Faculty Opinions recommendation of Synergistic interactions of SQ109, a new ethylene diamine, with front-line antitubercular drugs in vitro.

Author(s):  
Susan Swindells
Author(s):  
Juan Ramón Zapata-Morales ◽  
Angel Josabad Alonso-Castro ◽  
Gloria Sarahí Muñoz-Martínez ◽  
María Mayela Martínez-Rodríguez ◽  
Mónica Esther Nambo-Arcos ◽  
...  

Nanoscale ◽  
2021 ◽  
Author(s):  
Sanjay Pal ◽  
Vijay Soni ◽  
Sandeep Kumar ◽  
Somesh K Jha ◽  
Nihal Medatwal ◽  
...  

We present a non-immunogenic, injectable, low molecular weight, amphiphilic hydrogel-based drug delivery system (TB-Gel) that can entrap a cocktail of four front-line antitubercular drugs isoniazid, rifampicin, pyrazinamide, and ethambutol. We...


2004 ◽  
Vol 48 (9) ◽  
pp. 3317-3322 ◽  
Author(s):  
Francesco Barchiesi ◽  
Elisabetta Spreghini ◽  
Monia Maracci ◽  
Annette W. Fothergill ◽  
Isabella Baldassarri ◽  
...  

ABSTRACT Candida glabrata has recently emerged as a significant pathogen involved in both superficial and deep-seated infections. In the present study, a checkerboard broth microdilution method was performed to investigate the in vitro activities of voriconazole (VOR) in combination with terbinafine (TRB), amphotericin B (AMB), and flucytosine (5FC) against 20 clinical isolates of C. glabrata. Synergy, defined as a fractional inhibitory concentration (FIC) index of ≤0.50, was observed in 75% of VOR-TRB, 10% of VOR-AMB, and 5% of VOR-5FC interactions. None of these combinations yielded antagonistic interactions (FIC index > 4). When synergy was not achieved, there was still a decrease in the MIC of one or both drugs used in the combination. In particular, the MICs were reduced to ≤1.0 μg/ml as a result of the combination for all isolates for which the AMB MIC at the baseline was ≥2.0 μg/ml. By a disk diffusion assay, the halo diameters produced by antifungal agents in combination were greater that those produced by each drug alone. Finally, killing curves showed that VOR-AMB exhibited synergistic interactions, while VOR-5FC sustained fungicidal activities against C. glabrata. These studies demonstrate that the in vitro activity of VOR against this important yeast pathogen can be enhanced upon combination with other drugs that have different modes of action or that target a different step in the ergosterol pathway. Further studies are warranted to elucidate the potential beneficial effects of such combination regimens in vivo.


2018 ◽  
Vol 33 (7) ◽  
pp. 989-996 ◽  
Author(s):  
Gangquan Chen ◽  
Yaling Wu ◽  
Dongping Yu ◽  
Rubing Li ◽  
Wenyuan Luo ◽  
...  

Poor blood circulation makes it difficult for antitubercular drugs to achieve effective bactericidal concentration at tuberculose focus. The residual Mycobacterium tuberculosis around surgical wound would multiply, resulting in nonunion or sinus formation. Carbon nanotubes have strong tissue penetration and can cross many kinds of physiological barriers. Here, we constructed a chitosan/carbon nanotubes nanoparticles to control slow release of isoniazid. Transmission electron microscopy and nanoparticle tracking and analysis results showed that the diameter of chitosan/carbon nanotubes nanoparticles was between 150 and 250 nm. Chitosan/carbon nanotubes nanoparticles significantly prolonged the release time of isoniazid, and the release rate was more uniform, no sudden release was observed. In vitro experiments showed that chitosan/carbon nanotubes nanoparticles did not destroy biological function of isoniazid, but could reduce its cytotoxicity and inflammation. We further constructed animal model of tuberculous ulcer. The results showed that isoniazid/chitosan/carbon nanotubes nanoparticles promoted the healing of tuberculosis ulcer. Compared with isoniazid group and isoniazid/carbon nanotubes group, the area of wounds decreased by 94.6% and 89.8%, respectively. Immunohistochemistry showed that CD3+ and CD4+ T cell number decreased significantly in isoniazid/chitosan/carbon nanotubes group. In conclusion, we constructed a kind of isoniazid/chitosan/carbon nanotubes nanoparticles, which can significantly promote the healing of tuberculosis ulcer. Our study provided an effective way for the treatment of secondary wound healing of bone tuberculosis.


2010 ◽  
Vol 59 (5) ◽  
pp. 567-572 ◽  
Author(s):  
Fa Ge ◽  
Fanli Zeng ◽  
Siguo Liu ◽  
Na Guo ◽  
Haiqing Ye ◽  
...  

