scholarly journals Limited Effect of Later-Generation Fluoroquinolones in the Treatment of Ofloxacin-Resistant and Moxifloxacin-Susceptible Multidrug-Resistant Tuberculosis

2017 ◽  
Vol 62 (2) ◽  
Author(s):  
Hyun Lee ◽  
Soohyun Ahn ◽  
Na Young Hwang ◽  
Kyeongman Jeon ◽  
O Jung Kwon ◽  
...  
Keyword(s):  
Treatment Outcomes ◽  
Multidrug Resistant ◽  
Aminosalicylic Acid ◽  
Logistic Analysis ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Mdr Tb ◽  
Resistant Group ◽  
Susceptible Group

ABSTRACT Recent data conflict on the clinical efficacy of later-generation fluoroquinolones, such as moxifloxacin or levofloxacin, for the treatment of multidrug-resistant tuberculosis (MDR-TB) that is resistant to ofloxacin but susceptible to moxifloxacin. The purpose of the present study was to evaluate whether later-generation fluoroquinolones can improve treatment outcomes in patients with ofloxacin-resistant, moxifloxacin-susceptible MDR-TB. A retrospective cohort study was performed on 208 patients with moxifloxacin-susceptible MDR-TB who were treated between 2006 and 2011. Later-generation fluoroquinolones were used for all patients. Overall, 171 patients (82%) had ofloxacin-susceptible, moxifloxacin-susceptible MDR-TB (ofloxacin-susceptible group), and 37 (18%) had ofloxacin-resistant, moxifloxacin-susceptible MDR-TB (ofloxacin-resistant group). Compared to the ofloxacin-susceptible group, the ofloxacin-resistant group was more likely to have a history of MDR-TB treatment (P < 0.001) and cavitary lesions on chest radiography (P < 0.001). In addition, the ofloxacin-resistant group was more likely than the ofloxacin-susceptible group to have resistance to the drugs pyrazinamide (P = 0.003), streptomycin (P = 0.015), prothionamide (P < 0.001), and para-aminosalicylic acid (P < 0.001). Favorable outcomes were more frequently achieved for the ofloxacin-susceptible group than for the ofloxacin-resistant group (91% [156/171] versus 57% [21/37], respectively [P < 0.001]). In multivariable regression logistic analysis, the ofloxacin-susceptible group was about 5.36 (95% confidence interval, 1.55 to 18.53) times more likely than the ofloxacin-resistant group (P < 0.001) to have favorable outcomes. Despite in vitro moxifloxacin susceptibility, the frequency of favorable treatment outcomes for ofloxacin-resistant MDR-TB was significantly lower than that for ofloxacin-susceptible MDR-TB, even when later-generation fluoroquinolones were used, indicating that more-aggressive therapies may be needed for ofloxacin-resistant MDR-TB.

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 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.

scholarly journals Treatment Outcomes and Adverse Drug Effects of Ethambutol, Cycloserine, and Terizidone for the Treatment of Multidrug-Resistant Tuberculosis in South Africa

2020 ◽  
Vol 65 (1) ◽  
pp. e00744-20
Author(s):  
Martha L. van der Walt ◽  
Karen Shean ◽  
Piet Becker ◽  
Karen H. Keddy ◽  
Joey Lancaster
Keyword(s):  
Treatment Outcomes ◽  
Adverse Drug Events ◽  
Drug Effects ◽  
Multidrug Resistant ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Default Rates ◽  
Conversion Rates ◽  
Mdr Tb ◽  
Culture Conversion

