Cryptococcus neoformans tibial osteomyelitis in an immunocompetent host: a case diagnosed by tNGS

Abstract

Background

Cryptococcus neoformansis widely distributed in nature and primarily causes infections in various parts of the body through inhalation into the lungs. While C.neoformans infection predominantly occurs in immunocompromised individuals, there has been a significant increase in reports among immunocompetent hosts in recent years. Although the lungs and central nervous system constitute the most common sites of infection, cryptococcal osteomyelitis remains exceptionally rare and is typically associated with disseminated disease in immunodeficient patients. Herein, we present a rare case of isolated tibial cryptococcal osteomyelitis in an immunocompetent patient.

Case presentation

We report a case of a 64-year-old female who presented with pain, swelling, and increased local skin temperature in the left lower limb for one month without any obvious cause. The patient was initially diagnosed with osteomyelitis at a local county hospital and underwent surgical treatment. Due to poor postoperative healing, she was referred to our hospital for surgical debridement. Preoperative wound specimen culture revealed Luteimonas deserti. Simultaneously, intraoperative tissue samples were taken from the patient for targeted next-generation sequencing (tNGS) testing, which revealed the presence of C. neoformans. While the culture was negative, the C. neoformans capsular antigen test was positive. The patient had normal immune function and no underlying diseases. Ultimately, the patient was treated with fluconazole and surgery, resulting in a good prognosis.

Conclusions

we report a case of tibial osteomyelitis caused by Cryptococcus neoformans in an immunocompetent patient, with diagnosis confirmed through targeted next-generation sequencing (tNGS) and serum Cryptococcal capsular antigen testingOur results demonstrate the great potential of tNGS in the detection of infectious pathogens. In patients with negative culture results, tNGS can quickly detect various pathogens, providing accurate diagnosis and facilitating appropriate treatment for patients.

Supplementary Information

The online version contains supplementary material available at 10.1186/s12879-025-11451-y.

Background

Cryptococcus spp. are yeast-like fungus and the pathogens of cryptococcosis; among Cryptococcus species, Cryptococcus neoformans and Cryptococcus gattii can both cause cryptococcosis in humans, with C. neoformans infections being the most common. C. neoformans is widely distributed in nature; it is commonly found in the feces of pigeons and other birds as well as in soil contaminated by bird feces. C. neoformans is not typically found in fresh feces, but rather in long-accumulated bird droppings on windowsills and other roosting sites and in vacant buildings [1]. In contrast, C. gattii is mainly found in eucalyptus environments in tropical and subtropical region [2]. The infection route of C. neoformans is generally thought to be the inhalation of fungal spores into the lungs via the respiratory tract, which can cause pneumonia in immunosuppressed patients. However, in immunocompetent hosts, the fungal spores are either cleared by the immune system or form asymptomatic latent infections. In some individuals, immunosuppression can lead to the activation of latent infections, which then spread through the bloodstream to other tissues such as the central nervous system, skin, bones, joints, and other parts of the body. However, the fungus is more invasive in the central nervous system [3, 4]. While cryptococcal osteomyelitis was historically considered to occur almost exclusively in immunocompromised individuals (e.g., AIDS patients), emerging case series have revealed that > 87% of non-HIV-infected individuals with this condition exhibit no identifiable immunologic compromise [5]. C. neoformans osteomyelitis is exceptionally uncommon and typically manifests as part of disseminated disease. Its occurrence in non-HIV-infected, immunocompetent hosts represents an even rarer clinical entity. Herein, We report a case of isolated C. neoformans tibial osteomyelitis in an immunocompetent host. L. deserti was concomitantly isolated from the identical osteomyelitic lesion. L. deserti is a novel strain, first reported to be isolated from desert soil in Inner Mongolia, China, in 2021 [6].

