Genomic investigation of bone tuberculosis highlighted the role of subclinical pulmonary tuberculosis in transmission.

BACKGROUND: Extrapulmonary tuberculosis (EPTB) without symptomatic pulmonary involvement has been thought to be non-transmissible, but EPTB with asymptomatic pulmonary tuberculosis (PTB) could transmit tuberculosis (TB). Genomic investigation of Mycobacterium tuberculosis (Mtb) isolates from EPTB may provide insight into its epidemiological role in TB transmission. METHODS: Between January 2017 and May 2020, 107 Mtb isolates were obtained from surgical drainage of bone TB patients at the Beijing Chest Hospital, and 218 Mtb strains were isolated from PTB cases. These 325 Mtb isolates were whole-genome sequenced to reconstruct a phylogenetic tree, identify transmission clusters, and infer transmission links using a Bayesian approach. Possible subclinical PTB in the bone TB patients was investigated with chest imaging by two independent experts. RESULTS: Among 107 bone TB patients, 10 were in genomic clusters (≤12 SNPs). Phylogenetic analysis suggested that three bone TB patients transmitted the infection to secondary cases, supported by epidemiological investigations. Pulmonary imaging of 44 bone TB patients revealed that 79.5 % (35/44) had radiological abnormalities suggestive of subclinical PTB. CONCLUSIONS: This study provides genomic evidence that bone TB patients without clinically diagnosed PTB can be sources of TB transmission, underscoring the importance of screening for subclinical, transmissible PTB among EPTB cases.

Differential distribution of linezolid in diseased and nondiseased bones in patients with spinal tuberculosis.

BACKGROUND: Linezolid exhibits antibacterial activity against sensitive and drug-resistant strains of Mycobacterium tuberculosis. Knowledge on the distribution of linezolid in different types of bones in patients with spinal tuberculosis (TB) is lacking, which limits the pharmacokinetic and pharmacodynamic studies of linezolid. This study aimed to evaluate the distribution of linezolid in diseased and nondiseased bones in patients with spinal TB. METHODS: Spinal TB patients treated with linezolid-containing regimens and whose diseased and nondiseased bones were collected during surgery were enrolled retrospectively from January 2017 to February 2022. Blood, nondiseased bones, and diseased bones were collected simultaneously during the operation. Linezolid concentrations in the plasma, nondiseased bones, and diseased bones were subjected to high-performance liquid chromatography-tandem mass spectrometry. RESULTS: Seven eligible spinal TB patients, including one rifampicin-resistant case, were enrolled. Following a 600 mg oral administration of linezolid before surgery, the median concentrations of linezolid in plasma, nondiseased bone, and diseased bone of the seven patients were 8.23, 1.01, and 2.13 mg/L, respectively. The mean ratios of linezolid concentration in nondiseased bones/plasma, diseased bones/plasma and diseased bones/nondiseased bones reached 0.26, 0.49, and 2.27, respectively. The diseased bones/plasma presented a higher mean ratio of linezolid concentration than nondiseased bones/plasma, and the difference was statistically significant (t = 2.55, p = 0.025). Pearson's correlation analysis showed the positively correlation of linezolid concentrations in diseased and nondiseased bones (r = 0.810, p = 0.027). CONCLUSIONS: Linezolid exhibits a higher concentration distribution in diseased bones than in nondiseased bones.

Corrigendum: Diagnostic efficiency of metagenomic next-generation sequencing for suspected spinal tuberculosis in China: a multicenter prospective study.

[This corrects the article DOI: 10.3389/fmicb.2022.1018938.].

Diagnostic efficiency of metagenomic next-generation sequencing for suspected spinal tuberculosis in China: A multicenter prospective study.

