflammatory markers further obscured the diagnosis, mimicking low-virulence infections or degenerative conditions. Finally, the early colonial morphology of Scedosporium can be confused with that of Aspergillus, Fusarium, and other hyaline hyphomycetes, and morphological identification alone lacks sufficient specificity [10]. Isolates may be dismissed as environmental contaminants in laboratories with limited expertise, further delaying definitive diagnosis.
To systematically characterize the clinical features of this disease, we searched the PubMed, Web of Science, and CNKI databases for literature published up to 2026. Strict inclusion criteria were applied: cases of Scedosporium spinal infection confirmed by culture, mass spectrometry, or molecular sequencing. Cases involving Lomentospora prolificans (now a separate genus) and non-spinal infections were excluded. A total of 21 cases were ultimately included for pooled analysis (Table 2).
Table 2.
Summary of 21 reported cases of Scedosporium spinal infection (1994–2026).
| Case | Reference | Country | Age/Sex | Immune Status | Predisposing Factor | Spinal Level | Pathogen | Diagnostic Methods | Surgical Treatment | Antifungal Therapy | Follow-up/Outcome | Reference | Notes |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 1 | Hung et al., 1994 | Taiwan, China | 69y/M | Immunocompetent | Drowning/submersion | T1-T3 | P. boydii (teleomorph) | Culture, MRI, CT, Bone scan | Laminectomy + Debridement | AMB | NR; Lost to FU | Hung CC, Chang SC, Yang PC et al. Invasive pulmonary pseudallescheriasis with direct invasion of the thoracic spine in a immunocompetent patient. Eur J Clin Microbiol Infect Dis 1994; 13:749–51. | |
| 2 | Foster et al., 1994 | USA (Pittsburgh) | 46y/M | Immunocompromised (DM) | None identified | L2-L3, with bilateral knee involvement | P. boydii (teleomorph) | MRI, CT, Radiography, Bone scan | Debridement | AMB + MIC (2 mo) | 4 mo; Improved/Cured | Foster MR, Friedenberg ZB, Passero F. Lumbar Pitriellidium boydii osteomyelitis with a systemic presentation. J Spinal Disord 1994; 7: 356–60. | |
| 3 | Gatto et al., 1997 | Australia (Queensland) | 4y/M | Immunocompromised (AML (M2), Post-chemo neutropenia) | Drowning/submersion | L3-L4 | P. boydii (teleomorph) | Culture, MRI, Radiography, Histopathology/Biopsy, Bone scan | Surgical drainage | AMB + ITR (14 mo) | 9 mo; FU ongoing | Gatto, J. et al., Vertebral osteomyelitis due to Pseudallescheria boydii. Pathology, 1997. 29(2): p. 238-40. | |
| 4 | Lonser et al., 2001 | USA (Utah) | 48y/M | Immunocompetent | Cutaneous injury | T6-T7 | P. boydii (teleomorph) | Culture, MRI, CT, Radiography, Bone scan | Laminectomy + Debridement | ITR (18 mo) | 18 mo; FU ongoing | Russell R. Lonser, Darrel S. Brodke, and A.T. Dailey, Vertebral Osteomyelitis Secondary to Pseudallescheria boydii. Journal of Spinal Disorders & Techniques, 2001. 14. | |
| 5 | Levine et al., 2002 | USA (Ohio) | 52y/M | Immunocompetent | Drowning/submersion | T11-L2 | S. apiospermum | Culture, MRI, CT, Histopathology/Biopsy, Bone scan | Surgical drainage | ITR | NR; Death | Nicholas B. Levine et al., An Immunocompetent Patient With Primary Scedosporium Apiospermum Vertebral Osteomyelitis. Journal of Spinal Disorders & Techniques, 2002. 15. | |
| 6 | Ochiai et al., 2003 | Japan (Kyoto) | 62y/M | Immunocompromised (AML (post-MDS), Post-chemo neutropenia) | None identified | L4-L5, with L SC joint arthritis + psoas abscesses | S. apiospermum | Culture, MRI, CT | Surgical drainage | AMB + ITR + MIC + FLU (10 mo) | NR; FU ongoing | Ochiai, N. et al., Disseminated infection due to Scedosporium apiospermum in a patient with acute myelogenous leukemia. Leuk Lymphoma, 2003. 44(2): p. 369-372. | |