ABSTRACTTreatment outcomes among multidrug-resistant tuberculosis (MDR-TB) patients receiving ethambutol, cycloserine, or terizidone as part of a standardized regimen were compared, determining occurrence of serious adverse drug events (SADEs). Newly diagnosed adult MDR-TB patients were enrolled between 2000 and 2004, receiving a standardized multidrug regimen for 18 to 24 months, including ethambutol, cycloserine, or terizidone. Cycloserine and terizidone were recorded individually. SADEs and factors associated with culture conversion and unfavorable treatment outcomes (default, death, treatment failure) were determined. Of 858 patients, 435 (51%) received ethambutol, 278 (32%) received cycloserine, and 145 (17%) received terizidone. Demographic and baseline clinical data were comparable. Successful treatment occurred in 56%, significantly more in patients receiving cycloserine (60%) and terizidone (62%) than in those receiving ethambutol (52% [P = 0.03]). Defaults rates were 30% in ethambutol patients versus 15% and 11% for cycloserine and terizidone patients, respectively. Terizidone was associated with fewer unfavorable outcomes (adjusted odds ratio [AOR], 0.4; P = 0.008; 95% confidence interval [CI], 0.2 to 0.8). Patients receiving cycloserine were more likely to achieve culture conversion than those receiving ethambutol or terizidone (AOR, 2.2; P = 0.02; 95% CI, 1.12 to 4.38). Failure to convert increased the odds of unfavorable outcomes (AOR, 23.7; P < 0.001; 95% CI, 13 to 44). SADEs were reported in two patients receiving ethambutol, seven patients receiving cycloserine, and three receiving terizidone (P = 0.05). Ethambutol was associated with high culture conversion and default rates. Cycloserine achieved higher culture conversion rates than terizidone. Fewer patients on terizidone experienced SADEs, with lower default rates. The differences that we observed between cycloserine and terizidone require further elucidation.

scholarly journals Synthesis, Characterization and Antituberculosis Activity of Biologically Nanostructured Zinc and Titanium Metal Compounds

2020 ◽  
Vol 32 (6) ◽  
pp. 1286-1290
Author(s):  
Savita Belwal ◽  
Sujana Kariveda ◽  
Saritha Ramagiri
Keyword(s):  
Multidrug Resistant ◽  
Metal Compounds ◽  
Zinc Compounds ◽  
Macrotyloma Uniflorum ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Transmission Electron ◽  
H37rv Strain ◽  
Mdr Tb

Green chemistry was used to obtain nano-range sized titanium and zinc compounds from their macro-sizes by using an aqueous extract of horse gram (Macrotyloma uniflorum). Ultraviolet-visible (UV-vis) and Fourier-transform infrared (FTIR) spectrophotometers were employed for characterizing the nanoparticles of biosynthesized metal nanoparticles. Transmission electron microscopy (TEM) was used to analyse the reduced nanoparticles of Ti and Zn metals. Microdilution was employed to determine in vitro properties, such as effects of nanocomplex antimicrobials on Mycobacterium tuberculosis (MTB) H37RV strain. MTB strains isolated from patients with multidrug-resistant tuberculosis (MDR-TB) were resistant to first-line drugs. Novel synthesized nano-complexes exhibited potential antituberculosis activities. Titanium nanocomplexes exhibited the highest minimal inhibitory concentration (MIC) in comparison to zinc nanocomplex. In a cytotoxic study, an IC50 of 1000 μg/mL, for both Ti and Zn nanocomplexes, was reported, and thus, these complexes were non-toxic when compared to isoniazid.

scholarly journals Adverse treatment outcomes in multidrug resistant tuberculosis go beyond the microbe-drug interaction: Results of a multiple correspondence analysis.

Biomédica ◽  
2020 ◽  
Vol 40 (4) ◽  
pp. 616-625
Author(s):  
Ángela Tobón ◽  
Johana Rueda ◽  
Diego H. Cáceres ◽  
Gloria I. Mejía ◽  
Elsa M. Zapata ◽  
...  
Keyword(s):  
Treatment Outcomes ◽  
Treatment Success ◽  
Multidrug Resistant ◽  
Chronic Obstructive ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Mdr Tb ◽  
Poor Outcomes ◽  
Lost To Follow Up

