scholarly journals In Vitro Antimycobacterial Activity of Pakistani Beri Honey Using BACTEC MGIT 960

2014 ◽  
Vol 2014 ◽  
pp. 1-4
Author(s):  
Abdul Hannan ◽  
Saira Munir ◽  
Muhammad Usman Arshad ◽  
Nabila Bashir
Keyword(s):  
Growth Control ◽  
Antimycobacterial Activity ◽  
Multidrug Resistant ◽  
Bacterial Disease ◽  
First Line ◽  
Development Of Resistance ◽  
Extensively Drug Resistant ◽  
Mdr Tb ◽  
Growth Controls

Background. Tuberculosis (TB) is a chronic bacterial disease. Mycobacterium tuberculosis, being the leading member of the MTB complex, is the main cause of tuberculosis worldwide. Tuberculosis is managed with combination of drugs: streptomycin, isoniazid, rifampicin, ethambutol, and pyrazinamide. Over the recent past years resistance against first line antituberculous drugs has emerged rapidly throughout the world resulting in MDR strains. The new threat in the management of MDR-TB is the development of resistance against second line drugs: aminoglycosides, polypeptides, fluoroquinolones, and thioamides. Multidrug resistant (MDR) and extensively drug resistant TB (XDR) strains have become a major concern to control TB particularly in the developing countries. The need of the hour is to look for new modalities having antimycobacterial activity. Honey has been well known for its antibacterial activity. We intended to explore its antimycobacterial activity against MDR-TB. Objective. The objective of this study was to determine whether Pakistani Beri honey has any antimycobacterial activity. Method. The study was conducted in the Department of Microbiology, University of Health Sciences, Lahore. Clinical isolates (n=21) of MDR-MTB were evaluated for their susceptibility to Beri honey. The isolates were provided, courtesy of Pakistan Medical Research Council. These isolates were identified by MTBc ID test (Becton & Dickinson) and further tested for their antimycobacterial activity using Beri honey. The honey was tested at the following concentrations (v/v): 1%, 2%, 3%, 4%, and 5% in MGIT 960. Growth controls were also inoculated with each isolate (growth control has no concentration of honey, only containing growth of isolate). Results. MDR-TB isolates (n=21) were tested; 3 (14%) isolates were susceptible at 1% v/v honey, while at 2% v/v of honey 18 (86%) isolates were found to be susceptible. All the 21 isolates (n=21) were susceptible at 3% v/v of honey. Conclusion. The present study clearly demonstrates that Pakistani Beri honey possesses significant antimycobacterial activity in vitro. The antimycobacterial activity of Pakistani Beri honey may, therefore, be exploited in an appropriate mouse model.

scholarly journals New InhA Inhibitors Based on Expanded Triclosan and Di-Triclosan Analogues to Develop a New Treatment for Tuberculosis

2021 ◽  
Vol 14 (4) ◽  
pp. 361
Author(s):  
Sarentha Chetty ◽  
Tom Armstrong ◽  
Shalu Sharma Kharkwal ◽  
William C. Drewe ◽  
Cristina I. De Matteis ◽  
...  
Keyword(s):  
Multidrug Resistant ◽  
Protein Crystal ◽  
First Line ◽  
Isoniazid Resistance ◽  
Structure Based Drug Design ◽  
Extensively Drug Resistant ◽  
New Treatment ◽  
Flexible Ligands ◽  
Line Drug

The emergence of multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis (TB) has reinforced the need for the development of new anti-TB drugs. The first line drug isoniazid inhibits InhA. This is a prodrug requiring activation by the enzyme KatG. Mutations in KatG have largely contributed to clinical isoniazid resistance. We aimed to design new ‘direct’ InhA inhibitors that obviate the need for activation by KatG, circumventing pre-existing resistance. In silico molecular modelling was used as part of a rational structure-based drug-design approach involving inspection of protein crystal structures of InhA:inhibitor complexes, including the broad spectrum antibiotic triclosan (TCS). One crystal structure exhibited the unusual presence of two triclosan molecules within the Mycobacterium tuberculosis InhA binding site. This became the basis of a strategy for the synthesis of novel inhibitors. A series of new, flexible ligands were designed and synthesised, expanding on the triclosan structure. Low Minimum Inhibitory Concentrations (MICs) were obtained for benzylphenyl compounds (12, 43 and 44) and di-triclosan derivative (39), against Mycobacterium bovis BCG although these may also be inhibiting other enzymes. The ether linked di-triclosan derivative (38) displayed excellent in vitro isolated enzyme inhibition results comparable with triclosan, but at a higher MIC (125 µg mL−1). These compounds offer good opportunities as leads for further optimisation.