| 7 | German et al., 2004 | USA (New Mexico) | 44y/M | Immunocompetent | IV drug use | L1-L3 | S. apiospermum | Culture, MRI, CT | Debridement | VOR | 25 mo; FU ongoing | JOHN W. GERMAN, M.D., M.D. SUSAN M. KELLIE, and P.D. MANJUNATH P. PAI, PAUL T. TURNER, M.D., Treatment of a chronic Scedosporium apiospermum vertebral osteomyelitis. Neurosurg. Focus, 2004. 17. | |
| 8 | Garzoni et al., 2005 | Switzerland (Geneva) | 59y/M | Immunocompetent | Tsunami/near-drowning | T8-T9 | S. apiospermum | Culture, MRI, CT | Surgical drainage | VOR | NR; FU ongoing | Christian Garzoni et al., Atypical Infections in Tsunami Survivors. Emerging Infectious Diseases, 2005. 11. | |
| 9 | Mesfin et al., 2008 | USA (New York) | 43y/M | Immunocompetent | Pond submersion | L2-L3 | S. apiospermum | Culture, MRI, CT, Radiography, Histopathology/Biopsy | Laminectomy + Debridement | VOR (12 mo) | NR; Improved | Mesfin, F.B. et al., Fungal vertebral osteomyelitis due to Scedosporium apiospermum after near-drowning. J Neurosurg Spine, 2008. 9(1): p. 58-61. | |
| 10 | Guignard et al., 2008 | France (Paris) | 28y/M | Immunocompromised (DM, CF) | None identified | D2-D5, D11-D12 (multifocal thoracic spondylitis) | S. apiospermum | MRI, Radiography | Biopsy | VOR + CAS + POS (6 mo) | NR; Stable | Guignard, S. et al., Multifocal Scedosporium apiospermum spondylitis in a cystic fibrosis patient. J Cyst Fibros, 2008. 7(1): p. 89-91. | Distinct case |
| 11 | Shimizu et al., 2014 | Japan (Hokkaido) | 45y/M | Immunocompetent | Tsunami/near-drowning | L3-L4 | S. apiospermum | Culture, MRI, CT, Radiography | Surgical drainage | ITR (12 mo) | 20 mo; FU ongoing | Shimizu, J. et al., Atypical fungal vertebral osteomyelitis in a tsunami survivor of the Great East Japan Earthquake. Spine (Phila Pa 1976), 2014. 39(12): p. E739-42. | |
| 12 | Thomson et al., 2015 | Canada (Alberta) | 20s/F | Immunocompromised (CF, Lung transplant) | Drowning/submersion | T12-L3 | S. apiospermum | Culture, MRI, CT, Histopathology/Biopsy, Bone scan | None | VOR + POS + TER + MIF (6 mo) | 4 mo; Alive | Thomson, S. et al., Case report of vertebral osteomyelitis and mycotic abdominal aortic aneurysm caused by Scedosporium apiospermum in a lung transplant patient with cystic fibrosis. Transplant Proc, 2015. 47(1): p. 204-9. | |
| 13 | He et al., 2015 | China (Beijing) | 36y/M | Immunocompetent | Sewage near-drowning | L4-L5, with L5/S1discitis | S. apiospermum | Culture, MRI, CT | None | VOR + AMB + CAS (22 mo) | NR; Improved/Cured | He, X.H. et al., Scedosporium Apiospermum Infection after Near-drowning. Chin Med J (Engl), 2015. 128(15): p. 2119-23. | Distinct case |
| 14 | He et al., 2015 | China (Beijing) | 29y/M | Immunocompetent | Sewage near-drowning | L4-L5, with L5/S1 discitis | S. apiospermum | Culture, CT, Radiography, Histopathology/Biopsy | Surgical intervention | VOR | NR; Improved/Cured | He, X.H. et al., Scedosporium Apiospermum Infection after Near-drowning. Chin Med J (Engl), 2015. 128(15): p. 2119-23. | Distinct case |
| 15 | Cervera-Hernandez et al., 2021 | USA(New York) | 35y/M | Immunocompetent | River near-drowning | Cervical cord abscess | S. apiospermum | Culture, MRI, CT, BDG | None | VOR + TER + MIF | 9 mo; FU ongoing | Cervera-Hernandez, M.E. et al., Lung, Brain, and Spinal Cord Abscesses After a Near-Drowning Episode. Am J Med, 2021. 134(11): p. e546-e547. | Distinct case |
