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1.
Biomed Environ Sci ; 33(5): 350-358, 2020 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-32553079

RESUMO

OBJECTIVE: Moxifloxacin (MFX) shows good in vitro activity against Mycobacterium abscessus and can be a possible antibiotic therapy to treat M. abscessus infection; however, other studies have shown a lower or no activity. We aimed to evaluate MFX activity against M. abscessus using zebrafish (ZF) model in vivo. METHODS: A formulation of M. abscessus labeled with CM-Dil was micro-injected into ZF. Survival curves were determined by recording dead ZF every day. ZF were lysed, and colony-forming units (CFUs) were enumerated. Bacteria dissemination and fluorescence intensity in ZF were analyzed. Inhibition rates of MFX and azithromycin (AZM, positive control) were determined and compared. RESULTS: Significantly increased survival rate was observed with different AZM concentrations. However, increasing MFX concentration did not result in a significant decrease in ZF survival curve. No significant differences in bacterial burdens by CFU loads were observed between AZM and MFX groups at various concentrations. Bacterial fluorescence intensity in ZF was significantly correlated with AZM concentration. However, with increasing MFX concentration, fluorescence intensity decreased slightly when observed under fluorescence microscope. Transferring rates at various concentrations were comparable between the MFX and AZM groups, with no significant difference. CONCLUSION: MFX showed limited efficacy against M . abscessus in vivo using ZF model. Its activity in vivo needs to be confirmed.


Assuntos
Antibacterianos/farmacologia , Moxifloxacina/farmacologia , Infecções por Mycobacterium não Tuberculosas/tratamento farmacológico , Mycobacterium abscessus/efeitos dos fármacos , Peixe-Zebra , Animais , Modelos Animais de Doenças
2.
Biomed Environ Sci ; 30(2): 139-142, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28292352

RESUMO

We assessed the incidence of adverse drug reactions (ADRs) with anti-TB medications and evaluated the risk factors for developing ADRs in previously treated tuberculosis patients in China. All patients received the first-line anti-TB regimen (2HREZS/6HRE) as recommended by the national guidelines. Clinical and laboratory evaluations were performed once a month. Out of the 354 participants, 262 (74.0%) experienced ADRs such as hyperuricemia (65.0%, 230/354), hepatotoxicity (6.2%, 22/354) and hearing disturbances (4.8%, 17/354). ADRs were significantly associated with diabetes mellitus [OR (95% CI): 15.5 (2.07-115.87)]; however, weight more than 50 kg [OR (95% CI): 0.41 (0.22-0.85)] was a protective factor for occurrence of ADRs. Hyperuricemia is the most common adverse event but, most patients with hyperuricemia showed increased tolerance for high uric acid levels. Low body weight and diabetes mellitus increased the risk of the occurrence of ADRs during anti-TB treatment.


Assuntos
Antituberculosos/efeitos adversos , Antituberculosos/uso terapêutico , Tuberculose Pulmonar/tratamento farmacológico , Adolescente , Adulto , Diabetes Mellitus , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Retrospectivos , Fatores de Risco , Tuberculose Pulmonar/epidemiologia , Adulto Jovem
3.
Zhonghua Jie He He Hu Xi Za Zhi ; 34(10): 762-5, 2011 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-22321711

RESUMO

OBJECTIVE: To compare the antimycobacterial activities of rifampicin (RFP) and rifabutin (RBT), and to evaluate the correlation between RBT resistance and genetic alterations in the rpoB gene. METHODS: The microplate-based alamar blue assay (MABA) method was performed to detect the antimycobacterial activities of RFP and RBT in 168 strains of Mycobacterium tuberculosis (M. tuberculosis). Meanwhile, we also analyzed the 81 bp core region of rpoB gene by DNA sequencing. The rate of gene mutations was analyzed by chi-square test. RESULTS: RBT was sensitive for all of the 66 RFP-sensitive strains with no mutations in 81 bp core region of rpoB gene. But of the 102 RFP-resistant strains, 76 strains were also resistant to RBT. Cross resistance between RFP and RBT was 74.5% (76/102). Alterations at codons 516, 526, 531 in the rpoB gene correlated with resistance to both RFP and RBT. While point mutations at codons 511 and 533 possibly influenced the susceptibility to RFP but not to RBT. The mutation rate (92.1%, 70/76) of rpoB gene of RBT-resistant strains was significantly higher than that (23.9%, 22/92) of RBT-sensitive strains (χ(2) = 78.12, P < 0.05). CONCLUSIONS: RBT was more active against M. tuberculosis as compared to RFP. The RFP-resistant strains with MIC ≤ 4 mg/L were still susceptible to RBT. Our results suggest that analysis of genetic alterations in the rpoB gene is useful for predicting RFP-resistance, and may have implications for evaluating RBT-resistance.