Background: The pathogens of suspected spinal tuberculosis (TB) include TB and non-TB bacteria. A rapid and effective diagnostic method that can detect TB and non-TB pathogens simultaneously remains lacking. Here, we used metagenomic next-generation sequencing (mNGS) to detect the pathogens in patients with suspected spinal TB. Methods: The enrolled patients with suspected spinal TB were regrouped three times into patients with spinal infection and controls, patients with spinal TB and controls, and patients with non-TB spinal infection and controls. We tested the three groups separately by using mNGS and conventional detection methods. Results: Ultimately, 100 patients were included in this study. Pathogens were detected in 82 patients. Among the 82 patients, 37 had TB and 45 were infected with other bacteria. In patients with spinal infection, the sensitivity of the mNGS assay was higher than that of culture and pathological examination (p < 0.001, p < 0.001). The specificity of the mNGS assay was not statistically different from that of culture and pathological examination (p = 1.000, p = 1.000). In patients with spinal TB, no statistical difference was found between the sensitivity of the mNGS assay and that of Xpert and T-SPOT.TB (p = 1.000, p = 0.430). The sensitivity of the mNGS assay was higher than that of MGIT 960 culture and pathological examination (p < 0.001, p = 0.006). The specificities of the mNGS assay, Xpert, MGIT 960 culture, and pathological examination were all 100%. The specificity of T-SPOT.TB (78.3%) was lower than that of the mNGS assay (100%; p < 0.001). In patients with non-TB spinal infection, the sensitivity of the mNGS assay was higher than that of bacterial culture and pathological examination (p < 0.001, p < 0.001). The specificity of the mNGS assay was not statistically different from that of bacterial culture and pathological examination (p = 1.000, p = 1.000). Conclusion: Data presented here demonstrated that mNGS can detect TB and non-TB bacteria simultaneously, with high sensitivity, specificity and short detection time. Compared with conventional detection methods, mNGS is a more rapid and effective diagnostic tool for suspected spinal TB.

Impact of Xpert MTB/RIF on Outcomes of Adults Hospitalized With Spinal Tuberculosis: Findings From a Comparative Cohort in Beijing, China.

Background: Spinal tuberculosis (TB) is one of the most common forms of extrapulmonary tuberculosis, causing increased morbidity and lifelong disabilities. Here, we conducted a retrospective study to determine the impact on patient outcomes of the Xpert MTB/RIF test vs. phenotypical drug susceptibility testing for spinal TB. Methods: In-patients with spinal TB were enrolled in 2013 and 2017 at Beijing Chest Hospital. Data were collected from an electronic patient record system that documented demographic and clinical characteristics. All the patients were routinely followed-up at 1, 3, 6, 9, and 12 months after surgery during outpatient treatment. Results: A total of 361 patients affected by spinal TB were enrolled in our analysis, including 178 patients in 2013 and 183 patients in 2017. In 2013, the cumulative postoperative recurrence rate of patients with spinal TB was 23% (41/178), which was significantly higher than that in 2017 (8.2%, 15/183, P < 0.001). Additionally, the patients with spinal TB diagnosed in 2013 relapsed significantly sooner than those in 2017 (P < 0.001). In the multivariate analysis, rifampicin (RIF) resistance was associated with the recurrence of spinal TB. The turnaround time of Xpert ranged from 1 to 3 days, with a median of 1 day (IQR: 1-2). For the phenotypic drug susceptibility test (pDST)-based algorithm, the median turnaround time was 67 days, considerably longer than that of the Xpert-based algorithm (P < 0.001). Conclusion: The RIF resistance is an independent risk factor for postoperative recurrence in patients with spinal TB. Early detection of RIF resistance due to the application of Xpert is an effective strategy to reduce spinal TB recurrence.

Bone Penetration of Cycloserine in Osteoarticular Tuberculosis Patients of China.

The cycloserine concentrations in plasma and bone that were collected during operations on 28 osteoarticular tuberculosis (TB) patients treated daily with a 500-mg cycloserine-containing regimen were determined. The median concentrations in plasma and bone were 16.29 µg/mL (interquartile range [IQR], 6.47 µg/mL) and 24.33 µg/g (IQR, 14.68 µg/g), respectively. The median bone/plasma penetration ratio was 0.76 (range, 0.33 to 1.98). Cycloserine could effectively penetrate bone and acquire concentrations comparable to those in plasma, which favors its usage in osteoarticular TB treatment.

Mathematical Modeling and Nail Placement Accuracy Analysis of NF-1 Neurofibromatosis Scoliosis.