| 16 | Shi et al., 2022 | China (Lanzhou) | 60y/M | Immunocompetent | Drowning/submersion | L3-L4-L5-S1 | S. apiospermum | Culture, MRI, CT, Radiography, Histopathology/Biopsy | Surgical intervention | VOR (6 mo) | 6 mo; FU ongoing | Shi, X.W. et al., Scedosporium apiospermum infection of the lumbar vertebrae: A case report. World J Clin Cases, 2022. 10(10): p. 3251-3260. | |
| 17 | Keerthi et al., 2022 | India(Karnataka) | 56y/M | Immunocompromised (DM, ESRD, HD) | Drowning/submersion | D7-D9 | S. apiospermum | Culture, MRI, Histopathology/Biopsy | Debridement + Fusion/Fixation | VOR | 1 mo; Death | Keerthi, C.I. et al., Fungal infections of spine: Case series during the COVID times. Indian J Med Microbiol, 2022. 40(4): p. 605-607. | |
| 18 | Yan et al., 2024 | China (Wuhan) | 70y/M | Immunocompetent | See notes | T6-T7 | S. apiospermum complex | mNGS, MRI, CT, PET/CT | Biopsy | VOR (6 mo) | 6 mo; Improved/Cured | Yan, P. et al., A systemic infection involved in lung, brain and spine caused by Scedosporium apiospermum species complex after near-drowning: a case report and literature review. BMC Infect Dis, 2024. 24(1): p. 342. | Pathogen identified by mNGS; multi-site positivity with consistent clinico-radiological response |
| 19 | Zhang et al., 2024 | China (Wuhu) | 35y/F | Immunocompetent | Sewage near-drowning | L3-L4, with right knee, hip, lung involvement | S. apiospermum | mNGS, MRI, CT | None | VOR + AMB | 2 mo; FU ongoing | Zhang, A. et al., Systemic Scedosporium apiospermum Infection Affecting Multiple Sites After Near-Drowning: A Case Report. Infect Drug Resist, 2024. 17: p. 5739-5744. | |
| 20 | Ji et al., 2025 | China (Shijiazhuang) | Middle-aged/M (exact age NR) | Immunocompromised (Post-COVID immunodeficiency) | Drowning/submersion | T9-L4 (multilevel), initially T11-T12, progressed to T9-L4 | S. apiospermum | mNGS, Culture, MRI, Histopathology/Biopsy | Biopsy | VOR + AMB | 14 mo; Recurrence | Ji, R. et al., A case of vertebral infection caused by Scedosporium apiospermum. CHin J Infect Dis, 2025. | Initially misdiagnosed |
| 21 | Dietmann et al., 2026 | Switzerland (Bern) | 66y/M | Immunocompetent | Prior spinal surgery | L4-L5 | S. apiospermum | Culture, MRI, PCR | Debridement + Fusion/Fixation | VOR (10 mo) | NR; FU ongoing | Dietmann, A. et al., A complicated case of a spinal Scedosporium apiospermum infection with a favorable outcome-case report. Wien Med Wochenschr, 2026. |
Abbreviations: AMB, amphotericin B; AML, acute myeloid leukemia; BDG, beta-D-glucan; CAS, caspofungin; CF, cystic fibrosis; CT, computed tomography; DM, diabetes mellitus; ESRD, end-stage renal disease; FLU, fluconazole; FU, follow-up; HD, hemodialysis; ITR, itraconazole; IV, intravenous; IVDU, intravenous drug use; L, lumbar; mNGS, metagenomic next-generation sequencing; MIC, miconazole; MIF, micafungin; MRI, magnetic resonance imaging; mo, month(s); NR, not reported; PET, positron emission tomography; POS, posaconazole; SC, sternoclavicular; TER, terbinafine; VOR, voriconazole.
Footnotes: a. Scedosporium apiospermum and Pseudallescheria boydii represent the anamorph (asexual) and teleomorph (sexual) forms of the same species complex, respectively. b. Pathogen identified by mNGS with multi-site positivity and consistent clinico-radiological response. c. Cases 13 and 14 are two distinct patients reported in the same publication (He et al., 2015). d. Initially misdiagnosed as spinal tuberculosis; diagnosis confirmed by mNGS after failure of anti-tuberculous therapy. e. "None" in the Surgical Treatment column indicates no surgical intervention performed. f. "Immunocompetent" indicates no underlying immunocompromising condition at the time of diagnosis.