Introduction: Multidrug-resistant tuberculosis treatment is effective in 50% of patients due to several factors including antibiotic susceptibility of the microorganism, adverse treatment reactions, social factors, and associated comorbidities.Objectives: In this study, we describe the demographics, clinical characteristics, and factors associated with treatment outcomes in multidrug-resistant tuberculosis (MDR-TB) patients in Medellín, Colombia.Materials and methods: We conducted a retrospective analysis using data from patients diagnosed with MDR-TB attending Hospital La María in Medellín, Colombia, for treatment between 2010 and 2015. Patients were categorized as having successful (cured) or poor (failure, lost to follow-up, and death) treatment outcomes. Associations between demographic, clinical factors, laboratory results, treatment outcomes, and follow-up information were evaluated by univariate, multivariate, and multiple correspondence analyses.Results: Of the 128 patients with MDR-TB, 77 (60%) had successful outcomes. Of those with poor outcomes, 26 were lost to follow-up, 15 died, and 10 were treatment failures. Irregular treatment, the presence of comorbidities, and positive cultures after more than two months of treatment were associated with poor outcomes compared to successful ones (p<0.05 for all). The multiple correspondence analyses grouped patients who were lost to follow-up, had HIV, and drug addiction, as well as patients with treatment failure, irregular treatment, and chronic obstructive pulmonary disease.Conclusion: The recognition of factors affecting treatment is essential and was associated with treatment outcomes in this series of patients. Early identification of these factors should increase the rates of treatment success and contribute to MDR-TB control.

scholarly journals In VitroActivity of β-Lactams in Combination with β-Lactamase Inhibitors against Multidrug-Resistant Mycobacterium tuberculosis Isolates

2015 ◽  
Vol 60 (1) ◽  
pp. 393-399 ◽  
Author(s):  
Dan Zhang ◽  
Yufeng Wang ◽  
Jie Lu ◽  
Yu Pang
Keyword(s):  
Synergistic Effect ◽  
Multidrug Resistant ◽  
Nucleotide Substitutions ◽  
Single Nucleotide ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Mdr Tb ◽  
Amoxicillin Clavulanate ◽  
Increased Susceptibility

ABSTRACTThe combination of β-lactams and β-lactamase inhibitors has been shown to have potentin vitroactivity against multidrug-resistant tuberculosis (MDR-TB) isolates. In order to identify the most potent β-lactam–β-lactamase inhibitor combination against MDR-TB, we selected nine β-lactams and three β-lactamase inhibitors, which belong to different subgroups. A total of 121 MDR-TB strains were included in this study. Out of the β-lactams used herein, biapenem was the most effective against MDR-TB and had an MIC50value of 8 μg/ml. However, after the addition of clavulanate or sulbactam, meropenem exhibited the most potent anti-MDR-TB activity with an MIC50value of 4 μg/ml. For meropenem, 76 (62.8%), 41 (33.9%), and 22 (18.2%) of the 121 MDR-TB strains were subjected to a synergistic effect when the drug was combined with sulbactam, tazobactam, or clavulanate, respectively. Further statistical analysis revealed that significantly more strains experienced a synergistic effect when exposed to the combination of meropenem with sulbactam than when exposed to meropenem in combination with tazobactam or clavulanate, respectively (P< 0.01). In addition, a total of 10.7% (13/121) of isolates harbored mutations in theblaCgene, with two different nucleotide substitutions: AGT333AGG and ATC786ATT. For the strains with a Ser111Arg substitution in BlaC, a better synergistic effect was observed in the meropenem-clavulanate and in the amoxicillin-clavulanate combinations than that in a synonymous single nucleotide polymorphism (SNP) group. In conclusion, our findings demonstrate that the combination of meropenem and sulbactam shows the most potent activity against MDR-TB isolates. In addition, the Ser111Arg substitution of BlaC may be associated with an increased susceptibility of MDR-TB isolates to meropenem and amoxicillin in the presence of clavulanate.

scholarly journals Effectiveness and Safety of Bedaquiline-containing Regimens for Treatment on Patients With Refractory Rifampicin/multidrug-resistant Tuberculosis: A Retrospective Cohort Study in East China

2021 ◽  
Author(s):  
Shao-Jun Zhang ◽  
Yan Yang ◽  
Wen-Wen Sun ◽  
Zhong-Shun Zhang ◽  
He-ping Xiao ◽  
...  
Keyword(s):  
Treatment Outcomes ◽  
Treatment Success ◽  
Multidrug Resistant ◽  
East China ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Conversion Rates ◽  
Mdr Tb ◽  
Culture Conversion ◽  
Closing Rate

