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.

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 Plasma Levels of Cytokines (IL-10, IFN-γ and TNF-α) in Multidrug Resistant Tuberculosis and Drug Responsive Tuberculosis Patients in Ghana

Diseases ◽  
2018 ◽  
Vol 7 (1) ◽  
pp. 2 ◽  
Author(s):  
Anthony Basingnaa ◽  
Samuel Antwi-Baffour ◽  
Dinah Nkansah ◽  
Emmanuel Afutu ◽  
Enid Owusu
Keyword(s):  
Plasma Levels ◽  
Sandwich Elisa ◽  
Plasma Concentrations ◽  
Multidrug Resistant ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Tnf Α ◽  
Mdr Tb ◽  
Ifn Γ ◽  
Socio Economic Factors

The emergence of multidrug-resistant tuberculosis (MDR–TB) and more recently, extensively drug-resistant (XDR) TB has intensified the need for studies aimed at identifying factors associated with TB drug resistance. This study determined the differences in plasma concentrations of pro-inflammatory (IFN-γ and TNF-α) and anti-inflammatory (IL-10) cytokines in MDR-TB and drug-susceptible (DS) TB patients, in addition to some socio-economic factors. Plasma levels of IL-10, IFN-γ and TNF-α were measured in 83 participants (comprising 49 MDR-TB and 34 DS-TB patients) using sandwich ELISA. Levels of the three cytokines were elevated in MDR-TB patients compared to DS-TB patients. The mean level of IL-10 (7.8 ± 3.61 ρg/mL) measured in MDR-TB cases was relatively higher than those of TNF-α and IFN-γ, and statistically significant (p = 0.0022) when compared to the level of IL-10 (4.8 ± 4.94 ρg/mL) in the DS-TB cases. There were statistically significant associations between MDR-TB and factors such as education level (X2 = 9.895, p = 0.043), employment status (X2 = 19.404, p = 0.001) and alcoholism (X2 = 3.971, p = 0.046). This study adds to the knowledge that IFN-γ, TNF-α and IL-10 play a role in the host response to Mycobacterium tuberculosis (MTB). Alcohol intake can be considered as an important MDR-TB risk factor.

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 Pyrazinamide Resistance Assays and Two-Month Sputum Culture Status in Patients with Multidrug-Resistant Tuberculosis

2016 ◽  
Vol 60 (11) ◽  
pp. 6766-6773 ◽  
Author(s):  
Gustavo E. Velásquez ◽  
Roger I. Calderon ◽  
Carole D. Mitnick ◽  
Mercedes C. Becerra ◽  
Chuan-Chin Huang ◽  
...  
Keyword(s):  
Gold Standard ◽  
Latent Class ◽  
Multidrug Resistant ◽  
Drug Susceptibility Testing ◽  
Content Type ◽  
Antituberculous Drugs ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Mdr Tb

ABSTRACTPhenotypic drug susceptibility testing is the current “gold standard” for detectingMycobacterium tuberculosissusceptibility to antituberculous drugs. Pyrazinamide is one antituberculous drug for which the correlation betweenin vitroresistance and clinical outcomes remains unclear. Here we performed latent class analysis (LCA) to develop a consensus gold standard definition of pyrazinamide resistance using three paired standard pyrazinamide resistance assays. We then compared this consensus measure to the 2-month culture results for patients with multidrug-resistant tuberculosis (MDR-TB) who were treated for 2 months with first-line antituberculous drugs before their resistance results were known. Among 121 patients with MDR-TB, 60 (49.6%) were resistant to pyrazinamide by the Wayne method (L. G. Wayne, Am Rev Respir Dis 109:147–151, 1974), 71 (58.7%) were resistant by the Bactec MGIT 960 method, and 68 (56.2%) were resistant bypncAsequencing. LCA grouped isolates with positive results by at least two assays into a category which we considered the “consensus gold standard” for pyrazinamide resistance. The sensitivity and specificity for this consensus gold standard were 82.4% and 92.5%, respectively, for the Wayne method; 95.6% and 88.7%, respectively, for the Bactec MGIT 960 method; and 92.6% and 90.6%, respectively, forpncAsequencing. After we adjusted for other factors associated with poor outcomes, including age, sex, alcohol use, and baseline ethambutol resistance, patients whose isolates were resistant by the LCA-derived consensus gold standard were more likely to be culture positive at 2 months with an odds ratio of 1.95 (95% confidence interval, 0.74 to 5.11), but this result was not statistically significant. These findings underscore the need for improved diagnostics for routine use in programmatic settings.

scholarly journals Patients with Multidrug-Resistant Tuberculosis Display Impaired Th1 Responses and Enhanced Regulatory T-Cell Levels in Response to an Outbreak of Multidrug-Resistant Mycobacterium tuberculosis M and Ra Strains