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 Current Prospects for the Fluoroquinolones as First-Line Tuberculosis Therapy

2011 ◽  
Vol 55 (12) ◽  
pp. 5421-5429 ◽  
Author(s):  
Howard Takiff ◽  
Elba Guerrero
Keyword(s):  
Multidrug Resistant ◽  
Phase Iii ◽  
Phase Ii Trials ◽  
First Line ◽  
Current Standard ◽  
Standard Drug ◽  
First Line Therapy ◽  
Development Of Resistance ◽  
Mdr Tb ◽  
Phase Iii Trials

ABSTRACTWhile fluoroquinolones (FQs) have been successful in helping cure multidrug-resistant tuberculosis (MDR TB), studies in mice have suggested that if used as first-line agents they might reduce the duration of therapy required to cure drug-sensitive TB. The results of phase II trials with FQs as first-line agents have been mixed, but in at least three studies where moxifloxacin substituted for ethambutol, there was an increase in the early percentage of sputa that converted to negative for bacilli. Phase III trials are in progress to test the effectiveness of 4-month FQ-containing regimens, but there is concern that the widespread use of FQs for other infections could engender a high prevalence of FQ-resistant TB. However, several studies suggest that despite wide FQ use, the prevalence of FQ-resistant TB is low, and the majority of the resistance is low-level. The principal risk for resistance may be when FQs are used to treat nonspecific respiratory symptoms that are in fact TB, so curtailing this use of FQs could reduce the development of resistance and also the delays in TB diagnosis and treatment that have been documented when an FQ is given in this setting. While the future of FQs as first-line therapy will likely depend upon the results of the ongoing phase III trials, if they are to be effectively employed in high-TB-burden regions their use for community-acquired pneumonias should be restricted, the prevalence of FQ-resistant TB should be monitored, and the cost of the treatment should be comparable to that of current standard drug regimens.

scholarly journals A Repurposing Approach for Uncovering the Anti-Tubercular Activity of FDA-Approved Drugs with Potential Multi-Targeting Profiles

Molecules ◽  
2019 ◽  
Vol 24 (23) ◽  
pp. 4373 ◽  
Author(s):  
Basem Battah ◽  
Giulia Chemi ◽  
Stefania Butini ◽  
Giuseppe Campiani ◽  
Simone Brogi ◽  
...  
Keyword(s):  
Mononuclear Cells ◽  
Rapid Development ◽  
Antimycobacterial Activity ◽  
Multidrug Resistant ◽  
Biological Evaluation ◽  
Peripheral Blood Mononuclear ◽  
Development Of Resistance ◽  
Approved Drugs ◽  
Fda Approved Drugs

Tuberculosis (TB) is one of the top 10 causes of death worldwide. This scenario is further complicated by the insurgence of multidrug-resistant (MDR) and extensively drug-resistant (XDR) TB. The identification of appropriate drugs with multi-target affinity profiles is considered to be a widely accepted strategy to overcome the rapid development of resistance. The aim of this study was to discover Food and Drug Administration (FDA)-approved drugs possessing antimycobacterial activity, potentially coupled to an effective multi-target profile. An integrated screening platform was implemented based on computational procedures (high-throughput docking techniques on the target enzymes peptide deformylase and Zmp1) and in vitro phenotypic screening assays using two models to evaluate the activity of the selected drugs against Mycobacterium tuberculosis (Mtb), namely, growth of Mtb H37Rv and of two clinical isolates in axenic media, and infection of peripheral blood mononuclear cells with Mtb. Starting from over 3000 FDA-approved drugs, we selected 29 marketed drugs for submission to biological evaluation. Out of 29 drugs selected, 20 showed antimycobacterial activity. Further characterization suggested that five drugs possessed promising profiles for further studies. Following a repurposing strategy, by combining computational and biological efforts, we identified marketed drugs with relevant antimycobacterial profiles.

