• Adult
• Antitubercular Agents/therapeutic use
• Bacterial Proteins/genetics
• Child
• Cluster Analysis
• DNA-Directed RNA Polymerases
• Democratic Republic of the Congo/epidemiology
• Female
• Humans
• Male
• Middle Aged
• Mutation
• Phenotype
• Rifampin/therapeutic use
• Rural Population
• Sequence Analysis, DNA
• Treatment Outcome
• Tuberculosis, Multidrug-Resistant/drug therapy
• Tuberculosis, Multidrug-Resistant/epidemiology
• Young Adult

To evaluate a biochip system in determining isoniazid and rifampicin resistances of Mycobacterium tuberculosis in sputum samples in a Chinese population.

We assembled 907 sputum smeared positive specimens of tuberculosis patients in total. Each sample would be separated into two parts for culture and biochip assay simultaneously. And those cultured positive and having full drug resistance results would be used as reference. The McNemar χ² test was adopted for evaluating the paired 2×2 table.

Compared with drug sensitivity test, the agreement rates of the two methods in detecting rifampicin and isoniazid resistances were 93.37% and 94.49%, respectively. The sensitivity and specificity of biochip in detecting isoniazid were 74.31% and 96.92%, respectively. Meanwhile, the sensitivity and specificity for rifampicin were 79.76% and 96.53%, respectively. For multi-drug resistance, the sensitivity and specificity were 64.62% and 97.75%, respectively.

The biochip system is a rapid and accurate method for drug resistant tuberculosis diagnosis using sputum samples directly, especially for rifampicin resistance detection.

Antimicrobial resistance, which has been reported against almost every antibiotic discovered, is one of the most urgent public health problems, threatening to undermine the effectiveness of infectious disease treatment worldwide. Since penicillin ushered in the antibiotic era in the mid 20th century, the scientific world had engaged in a war between the development of antibacterial agents and bacterial resistance. During the first decade of the 21st century, grave concern has been expressed over the evolution of multi-drug resistant staphylococci, enterococci, and mycobacteria, which pose serious clinical and public health challenge to humans. The present picture is frighteningly similar to the pre-antibiotic era, with reports of nosocomial spread and intercontinental dissemination of multi-drug resistant bacteria. For infected patients, there is no magic bullet. The microbial pathogens appear to be gaining the upper hand, coupled with a recent dramatic reduction in antibiotic research by pharmaceutical companies because of the high cost of drug research. Several compounds that have recently been developed or resurrected to treat gram-positive infections are still unable to meet the armamentarium of resistance mechanisms of these pathogens. The situation is worse for gram-negative organisms, where no new drug is currently being developed against them. A multi-disciplinary approach to combat resistance is required, which must be applied, sustained, and continuously refined. The key components for maintaining effective antimicrobial chemotherapy will include better use of existing agents, coupled with continuous investment in new and innovative technologies, which must include diagnostics and vaccines in addition to new antimicrobial agents.

• Antimicrobial
• Resistance
• Bugs
• Public health

Leukocyte migration into the epithelial compartment is an important feature in the active phase of mycobacterial infections. In this study, we used the Transwell model to investigate the mechanisms behind mycobacteria-induced leukocyte recruitment and investigated the role of TLR2 and TLR4 in this process. Infection of epithelial cells resulted in significantly increased secretion of the neutrophil chemotactic CXCL8 and IL-6, but no secretion of monocyte chemotactic CCL2 or TNF-α was observed. In contrast to epithelial response, mycobacteria-infected neutrophils and monocytes secreted all these cytokines. Corresponding with epithelial cytokine response, mycobacterial infection of the epithelial cells increased neutrophil diapedesis, but decreased monocyte recruitment. However, monocyte recruitment towards mycobacteria infected epithelial cells significantly increased following addition of neutrophil pre-conditioned medium. Mycobacterial infection also increases alveolar epithelial expression of TLR2, but not TLR4, as analyzed by flow cytometry, Western blotting and visualized by confocal microscopy. Blocking of TLR2 inhibited neutrophil recruitment and cytokine secretion, while blocking of TLR4 had a lesser effect. To summarize, we found that primary alveolar epithelial cells produced a selective TLR2-dependent cytokine secretion upon mycobacterial infection. Furthermore, we found that cooperation between cells of the innate immunity is required in mounting proper antimicrobial defence.