Case presentation

The patient, a 64-year-old female, presented with pain, swelling, and increased local skin temperature in the left lower limb for over a month without any obvious cause, occasionally accompanied by low fever. She later visited the local county people’s hospital, where she was diagnosed with “osteomyelitis” and underwent surgical treatment, the details of which are unknown. After discharge, the patient experienced poor wound healing and exudation around the surgical site, prompting her to seek inpatient treatment at our hospital. Upon admission, examination revealed a surgical wound on the distal end of the patient’s left calf, with local sinus tract formation, a small amount of discharge, redness and swelling of the wound edges, and significant swelling of the left dorsum of the foot. A CT scan of the left calf showed osteomyelitis of the lower segment of the left tibia with postoperative changes(Fig. 1). A pulmonary CT scan showed a nodular high-density focus in the right lung with relatively clear boundaries; multiple small nodules in both lungs, possibly inflammatory; and chronic inflammation in both lungs. The preliminary diagnosis was postoperative osteomyelitis of the left calf and poor wound healing of the left calf. Due to the patient’s poor wound healing and significant postoperative exudation, surgical debridement is required(Fig. 2).

Fig. 1.

CT images of the left tibia

Fig. 2.

Intraoperative images

Before the operation, sterile saline was used to remove the surface secretions of the wound, and a sampling swab was used to take samples from the fresh edge of the lesion for bacterial culture and smear examination. Within 2 h after specimen collection, the specimens were inoculated on blood agar plates and MacConkey agar plates and cultured for 18–20 h at 35℃ in a 5% CO₂ environment. On the blood agar plate (Supplementary Image 1), seven medium-sized yellow monomorphic colonies were observed in the original streaking area; A single colony was selected and cultured on blood agar plates for 48 h, after which visible growth of medium-sized, orange-yellow colonies was observed(Supplementary Image 2); And no growth was seen on the MacConkey agar plate (Supplementary Image 3). The pure culture colonies were Gram-negative rods when stained with Gram stain (Supplementary Image 4). The colonies were picked and subjected to matrix-assisted laser desorption/ionization time-of-flight Mass spectrometry using Autobio and Bruker instruments, yielding no results. The strain was then sent out for 16 S targeted DNA sequencing (Supplementary Image 5). The gene amplification showed a single clear target band. After blast comparison, the sequencing results indicated that the bacterium was L. deserti (NR181370.1) with a similarity of 99.225%.

No bacteria were seen in the bacterial smear results. The blood routine results were as follows: white blood cells (WBC), 7.73 × 10⁹/L(normal 3.5–9.5 × 10⁹/L); neutrophil percentage, 0.839(normal 0.40–0.750); procalcitonin (PCT), 0.032 ng/mL(normal 0–0.05 ng/mL); C-reactive protein (CRP), 3.50 mg/L(normal 0–6.0 mg/L); and erythrocyte sedimentation rate (ESR), 24 mm/h(normal 0–20 mm/h). Liver and kidney function were normal, and the results were negative for human immunodeficiency virus antigen and antibody(HIV Ag/Ab), hepatitis B virus surface antigen(HBsAg), hepatitis C virus antibody(anti-HCV), and syphilis antibody(syphilis Ab). The doctor then performed debridement surgery and collected intraoperative tissue for culture, gram staining, and targeted next-generation sequencing (tNGS) detection. For the specific tNGS detection methodology, please refer to our previously published article [7]. Histopathological examination was not performed on the intraoperative tissue specimen. Gram staining of intraoperative tissue specimens revealed sparse yeast-like cells exhibiting characteristic morphological features consistent with Cryptococcus spp. However, bacterial and fungal cultures performed simultaneously on the intraoperative tissue sample both demonstrated no growth. The tNGS analysis demonstrated significant genomic coverage of C. neoformans (71,105 sequencing reads) and a quantified concentration of 3 × 10⁴ copies/mL in the specimen, corroborated by a positive serum cryptococcal capsular antigen detection via colloidal gold immunochromatographic assay (CrAg-LFA). In contrast, routine aerobic bacterial and fungal cultures of sputum specimens yielded no growth. Subsequently, the patient was finally diagnosed with C. neoformans tibial osteomyelitis.

