Pathogenic Detection by Metagenomic Next-Generation Sequencing in Osteoarticular Infections.

Zi-Da Huang,Jian-Hua Lin,Wen-Ming Zhang,Chong-Jing Zhang,Chao-Fan Zhang,Xin-Yu Fang,Zi-Jie Zhang,Bin Yang,Wen-Bo Li

doi:10.3389/fcimb.2020.00471

Abstract

Objectives: To evaluate metagenomic next-generation sequencing (mNGS) as a diagnostic tool in detecting pathogens from osteoarticular infection (OAI) samples.Methods: 130 samples of joint fluid, sonicate fluid, and tissue were prospectively collected from 92 patients with OAI. The performance of mNGS and microbiology culture was compared pairwise.Results: The overall sensitivity of mNGS was 88.5% (115/130), significantly higher than that of microbiological culture, which had a sensitivity of 69.2% (90/130, p < 0.01). Sensitivity was significantly higher for joint fluid (mNGS: 86.7% vs. microbiology culture: 68.7%, p < 0.01) and sonicate fluid (mNGS: 100% vs. microbiology culture: 66.7%, p < 0.05) samples. mNGS detected 12 pathogenic strains undetected by microbiological culture. Additional pathogens detected by mNGS were Coagulase-negative Staphylococci, Gram-negative Bacillus, Streptococci, Anaerobe, non-tuberculosis mycobacterium, MTCP (p > 0.05), and Mycoplasma (OR = ∞, 95% confidence interval, 5.12–∞, p < 0.001). Additionally, sensitivity by mNGS was higher in antibiotic-treated samples compared to microbiological culture (89.7 vs. 61.5%, p < 0.01).Conclusions: mNGS is a robust diagnostic tool for pathogenic detection in samples from OAI patients, compared to routine cultures. The mNGS technique is particularly valuable to diagnose pathogens that are difficult to be cultured, or to test samples from patients previously treated with antibiotics.

Highlights

Osteoarticular infections (OAI), infections of the bone or joint, can be very serious
Ninety-two samples were collected from prosthetic joint infection (PJI), while 18 from primary septic arthritis (PSA), 6 from Implant-associated infection (IAI), 11 from SSI, and 3 from OM (Figure 1B)
An average of 21,142,755 total reads were generated from sequencing. 124 pathogens were identified at the genus level in the interpreted results of Metagenomic next-generation sequencing (mNGS) (Figure 2A), with

Summary

Introduction

Osteoarticular infections (OAI), infections of the bone or joint, can be very serious. OAI might be difficult to be treated, which is associated with a high recurrence rate, long-term disability, and even mortality (Parvizi et al, 2014; Yombi et al, 2017). The incidence of culture-positive infection is reported to be 40–70% (Trampuz et al, 2007), affected by prior antibiotic usage, fastidious pathogens, and biofilm adhered to surface of Metagenomic Diagnosis of Osteoarticular Infections implant (Tzeng et al, 2015). It always takes 2–14 days and even 6 weeks to culture and subsequently identify the microorganisms.

Objectives

Results

Conclusion