The Potential of Ganoderma Lucidum as Antimicrobial Agent for Multidrug- Resistant Mycobacterium Tuberculosis

2018 ◽  
Vol 16 (1) ◽  
pp. 11-14 ◽  
Author(s):  
Meira Erawati ◽  
Megah Andriany ◽  
Niken Safitri Dyan Kusumaningrum
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Antimicrobial Agent ◽  
Ganoderma Lucidum ◽  
Bacterial Resistance ◽  
Multidrug Resistant ◽  
Resistant Bacteria ◽  
Dilution Method ◽  
Resistant Tuberculosis ◽  
Mdr Tb

Background: The problem of bacterial resistance of Mycobacterium tuberculosis should be solved by seeking for alternative substances that potentially inhibit the growth or kill the bacteria. Ganoderma lucidum is one type of fungus which is potential to be an antimicrobial agent. This study aimed to determine the potential of G. lucidum on inhibiting the growth of multidrug-resistant bacteria of M. tuberculosis in vitro. Methods: This study used a solid dilution method to test the extract of G. lucidum as an antibacterial agent. Results and Conclusion: Results showed that all strains of multidrug-resistant tuberculosis (MDR-Tb) gave similar responses to G. lucidum extract at various concentrations. The bacteria did not grow on the medium containing G. lucidum extract at the smallest concentration of 12.5%, as well as concentrations of 25% and 50%. Ganoderma lucidum can be used as one of the alternatives for MDR-Tb drugs in the future.

scholarly journals In Vitro Activity of Tetracycline Analogs against Multidrug-resistant and Extensive drug resistance Clinical Isolates of Mycobacterium tuberculosis

2019 ◽  
Author(s):  
Qi Ouyang ◽  
Dachuan Lin ◽  
Guofang Deng ◽  
Zhihua Wen ◽  
Houming Liu ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Peak Plasma ◽  
Peak Plasma Concentration ◽  
Underlying Mechanism ◽  
Multidrug Resistant ◽  
Clinical Isolates ◽  
Ammonium Bromide ◽  
Resistant Tuberculosis ◽  
Mdr Tb

Abstract Background Multidrug-resistant tuberculosis (MDR-TB) has become a big threaten to global health . The current strategy for treatment of MDR-TB and extensive drug resistant tuberculosis (XDR-TB) is with low efficacy and high side effect. While new drug is fundamental for cure MDR-TB, repurposing the Food and Drug Administration (FDA)-approved drugs represents an alternative soluation with less cost.Methods The activity of 8 tetracycline-class antibiotics against mycobacterium tuberculosis ( M.tb ) were determined by Minimum Inhibitory Concentration (MIC) in vitro. A transposon M.smeg libraries was generated by using the Harm phage and then used to isolate the conditional growth mutants in doxycycline containing plate. 11 mutants were isolated and genomic DNAs were extracted using the cetyltrimethyl ammonium bromide (CTAB) method and analyzed by whole genome sequencing.Results We found that three of eight drugs efficiently inhibited mycobacteria growth under the peak plasma concentration in the human body. Further tests showed these three tetracycline analogs (demeclocycline, doxycycline and methacycline) had antimicrobial activity against seven clinical isolates, including MDR and XDR strains. Among them, Doxycycline had the lowest MICs in all mycobacteria strains tested in this study. By using a transposon library, we identify the insertion of transposon in two genes, porin and MshA, associate with the resistant to doxycycline.Conclusions Our findings show that tetracycline analogs such as doxycycline, has bactericidal activity against not only drug sensitive M.tb , but also clinical MDR and XDR strains, provided proof of concept to repurpose doxycycline to fight MDR-TB and XDR-TB. Further investigations are warranted to clarify the underlying mechanism and optimize the strategy in combination with other anti-TB drugs.

scholarly journals Aktivitas Anti-Mycobacterium tuberculosis Kombinasi (-)-Epigallocatechin-Gallate (EGCG) dan Obat Antituberkulosis Lini Pertama

