scholarly journals Genetic Determinants Involved inp-Aminosalicylic Acid Resistance in Clinical Isolates from Tuberculosis Patients in Northern China from 2006 to 2012

2014 ◽  
Vol 59 (2) ◽  
pp. 1320-1324 ◽  
Author(s):  
Xiaobing Zhang ◽  
Liguo Liu ◽  
Yan Zhang ◽  
Guangming Dai ◽  
Hairong Huang ◽  
...  
Keyword(s):  
Acid Resistance ◽  
Northern China ◽  
Multidrug Resistant ◽  
Clinical Isolates ◽  
Aminosalicylic Acid ◽  
Genetic Determinants ◽  
Systematic Analysis ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Folate Pathway

ABSTRACTp-Aminosalicylic acid (PAS) is an important compound for treating multidrug-resistant tuberculosis (TB). Previous studies showed thatthyAmutations are often related to PAS resistance in clinical isolates. We performed a systematic analysis of isolate genotypes and detected mutations in three folate pathway genes (folC,thyA, andribD) in 61.1% (127/208) of PAS-resistant isolates, including 11 double mutants. This result expands our knowledge about the distribution and frequency of mutations related to PAS resistance in mycobacterial clinical isolates.

Treatment outcomes in multidrug-resistant tuberculosis according to pyrazinamide susceptibility

2020 ◽  
Vol 24 (2) ◽  
pp. 233-239
Author(s):  
S. Park ◽  
K-W. Jo ◽  
T. S. Shim
Keyword(s):  
Success Rate ◽  
Treatment Outcomes ◽  
Treatment Success ◽  
Multidrug Resistant ◽  
Treatment Success Rate ◽  
Aminosalicylic Acid ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Mdr Tb ◽  
Effective Drugs

BACKGROUND: Pyrazinamide (PZA) is an important anti-tuberculosis drug for multidrug-resistant tuberculosis (MDR-TB). However, PZA has recently been demoted within the hierarchy of TB drugs used for MDR-TB.METHODS: We conducted a retrospective cohort study to investigate treatment outcomes for simple MDR-TB (susceptible to both second-line injectable drugs and fluoroquinolones) according to PZA susceptibility.RESULTS: Among 216 pulmonary MDR-TB patients included in the study, 68 (31.5%) were PZA-resistant (PZA-R). The mean age was 41.8 years, and 63.4% were male. Baseline characteristics such as comorbidity, previous TB history, acid-fast bacilli (AFB) smear positivity and cavitation were similar in PZA-susceptible (PZA-S) and PZA-R patients. The number of potentially effective drugs was slightly higher among PZA-S patients than among the PZA-R (5.1 vs. 4.8, respectively; P = 0.003). PZA was more frequently used in PZA-S patients (73.0%) than in the PZA-R (14.7%), while para-aminosalicylic acid was more frequently used in PZA-R than in PZA-S patients (76.5% vs. 50.7%). The treatment success rate was similar in PZA-S (77.7%) and PZA-R (75.0%) patients. PZA resistance was not associated with treatment success in multivariate analysis.CONCLUSIONS: PZA-resistant simple MDR-TB patients had the same treatment success rate as the PZA-susceptible group even without using novel anti-TB drugs.

scholarly journals Effects of the encapsulation of usnic acid into liposomes and interactions with antituberculous agents against multidrug-resistant tuberculosis clinical isolates

2016 ◽  
Vol 111 (5) ◽  
pp. 330-334 ◽  
Author(s):  
Rafaela S Ferraz-Carvalho ◽  
Marcela A Pereira ◽  
Leonardo A Linhares ◽  
Mariane CB Lira-Nogueira ◽  
Isabella MF Cavalcanti ◽  
...  
Keyword(s):  
Usnic Acid ◽  
Multidrug Resistant ◽  
Clinical Isolates ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis

scholarly journals An updated systematic review and meta-analysis for treatment of multidrug-resistant tuberculosis

2017 ◽  
Vol 49 (3) ◽  
pp. 1600803 ◽  
Author(s):  
Mayara Lisboa Bastos ◽  
Zhiyi Lan ◽  
Dick Menzies
Keyword(s):  
Systematic Review ◽  
Treatment Outcomes ◽  
Multidrug Resistant ◽  
Current Evidence ◽  
Aminosalicylic Acid ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
End Of Treatment ◽  
Mdr Tb ◽  
Culture Conversion

This systematic review aimed to update the current evidence for multidrug-resistant tuberculosis (MDR-TB) treatment.We searched for studies that reported treatment information and clinical characteristics for at least 25 patients with microbiologically confirmed pulmonary MDR-TB and either end of treatment outcomes, 6-month culture conversion or severe adverse events (SAEs). We assessed the association of these outcomes with patients' characteristics or treatment parameters. We identified 74 studies, including 17 494 participants.The pooled treatment success was 26% in extensively drug-resistant TB (XDR-TB) patients and 60% in MDR-TB patients. Treatment parameters such as number or duration and individual drugs were not associated with improved 6-month sputum culture conversion or end of treatment outcomes. However, MDR-TB patients that received individualised regimens had higher success than patients who received standardised regimens (64% versus 52%; p<0.0.01). When reports from 20 cohorts were pooled, proportions of SAE ranged from 0.5% attributed to ethambutol to 12.2% attributed to para-aminosalicylic acid. The lack of significant associations of treatment outcomes with specific drugs or regimens may reflect the limitations of pooling the data rather than a true lack of differences in efficacy of regimens or individual drugs.This analysis highlights the need for stronger evidence for treatment of MDR-TB from better-designed and reported studies.