Reports have shown that oleanolic acid (OA), a triterpenoid, exists widely in food, medicinal herbs and other plants, and that it has antimycobacterial activity against the Mycobacterium tuberculosis strain H37Rv (ATCC 27294). In this study it was found that OA had antimycobacterial properties against eight clinical isolates of M. tuberculosis and that the MICs of OA against drug-sensitive and drug-resistant isolates were 50–100 and 100–200 μg ml−1, respectively. The combination of OA with isoniazid (INH), rifampicin (RMP) or ethambutol (EMB) showed favourable synergistic antimycobacterial effects against six drug-resistant strains, with fractional inhibitory concentration indices of 0.121–0.347, 0.113–0.168 and 0.093–0.266, respectively. The combination treatments of OA/INH, OA/RMP and OA/EMB displayed either a synergistic interaction or did not show any interaction against two drug-sensitive strains. No antagonism resulting from the OA/INH, OA/RMP or OA/EMB combination was observed for any of the strains tested. OA exhibited a relatively low cytotoxicity in Vero cells. These results indicate that OA may serve as a promising lead compound for future antimycobacterial drug development.


Oncotarget ◽  
2017 ◽  
Vol 8 (19) ◽  
pp. 31478-31493 ◽  
Author(s):  
Tri Nguyen ◽  
Rebecca Parker ◽  
Elisa Hawkins ◽  
Beata Holkova ◽  
Victor Yazbeck ◽  
...  

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Yaojie Shen ◽  
Xuyang Wang ◽  
Jialin Jin ◽  
Jing Wu ◽  
Xuelian Zhang ◽  
...  

Objective. Nontuberculous mycobacteria (NTM) cause various diseases in humans and animals. Recently, the prevalence of NTM-related disease has been on the rise, becoming an emerging public health problem. The aim of this study was to determine the antibiotic susceptibility profiles of clinical isolates of Mycobacterium abscessus and Mycobacterium fortuitum. Methods. We performed susceptibility tests on 37 clinical NTM isolates to 30 antibiotics with the microdilution method recommended by the Clinical and Laboratory Standards Institute. Results. Both M. abscessus and M. fortuitum were highly resistant to antitubercular drugs such as isoniazid, rifampin, ethambutol, clofazimine, ethionamide, and rifabutin. M. abscessus showed the lowest resistant rates to cefoxitin (10%), azithromycin (10%), amikacin (10%), and clarithromycin (20%) and very high resistant to sulfamethoxazole, vancomycin, oxacillin, clindamycin, and all fluoroquinolones. M. fortuitum showed low resistance to tigecycline (0%), tetracycline (0%), cefmetazole (12%), imipenem (12%), linezolid (18%), and the aminoglycosides amikacin (0%), tobramycin (0%), neomycin (0%), and gentamycin (24%). Conclusion. Amikacin, cefoxitin, and azithromycin have the highest in vitro activity against M. abscessus. Isolates of M. fortuitum need to be individually evaluated for drug susceptibility before choosing an effective antimicrobial regimen for treatment of infections.


2008 ◽  
Vol 23 (2) ◽  
pp. 97-107 ◽  
Author(s):  
◽  
Binith Cheeran ◽  
Leonardo Cohen ◽  
Bruce Dobkin ◽  
Gary Ford ◽  
...  

Background. Major advances during the past 50 years highlight the immense potential for restoration of function after neural injury, even in the damaged adult human brain. Yet, the translation of these advances into clinically useful treatments is painstakingly slow. Objective. Here, we consider why the traditional model of a “translational research pipeline” that transforms basic science into novel clinical practice has failed to improve rehabilitation practice for people after stroke. Results. We find that (1) most treatments trialed in vitro and in animal models have not yet resulted in obviously useful functional gains in patients; (2) most clinical trials of restorative treatments after stroke have been limited to small-scale studies; (3) patient recruitment for larger clinical trials is difficult; (4) the determinants of patient outcomes and what patients want remain complex and ill-defined, so that basic scientists have no clear view of the clinical importance of the problems that they are addressing; (5) research in academic neuroscience centers is poorly integrated with practice in front-line hospitals and the community, where the majority of patients are treated; and (6) partnership with both industry stakeholders and patient pressure groups is poorly developed, at least in the United Kingdom where research in the translational restorative neurosciences in stroke depends on public sector research funds and private charities. Conclusions. We argue that interaction between patients, front-line clinicians, and clinical and basic scientists is essential so that they can explore their different priorities, skills, and concerns. These interactions can be facilitated by funding research consortia that include basic and clinical scientists, clinicians and patient/carer representatives with funds targeted at those impairments that are major determinants of patient and carer outcomes. Consortia would be instrumental in developing a lexicon of common methods, standardized outcome measures, data sharing and long-term goals. Interactions of this sort would create a research-friendly, rather than only target-led, culture in front-line stroke rehabilitation services.


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