2020 ◽  
pp. 59-66
Author(s):  
Anggita Mirzautika ◽  
Isnaeni Isnaeni ◽  
Djoko Agus Purwanto
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Epigallocatechin Gallate ◽  
Multidrug Resistant ◽  
Dilution Method ◽  
First Line ◽  
Resistant Tuberculosis ◽  
Potentiation Effect ◽  
Before And After ◽  
Tuberculosis Activity

Tuberculosis is a global health problem, and there is even an increase in cases of multidrug-resistant tuberculosis in the world. Therefore, research is needed that can find new anti-tuberculosis drugs (OAT) that are more effective for tuberculosis treatment. In this study, the effect of (-)-epigallocatechin-gallate (EGCG) of tea leaves (Camellia sinensis) combined with the first-line OAT will be observed, in order to find out whether EGCG has anti-tuberculosis activity and can increase the potential of first-line OAT in-vitro. The anti-tuberculosis activity of EGCG was determined by broth dilution method using Middlebrook 7H9 media at concentration of 50, 100, 150, dan 200 ppm, then the potential of first-line OAT before and after combined with the EGCG was observed. The results showed that the activity of EGCG at concentration 50 ppm and 100 ppm could inhibit the Mycobacterium tuberculosis growth by 80%, at concentration 150 ppm by 90%, and at concentration 200 ppm by 100%. First-line OAT activity before combined with EGCG was ≥ 90% at 5 ppm rifampicin, 0.5 ppm isoniazid, 50 ppm pyrazinamide, and 5 ppm ethambutol. Whereas after combined with EGCG, the potential of each drug increased, marked by anti-tuberculosis activity achieved ≥ 90% at lower concentrations, i.e. rifampicin 0.5 ppm, isoniazid 0.25 ppm, pyrazinamide 20 ppm, and ethambutol 2 ppm. These results indicated that the potential of each first-line OAT increases after being combined with EGCG, and EGCG has potentiation effect when combined with those drugs. In conclusion, EGCG can increase the first-line OAT activity

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 Tigecycline: a review of the literature

2006 ◽  
Vol 7 (4) ◽  
pp. 211-222
Author(s):  
Mario Venditti ◽  
Maria Elena Pompeo ◽  
Flavia Fabi
Keyword(s):  
Antimicrobial Agent ◽  
Broad Spectrum ◽  
Bacterial Infections ◽  
Bacterial Resistance ◽  
Multidrug Resistant ◽  
Resistance Mechanisms ◽  
Resistant Bacteria ◽  
Antibiotic Administration ◽  
Spectrum Activity

Tigecycline is a new first-in-class glycylcycline antimicrobial agent with expanded broad-spectrum activity. It was developed to overcome the two key resistance mechanisms, efflux pumps and ribosomal protection, that limit the use of tetracycline. The spectrum of activity extends to clinically relevant susceptible and multidrug resistant bacteria, as methicillin resistant Staphylococcus aureus (MRSA), Streptococcus pneumoniae, vancomycin resistant Enterococci, Acinetobacter spp, Acinetobacter baumannii and Enterobacteriaceae, including extended-spectrum β-lactamase-producing strains (ESBLs). Tigecycline has been introduced into clinical practice as part of the effort to combat the growing problem of bacterial resistance to anti-infective therapy: tigecycline could replace some broad-spectrum agents for approved indications reducing the selective pressure provided by antibiotic administration. The expanded in vitro activity against a broad range of bacteria, including resistant pathogens, of tigecycline suggest that this novel antimicrobial agent should offer clinicians an option for the treatment of patients with serious bacterial infections.

scholarly journals Comparison of In Vitro Activity and MIC Distributions between the Novel Oxazolidinone Delpazolid and Linezolid against Multidrug-Resistant and Extensively Drug-Resistant Mycobacterium tuberculosis in China