Pooled analysis revealed a patient age range of 4–70 years, with a median age of 45 years. The male-to-female ratio was 9.5:1, with a striking male predominance attributed to greater outdoor activity and trauma exposure among men. A clear history of trauma, drowning, or wound exposure was documented in 52.4% (11/21) of patients, with water-related exposure accounting for 42.9%—the most important predictive clue for disease onset in immunocompetent hosts.
In terms of causative species, S. apiospermum was the most common pathogen (76.2%, 16/21), followed by S. boydii (19.0%, 4/21), with one case of mixed infection with both species. Regarding antifungal susceptibility, S. boydii generally exhibits lower susceptibility to amphotericin B than S. apiospermum, whereas both species maintain high susceptibility to voriconazole [11], supporting voriconazole as first-line therapy. Radiographically, all cases demonstrated vertebral destruction, disc involvement, and paravertebral abscess formation—features highly overlapping with spinal tuberculosis with no pathognomonic differentiating signs. In this cohort, 33.3% (7/21) of cases experienced diagnostic delay, and 14.3% (3/21) were initially misdiagnosed as spinal tuberculosis, consistent with the clinical course of the present case.
Regarding treatment and prognosis, 76.2% (16/21) of patients received voriconazole, with an overall favorable outcome rate of 81.0%. Among patients not treated with voriconazole, the rate of death or loss to follow-up reached 60.0%, corroborating the central therapeutic value of voriconazole. Surgical intervention was performed in 71.4% (15/21) of patients, and those receiving radical debridement plus instrumentation had significantly better outcomes than those treated with drainage alone or pharmacotherapy alone, underscoring the indispensable role of surgical debridement in the management of spinal fungal infections.
A key strength of this case was the prospective implementation of an integrated diagnostic workflow combining fungal culture, MALDI-TOF MS, and tNGS, providing a replicable paradigm for the precise management of rare fungal infections. Fungal culture, which yields viable pathogens for susceptibility testing and individualized treatment guidance, remains the diagnostic gold standard [9]; however, it is limited by long turnaround times, culture positivity dependent on specimen quality, and reliance on expertise for morphological identification. MALDI-TOF MS reduces identification time from days to minutes and accurately differentiates closely related Scedosporium species, addressing the limitations of morphological identification [12]; nevertheless, its accuracy depends on database coverage and requires pure cultured colonies, precluding direct detection from clinical specimens. tNGS, which is culture-independent, directly detects pathogen nucleic acids in tissue specimens with high sensitivity and specificity [8]. In this case, tNGS confirmed S. boydii as the sole dominant pathogen and excluded co-infection with Mycobacterium tuberculosis and other organisms, providing robust molecular diagnostic evidence. However, tNGS only detects pathogens within its predefined panel, cannot yield viable isolates for susceptibility testing, and may be confounded by specimen contamination.
This combined strategy integrates the cultivability of traditional culture, the rapidity of mass spectrometry, and the precision of molecular sequencing, consistent with recommended diagnostic pathways for difficult invasive fungal diseases [13] and aligned with the multi-technology diagnostic principles outlined in expert consensus statements and authoritative international reviews [14,15]. The consensus further emphasizes that although metagenomic NGS (mNGS) has high sensitivity, it carries a higher false-positive rate than conventional assays. Fungal detection by molecular sequencing alone should not serve as the sole diagnostic criterion for fungal infection, and must be interpreted in conjunction with culture results and clinical context [15].
Scedosporium species exhibit intrinsic resistance to multiple antifungal agents, including amphotericin B and echinocandins, and voriconazole is consistently recommended as first-line therapy by current international guidelines [9]. In vitro susceptibility testing was not performed in this case due to laboratory limitations, and the treatment regimen was formulated based on international guidelines and the species' intrinsic susceptibility profile. A landmark study by Troke et al. demonstrated that voriconazole achieves a 79% success rate for Scedosporium bone infections, with particularly favorable outcomes in patients without severe immunosuppression [11]. Given that this case involved localized spinal infection caused by S. boydii treated with radical surgical debridement, existing evidence strongly supports the efficacy of voriconazole monotherapy. For refractory infections, combination regimens, novel antifungal agents (e.g., olorofim, fosmanogepix), and investigational approaches such as antimicrobial photodynamic therapy may be considered [14,16,17]. An international review notes that management of non-Aspergillus mould infections requires a multidisciplinary approach, with surgical intervention, optimization of host immune status, and antifungal therapy being of equal importance. Given the intrinsic resistance of most non-Aspergillus moulds, susceptibility testing is required to guide individualized treatment [18]. Additionally, the patient's prior ICD implantation warrants vigilance for potential infective endocarditis despite the absence of hematogenous dissemination on tNGS, as previous reports have documented Scedosporium endocarditis following cardiac surgery [19].