Abstract Objective: To compare the effectiveness and safety of bedaquiline-containing and bedaquiline-free regimens for treatment of patients with refractory rifampicin-resistant/multidrug-resistant tuberculosis (RR/MDR-TB).Methods: Patients with refractory RR/MDR-TB receiving bedaquiline-containing regimens (bedaquiline group, n=102) and bedaquiline-free regimens (non-bedaquiline group, n=100) were included in this retrospective historical control study across East China. The culture conversion, end-of-treatment outcomes, cavity closing rate, and adverse events (AEs) were compared between the two groups. Univariate and multivariate analyses were performed to identify independent predictors of treatment success and culture reversion.Results: The baseline characteristics of the patients were well balanced between the two groups. The culture conversion rates in the bedaquiline group at month 3 (89.2% vs. 66.0%), month 6 (90.2% vs. 72.0%), month 9 (91.2% vs. 66.0%), and month 12 (94.1% vs. 65.0%) were all significantly higher than those in the non-bedaquiline group (all p<0.001). Similar results were observed in the cavity closing rate at month 9 (19.6% vs. 8.0%, p=0.017) and month 12 (39.2% vs. 15.0%, p<0.001). Patients receiving bedaquiline-containing regimens had more treatment success than those receiving bedaquiline-free regimens (p<0.001; cure rate, 69.6% vs. 45.0%; complete the treatment, 22.5% vs. 18.0%; treatment success, 92.2% vs. 63.0%). The use of bedaquiline was identified as an independent predictor of both treatment success (OR=7.356, 95% CI: 2.920–18.530, p<0.001) and culture reversion (OR=0.124, 95% CI: 0.035–0.452, p<0.001). AEs were similarly reported in 26.5% of patients in the bedaquiline group and 19.0% in the non-bedaquiline group (p=0.206).Conclusions: Bedaquiline-containing regimens resulted in better treatment outcomes and similar safety relative to bedaquiline-free regimens for patients with refractory pulmonary RR/MDR-TB.

scholarly journals Differential Gene Expression in Response to Adjunctive Recombinant Human Interleukin-2 Immunotherapy in Multidrug-Resistant Tuberculosis Patients

1998 ◽  
Vol 66 (6) ◽  
pp. 2426-2433 ◽  
Author(s):  
Barbara J. Johnson ◽  
Iris Estrada ◽  
Zhu Shen ◽  
Stan Ress ◽  
Paul Willcox ◽  
...  
Keyword(s):  
Differential Display ◽  
Interleukin 2 ◽  
Multidrug Resistant ◽  
Rt Pcr ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Mdr Tb ◽  
Ifn Γ ◽  
Baseline Levels

ABSTRACT Administration of low-dose recombinant human interleukin 2 (rhuIL-2) in combination with multidrug chemotherapy to patients with multidrug-resistant tuberculosis (MDR TB) induces measurable changes in in vitro immune response parameters which are associated with changes in the clinical and bacteriologic status of the patients. To determine the molecular basis of these changes, we have used semiquantitative reverse transcriptase-initiated PCR (RT-PCR) and differential display technology. During rhuIL-2 treatment of MDR TB patients, decreased levels of gamma interferon (IFN-γ) mRNA in peripheral blood mononuclear cells (PBMC) relative to baseline levels were observed. However, at the site of a delayed-type hypersensitivity (DTH) response to purified protein derivative of tuberculin (PPD), the expression of cellular IFN-γ and IL-2 mRNAs was increased during rhuIL-2 therapy. Levels of other cytokine mRNAs were not significantly affected by rhuIL-2 administration. Using differential-display RT-PCR, we identified several genes expressed at the DTH skin test site which were up- or down-regulated during rhuIL-2 treatment. Cytochrome oxidase type I mRNA was increased in response to rhuIL-2 therapy relative to baseline levels, as was heterogeneous nuclear ribonuclear protein G mRNA. CD63, clathrin heavy chain, and β-adaptin mRNAs, all of which encode proteins associated with the endocytic vacuolar pathway of cells, were also differentially regulated by rhuIL-2 administration. The differential effects of IL-2 were confirmed in vitro by using PBMC obtained from PPD-positive individuals stimulated withMycobacterium tuberculosis and IL-2. The differential expression of genes may provide a surrogate marker for leukocyte activation at a mycobacterial antigen-specific response site and for the development of an enhanced antimicrobial response which may result in improved outcomes in MDR TB patients.

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