We have analyzed the arch root morphology, nail placement accuracy, degree of arch deformity, and three-dimensional Cobb angle in patients with NF scoliosis by CT 3D reconstruction. Likewise, we have thoroughly examined arch root morphology, nail placement accuracy, degree of arch deformity, and three-dimensional Cobb angle in patients with idiopathic scoliosis by CT 3D reconstruction. The results of the two groups were statistically analyzed and compared to assess the efficacy and other morphological differences between these groups. For this purpose, 276 patients with scoliosis, including 221 with idiopathic scoliosis and 16 with neurofibromatosis scoliosis, were treated in the hospital, which is from May 2008 to December 2016. The 16 patients with idiopathic scoliosis were matched with patients with neurofibromatosis, and the postoperative CT data were reconstructed in three dimensions, and the measurements included arch morphology, arch transverse diameter, arch-rib joint transverse diameter, three-dimensional coronal Cobb angle, and correction rate. The data of the two groups were statistically analyzed to compare the arch morphology, nail placement accuracy, and treatment effect between patients with NF and patients with AIS. Statistical analysis was performed to compare the differences between NF and AIS patients in terms of morphology, nail placement accuracy, and treatment outcome. The results showed that there were more severely deformed pedicles in NF patients than in idiopathic scoliosis, and the difference between them was statistically significant. Of the 142 screws placed in the NF group, 88 screws were in a good position, and the remaining 54 screws were misplaced.

The Comparative Influence of 2 and 4 Weeks Preoperative Antituberculosis Treatment on Spinal Tuberculosis Surgery: A Multicenter, Prospective, Randomized Clinical Trial.

INTRODUCTION: A trade-off between successful surgery and minimizing the operation delay for patients with spinal tuberculosis (TB) is a major consideration to determine the duration of preoperational anti-TB treatment (AAT). In this study, 2 and 4 weeks preoperative AAT durations were compared for their influence on the operation outcomes. METHOD: A multicenter, prospective, randomized trial was conducted in four hospitals in China. New patients with spinal TB were recruited and randomly allocated to two groups (2 or 4 weeks' preoperative treatment) and administered the standardized first-line anti-TB drugs. The symptom changing and indicators reflecting recovery and side effects of the treatment were monitored. Patient was followed up for another 18 months after completion of treatment. RESULTS: In total, 150 eligible patients were enrolled between June 2014 and December 2016, and 13 patients were excluded after the enrollment. The remaining 137 participants were randomly allocated to the 2-week group (n = 68) or the 4-week group (n = 69). These two groups acquired similar surgical outcomes, considering wound healing rate within 3 months after the operation (94.20%, 65/69 vs 89.71%, 61/68; P = 0.333) and bony fusion rate within 6 months (98.46%, 64/65 vs 95.45%, 63/66; P = 0.317). However, the culture positive rate of pus collected during operation in the 4-week group (41.94%) was significantly lower than that of the 2-week group (60.94%, P = 0.033). No reoccurrence of disease was observed in either group during the 18-month follow-up period. CONCLUSION: Patients with spinal TB administered 2 or 4 weeks of preoperative anti-TB treatment acquired similar surgical outcomes. However, patients who underwent the operation sooner suffered 2 weeks less agony from the disease.

Bone penetration of linezolid in osteoarticular tuberculosis patients of China.

BACKGROUND: Linezolid presents strong antimicrobial activity against multidrug-resistant (MDR) pulmonary tuberculosis (TB), but its application in osteoarticular tuberculosis treatment remains understudied. Our objective was to analyze the bone penetration efficiency of linezolid in osteoarticular TB patients. METHODS: Osteoarticular TB patients, treated with 600 mg q 24 h linezolid-containing regimens and undergoing surgery, were prospectively and consecutively enrolled. One dose linezolid was administered before surgery. Blood and bone samples were collected simultaneously during operation, and their linezolid concentrations were then detected using high-performance liquid chromatography-tandem mass spectrometry. Pus samples were subjected to mycobacterial culture and GeneXpert MTB/RIF assay. The minimum inhibition concentrations (MICs) and drug susceptibility testing were performed with the recovered isolates. RESULTS: A total of 36 eligible osteoarticular TB patients were enrolled, including five MDR/rifampicin-resistant cases. All the 12 recovered isolates had MICs ≤0.5 µg/mL for linezolid. Mean concentrations in plasma, collected 100-510 min after the preoperative dosing, were 10.43 ± 4.83 µg/mL (range 3.29-22.26 µg/mL), and median concentrations in bone were 3.93 µg/mL (range 0.61-16.34 µg/mL). The median bone/plasma penetration ratio was 0.42 (range 0.14-0.95 µg/mL). Linezolid concentration in bone had a linear correlation with the drug concentration in plasma (r = 0.7873, p < 0.0001), while plasma concentration could explain 61.98% of the variation of concentration in bone (R2 = 0.6198). Notably, stratification analysis by sampling time demonstrated that samples collected 200-510 min after dosing had very good linear relationships between their bone and plasma concentrations (r = 0.9323). CONCLUSIONS: Linezolid penetrates from blood to bone efficiently, and the penetration further stabilizes ∼3 h after dosing.

