OBJECTIVE: To investigate the effectiveness of one-stage total knee arthroplasty (TKA) in the treatment of advanced active knee tuberculosis. METHODS: The clinical data of 38 patients with advanced active knee tuberculosis who received one-stage TKA between January 2011 and December 2020 were retrospectively analyzed. There were 20 males and 18 females. The age ranged from 20 to 84 years, with an average of 52.8 years. The body mass index ranged from 17 to 36 kg/m ², with an average of 23.05 kg/m ². The preoperative C reactive protein (CRP) was (23.49±4.72) mg/L, erythrocyte sedimentation rate (ESR) was (45.95±8.82) mm/1 h. The Hospital for Special Surgery (HSS) score was 48.8±9.1. During the operation, the infected lesions of the knee joint were completely removed, and the operative area was repeatedly soaked with 3% hydrogen peroxide solution and 0.5% povidone iodine solution. The intraoperative pathological examination confirmed the tuberculosis of the knee joint, and systemic anti-tuberculosis treatment was performed. The operation time, postoperative hospitalization stay, postoperative anti-tuberculosis chemotherapy time, and complications were recorded. CRP and ESR were recorded and compared before and after operation. Anteroposterior and lateral X-ray films of the knee joint were taken to evaluate whether the prosthesis had signs of loosening and sinking, and to determine whether there was recurrence of tuberculosis. The knee joint function was evaluated by HSS score. With treatment failure due to any reason as the end event, the survival time of prosthesis was analyzed by Kaplan-Meier survival curve. RESULTS: All operations were successfully completed without fracture, vascular and nerve injury, deep vein thrombosis, and other complications. All incisions healed by first intention after operation. The operation time ranged from 80 to 135 minutes, with an average of 102.76 minutes; postoperative hospitalization stay was 5-16 days, with an average of 9.7 days; the duration of postoperative anti-tuberculosis chemotherapy ranged from 1 to 18 months, and the median duration was 12 months. All 38 cases were followed up 3-133 months (mean, 63.7 months). At last follow-up, CRP was (4.88±1.24) mg/L and ESR was (13.00±2.97) mm/1 h, both of which were significantly lower than those before operation ( t=20.647, P<0.001; t=20.886, P<0.001). During the follow-up, 3 patients (7.89%) had tuberculosis recurrence. Two patients had tuberculosis recurrence due to withdrawal of anti-tuberculosis chemotherapy at 1 and 2 months after operation, respectively. One patient was cured after debridement, preservation of prosthesis and anti-tuberculosis chemotherapy for 12 months, and 1 patient was cured after oral administration of anti-tuberculosis drugs for 12 months. Another 1 patient had recurrent tuberculosis and mixed infection ( Corynebacterium gehreni) at 2 months after operation, and the infection was not controlled after debridement, and finally the thigh was amputated. Except for the patients with recurrent infection, no complications such as prosthesis loosening, periprosthetic fracture, and periprosthetic infection were found. At last follow-up, the HSS score of the knee joint was 86.8±4.8, and the knee joint function significantly improved when compared with that before operation ( t=-31.198, P<0.001). Prosthesis survival time was (122.57±5.77) months [95% CI (111.25, 133.88) months], and the 10-year survival rate was 92.1%. CONCLUSION One-stage TKA combined with postoperative antituberculous chemotherapy in the treatment of advanced active knee tuberculosis can achieve satisfactory infection control and joint function.
Female ; Male ; Humans ; Young Adult ; Adult ; Middle Aged ; Aged ; Aged, 80 and over ; Arthroplasty, Replacement, Knee ; Retrospective Studies ; Knee Joint ; Tuberculosis ; Antitubercular Agents/therapeutic use*

OBJECTIVE: This study aims to estimate the cost-effectiveness of the combined chemotherapy regimen containing Bedaquiline (BR) and the conventional treatment regimen (CR, not containing Bedaquiline) for the treatment of adults with multidrug-resistant tuberculosis (MDR-TB) in China. METHODS: A combination of a decision tree and a Markov model was developed to estimate the cost and effects of MDR patients in BR and CR within ten years. The model parameter data were synthesized from the literature, the national TB surveillance information system, and consultation with experts. The incremental cost-effectiveness ratio (ICER) of BR vs. CR was determined. RESULTS: BR ( vs. CR) had a higher sputum culture conversion rate and cure rate and prevented many premature deaths (decreased by 12.8%), thereby obtaining more quality-adjusted life years (QALYs) (increased by 2.31 years). The per capita cost in BR was as high as 138,000 yuan, roughly double that of CR. The ICER for BR was 33,700 yuan/QALY, which was lower than China's 1× per capita Gross Domestic Product (GDP) in 2020 (72,400 yuan). CONCLUSION BR is shown to be cost effective. When the unit price of Bedaquiline reaches or falls below 57.21 yuan per unit, BR is expected to be the dominant strategy in China over CR.
Adult ; Humans ; Antitubercular Agents/therapeutic use* ; Cost-Effectiveness Analysis ; Cost-Benefit Analysis ; Tuberculosis, Multidrug-Resistant/drug therapy* ; China/epidemiology*