Synthesis, Spectroscopic, In-vitro and Computational Analysis of Hydrazones as Potential Antituberculosis Agents: (Part-I)

2020 ◽  
Vol 23 (5) ◽  
pp. 392-401 ◽  
Author(s):  
Bapu R. Thorat ◽  
Deepa Rani ◽  
Ramesh S. Yamgar ◽  
Suraj N. Mali
Keyword(s):  
Electronic Excitation ◽  
Condensation Reaction ◽  
Multidrug Resistant ◽  
Healthcare Sector ◽  
Spectroscopic Techniques ◽  
Resistant Tuberculosis ◽  
Extensively Drug Resistant ◽  
In Silico Admet ◽  
Mdr Tb

Background: Since the last few decades, the healthcare sector is facing the problem of the development of multidrug-resistant (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB) infections all over the world. Regardless of the current healthcare progress for the treatment of mycobacterial infections, we are still unable to control addition of every year 9 million new cases of tuberculosis (TB). Objective: We had an objective to synthesize some novel hydrazones, which were further subjected to characterization, Photoluminescence study, in vitro anti-mycobacterium testing and in silico ADMET predictions. Methods: Some new hydrazone derivatives have been successfully prepared by the condensation reaction in the present study. All the compounds were characterized by using FTIR, NMR, UV, Fluorescence spectroscopic techniques. Results: All our newly synthesized compounds showed strong electronic excitation at 292.6 – 319.0 nm and displayed more intense emissions in the 348 – 365 nm regions except compound 3i. The newly synthesized hydrazones 3a, 3b, 3f and 3g were found to be the most active compounds and showed MIC (Minimum inhibitory concentrations) values of 12.5 μg/mL. Conclusion: In the realm of development of more potent, effective, safer and less toxic antituberculosis agents; our current study would definitely help the medicinal chemists to develop potent analogues containing hydrazine motifs in them.

scholarly journals Fosfomycin

2016 ◽  
Vol 29 (2) ◽  
pp. 321-347 ◽  
Author(s):  
Matthew E. Falagas ◽  
Evridiki K. Vouloumanou ◽  
George Samonis ◽  
Konstantinos Z. Vardakas
Keyword(s):  
Bacterial Infections ◽  
Clinical Effectiveness ◽  
Multidrug Resistant ◽  
Resistant Bacteria ◽  
Drug Resistant ◽  
Antibiotic Resistant ◽  
Development Of Resistance ◽  
Extensively Drug Resistant ◽  
New Antibiotics

SUMMARYThe treatment of bacterial infections suffers from two major problems: spread of multidrug-resistant (MDR) or extensively drug-resistant (XDR) pathogens and lack of development of new antibiotics active against such MDR and XDR bacteria. As a result, physicians have turned to older antibiotics, such as polymyxins, tetracyclines, and aminoglycosides. Lately, due to development of resistance to these agents, fosfomycin has gained attention, as it has remained active against both Gram-positive and Gram-negative MDR and XDR bacteria. New data of higher quality have become available, and several issues were clarified further. In this review, we summarize the available fosfomycin data regarding pharmacokinetic and pharmacodynamic properties, thein vitroactivity against susceptible and antibiotic-resistant bacteria, mechanisms of resistance and development of resistance during treatment, synergy and antagonism with other antibiotics, clinical effectiveness, and adverse events. Issues that need to be studied further are also discussed.

scholarly journals Validation of Cycloserine Efficacy in Treatment of Multidrug-Resistant and Extensively Drug-Resistant Tuberculosis in Beijing, China

2018 ◽  
Vol 62 (3) ◽  
Author(s):  
Xia Yu ◽  
Xiling Zeng ◽  
Wenhui Shi ◽  
Yanjie Hu ◽  
Wenjuan Nie ◽  
...  
Keyword(s):  
Treatment Outcomes ◽  
Multidrug Resistant ◽  
Peak Serum ◽  
Drug Resistant ◽  
Serum Concentrations ◽  
Wild Type ◽  
Resistant Tuberculosis ◽  
Extensively Drug Resistant ◽  
Mdr Tb