2009 ◽  
Vol 77 (11) ◽  
pp. 5025-5034 ◽  
Author(s):  
Laura Geffner ◽  
Noemí Yokobori ◽  
Juan Basile ◽  
Pablo Schierloh ◽  
Luciana Balboa ◽  
...  
Keyword(s):  
T Cells ◽  
Mycobacterium Tuberculosis ◽  
Mononuclear Cells ◽  
Multidrug Resistant ◽  
Interleukin 4 ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Mdr Tb ◽  
Ifn Γ ◽  
Ctl Activity

ABSTRACT In Argentina, multidrug-resistant tuberculosis (MDR-TB) outbreaks emerged among hospitalized patients with AIDS in the early 1990s and thereafter disseminated to the immunocompetent community. Epidemiological, bacteriological, and genotyping data allowed the identification of certain MDR Mycobacterium tuberculosis outbreak strains, such as the so-called strain M of the Haarlem lineage and strain Ra of the Latin America and Mediterranean lineage. In the current study, we evaluated the immune responses induced by strains M and Ra in peripheral blood mononuclear cells from patients with active MDR-TB or fully drug-susceptible tuberculosis (S-TB) and in purified protein derivative-positive healthy controls (group N). Our results demonstrated that strain M was a weaker gamma interferon (IFN-γ) inducer than H37Rv for group N. Strain M induced the highest interleukin-4 expression in CD4+ and CD8+ T cells from MDR- and S-TB patients, along with the lowest cytotoxic T-lymphocyte (CTL) activity in patients and controls. Hence, impairment of CTL activity is a hallmark of strain M and could be an evasion mechanism employed by this strain to avoid the killing of macrophages by M-specific CTL effectors. In addition, MDR-TB patients had an increased proportion of circulating regulatory T cells (Treg cells), and these cells were further expanded upon in vitro M. tuberculosis stimulation. Experimental Treg cell depletion increased IFN-γ expression and CTL activity in TB patients, with M- and Ra-induced CTL responses remaining low in MDR-TB patients. Altogether, these results suggest that immunity to MDR strains might depend upon a balance between the individual host response and the ability of different M. tuberculosis genotypes to drive Th1 or Th2 profiles.

Fidaxomicin has high in vitro activity against Mycobacterium tuberculosis

2021 ◽  
Author(s):  
Qing Sun ◽  
Shuqi Wang ◽  
Xinlei Liao ◽  
Guanglu Jiang ◽  
Hairong Huang ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Type Species ◽  
Multidrug Resistant ◽  
Alamar Blue ◽  
In Vitro Activity ◽  
Content Type ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Mdr Tb

This study aimed to evaluate whether the antibiotic fidaxomicin has in vitro activity against Mycobacterium tuberculosis (Mtb). 38 fully drug-sensitive Mtb strains and 34 multidrug-resistant tuberculosis (MDR-TB) strains were tested using the microplate alamar blue assay (MABA) method to determine the minimum inhibitory concentrations (MICs) for fidaxomicin and rifampicin. Fidaxomicin has high in vitro activity against Mtb and is a potential drug to treat Mtb, and MDR-TB infections in particular.

scholarly journals KALIUM DI MULTIDRUG RESISTANCE TUBERKULOSIS DENGAN PENGOBATAN KANAMISIN (Potassium in Multidrug Resistance Tuberculosis with Kanamycin)

2018 ◽  
Vol 21 (1) ◽  
pp. 16 ◽  
Author(s):  
J.B. Suparyatmo ◽  
B. Rina AS ◽  
Harsini Harsini ◽  
Sukma Sukma
Keyword(s):  
Multidrug Resistance ◽  
Potassium Level ◽  
Multidrug Resistant ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Before And After ◽  
Mdr Tb ◽  
The Difference ◽  
Antibiotic Agents

Multidrug-Resistant Tuberculosis (MDR-TB) with bacillary resistance to at least isoniazid and rifampicin in vitro is a worldwidephenomenon. For MDR-TB second-line antibiotic agents that are more potent and more toxic must be used. . One of them is kanamycingiven intravenously every day for six (6) months therapy. Kanamycin is nephrotoxic and can lead to hypokalemia. This study is carriedout to know the comparison between the potasium level before and after kanamycin therapy (2, 4 and 6 months after therapy). Thisstudy is a cohort retrospective design, comprising 34 patients who had a potassium baseline before therapy in Moewardi Hospital,Surakarta from January 2011–August 2012. The characteristic data included: age, sex, weight and comorbidity. The potassium levelafter 2, 4 and 6 months post therapy was compared with the potassium data baseline using One Way ANOVA test with p< 0.05, CI95%. The difference between the potassium level after 6 months therapy and potassium baseline was significant, p < 0.05. However,the difference of the kalium level after 2 and 4 months after therapy was not significant, p > 0.05. Hypokalemia occurred in 6 patientsafter 2 months therapy, 8 patients after 4 months therapy and 3 patients after 6 months therapy. There was a significant differencebetween the potassium level after 6 months therapy and potassium baseline. Further study should be continued to know the existenceof hypokalemia among MDR-TB patients

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.

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