2018 ◽  
Vol 62 (8) ◽  
Author(s):  
Zhaojing Zong ◽  
Wei Jing ◽  
Jin Shi ◽  
Shu'an Wen ◽  
Tingting Zhang ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Novel Mutation ◽  
Multidrug Resistant ◽  
23S Rrna ◽  
Drug Resistant ◽  
Content Type ◽  
Extensively Drug Resistant ◽  
Significant Difference ◽  
Mdr Tb

ABSTRACT Oxazolidinones are efficacious in treating mycobacterial infections, including tuberculosis (TB) caused by drug-resistant Mycobacterium tuberculosis. In this study, we compared the in vitro activities and MIC distributions of delpazolid, a novel oxazolidinone, and linezolid against multidrug-resistant TB (MDR-TB) and extensively drug-resistant TB (XDR-TB) in China. Additionally, genetic mutations in 23S rRNA, rplC, and rplD genes were analyzed to reveal potential mechanisms underlying the observed oxazolidinone resistance. A total of 240 M. tuberculosis isolates were included in this study, including 120 MDR-TB isolates and 120 XDR-TB isolates. Overall, linezolid and delpazolid MIC90 values for M. tuberculosis isolates were 0.25 mg/liter and 0.5 mg/liter, respectively. Based on visual inspection, we tentatively set epidemiological cutoff (ECOFF) values for MIC determinations for linezolid and delpazolid at 1.0 mg/liter and 2.0 mg/liter, respectively. Although no significant difference in resistance rates was observed between linezolid and delpazolid among XDR-TB isolates (P > 0.05), statistical analysis revealed a significantly greater proportion of linezolid-resistant isolates than delpazolid-resistant isolates within the MDR-TB group (P = 0.036). Seven (53.85%) of 13 linezolid-resistant isolates were found to harbor mutations within the three target genes. Additionally, 1 isolate exhibited an amino acid substitution (Arg126His) within the protein encoded by rplD that contributed to high-level resistance to linezolid (MIC of >16 mg/liter), compared to a delpazolid MIC of 0.25. In conclusion, in vitro susceptibility testing revealed that delpazolid antibacterial activity was comparable to that of linezolid. A novel mutation within rplD that endowed M. tuberculosis with linezolid, but not delpazolid, resistance was identified.

scholarly journals Sulfamethoxazole Susceptibility of Mycobacterium tuberculosis Isolates from HIV-Infected Ugandan Adults with Tuberculosis Taking Trimethoprim-Sulfamethoxazole Prophylaxis

2015 ◽  
Vol 59 (9) ◽  
pp. 5844-5846 ◽  
Author(s):  
Sam Ogwang ◽  
Caryn E. Good ◽  
Brenda Okware ◽  
Mary Nsereko ◽  
Michael R. Jacobs ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Multidrug Resistant ◽  
Sub Saharan Africa ◽  
Content Type ◽  
Pulmonary Tb ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Sub Saharan

ABSTRACTAdditional drugs are needed for the treatment of multidrug-resistant tuberculosis (TB). Sulfamethoxazole has been shown to havein vitroactivity againstMycobacterium tuberculosis; however, there is concern about resistance given the widespread use of trimethoprim-sulfamethoxazole prophylaxis among HIV-infected patients in sub-Saharan Africa. Thirty-eight of 40Mycobacterium tuberculosisisolates (95%) from pretreatment sputum samples from Ugandan adults with pulmonary TB, including HIV-infected patients taking trimethoprim-sulfamethoxazole prophylaxis, were susceptible with MICs of ≤38.4 μg/ml.

scholarly journals Molecular Characterization of Multidrug-Resistant Mycobacterium tuberculosis Isolated in Nepal

2012 ◽  
Vol 56 (6) ◽  
pp. 2831-2836 ◽  
Author(s):  
Ajay Poudel ◽  
Chie Nakajima ◽  
Yukari Fukushima ◽  
Haruka Suzuki ◽  
Basu Dev Pandey ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Promoter Region ◽  
Multidrug Resistant ◽  
Content Type ◽  
Molecular Tests ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Mdr Tb ◽  
Substitution Mutations ◽  
Drug Resistant Strains