Based on the examination results, the patient was treated with fluconazole sodium chloride injection (600 mg qd ivgtt; 800 mg qd ivgtt on the first day). After 7 d, the treatment was changed to fluconazole tablets (400 mg qd po) for an 8-week course. Subsequently, the treatment was adjusted to 200 mg qd po for a course of 6–12 months. The patient was discharged 10 d after the operation.

One month later, the patient was readmitted for surgical debridement due to poor wound healing. Preoperatively, wound secretions were taken for bacterial and fungal cultures, both of which were negative. During surgery, tissue samples were taken for bacterial and fungal cultures and tNGS testing. The culture results were all negative, while tNGS detected significant genomic evidence of Enterococcus faecalis (272,750 high-quality sequencing reads), comprehensive pathogen screening concurrently demonstrated the absence of Cryptococcus species across all analyzed genomic targets. During hospitalization, bacterial and fungal cultures of the drainage fluid were tested, all of which were negative. Two weeks later, due to poor wound healing, another debridement surgery was performed; no bacterial or fungal cultures were conducted before or after the debridement. Ten days later, the patient was discharged in good condition.

Discussion and conclusions

Cryptococcosis has caused a significant morbidity and mortality worldwide. In 2022, the World Health Organization listed C. neoformans as a top-priority fungal pathogen [36]. Cryptococcus spp. are opportunistic pathogens that does not spread between patients. Cryptococcal infections mainly occur in immunocompromised individuals, including patients with tumors, sarcoidosis, diabetes, autoimmune diseases, leukemia, and human immunodeficiency virus along with those who have received solid organ transplants and immunosuppressive therapy [4, 37]. The majority of C. gattii infections occur in immunocompetent hosts [2, 4, 38]. However, with recent improvements in diagnosis and treatment, reports of C. neoformans infections have been increasing in immunocompetent patients [37]. Cryptococcal osteomyelitis is quite rare, accounting for only approximately 5% of cryptococcosis cases, the majority of which are caused by C. neoformans [39–41].

The present study involved a systematic search of the PubMed database over the past 5 years for cases of cryptococcal osteomyelitis in non-HIV patients (Table 1). This systematic review identified 28 cases of cryptococcal osteomyelitis. Among these, 16 patients (57.1%) were male. The most commonly affected sites were the spine (n = 5), tibia (n = 5), ribs (n = 3), and calcaneus (n = 3). Underlying conditions were absent in 8 patients (28.6%). Prevalent comorbidities included autoimmune diseases (e.g., multiple sclerosis, Sjögren’s syndrome, rheumatoid arthritis; n = 6), chronic hepatitis B infection (n = 4), and solid organ transplantation (n = 3). Diagnosis was confirmed in all cases by culture and/or histopathological examination demonstrating Cryptococcus species. Notably, metagenomic next-generation sequencing (mNGS) concurrently detected Cryptococcus in 3 cases where it was employed. Regarding Management, combined surgical intervention and antifungal therapy were utilized in 16 cases (57.1%), while 12 patients (42.9%) received antifungal treatment alone. Ultimately, resolution of infection was achieved in 26 patients (92.9%).A literature review revealed that the vertebrae are the most common site of infection for cryptococcal osteomyelitis, with the tibia being less common [12, 17, 40].

Table 1.

