scholarly journals Novel Administration of Clofazimine for the Treatment of Mycobacterium avium Infection

2020 ◽  
Vol 7 (6) ◽  
Author(s):  
Ethan Valinetz ◽  
Helen Stankiewicz Karita ◽  
Paul S Pottinger ◽  
Rupali Jain
Keyword(s):  
Cystic Fibrosis ◽  
Lung Transplantation ◽  
Mycobacterium Avium ◽  
Nontuberculous Mycobacteria ◽  
Vitro Activity ◽  
The Novel ◽  
In Vitro Activity ◽  
Avium Infection ◽  
Mycobacterium Avium Infection

Abstract Clofazimine has demonstrated in vitro activity against many nontuberculous mycobacteria. We present the case of a woman with cystic fibrosis who developed disseminated macrolide-resistant Mycobacterium avium infection following lung transplantation treated in part with clofazimine. We describe the novel administration of clofazimine via gastrostomy tube.

scholarly journals In Vitro Activity of Rifamycin Derivatives against Nontuberculous Mycobacteria, Including Macrolide- and Amikacin-Resistant Clinical Isolates

2021 ◽  
Vol 65 (5) ◽  
Author(s):  
Dae Hun Kim ◽  
Su-Young Kim ◽  
Hee Jae Huh ◽  
Nam Yong Lee ◽  
Won-Jung Koh ◽  
...  
Keyword(s):  
Mycobacterium Avium ◽  
Nontuberculous Mycobacteria ◽  
Therapeutic Option ◽  
Vitro Activity ◽  
Clinical Isolates ◽  
Drug Resistant ◽  
In Vitro Activity ◽  
Content Type ◽  
Resistant Disease

ABSTRACT We evaluated the in vitro activity of rifamycin derivatives, including rifampin, rifapentine, rifaximin, and rifabutin, against clinical nontuberculous mycobacteria (NTM) isolates. Of the rifamycin derivatives, rifabutin showed the lowest MICs against all NTM species, including Mycobacterium avium complex, M. abscessus, and M. kansasii. Rifabutin also had effective in vitro activity against macrolide- and aminoglycoside-resistant NTM isolates. Rifabutin could be worth considering as a therapeutic option for NTM disease, particularly drug-resistant disease.

scholarly journals In Vitro Activity of Bedaquiline and Delamanid against Nontuberculous Mycobacteria, Including Macrolide-Resistant Clinical Isolates

2019 ◽  
Vol 63 (8) ◽  
Author(s):  
Dae Hun Kim ◽  
Byung Woo Jhun ◽  
Seong Mi Moon ◽  
Su-Young Kim ◽  
Kyeongman Jeon ◽  
...  
Keyword(s):  
Mycobacterium Avium ◽  
Nontuberculous Mycobacteria ◽  
Mycobacterium Abscessus ◽  
Vitro Activity ◽  
Clinical Isolates ◽  
In Vitro Activity ◽  
Mycobacterium Kansasii ◽  
Antimicrobial Drugs ◽  
Content Type

ABSTRACT We evaluated the in vitro activities of the antimicrobial drugs bedaquiline and delamanid against the major pathogenic nontuberculous mycobacteria (NTM). Delamanid showed high MIC values for all NTM except Mycobacterium kansasii. However, bedaquiline showed low MIC values for the major pathogenic NTM, including Mycobacterium avium complex, Mycobacterium abscessus subsp. abscessus, M. abscessus subsp. massiliense, and M. kansasii. Bedaquiline also had low MIC values with macrolide-resistant NTM strains and warrants further investigation as a potential antibiotic for NTM treatment.