Metagenomic Next-Generation Sequencing Improves Diagnosis of Osteoarticular Infections From Abscess Specimens: A Multicenter Retrospective Study.

Background: We conducted this retrospective study to reveal the accuracy of metagenomic next-generation sequencing (mNGS) for diagnosing osteoarticular infections from fresh abscess specimens obtained from patients in an HIV-naive population. Methods: We retrospectively analyzed hospital records at three participating TB-specialized hospitals for patients admitted with suggestive diagnoses of osteoarticular tuberculosis between January 2018 and August 2019. Abscess specimens obtained from each patient were tested via pathogen culture, GeneXpert Mycobacterium tuberculosis (MTB)/rifampicin (RIF), and mNGS assay. Results: A total of 82 abscess samples were collected from patients with osteoarticular infections, including 53 cases with (64.6%) bacterial, 21 (25.6%) with mycobacterial, 7 (8.5%) with fungal, and 1 (1.2%) with actinomycetal organisms detected. Analysis of mNGS assay results identified potential pathogens in all cases, with M. tuberculosis complex (MTBC) most frequently isolated, followed by Staphylococcus aureus and Brucella melitensis. Conventional culture testing identified causative pathogens in only 48.4% of samples, a significantly lower rate than the mNGS pathogen identification rate (100%, p < 0.01). Culture-positive group specimens yielded significantly greater numbers of sequence reads than did culture-negative group specimens (p < 0.01). Of patients receiving surgical interventions and mNGS-guided treatment, 76 (92.7%) experienced favorable outcomes by the time of follow-up assessment at 3 months post-treatment. Notably, MTBC detection in two patients experiencing treatment failure suggests that they had mixed infections with MTBC and other pathogens. Conclusion: Results presented here demonstrate that mNGS has a greater pathogen detection rate in osteoarticular infections than conventional culture-based methods.

Epidemiology of skeletal tuberculosis in Beijing, China: a 10-year retrospective analysis of data.

Skeletal tuberculosis (STB) is one of the most common forms of extrapulmonary tuberculosis; however, limited epidemiological data are available on this public health concern worldwide, especially in developing countries. The aims of this study were to analyze the epidemiological characteristics of STB cases and to identify risk factors associated with drug resistance among STB cases in China. We included STB inpatients at Beijing Chest Hospital from January 2009 through December 2018. The multiple demographic and clinical variables of patients were collected from the hospital's electronic patient record. In total, 3086 STB patients were hospitalized in Beijing Chest Hospital. Of these cases, 1988 (64.4%) were spinal TB cases, 991 (32.1%) were joint TB cases, and 107 (3.5%) were concurrent spinal-joint TB cases. The most frequent localization of the infections in joints included the knee (21.5%), hip (17.9%), and elbow (10.3%). For spinal TB, lumbar, thoracic, and cervical spinal TB were present in 51.7%, 40.6%, and 4.4% of cases, respectively. Positive cultures were reported in only 16.0% of STB cases. When patients aged ≥ 60 years old were used as the control group, youths (< 18 years old) were less likely to have spinal TB (aOR, 0.29; 95% CI, 0.21-0.41). The prevalence of MDR-TB was 12.5% among the STB cases, and more female cases were afflicted with drug-resistant STB than with drug-susceptible STB (aOR, 0.50; 95% CI, 0.27-0.94). In addition, patients aged < 18 years had significantly higher odds of having drug-resistant STB compared with those aged ≥ 60 years (aOR, 20.778; 95% CI, 4.49-96.149). In conclusion, our data demonstrate that spinal TB is the most frequent form of STB in China. The youths are less likely to have spinal TB compared with elderly patients, while the patients aged < 18 years have significantly higher odds of having drug-resistant STB than elderly patients.

Distribution of Linezolid in Tuberculosis Lesions in Patients with Spinal Multidrug-Resistant Tuberculosis.