ABSTRACTCycloserine (Cs) is recommended by the World Health Organization as a second-line drug to treat multidrug-resistant tuberculosis (MDR-TB); however, its efficacy has never been sufficiently evaluated. To gain some insights into the value of cycloserine for MDR-TB treatment,in vitrobacteriostatic effect was determined and patient validations were performed prospectively. Thein vitroactivity of Cs against 104 wild-typeMycobacterium tuberculosisstrains was determined, and serum Cs concentrations were measured for 73 MDR TB patients 2 h after administration. The treatment outcomes for 27 MDR-TB patients who had baseline isolates and were treated with Cs-containing regimens were followed up. The MICs for 90% of the recruited 104 wild-type strains were below 32 μg/ml. Eighteen out of 52 patients had peak serum concentrations (Cmax) below 20 μg/ml at the dosage of 500 mg daily, while 13 out of 21 patients had peak serum concentrations higher than 35 μg/ml at the dosage of 750 mg daily. The percentage of favorable treatment outcomes among patients with aCmax/MIC ratio of ≥1 was statistically significantly higher than that among the group with aCmax/MIC ratio of <1 (P= 0.022). The epidemiological cutoff value for Cs susceptibility testing was 32 μg/ml. A high percentage of patients receiving the recommended dosage of 10 mg/kg for Cs administration could not acquire desirable blood concentrations; therefore, adjusting the dosage according to drug concentration monitoring is necessary. TheCmax/MIC ratio might be a good indicator for predicting the treatment outcome for patients with MDR-TB or extensively drug-resistant TB (XDR-TB) who are being administered Cs-containing regimens.

scholarly journals Prevalence of extensively drug-resistant tuberculosis in a Chinese multidrug-resistant TB cohort after redefinition

2021 ◽  
Vol 10 (1) ◽  
Author(s):  
Cong Yao ◽  
Haiping Guo ◽  
Qiang Li ◽  
Xuxia Zhang ◽  
Yuanyuan Shang ◽  
...  
Keyword(s):  
Target Genes ◽  
Multidrug Resistant ◽  
23S Rrna ◽  
Great Promise ◽  
Genetic Mutations ◽  
Drug Resistant ◽  
Extensively Drug Resistant ◽  
Broth Microdilution Method ◽  
Mdr Tb

Abstract Objectives Recently, the definition of extensively drug-resistant TB (XDR-TB) has been revised. In this study, we conducted a descriptive and retrospective study to determine the prevalence of XDR-TB in a Chinese multidrug-resistant TB (MDR-TB) cohort. Methods Broth microdilution method was performed to determine in vitro susceptibilities of Mycobacterium tuberculosis (MTB) isolates to (FQs), bedaquiline (BDQ) and linezolid (LZD). The putative drug target genes conferring drug resistance were screened by DNA sequencing. Results A total of 425 MDR-TB isolates were included from 13 pilots in China. LZD and BDQ resistance were noted in 30 (7.1%) and 10 (2.4%) isolates. On the basis of latest definitions, 114 (26.8%) were MDR-TB, 282 (66.4%) were pre-XDR-TB, and 29 (6.8%) were XDR-TB. Among 311 FQ-resistant isolates, 265 harbored genetic mutations within QRDRs. The most common mutations were observed at codon 94 of gyrA, accounting for 47.2% of FQ-resistant MTB isolates. Only mutations within the Rv0678 gene were found to confer BDQ resistance in our cohort, conferring 40.0% of BDQ resistance. For LZD resistance, 53.3% of LZD-resistant isolates carried genetic mutations in rplC or 23S rRNA. The most frequent mutation was Cys154Arg in the rplC gene. In addition, we recorded two MDR-TB patients with resistance to both BDQ and LZD, of which one patient experienced continuous positive culture of MTB despite inclusion of efficacious moxifloxacin. Conclusion Our results demonstrate that the low prevalence of XDR-TB holds great promise for MDR-TB treatment with WHO-endorsed regimens containing BDQ-LZD combination, whereas the high prevalence of FQ-resistance in MDR-TB patients warrants national attention.

Sign in / Sign up

Export Citation Format

Share Document