Summary of cases of Cryptococcal osteomyelitis in HIV-Negative patients

Year	Country	Age(years) /Sex	Location	Initial diagnosis	Fundamental disease	Diagnostic methods	First-line therapy	Surgery	Outcome
2025[8]	India	35/M	Tibia, Radius	Diagnosis remained unestablished	Post-renal, transplantation, Tuberculosis, Diabetes mellitus	Culture, Histopathological examination	Intravenous liposomal amphotericin B (L-AMB) 200 mg daily (5 mg/kg/day); Oral flucytosine 1250 mg every 6 h.	YES	Cured
2025[9]	USA	89/M	Spine	Diagnosis remained unestablished	NO	Culture, CrAg	Liposomal Amphotericin B	NO	Improved
2025[10]	India	27/M	Calcaneus, Tibia	Tuberculosis	Leprosy	Culture, Histopathological examination	liposomal amphotericin B (3 mg/kg IV daily), oral fluconazole (400 mg daily)	YES	Cured
2024[11]	India	27/M	Calcaneus, Tibia	Diagnosis remained unestablished	Leprosy	Culture, Histopathological examination	Fluconazole (400 mg daily) for long-term	YES	Cured
2024[12]	China	41/F	Radius	Bacterial osteomyelitis	Chronic hepatitis B	Culture, Histopathological examination, mNGS	Oral fluconazole consolidation therapy: 200 mg twice daily for 12 weeks.	YES	Cured
2024[13]	China	28/M	multiple bones	Diagnosis remained unestablished	Chronic hepatitis B	Culture	Initial therapy: IV amphotericin B + oral flucytosine for 4 weeks.Consolidation: Oral fluconazole for 1 year.	NO	Cured
2024[14]	China	56/F	Spine	Tuberculosis	Tuberculosis	Histopathological examination, CrAg,	Induction: Amphotericin B (0.6 mg/kg/day IV) + flucytosine (100 mg/kg/day PO) × 4 weeks	NO	Cured
							Consolidation: Fluconazole 400 mg/day PO × 8 weeks
							Maintenance: Fluconazole 200 mg/day PO ≥ 6 months
2024[15]	United States	45/M	Humeral	Pneumonia	Esophageal Adenocarcinoma, Crohn’s Disease	Culture, CrAg,	Flucytosine (5-FC) and Amphotericin B	YES	Death
2024[16]	China	67/F	Ankle, Fibula	Tuberculosis	Tuberculosis	mNGS, Histopathological examination, CrAg	Flucytosine 1 g IV q12h × 25 d + Fluconazole 400 mg IV daily → Fluconazole 300 mg PO daily × 12mo	YES	Cured
2023[17]	China	37/M	Sacrum	Tumor, Tuberculosis	NO	Culture, Histopathological examination	IV fluconazole (4 weeks) → Oral fluconazole consolidation (8 weeks)	YES	Cured
2023[18]	Australia	53/M	Spine	Diagnosis remained unestablished	HLA-B27-associated chronic uveitis, hypertension	Histopathological examination, CrAg	Induction: Liposomal amphotericin B + flucytosine × 4 weeks→ Consolidation & maintenance: Fluconazole	NO	Cured
2023[19]	India	42/M	Ischial, Pubis	Diagnosis remained unestablished	Diabetes	Histopathological examination, CrAg	Liposomal amphotericin B IV + Flucytosine IV→ Fluconazole 400 mg daily × 6 months	YES	Cured
2023[20]	Greece	82/F	Tibia	Diagnosis remained unestablished	Diabetes, Chronic Kidney Disease, Rheumatoid Arthritis	Culture	Fluconazole IV loading dose 800 mg → 400 mg daily × 3 weeks → Fluconazole 200 mg PO every 12 h × 9 months	YES	Cured
2023[21]	China	16/F	Disseminated Cryptococcal Infection Without Specified Osteomyelitis Site	Tumor	Idiopathic Thrombocytopenic Purpura, Yolk Sac Tumor,	Culture	Fluconazole IV (loading 800 mg → 400 mg daily) + Flucytosine 150 mg 6 h, Added Liposomal Amphotericin B 60 mg/day IV	NO	Cured
2023[22]	China	31/F	Acetabulum	Diagnosis remained unestablished	Chronic hepatitis B	Histopathological examination	Fluconazole and Flucytosine	NO	Cured
2022[23]	United States	46/F	Rib	Pneumonia	Multiple sclerosis	Culture, CrAg	Liposomal amphotericin B IV + Flucytosine PO × 2 weeks, Maintenance: Fluconazole 400 mg PO daily × 6–12 months	NO	Cured
2022[24]	Brazil	20/F	Femur	Bacterial osteomyelitis	NO	Culture, Histopathological examination	Amphotericin B deoxycholate IV × 2 weeks, Fluconazole PO × 6 months (maintenance)	YES	Cured
2022[25]	United States	29/M	Humerus	Skin and subcutaneous infections	NO	Culture, CrAg	Fluconazole 800 mg once daily for 2 weeks → 400 mg once daily for 6 months	YES	Cured
2022[26]	China	79/F	Ulna	Bacterial osteomyelitis	NO	Culture	Fluconazole 200 mg IV twice daily → transitioned to oral 400 mg once daily.	YES	Cured
2022[27]	China	45/F	Pubis	Tumor	NO	Culture, Histopathological examination	luconazole 400 mg daily for 16 weeks	NO	Cured
2022[28]	United States	50/F	Femoral, Humeral	Multiple myeloma	NO	Culture, Histopathological examination, CrAg	Liposomal amphotericin B IV + Flucytosine PO × 2 weeks, Fluconazole 400 mg/day PO × 8 weeks, Fluconazole 200 mg/day PO × 12 months	NO	Cured
2022[29]	USA	36/M	Tibia	Diagnosis remained unestablished	Chronic hepatitis B, Tuberculosis	Culture,	Fluconazole and Amphotericin B	YES	Cured
2022[30]	China	41/M	Spine	Tumor	NO	Histopathological examination, mNGS	Discontinued flucytosine + amphotericin B 5 days, Fluconazole 400 mg daily	YES	Cured
2021[31]	China	46/F	Spine	Tumor	Sjögren’s Syndrome	Histopathological examination	Fluconazole 400 mg daily for 6 months	NO	Cured
2021[32]	USA	11/M	Rib	Bacterial osteomyelitis	Lung Transplantation	Culture, Histopathological examination, CrAg	Fluconazole 400 mg daily + Flucytosine 750 mg q6h × 14mo	NO	Cured
2021[33]	Argentina	69/F	Calcaneus	Diagnosis remained unestablished	Renal Transplantation	Histopathological examination	Liposomal amphotericin B 3 mg/kg/day IV × 25 days, Fluconazole 400 mg/day PO × 8 weeks	YES	Cured
2020[34]	India	20/M	Rib	Tuberculosis	Primary T-Cell Immunodeficiency	Histopathological examination	Liposomal amphotericin B 4 mg/kg/day IV + Flucytosine 100 mg/kg/day PO in 4 divided doses × 6 weeks, Fluconazole 800 mg/day PO × 8 weeks	NO	Cured
2020[35]	Japan	70/M	Humerus	Bacterial osteomyelitis	Multiple Sclerosis	Histopathological examination, CrAg	Fluconazole 400 mg/day PO × 5 months,200 mg/day PO × 17 months	YES	Cured