Linezolid has strong antimicrobial activity against the multidrug-resistant (MDR) strains of Mycobacterium tuberculosis Little is known about the distribution of linezolid in tuberculosis (TB) lesions in patients with MDR-TB. The aim of this study was to evaluate the distribution of linezolid in TB lesions in patients with spinal MDR-TB. Nine patients with spinal MDR-TB were enrolled prospectively from August 2019 to February 2020. The patients received a linezolid-containing anti-TB treatment regimen and needed surgery for the removal of TB lesions. During the operation, nine blood samples, eight diseased bone tissue samples, seven pus samples, and four granulation tissue samples were collected simultaneously and 2 h after the oral administration of 600 mg of linezolid. Linezolid concentrations in plasma, diseased bone tissue, pus, and granulation tissue samples were subjected to high-performance liquid chromatography-tandem mass spectrometry. At sample collection, the mean concentrations of linezolid in plasma, diseased bone tissue, pus, and granulation tissue samples of the nine patients were 11.14 ± 5.82, 5.94 ± 4.27, 11.09 ± 4.58, and 14.08 ± 10.61 mg/liter, respectively. The mean ratios of linezolid concentration in diseased bone/plasma, pus/plasma, and granulation/plasma were 53.84%, 91.69%, and 103.57%, respectively. The mean ratios of linezolid concentration in pus/plasma and granulation/plasma were higher than those in diseased bone/plasma, and the difference was statistically significant (t = -2.810, P = 0.015; t = -4.901, P = 0.001). In conclusion, linezolid had different concentration distributions in different types of TB-infected tissues in patients with spinal MDR-TB.

Comparison of Lowenstein-Jensen medium and MGIT culture system for recovery of Mycobacterium tuberculosis from abscess samples.

PURPOSE: In this study, our aim was to assess Lowenstein-Jensen (L-J) medium and MGIT culture system for recovery of Mycobacterium tuberculosis (MTB) from abscess samples in skeletal tuberculosis (TB) cases. METHODS: Abscess samples were collected from patients suggestive of skeletal TB in Beijing Chest Hospital for laboratory examination, including smear microscopy, L-J culture and MGIT culture. RESULTS: Of the 232 abscess samples, 72 (31.0%) were culture-positive for mycobacteria. Of 72 isolates recovered, 94.4% were detected in MGIT 960 and 75.0% on L-J medium. MGIT could recover significantly higher rate of MTB isolates from smear-positive specimens than L-J medium. The mean time to detection of MTB in MGIT 960 was significantly lower than that on L-J medium. CONCLUSION: The BACTEC MGIT 960 outperforms the conventional L-J medium in recovering MTB from abscess samples. The combination of MGIT and L-J method also increases the overall recovery rate of MTB in culture.

Penetration of linezolid into bone tissue 24 h after administration in patients with multidrug-resistant spinal tuberculosis.

BACKGROUND: Linezolid has shown strong antimicrobial activity against multidrug-resistant (MDR)/rifampin-resistant strains of Mycobacterium tuberculosis. Linezolid achieves clinical efficacy mainly through area under the concentration time curve/minimum inhibitory concentration ratio in the infected lesion site. Previous studies mainly focused on the relationship between linezolid concentrations in the blood and infected bone tissue when the blood drug concentration reached the peak 2 h after administration. However, we do not know whether linezolid can maintain the same bone/plasma ratio in infected bone tissue when the blood concentration reaches the trough level. Therefore, this study aimed to evaluate the penetrability of linezolid into bone tissue 24 h after administration in patients with MDR spinal tuberculosis (TB). METHODS: Nine MDR spinal TB patients, who received a treatment regimen including linezolid and underwent surgery, were enrolled prospectively from April 2017 to March 2019. Blood and diseased bone tissue specimens were collected simultaneously during operations 24 h after taking 600 mg of linezolid orally. Linezolid concentrations in plasma and diseased bone tissue specimens were determined by high-performance liquid chromatography-tandem mass spectrometry. RESULTS: Following a 600 mg oral administration of linezolid 24 h before surgery, median concentrations of linezolid in plasma and diseased bone tissue for the 9 patients were 1.98 mg/L (range 0.30-3.44 mg/L) and 0.60 mg/L (range 0.18-2.13 mg/L), respectively, at resection time. The median diseased bone/plasma linezolid concentration ratio was 0.48 (range 0.30-0.67). Pearson's correlation analysis showed that linezolid concentrations in the plasma were positively related to those in diseased bone tissue (r = 0.949, p < 0.001). CONCLUSIONS: After 24 h of medication, linezolid still had good penetrability into diseased bone tissue in patients with MDR spinal TB.

Epidemiology of Extrapulmonary Tuberculosis among Inpatients, China, 2008-2017.