Multidrug-resistant tuberculosis (MDR-TB) has become one of the major challenges in the global tuberculosis (TB) control.Despite years of efforts on MDR-TB control,the treatment success rates in China have increased slowly,which indicates possible deficiencies in the management of prevention and control work.Therefore,it is necessary to analyze the current status of MDR-TB prevention and treatment based on the patient pathway.This review summarizes the current drop-out situation of MDR-TB patients in the diagnosis and treatment pathway and the factors affecting patients' outcomes in the whole pathway,so as to provide a scientific reference for the prevention and control of MDR-TB.
Humans ; Antitubercular Agents/therapeutic use* ; Tuberculosis, Multidrug-Resistant/prevention & control* ; Treatment Outcome ; China

Tuberculosis (TB) prophylactic therapy for latent infection, which can reduce the risk for the development of active TB, is an important measure in TB control. China recommends prophylactic therapy for latent tuberculosis infection (LTBI) in some key populations to reduce the risk for TB. Contacts of patients with multi-drug and rifampicin-resistant TB (MDR/RR-TB) are at high risk for the infection with drug-resistant pathogen, however, no unified prophylactic therapy regimen has been recommended for LTBI due to exposure to MDR/RR-TB patients. This paper summarizes the current MDR/RR-TB prophylactic therapy regimen and its protection effect based on the results of the retrieval of literature, guidelines, expert consensus and technical specifications to provide reference for the prevention and control of LTBI.
Humans ; Rifampin/therapeutic use* ; Tuberculosis, Multidrug-Resistant/prevention & control* ; Tuberculosis/drug therapy* ; Latent Tuberculosis/chemically induced* ; China ; Antitubercular Agents/therapeutic use*

Tuberculosis (TB) is an ancient infectious disease. Before the availability of effective drug therapy, it had high morbidity and mortality. In the past 100 years, the discovery of revolutionary anti-TB drugs such as streptomycin, isoniazid, pyrazinamide, ethambutol and rifampicin, along with drug combination treatment, has greatly improved TB control globally. As anti-TB drugs were widely used, multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains of Mycobacterium tuberculosis emerged due to acquired genetic mutations, and this now presents a major problem for effective treatment. Genes associated with drug resistance have been identified, including katG mutations in isoniazid resistance, rpoB mutations in rifampin resistance, pncA mutations in pyrazinamide resistance, and gyrA mutations in quinolone resistance. The major mechanisms of drug resistance include loss of enzyme activity in prodrug activation, drug target alteration, overexpression of drug target, and overexpression of the efflux pump. During the disease process, Mycobacterium tuberculosis may reside in different microenvironments where it is expose to acidic pH, low oxygen, reactive oxygen species and anti-TB drugs, which can facilitate the development of non-replicating persisters and promote bacterial survival. The mechanisms of persister formation may include toxin-antitoxin (TA) modules, DNA protection and repair, protein degradation such as trans-translation, efflux, and altered metabolism. In recent years, the use of new anti-TB drugs, repurposed drugs, and their drug combinations has greatly improved treatment outcomes in patients with both drug-susceptible TB and MDR/XDR-TB. The importance of developing more effective drugs targeting persisters of Mycobacterium tuberculosis is emphasized. In addition, host-directed therapeutics using both conventional drugs and herbal medicines for more effective TB treatment should also be explored. In this article, we review historical aspects of the research on anti-TB drugs and discuss the current understanding and treatments of drug resistant and persistent tuberculosis to inform future therapeutic development.
Humans ; Pyrazinamide/therapeutic use* ; Isoniazid/therapeutic use* ; Antitubercular Agents/therapeutic use* ; Tuberculosis, Multidrug-Resistant/microbiology* ; Mycobacterium tuberculosis/genetics* ; Tuberculosis/drug therapy* ; Rifampin/therapeutic use* ; Mutation ; Drug Resistance, Multiple, Bacterial/genetics*