Assuntos
Antibacterianos/farmacologia , Proteínas de Bactérias/genética , Farmacorresistência Bacteriana/genética , Mycobacterium tuberculosis/genética , Rifabutina/farmacologia , Rifampina/farmacologia , Análise Mutacional de DNA , RNA Polimerases Dirigidas por DNA , Testes de Sensibilidade Microbiana , Mutação , Mycobacterium tuberculosis/efeitos dos fármacos , Mycobacterium tuberculosis/isolamento & purificação , Análise de Sequência de DNA
4.
Zhonghua Jie He He Hu Xi Za Zhi ; 28(8): 545-9, 2005 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-16207403

RESUMO

OBJECTIVE: To investigate the in-vitro interferon-gamma (IFN-gamma) release assay based on three different Mycobacterium tuberculosis antigens in the diagnosis of tuberculosis and Mycobacterium tuberculosis infections. METHODS: The peripheral blood mononuclear cells (PBMC) were collected from the patients with tuberculosis (tuberculosis group, n = 57), patients with lung cancer (lung cancer group, n = 29), and healthy controls (healthy control group 2, n = 27). The PBMCs were co-cultured for 5 days with different antigens: purified protein derivatives (PPD) of tuberculin, early secretary antigenic target 6,000 protein (ESAT6) and 38,000 antigen. The protein levels of IFN-gamma were detected by ELISA, and the results were compared to those with the tuberculin skin test (TST). RESULTS: (1) For healthy controls, the TST was positively related to the history of BCG vaccination and the closeness of contact with sputum-positive tuberculosis patients (P = 0.047, P = 0.041 respectively). The ESAT6 based IFN-gamma release assay was only significantly related to the closeness of contact with sputum-positive tuberculosis patients (P = 0.005), but not to the history of BCG vaccination. (2) There was no significant difference of the TST results among the three groups (P > 0.05). (3) The receiver operating characteristic (ROC) curve analysis indicated that the sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of the IFN-gamma release assay based on 38,000 antigen were 64.9%, 89.3%, 77.0%, 86.0%, and 71.0% respectively for the diagnosis of tuberculosis. CONCLUSIONS: IFN-gamma release assay based on ESAT6 appears to be better than TST in the diagnosis of infection of Mycobacterium tuberculosis, while IFN-gamma release assay based on 38,000 may be helpful for the diagnosis of tuberculosis.


Assuntos
Interferon gama/sangue , Leucócitos Mononucleares/metabolismo , Tuberculose/diagnóstico , Adulto , Idoso , Antígenos de Bactérias/imunologia , Proteínas de Bactérias , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mycobacterium tuberculosis , Valor Preditivo dos Testes , Curva ROC , Sensibilidade e Especificidade , Teste Tuberculínico , Tuberculose/sangue , Tuberculose/imunologia
5.
Zhonghua Jie He He Hu Xi Za Zhi ; 27(12): 815-9, 2004 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-15730780

RESUMO

OBJECTIVE: To rapidly identify drug-resistant Mycobacterium tuberculosis using phenotypic and genotypic methods and to evaluate the clinical significance of rapid phenotypic susceptibility test by phage amplified biologically assay (PhaB). METHODS: PhaB, DNA sequencing and polymerase chain reaction-single strand conformational polymorphism (PCR-SSCP) were performed on the 91 rifampicin (RFP)-resistant strains (including 82 multi-drug resistant Mycobacterium tuberculosis strains), 42 RFP-susceptible strains, 75 ofloxacin (OFLX)-resistant strains and 40 OFLX-susceptible strains at the same time. RESULTS: The results obtained using PhaB assay, DNA sequencing and PCR-SSCP were compared with the absolute concentration method. For RFP susceptibility, the accordance, sensitivity and specificity of PhaB were 93%, 92% and 95% respectively; the accordance, sensitivity and specificity of DNA sequencing were 93%, 90% and 100% respectively; those of PCR-SSCP were 90%, 86% and 100% respectively. For OFLX susceptibility, the accordance, sensitivity and specificity of PhaB assay were 95%, 95% and 95%; those of DNA sequencing were 80%, 71% and 98% respectively; those of PCR-SSCP were 75%, 63% and 98% respectively. CONCLUSIONS: PhaB assay is a low-cost, rapid, and sensitive method and shows high accordance with absolute concentration technology. It can give drug susceptibility test results within 48 - 96 h, and is a promising technology in clinical laboratory.


Assuntos
Farmacorresistência Bacteriana/genética , Micobacteriófagos , Mycobacterium tuberculosis/efeitos dos fármacos , Rifampina/farmacologia , Antibióticos Antituberculose/farmacologia , Sequência de Bases , Contagem de Colônia Microbiana , Testes de Sensibilidade Microbiana/métodos , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/isolamento & purificação , Reação em Cadeia da Polimerase/métodos , Polimorfismo Conformacional de Fita Simples , Sensibilidade e Especificidade , Análise de Sequência de DNA
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