We investigated the epidemiology of extrapulmonary tuberculosis (TB) among patients admitted to Beijing Chest Hospital, Beijing, China, during January 2008-December 2017. Of 19,279 hospitalized TB patients, 33.4% (6,433) had extrapulmonary TB and 66.6% (12,846) had pulmonary TB. The most frequent forms of extrapulmonary TB observed were skeletal TB (41.1%) and pleural TB (26.0%). Younger, female patients from rural areas were more likely to have extrapulmonary TB. However, patients with diabetes mellitus were less likely to have extrapulmonary TB compared with patients without diabetes. A higher proportion of multidrug-resistant (MDR) TB was observed among patients with extrapulmonary TB than among patients with pulmonary TB. We observed a large increase in MDR TB, from 17.3% to 35.7%, for pleural TB cases. The increasing rate of drug resistance among extrapulmonary TB cases highlights the need for drug susceptibility testing and the formulation of more effective regimens for extrapulmonary TB treatment.

Diagnostic efficiency of Xpert MTB/RIF assay for osteoarticular tuberculosis in patients with inflammatory arthritis in China.

BACKGROUND: Both osteoarticular tuberculosis (OA-TB) and inflammatory arthritis can lead to osteoarticular structural damage. These conditions exhibit similar symptoms, physical signs, and imaging features. Rapidly and accurately diagnosing OA-TB in patients with inflammatory arthritis presents a challenge to clinicians. Xpert MTB/RIF (Xpert) has been endorsed by the World Health Organization (WHO) as a rapid diagnostic tool for diagnosis of pulmonary and extrapulmonary TB. This study was designed to investigate diagnostic efficiency of Xpert for OA-TB in patients with inflammatory arthritis in China. METHODS: A total of 83 consecutive patients with inflammatory arthritis and suspected OA-TB were enrolled prospectively from June 2014 to May 2018. Demographic, clinical, and biological data were recorded. Xpert assay, smear microscopy examination (smear), BACTEC MGIT 960 (MGIT 960), pathological examination, and T-SPOT.TB test were performed for each patient who received operations. Diagnostic efficiency of Xpert was evaluated based on a composite reference standard (CRS). RESULTS: A total of 49 out of 83 patients with inflammatory arthritis and suspected OA-TB received operations, and 49 specimens were obtained during operations. According to CRS, 36 out of 49 patients with inflammatory arthritis were diagnosed with OA-TB, and 13 were not affected by the condition. Sensitivity of Xpert assay, smear, MGIT 960, pathological examination, and T-SPOT.TB test reached 66.70% (24/36), 25.00% (9/36), 30.55% (11/36), 47.22% (17/36), and 80.55% (29/36), respectively. Specificity of Xpert assay, smear, MGIT 960, and pathological examination was all 100% (13/13). Specificity of T-SPOT.TB test was 53.84% (7/13). Sensitivity of Xpert was higher than that of smear, MGIT 960 and pathological examination, but the sensitivity of Xpert was lower than that of T-SPOT.TB. Sensitivity of Xpert was statistically different from that of smear and MGIT 960 (P<0.001, P = 0.002), but the sensitivity of Xpert was not significantly different from that of pathological examination and T-SPOT.TB (P = 0.096, P = 0.181). Specificity of T-SPOT.TB was less than that of Xpert, smear, MGIT 960, and pathological examination, and the difference between them was statistically significant (P = 0.015). Among the 27 OA-TB patients with smear negative results, Xpert had the highest sensitivity, but sensitivity of Xpert was not significantly different from that of pathological examination and T-SPOT.TB (P = 0.413, P = 0.783). 2 of 36 OA-TB patients exhibited RIF resistance. Xpert was concordant with MGIT 960-based drug susceptibility testing (DST) in detecting rifampin (RIF) resistance. CONCLUSIONS: Xpert is an efficient tool with high sensitivity and specificity for OA-TB diagnosis in patients with inflammatory arthritis in high-TB prevalence countries. Compared with conventional methods, Xpert has two advantages: one is fast, and the other is able to provide RIF resistance information simultaneously.

Diagnostic accuracy evaluation of the conventional and molecular tests for Spinal Tuberculosis in a cohort, head-to-head study.