Murepavadin antimicrobial activity against and resistance development in cystic fibrosis Pseudomonas aeruginosa isolates

2020 ◽  
Author(s):  
María Díez-Aguilar ◽  
Marta Hernández-García ◽  
María-Isabel Morosini ◽  
Ad Fluit ◽  
Michael M Tunney ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Pseudomonas Aeruginosa ◽  
Antimicrobial Activity ◽  
Spontaneous Mutation ◽  
Lung Surfactant ◽  
Vitro Activity ◽  
In Vitro Activity ◽  
Broth Microdilution ◽  
Agar Dilution

Abstract Background Murepavadin, a novel peptidomimetic antibiotic, is being developed as an inhalation therapy for treatment of Pseudomonas aeruginosa respiratory infection in people with cystic fibrosis (CF). It blocks the activity of the LptD protein in P. aeruginosa causing outer membrane alterations. Objectives To determine the in vitro activity of murepavadin against CF P. aeruginosa isolates and to investigate potential mechanisms of resistance. Methods MIC values were determined by both broth microdilution and agar dilution and results compared. The effect of artificial sputum and lung surfactant on in vitro activity was also measured. Spontaneous mutation frequency was estimated. Bactericidal activity was investigated using time–kill assays. Resistant mutants were studied by WGS. Results The murepavadin MIC50 was 0.125 versus 4 mg/L and the MIC90 was 2 versus 32 mg/L by broth microdilution and agar dilution, respectively. Essential agreement was >90% when determining in vitro activity with artificial sputum or lung surfactant. It was bactericidal at a concentration of 32 mg/L against 95.4% of the strains within 1–5 h. Murepavadin MICs were 2–9 two-fold dilutions higher for the mutant derivatives (0.5 to >16 mg/L) than for the parental strains. Second-step mutants were obtained for the PAO mutS reference strain with an 8×MIC increase. WGS showed mutations in genes involved in LPS biosynthesis (lpxL1, lpxL2, bamA2, lptD, lpxT and msbA). Conclusions Murepavadin characteristics, such as its specific activity against P. aeruginosa, its unique mechanism of action and its strong antimicrobial activity, encourage the further clinical evaluation of this drug.

scholarly journals In vitro activity of the novel echinocandin CD101 at pH 7 and 4 against Candida spp. isolates from patients with vulvovaginal candidiasis

2017 ◽  
Vol 72 (5) ◽  
pp. 1355-1358 ◽  
Author(s):  
Dina A. Boikov ◽  
Jeffrey B. Locke ◽  
Kenneth D. James ◽  
Ken Bartizal ◽  
Jack D. Sobel
Keyword(s):  
Vulvovaginal Candidiasis ◽  
Vitro Activity ◽  
The Novel ◽  
In Vitro Activity ◽  
Candida Spp

In vitro activity of the novel antibacterial agent ibezapolstat (ACX-362E) against Clostridioides difficile

2020 ◽  
Author(s):  
Beverly Murray ◽  
Cindy Wolfe ◽  
Andrea Marra ◽  
Chris Pillar ◽  
Dean Shinabarger
Keyword(s):  
Therapeutic Potential ◽  
Oral Treatment ◽  
Clinical Development ◽  
Vitro Activity ◽  
The Novel ◽  
In Vitro Activity ◽  
Clostridioides Difficile ◽  
Clostridioides Difficile Infection ◽  
Time Kill

Abstract Background Ibezapolstat (ACX-362E) is the first DNA polymerase IIIC inhibitor undergoing clinical development for the oral treatment of Clostridioides difficile infection (CDI). Methods In this study, the in vitro activity of ibezapolstat was evaluated against a panel of 104 isolates of C. difficile, including those with characterized ribotypes (e.g. 027 and 078) and those producing toxin A or B and was shown to have similar activity to those of comparators against these strains. Results The overall MIC50/90 (mg/L) for ibezapolstat against evaluated C. difficile was 2/4, compared with 0.5/4 for metronidazole, 1/4 for vancomycin and 0.5/2 for fidaxomicin. In addition, the bactericidal activity of ibezapolstat was evaluated against actively growing C. difficile by determining the MBC against three C. difficile isolates. Time–kill kinetic assays were additionally performed against the three C. difficile isolates, with metronidazole and vancomycin as comparators. Conclusions The killing of C. difficile by ibezapolstat was observed to occur at concentrations similar to its MIC, as demonstrated by MBC:MIC ratios and reflected in time–kill kinetic assays. This activity highlights the therapeutic potential of ibezapolstat for the treatment of CDI.

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