In our case, the patient had tibial osteomyelitis caused by C. neoformans, and L. deserti was also isolated from the infected site. L. deserti is a novel strain that was first isolated from desert soil in Inner Mongolia, China, in 2021. To date, L. deserti has not been documented in human subjects within the indexed medical literature. In our case, L. deserti was cultured from the preoperative specimen during the first hospital admission of the patient. The bacterial and fungal cultures of the intraoperative tissue specimens were negative, and tNGS detected only C. neoformans. The inconsistent results of the two cultures before and during the operation may be attributed to the presence of L. deserti on the wound surface of the patient; the small amount of bacteria contained within the intraoperative tissue resulted in the negative culture results. Although the tNGS analysis of the intraoperative tissue revealed C. neoformans, the culture was negative. This may be because the content of C. neoformans in the specimen was low, and the sensitivity of tNGS is much higher than that of the culture. The targeted next-generation sequencing (tNGS) assay detected C. neoformans but did not identify L.deserti, as the latter species was not encompassed within the predefined genomic targets of the panel. As a detection method, tNGS has high sensitivity, especially for pathogens with negative cultures. Serologic surveillance revealed unremarkable inflammatory markers: WBC, CRP, PCT and ESR all remained within normal limits. L. deserti was only cultured from the wound specimen collected preoperatively during the patient’s first admission to our hospital. Subsequently, cultures from multiple wound specimens did not show any growth of this bacterium. Further mechanistic investigations are warranted to elucidate the pathogenic potential of L. deserti and characterize its ecological role during co-isolation events with C. neoformans in human infections.Technical constraints precluded ancillary verification of L. deserti presence in intraoperative specimens. Consequently, the bacterium’s role in this infection remains undefined. Based on diagnostically confirmed evidence—including targeted next-generation sequencing (tNGS) detection and positive serum cryptococcal capsular antigen testing—C. neoformans was established as the primary etiologic agent of the tibial osteomyelitis.