Dose Regimen of Para-Aminosalicylic Acid Gastro-Resistant Formulation (PAS-GR) in Multidrug-Resistant Tuberculosis

2014 ◽  
Vol 34 (4) ◽  
pp. 269-276 ◽  
Author(s):  
Yves Kibleur ◽  
Hervé Brochart ◽  
Hendrik S. Schaaf ◽  
Andre H. Diacon ◽  
Peter R. Donald
Keyword(s):  
Dose Regimen ◽  
Multidrug Resistant ◽  
Aminosalicylic Acid ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis

scholarly journals Binding Pocket Alterations in Dihydrofolate Synthase Confer Resistance topara-Aminosalicylic Acid in Clinical Isolates of Mycobacterium tuberculosis

2013 ◽  
Vol 58 (3) ◽  
pp. 1479-1487 ◽  
Author(s):  
Fei Zhao ◽  
Xu-De Wang ◽  
Luke N. Erber ◽  
Ming Luo ◽  
Ai-zhen Guo ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Resistance Mechanism ◽  
Binding Pocket ◽  
Multidrug Resistant ◽  
Clinical Isolates ◽  
Missense Mutations ◽  
Aminosalicylic Acid ◽  
Content Type ◽  
Resistant Tuberculosis ◽  
Mechanistic Basis

ABSTRACTThe mechanistic basis for the resistance ofMycobacterium tuberculosistopara-aminosalicylic acid (PAS), an important agent in the treatment of multidrug-resistant tuberculosis, has yet to be fully defined. As a substrate analog of the folate precursorpara-aminobenzoic acid, PAS is ultimately bioactivated to hydroxy dihydrofolate, which inhibits dihydrofolate reductase and disrupts the operation of folate-dependent metabolic pathways. As a result, the mutation of dihydrofolate synthase, an enzyme needed for the bioactivation of PAS, causes PAS resistance inM. tuberculosisstrain H37Rv. Here, we demonstrate that various missense mutations within the coding sequence of the dihydropteroate (H2Pte) binding pocket of dihydrofolate synthase (FolC) confer PAS resistance in laboratory isolates ofM. tuberculosisandMycobacterium bovis. From a panel of 85 multidrug-resistantM. tuberculosisclinical isolates, 5 were found to harbor mutations in thefolCgene within the H2Pte binding pocket, resulting in PAS resistance. While these alterations in the H2Pte binding pocket resulted in reduced dihydrofolate synthase activity, they also abolished the bioactivation of hydroxy dihydropteroate to hydroxy dihydrofolate. Consistent with this model for abolished bioactivation, the introduction of a wild-type copy offolCfully restored PAS susceptibility infolCmutant strains. Confirmation of this novel PAS resistance mechanism will be beneficial for the development of molecular method-based diagnostics forM. tuberculosisclinical isolates and for further defining the mode of action of this important tuberculosis drug.

scholarly journals Activities of Moxifloxacin Alone and in Combination with Other Antimicrobial Agents against Multidrug-Resistant Mycobacterium tuberculosis Infection in BALB/c Mice

2003 ◽  
Vol 47 (1) ◽  
pp. 360-362 ◽  
Author(s):  
Lanfranco Fattorini ◽  
Dejiang Tan ◽  
Elisabetta Iona ◽  
Maurizio Mattei ◽  
Federico Giannoni ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Antimicrobial Agents ◽  
Multidrug Resistant ◽  
Tuberculosis Infection ◽  
Aminosalicylic Acid ◽  
Mycobacterium Tuberculosis Infection ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis

ABSTRACT The activity of moxifloxacin was enhanced by the addition of ethionamide but not by that of cycloserine, thiacetazone, capreomycin, para-aminosalicylic acid, or linezolid in BALB/c mice infected with a strain of Mycobacterium tuberculosis resistant to isoniazid, rifampin, and six other drugs. These observations are important for the therapy of multidrug-resistant tuberculosis.

scholarly journals Implications of a school outbreak of multidrug-resistant tuberculosis in Northern China

2018 ◽  
Vol 146 (5) ◽  
pp. 584-588 ◽  
Author(s):  
Xiaoguang Wu ◽  
Yu Pang ◽  
Yanhua Song ◽  
Wenzhu Dong ◽  
Tingting Zhang ◽  
...  
Keyword(s):  
Treatment Outcomes ◽  
Diagnostic Delay ◽  
Northern China ◽  
Multidrug Resistant ◽  
Preventive Therapy ◽  
Primary Role ◽  
Pulmonary Tb ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Mdr Tb

AbstractIn this study, we identified a multidrug-resistant tuberculosis (MDR-TB) outbreak in a high school in northern China. The aim of this work was to describe TB transmission, drug resistance and treatment outcomes for this patient cluster. In January 2017, pulmonary TB was identified in a 17-year-old boy in northern China. Subsequently, a total of 11 TB cases were identified during 6-month follow-up of attendees of the same school. Of five students with latent TB infection (LTBI) receiving isoniazid preventive therapy (IPT), two pulmonary TB cases (40.0%) emerged in March and April, for an active case rate not significantly different from that of the non-IPT group (4/16, 25.0%, P = 0.598). All TB patients were first treated with a standardised first-line treatment regimen administered by the local TB hospital, with 11 of 12 active TB patients exhibiting poor treatment outcomes. Further data demonstrated that all nine patient isolates collected during this outbreak were MDR-TB and shared a common genotypic profile. In conclusion, our data demonstrate that diagnostic delay for the index MDR-TB case of this outbreak played a primary role in transmission of MDR-TB infection within a school setting. Importantly, IPT failed to prevent progression of MDR-TB from LTBI to active TB.

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