Early diagnosis of spinal tuberculosis (TB) is hampered by the flaws of conventional tests. The aim of this study was to assess the value of new and existing molecular tests in a prospective, head-to-head cohort study. Specimens were consecutively collected from spinal TB suspects in four hospitals in Beijing, China. Smear, culture, histopathology, Xpert MTB/RIF (Xpert), and MeltPro TB assays were performed in parallel using the same specimen from each patient. Drug-susceptibility testing (DST) was conducted on the isolates recovered. In total, 438 suspects were recruited; 319 of them were diagnosed with spinal TB according to the composite reference standard (CRS), which was composed of clinical, laboratory, histopathological, and radiological examinations and 18 months of follow-up. Based on conventional testing, 74.29% of patients were classified as confirmed cases, which increased to 90.6% when Xpert outcomes were integrated. Further, 76.60% of probable and 45.71% of possible cases were re-classified as confirmed cases with Xpert. Xpert (85.27%) produced higher sensitivity than histopathology (73.04%), MeltPro TB (57.68%), culture (51.72%) and smear (24.45%) (all P <0.001). Xpert was 100% concordant with phenotypic DST regarding rifampicin resistance detection. The sensitivity and specificity of MeltPro TB for rifampicin resistance detection were 100% and 97.96%, respectively, and 95.00% and 93.88% for isoniazid resistance detection. New molecular tests demonstrated excellent efficiency for spinal TB diagnosis in this cohort study, so their application as initial diagnostic tools would greatly increase the proportion of confirmed cases and dramatically reduce the delay of appropriate treatment. An updated laboratory testing algorithm of the disease is desirable.

The Clinical Features and Bacteriological Characterizations of Bone and Joint Tuberculosis in China.

Bone and Joint tuberculosis (BJTB) constitutes about 10% of total extra-pulmonary TB cases. Since the BJTB is a paucibacillary condition, there has been no systematic study on the bacterial characterization, especially the epidemiological feature. Here we collected the mycobacterial clinical isolates, analyzed the clinical features and the bacteriological characteristics from 113 BJTB cases reported in China. The mean age of the cases was 40.33 years while most of the patients fell into the 20-29 year age group; local pain was the most common onset symptom of BJTB cases; mean time from symptom onset to BJTB diagnosis was 13.16 months. 31 isolates were defined as drug resistant, including 15 multidrug resistant (MDR) and 2 extensively drug resistant (XDR) isolates according to the drug susceptibility test outcomes; after spoligotyping, 87.6% (99/113) isolates were categorized as Beijing family. In contrast to the isolates from pulmonary tuberculosis patients, here the MIRU-VNTR assay did not find anything significant. A prolonged time span for BJTB diagnosis highlights the requirement of paying further attention to BJTB infection in China. This study provides essential insights into the demographic and microbial characteristics of BJTB cases in China.

Xpert MTB/RIF and GenoType MTBDRplus assays for the rapid diagnosis of bone and joint tuberculosis.

BACKGROUND: Bone and joint tuberculosis (BJTB) constitutes about 10-20% of the extrapulmonary tuberculosis (EPTB) cases in China. The GenoType MTBDRplus assay (MTBDR) has been endorsed by the World Health Organization (WHO) for the diagnosis of pulmonary TB (PTB), while the Xpert MTB/RIF assay (Xpert) has also been endorsed by the WHO for the diagnosis of both PTB and EPTB. The diagnostic utility of these two techniques for BJTB was investigated prospectively. METHODS: Sixty pus specimens were obtained from orthopedic patients. Smear, culture, Xpert, and MTBDR assays were performed for each specimen, and MGIT 960-based drug susceptibility testing (DST) was conducted for all of the isolates recovered. The diagnostic efficiency of Xpert and MTBDR was evaluated on the basis of bacteriological examination and the composite reference standard (CRS). RESULTS: Fifty of the 60 patients were considered to have BJTB according to the CRS. The sensitivities of smear, culture, Xpert, and MTBDR were 26% (13/50), 48% (24/50), 82% (41/50), and 72% (36/50) respectively, while the specificities of all of the tests were 100% (10/10). Xpert was 100% concordant with MGIT 960-based DST for the detection of rifampicin resistance. MTBDR had a sensitivity of 83.3% and a specificity of 100% for the detection of rifampicin resistance and a sensitivity of 85.7% and specificity of 100% for the detection of isoniazid resistance. CONCLUSION: With their high sensitivities, short turnaround times, and ability to diagnose TB and detect drug resistance simultaneously, both Xpert and MTBDR are feasible as diagnostic tools for BJTB in clinical practice.