This case is an elderly woman who presented with left lower limb pain, swelling, and increased local skin temperature without any obvious cause. The patient was immunocompetent and had no underlying diseases such as diabetes, tuberculosis, or autoimmune disease. The patient had also not received any immunosuppressive agents such as corticosteroids or biologics. Blood tests showed only a slight increase in ESR, normal infection indicators (PCT, CRP, and WBC), and normal liver and kidney function. Tests for human immunodeficiency virus antigen and antibodies, hepatitis B surface antigen, hepatitis C virus antibodies, and syphilis antibodies were negative. During the patient’s treatment in our hospital, antifungal therapy was initiated only after the tNGS report was received.

Common clinical manifestations of cryptococcal osteomyelitis include soft tissue swelling and tenderness. Imaging usually shows osteolytic lesions, which are difficult to distinguish from osteomyelitis caused by other pathogens such as Staphylococcus aureus, Mycobacterium tuberculosis, Brucella and Actinomyces [13, 17, 42, 43]. Analysis of the published cases revealed a consistent diagnostic challenge: cryptococcal osteomyelitis was frequently not considered initially. In the majority of cases identified in the literature (18/28, 64.3%), the initial differential diagnoses centered on tuberculosis, Malignancy, or common bacterial infection. Furthermore, in the remaining 10 cases (35.7%), while an infectious process was recognized, the specific pathogen remained unidentified and cryptococcal infection was excluded from the differential diagnosis (Table 1). Consistent with this pattern, cryptococcal osteomyelitis was also not initially suspected in our own case. C. neoformans tibial osteomyelitis is a diagnostic challenge due to its low incidence, atypical presentation, and non-specific imaging findings, which can easily lead to misdiagnosis.

The diagnosis of cryptococcosis can be confirmed by positive India ink staining, positive culture, or histopathological detection of Cryptococcus in the blood, deep tissue samples, or sterile body fluids (e.g., cerebrospinal fluid). The positive detection of C. neoformans polysaccharide antigen in cerebrospinal fluid and blood can also serve as confirmatory evidence for cryptococcosis [3, 4, 37]. Non-culture methods such as PCR and other molecular diagnostic techniques can also provide microbiological evidence for a presumptive diagnosis [37]. Although Cryptococcus smears with India ink staining are simple and rapid, the positive rate is low. Fungal culture is time consuming and also has a low positive rate. Histopathology is the gold standard but it is invasive and limited in its implementation. Serum C. neoformans capsular antigen detection has a sensitivity of over 99% and can be performed semi-quantitatively [3, 4, 44, 45]. However, this method cannot determine the site of infection, and many cases of cryptococcal osteomyelitis are diagnosed by culture or pathology before cryptococcal capsular antigen testing is performed [40], our occurred in the current case. In most cases, cryptococcal osteomyelitis is diagnosed by obtaining samples through puncture biopsy for culture and pathological examination [17]. In our case, cryptococcal osteomyelitis was diagnosed through tNGS and C. neoformans capsular antigen testing. tNGS based on multiplex PCR amplification or probe-targeted capture can selectively amplify or enrich target fragments and simultaneously detect dozens to hundreds of pathogens in a single sample, making tNGS an efficient, cost-effective, and accurate tool for pathogen detection [46–48]. Compared to mNGS, tNGS exhibits enhanced specificity through directed enrichment, reduced sequencing depth requirements, simplified bioinformatic processing, and higher sensitivity within a defined pathogen spectrum—alongside lower operational costs and shorter turnaround times. When benchmarked against conventional microbiological assays (e.g., staining, culture, serology, or PCR), tNGS demonstrates superior pathogen detection breadth and diagnostic yield [46, 48, 49]. Collective recommendations from multiple Chinese expert consensuses on tNGS advocate its implementation for spinal or osteoarticular infections when conventional microbiological assays yield negative results or empirical antimicrobial therapy fails to achieve clinical improvement within 48–72 h [49–51]. Studies have demonstrated that tNGS exhibits higher sensitivity than conventional culture for etiological detection in focal infections [48, 52, 53]. Multiple reported cases of cryptococcal osteomyelitis have successfully detected C. neoformans using mNGS [12, 16, 30]. In our case, C. neoformans was detected through the tNGS testing of intraoperative tissue, while the culture was negative. Subsequently, the serum C. neoformans capsular antigen test based on cryptococcal antigen lateral flow assay was positive. Based on these results, the clinicians changed the treatment plan and administered fluconazole to the patient, which reduced the risk of disease progression, shortened the patient’s hospital stay, and alleviated the economic burden.