ABSTRACTDespite the fact that Nepal is one of the first countries globally to introduce multidrug-resistant tuberculosis (MDR-TB) case management, the number of MDR-TB cases is continuing to rise in Nepal. Rapid molecular tests applicable in this setting to identify resistant organisms would be an effective tool in reversing this trend. To develop such tools, information about the frequency and distribution of mutations that are associated with phenotypic drug resistance inMycobacterium tuberculosisis required. In the present study, we investigated the prevalence of mutations inrpoBandkatGgenes and theinhApromoter region in 158M. tuberculosisisolates (109 phenotypically MDR and 49 non-MDR isolates collected in Nepal) by DNA sequencing. Mutations affecting the 81-bp rifampin (RIF) resistance-determining region (RRDR) ofrpoBwere identified in 106 of 109 (97.3%) RIF-resistant isolates. Codons 531, 526, and 516 were the most commonly affected, at percentages of 58.7, 15.6, and 15.6%, respectively. Of 113 isoniazid (INH)-resistant isolates, 99 (87.6%) had mutations in thekatGgene, with Ser315Thr being the most prevalent (81.4%) substitution. Mutations in theinhApromoter region were detected in 14 (12.4%) INH-resistant isolates. The results from this study provide an overview of the current situation of RIF and INH resistance inM. tuberculosisin Nepal and can serve as a basis for developing or improving rapid molecular tests to monitor drug-resistant strains in this country.

scholarly journals Mode of Action of Clofazimine and Combination Therapy with Benzothiazinones against Mycobacterium tuberculosis

2015 ◽  
Vol 59 (8) ◽  
pp. 4457-4463 ◽  
Author(s):  
Benoit Lechartier ◽  
Stewart T. Cole
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Bacterial Load ◽  
Multidrug Resistant ◽  
Content Type ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Drug Resistant Strains ◽  
Transfer Chain

ABSTRACTClofazimine (CZM) is an antileprosy drug that was recently repurposed for treatment of multidrug-resistant tuberculosis. InMycobacterium tuberculosis, CZM appears to act as a prodrug, which is reduced by NADH dehydrogenase (NDH-2), to release reactive oxygen species upon reoxidation by O2. CZM presumably competes with menaquinone (MK-4), a key cofactor in the mycobacterial electron transfer chain, for its reduction by NDH-2. We studied the effect of MK-4 supplementation on the activity of CZM againstM. tuberculosisand found direct competition between CZM and MK-4 for the cidal effect of CZM, against nonreplicating and actively growing bacteria, as MK-4 supplementation blocked the drug's activity against nonreplicating bacteria. We demonstrated that CZM, like bedaquiline, is synergisticin vitrowith benzothiazinones such as 2-piperazino-benzothiazinone 169 (PBTZ169), and this synergy also occurs against nonreplicating bacteria. The synergy between CZM and PBTZ169 was lost in an MK-4-rich medium, indicating that MK-4 is the probable link between their activities. The efficacy of the dual combination of CZM and PBTZ169 was testedin vivo, where a great reduction in bacterial load was obtained in a murine model of chronic tuberculosis. Taken together, these data confirm the potential of CZM in association with PBTZ169 as the basis for a new regimen against drug-resistant strains ofM. tuberculosis.

scholarly journals In VitroandIn VivoActivities of the Nitroimidazole TBA-354 against Mycobacterium tuberculosis

2014 ◽  
Vol 59 (1) ◽  
pp. 136-144 ◽  
Author(s):  
A. M. Upton ◽  
S. Cho ◽  
T. J. Yang ◽  
Y. Kim ◽  
Y. Wang ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Pharmacokinetic Profile ◽  
Multidrug Resistant ◽  
Phase Iii ◽  
Drug Resistant ◽  
Next Generation ◽  
Content Type ◽  
Resistant Tuberculosis

