Metagenomic next-generation sequencing assists the diagnosis treatment of fungal osteoarticular infections

Abstract

Background: Fungal osteoarticular infection (FOI) is not commonly seen in clinical practice but proposes a great challenge to orthopedic surgeons. In this study, we aimed to investigate the risk factors, the clinical features, and surgical outcomes of FOI in our institution. Specifically, we aimed to explore the role of metagenomic next-generation sequencing (mNGS) in the diagnosis and treatment of FOI.

Methods: All the patients who were diagnosed and managed with FOI in our institution from January 2007 to December 2020 were retrospectively reviewed, including primary fungal implant-related infection, primary fungal osteomyelitis or arthritis, and fungal infections secondary to bacterial osteomyelitis or implant-related bacterial infections. The potential risk factors and the clinical and surgical features were analyzed. The pathogen data were compared between culture and the mNGS test.

Results: A total of 25 patients were included, namely, 12 primary implant-related infections, 7 primary fungal osteomyelitis or arthritis, and 6 fungal infections secondary to bacterial osteomyelitis or implant-related bacterial infections. Most cases had undergone multiple surgeries or long-term antibiotic treatment. Diagnosis was mainly based on microbial culture and the mNGS test. Optimization of culture methods and the use of mNGS assisted the diagnosis. Specifically, mNGS was performed in 12 patients, 5 of whom were culture-negative. In the remaining seven cases, mNGS demonstrated the same results as culture. Management of FOI was complicated as most patients required multiple surgeries followed by long-term antifungal treatment. In selected cases, antifungal-impregnated cement spacer retention can be an optional choice. The overall success rate was 100% (25/25) for our cohort.

Conclusion: We concluded that patients with comorbidities and a history of multiple surgeries or long-term antibiotics are under higher risk for FOI. Use of mNGS assists the diagnosis and treatment of FOI. Surgery combined with long-term antifungal treatment achieved satisfactory outcomes. In selected cases, antifungal-impregnated cement spacer retention can be an optional treatment choice.

Keywords: fungal osteoarticular infection (FOI); metagenomic next-generation sequencing (mNGS); osteomyelitis; periprosthetic joint infection (PJI); septic arthritis.

Figure 1

The flow diagram of enrollment of patients.

Figure 2

(Case 2) A 58-year-old female patient, with a history of hypertension and diagnosed with knee OA, received left TKA surgery in an outsider hospital. She complained of continuous pain after surgery for 1 year before admitted to our department (A). PJI was highly suspected, and knee aspiration was performed. The synovial WBC count was 10,345.0 × 10⁶/L (PMN 60.1%), and culture showed Candida parapsilosis. A two-stage revision surgery was performed (B). The patient received oral fluconazole (300 mg qd) for 6 months, and re-admitted for the second-stage reimplantation at 1 year later. The reimplantation was performed (C). The intraoperative culture was negative. After a 57-month follow-up, no sign of infection was noted.

Figure 3

(Case 6) A 37-year-old female patient, with a history of hyperthyroidism, was diagnosed with knee synovitis and received multiple arthroscopic debridement surgeries, followed by TKA surgery, in an outsider hospital. She was later diagnosed with acute PJI and received one DAIR surgery. She complained of continuous pain after surgery and was admitted to our department (A). PJI was highly suspected, and knee aspiration was performed. The synovial WBC count was 3,210.0 × 10⁶/L (PMN 82.0%), and culture showed Candida parapsilosis, which was consistent with the mNGS result (Candida). A two-stage revision surgery was performed (B). The patient received oral fluconazole (300 mg qd) for 6 months and reimplantation was performed (C, D). After a 20-month follow-up, the position of the prosthesis was satisfactory, and no sign of infection was noted.

Figure 4

(Case 13) A 71-year-old male patient, with a history of diabetes, bilateral kidney stone, and hepatitis B, complained of left hip pain for 2 years (A). Chronic destructive hip arthritis was highly suspected, and hip aspiration was performed. The synovial WBC count was 4,520.0 × 10⁶/L (PMN 88.1%), and culture and mNGS both showed Candida albicans. After consent with the patient, a one-stage THA surgery was performed (B). The patient received oral fluconazole (300 mg qd) for 6 months. After a 31-month follow-up, the patient showed no sign of infection (C).