The patient in this case kept pigeons at home and had no history of trauma. Chest CT revealed nodules and chronic inflammation, and the patient’s immune function was normal. The patient underwent sputum culture, which did not detect C. neoformans. The patient did not undergo bronchoalveolar lavage fluid or cerebrospinal fluid examination because no obvious symptoms of respiratory or central nervous system infection were present. Therefore, it could not be determined whether the patient had pulmonary cryptococcosis. The patient’s infection with C. neoformans might have been caused by exposure to pigeon droppings in the environment; the spores of C. neoformans were likely inhaled into the lungs and subsequently spread to the tibial bone marrow through the bloodstream.

Currently, no clinical treatment guidelines or consensus are available for non-pulmonary, non-central nervous system cryptococcosis. Cryptococcal osteomyelitis is rare, and most patients are treated with a combination of surgery and antifungal therapy [37]. Among the reviewed cases, 16 (57.1%) received combined surgical and medical treatment, while 12 (42.9%) were Managed with medical therapy alone. Clinical resolution was achieved in 26 patients (92.9%) (Table 1). Most experts think that fluconazole monotherapy is sufficient for most cases of localized bone cryptococcosis [40]. For patients with the risk of hematogenous dissemination, some experts recommend that skeletal cryptococcosis be initially treated with amphotericin B combined with flucytosine [39]. In our case, the patient was treated with surgical debridement and fluconazole, and the prognosis was favorable.

In summary, We report a case of tibial osteomyelitis caused by C. neoformans in an immunocompetent patient, with diagnosis confirmed through targeted next-generation sequencing (tNGS) and serum cryptococcal capsular antigen testing. TNGS can rapidly detect a variety of pathogenic microorganisms in patients with negative results from traditional microbiological tests, thereby providing accurate diagnosis and facilitating appropriate treatment.

Abbreviations

tNGS

Targeted next-generation sequencing

WBC

White blood cells

PCT

Procalcitonin

CRP

C-reactive protein

ESR

Erythrocyte sedimentation rate

CT

Computed tomography

HIV

Human immunodeficiency virus.

Authors’ contributions

QWJ and GYN were responsible for the acquisition and interpretation of the patient data and writing the original draft. LZY, WHH and HHB prepared the patient data and supplementary Images. ZLY prepared figure 1 and TSL prepared figure 2. WXN and ZLY reviewed and edited the manuscript. XL supervised and reviewed the manuscript. Weijuan Qin and Yuni Guo contributed equally to this work and should be considered co-first authors. All authors read and approved the final manuscript.

Funding

This study was supported by Self-financed scientific research of Guangxi Zhuang Autonomous Region Health Commission in 2024(NO.Z-A20240638) and National Natural Science Foundation of China in 2024(NO.82360412).

Data availability

The datasets generated during this study are available in the NCBI GenBank repository under accession number PV400546 (https://www.ncbi.nlm.nih.gov/nuccore/PV400546.1/).

Declarations

Ethics approval and consent to participate

Not applicable.

Consent for publication

Written informed consent was obtained from the patient for the publication of this case report and any accompanying images, and other potentially identifiable data. The patient acknowledged reviewing the final manuscript prior to submission and understands that it, along with the associated multimedia files, will be publicly available.

Competing interests

The authors declare no competing interests.