ABSTRACTNitroimidazoles are a promising new class of antitubercular agents. The nitroimidazo-oxazole delamanid (OPC-67683, Deltyba) is in phase III trials for the treatment of multidrug-resistant tuberculosis, while the nitroimidazo-oxazine PA-824 is entering phase III for drug-sensitive and drug-resistant tuberculosis. TBA-354 (SN31354[(S)-2-nitro-6-((6-(4-trifluoromethoxy)phenyl)pyridine-3-yl)methoxy)-6,7-dihydro-5H-imidazo[2,1-b][1,3]oxazine]) is a pyridine-containing biaryl compound with exceptional efficacy against chronic murine tuberculosis and favorable bioavailability in preliminary rodent studies. It was selected as a potential next-generation antituberculosis nitroimidazole following an extensive medicinal chemistry effort. Here, we further evaluate the pharmacokinetic properties and activity of TBA-354 againstMycobacterium tuberculosis. TBA-354 is narrow spectrum and bactericidalin vitroagainst replicating and nonreplicatingMycobacterium tuberculosis, with potency similar to that of delamanid and greater than that of PA-824. The addition of serum protein or albumin does not significantly alter this activity. TBA-354 maintains activity againstMycobacterium tuberculosisH37Rv isogenic monoresistant strains and clinical drug-sensitive and drug-resistant isolates. Spontaneous resistant mutants appear at a frequency of 3 × 10−7.In vitrostudies andin vivostudies in mice confirm that TBA-354 has high bioavailability and a long elimination half-life.In vitrostudies suggest a low risk of drug-drug interactions. Low-dose aerosol infection models of acute and chronic murine tuberculosis reveal time- and dose-dependentin vivobactericidal activity that is at least as potent as that of delamanid and more potent than that of PA-824. Its superior potency and pharmacokinetic profile that predicts suitability for once-daily oral dosing suggest that TBA-354 be studied further for its potential as a next-generation nitroimidazole.

scholarly journals Multidrug-Resistant Tuberculosis in Children: A Single-Center Experience

2020 ◽  
Vol 54 (4) ◽  
pp. 208-214
Author(s):  
Deniz Aygün ◽  
Tarık Yıldırım ◽  
Özlem Başoğlu Öner ◽  
Sezer Toprak ◽  
Aylin Babalık ◽  
...  
Keyword(s):  
Family Members ◽  
Treatment Protocol ◽  
Multidrug Resistant ◽  
Nucleic Acid Amplification ◽  
Resistant Bacteria ◽  
Single Center Experience ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Total Treatment ◽  
Mdr Tb

Objective: Resistance to at least isoniazid and rifampicin, which are the most important drugs in TB treatment, is called multidrug-resistant tuberculosis (MDR-TB). MDR-TB is a life-threatening condition that affects children as well as adults. Material and Methods: The medical records of children diagnosed with MDR-TB between June 2015 and October 2018 were analyzed retrospectively. Results: Seven female (77.8%) and two male (22.2%) patients were included into the study. Their mean age was 11.58 ± 4.23 years (3.75-15 years). Five patients (55.5%) had family members with MDR-TB. All of them had pulmonary tuberculosis. Acid-resistant bacteria (ARB) were observed in three (33.3%) patients, nucleic acid amplification tests were positive in four (44.4%) patients, and positive cultures were observed in seven (77.7%) patients. Seven patients had microbiologically and two patients had clinically confirmed MDR-TB. Five patients (55.5%) had isoniazid and rifampicin resistance, two patients (22.2%) had isoniazid, rifampicin and streptomycin resistance. A treatment protocol consisting of pyrazinamide, ethambutol, amikacin, protionamide and moxifloxacin was started after evaluating the culture results of the patients and family members. Cycloserine was added to the treatment protocol of four (44.4%) patients. The total treatment process was continued for 18 months. Conclusion: Management of childhood MDR-TB is a long and difficult process, but it is a preventable and treatable disease.

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