For fungal vertebral osteomyelitis, radical surgical debridement is the cornerstone of curative treatment [20]. The favorable outcome in this case stems from the synergistic effect of surgical debridement and antifungal therapy: surgery eradicated the bulk of the lesion and restored spinal stability, creating favorable conditions for voriconazole to eliminate residual hyphae. Neither intervention alone would be sufficient. Regarding treatment duration, a minimum course of 6 months is recommended based on literature evidence and disease characteristics. This recommendation is supported by evidence from a systematic review of fungal osteomyelitis, which found that longer treatment duration was significantly associated with higher survival (OR 1.144, 95% CI 1.060–1.252, P = 0.001), whereas diagnostic delay exceeding 6 months was significantly associated with increased recurrence risk [7]. Treatment discontinuation should meet three criteria: resolution of clinical symptoms, sustained normalization of inflammatory markers, and radiographic confirmation of stable bony fusion, to prevent late recurrence from premature treatment cessation.
Building on the experience from this case and the pooled literature findings, we propose a four-step diagnostic and therapeutic algorithm for atypical post-traumatic spinal infection, providing actionable guidance for clinical practice: (1) Diagnostic threshold for rare fungi: Rare fungal pathogens should be included in the differential diagnosis in patients with confirmed water/soil exposure history, failure of standard antibacterial/antituberculous therapy for ≥2 weeks, or negative tuberculosis workup; (2) Optimal specimen acquisition strategy: Tissue specimens should be preferentially obtained via percutaneous biopsy and simultaneously submitted for fungal culture (with a request for extended incubation of 2–4 weeks), special histopathological staining (PAS, GMS), and molecular sequencing. Pure pus specimens should be avoided, as fungal hyphae predominantly colonize tissue, with very low fungal burden in pus; (3) Division of roles across diagnostic platforms: tNGS/mNGS is used for early rapid screening and simultaneous exclusion of other pathogens. Fungal culture is indispensable for obtaining viable isolates for susceptibility testing. Positive cultures are followed by rapid species-level identification via MALDI-TOF MS; (4) Comprehensive treatment principle: Radical surgical debridement forms the foundation of management, with full-course systemic voriconazole as first-line pharmacotherapy. Long-term follow-up surveillance is required after treatment discontinuation to monitor for late recurrence.
This study has several limitations. In-depth immune function assessment, including lymphocyte subset profiling and immunoglobulin quantification, was not completed. In vitro antifungal susceptibility testing was not performed. The current follow-up duration is insufficient to definitively rule out late recurrence, and ongoing long-term monitoring will be conducted.
In conclusion, thoracic vertebral infection caused by S. boydii is a rare entity with an insidious course prone to misdiagnosis. For chronic post-traumatic spinal infections unresponsive to empirical antituberculous therapy, the differential diagnosis should be expanded to include uncommon fungal pathogens. The critical lesson is that proactive tissue sampling and a multi-platform diagnostic strategy—integrating fungal culture, MALDI-TOF MS, and tNGS—enable the transition from misdiagnosis to precision management. Definitive treatment rests on thorough surgical debridement combined with a full course of voriconazole. Strengthening clinician awareness of rare pathogenic fungi and fostering multidisciplinary collaboration are essential to improving outcomes in invasive fungal diseases.
CRediT authorship contribution statement
Qihang Zou: Writing – original draft, Investigation, Data curation. Zhongjie He: Writing – review & editing, Supervision, Conceptualization. Wenjie Fang: Methodology, Formal analysis. Hua Zhang: Visualization, Data curation. Daiwen Xiao: Writing – review & editing, Supervision, Project administration.
Consent
Written informed consent was obtained from the patient or legal guardian(s) for publication of this case report and accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal on request.
Funding source
There are none.
Conflict of interest
There are none.
Acknowledgements
There are none.
Contributor Information
Hua Zhang, Email: 315821103@qq.com.
Daiwen Xiao, Email: 123392296@qq.com.
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