One fourth of the global population has been infected with Mycobacterium tuberculosis, and about 5%-10% of the infected individuals with latent tuberculosis infection (LTBI) will convert to active tuberculosis (ATB). Correct diagnosis and treatment of LTBI are important in ending the tuberculosis epidemic. Current methods for diagnosing LTBI, such as tuberculin skin test (TST) and interferon-γ release assay (IGRA), have limitations. Some novel biomarkers, such as transcriptome derived host genes in peripheral blood cells, will help to distinguish LTBI from ATB. More emphasis should be placed on surveillance in high-risk groups, including patients with HIV infection, those using biological agents, organ transplant recipients and those in close contact with ATB patients. For those with LTBI, treatment should be based on the risk of progression to ATB and the potential benefit. Prophylactic LTBI regimens include isoniazid monotherapy for 6 or 9 months, rifampicin monotherapy for 4 months, weekly rifapentine plus isoniazid for 3 months (3HP regimen) and daily rifampicin plus isoniazid for 3 months (3HR regimen). The success of the one month rifapentine plus isoniazid daily regimen (1HP regimen) suggests the feasibility of an ultra-short treatment strategy although its efficacy needs further assessment. Prophylactic treatment of LTBI in close contact with MDR-TB patients is another challenge, and the regimens include new anti-tuberculosis drugs such as bedaquiline, delamanid, fluoroquinolone and their combinations, which should be carefully evaluated. This article summarizes the current status of diagnosis and treatment of LTBI and its future development direction.
Humans ; Rifampin/therapeutic use* ; Isoniazid/therapeutic use* ; Latent Tuberculosis/drug therapy* ; HIV Infections/epidemiology* ; Antitubercular Agents/therapeutic use*

Antitubercular Agents/therapeutic use* ; Axilla ; Humans

Antitubercular Agents/therapeutic use* ; China/epidemiology* ; Drug Resistance, Multiple, Bacterial ; Extensively Drug-Resistant Tuberculosis ; Humans ; Kanamycin Resistance ; Microbial Sensitivity Tests ; Mycobacterium tuberculosis ; Ofloxacin/pharmacology* ; Tuberculosis, Multidrug-Resistant/epidemiology*

Rifamycins, a group of bacterial RNA polymerase inhibitors, are the firstline antimicrobial drugs to treat tuberculosis. In light of the emergence of rifamycinresistant bacteria, development of new RNA polymerase inhibitors that kill rifamycinresistant bacteria with high bioavailability is urgent. Structural analysis of bacterial RNA polymerase in complex with inhibitors by crystallography and cryo-EM indicates that RNA polymerase inhibitors function through five distinct molecular mechanisms:inhibition of the extension of short RNA; competition with substrates; inhibition of the conformational change of the'bridge helix'; inhibition of clamp opening;inhibition of clamp closure. This article reviews the research progress of these five groups of RNA polymerase inhibitors to provide references for the modification of existing RNA polymerase inhibitors and the discovery of new RNA polymerase inhibitors.
Antitubercular Agents ; therapeutic use ; Bacteria ; drug effects ; enzymology ; DNA-Directed RNA Polymerases ; metabolism ; Drug Discovery ; trends ; Drug Resistance, Bacterial ; Enzyme Activation ; drug effects ; Enzyme Inhibitors ; pharmacology ; Humans ; RNA, Bacterial ; Tuberculosis ; drug therapy ; enzymology

This retrospective study aims to demonstrate the effect of antitubercular treatment (ATT) on the pregnancy outcomes and prognoses of patients with genital tuberculosis (GTB) who had received laparoscopy and/or hysteroscopy. This study included 78 patients with infertility and who were diagnosed with GTB through laparoscopy and/or hysteroscopy over the period of November 2005 to October 2015. The recruited patients were divided into ATT and nonATT groups on the basis of ATT duration. The GTB recurrence rates, menstrual patterns, and pregnancy outcomes of the patients were determined at follow-up. Among the 78 patients, 46 received ATT and 32 did not receive ATT. The menstrual volumes of patients in the ATT group significantly decreased relative to those of patients in the nonATT group. GTB did not recur among all patients regardless of treatment. A total of 11 pregnancies (36.7%) in the ATT group and 19 pregnancies (63.3%) in the nonATT group were observed. Pregnancy rates significantly differed (P = 0.002) between the two groups. ATT may decrease the menstrual volume and pregnancy rates of patients who were diagnosed with GTB through laparoscopy and/or hysteroscopy. In addition, ATT did not improve the prognosis of patients with chronic GTB.
Adult ; Antitubercular Agents ; therapeutic use ; China ; Female ; Fertilization ; Humans ; Hysteroscopy ; Infertility, Female ; etiology ; Laparoscopy ; Pregnancy ; Pregnancy Outcome ; Pregnancy Rate ; Prognosis ; Retrospective Studies ; Tuberculosis, Female Genital ; complications ; drug therapy ; Young Adult