scholarly journals Comparison of the In Vitro Activity of the Glycylcycline Tigecycline (Formerly GAR-936) with Those of Tetracycline, Minocycline, and Doxycycline against Isolates of Nontuberculous Mycobacteria

2002 ◽  
Vol 46 (10) ◽  
pp. 3164-3167 ◽  
Author(s):  
Richard J. Wallace ◽  
Barbara A. Brown-Elliott ◽  
Christopher J. Crist ◽  
Linda Mann ◽  
Rebecca W. Wilson
Keyword(s):  
Therapeutic Potential ◽  
Nontuberculous Mycobacteria ◽  
Mycobacterium Abscessus ◽  
Vitro Activity ◽  
In Vitro Activity ◽  
Broth Microdilution ◽  
Rapidly Growing Mycobacteria

ABSTRACT We compared the in vitro activity of the glycylcycline tigecycline (formerly GAR-936) with those of tetracycline, doxycycline, and minocycline by broth microdilution against 76 isolates belonging to seven species of rapidly growing mycobacteria (RGM) and 45 isolates belonging to five species of slowly growing nontuberculous mycobacteria (NTM). By using a resistance breakpoint of >4 μg/ml for tigecycline and >8 μg/ml for tetracycline, all RGM were highly susceptible to tigecycline, with inhibition of 50% of isolates at ≤0.12 μg/ml and inhibition of 90% of isolates at 0.25 μg/ml for Mycobacterium abscessus and inhibition of both 50 and 90% of isolates at ≤0.12 μg/ml for M. chelonae and the M. fortuitum group. The MICs of tigecycline were the same for tetracycline-resistant and -susceptible strains, and RGM isolates were 4- to 11-fold more susceptible to tigecycline than to the tetracyclines. In contrast, no slowly growing NTM were susceptible to tigecycline, and isolates of M. marinum and M. kansasii were less susceptible to this agent than to minocycline. This new antimicrobial offers exciting therapeutic potential for the RGM, especially for isolates of the M. chelonae-M. abscessus group, against which the activities of the currently available drugs are limited.

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.

scholarly journals In Vitro Activity of Linezolid against Slowly Growing Nontuberculous Mycobacteria

2003 ◽  
Vol 47 (5) ◽  
pp. 1736-1738 ◽  
Author(s):  
Barbara A. Brown-Elliott ◽  
Christopher J. Crist ◽  
Linda B. Mann ◽  
Rebecca W. Wilson ◽  
Richard J. Wallace
Keyword(s):  
Therapeutic Potential ◽  
Nontuberculous Mycobacteria ◽  
Mycobacterium Marinum ◽  
Vitro Activity ◽  
In Vitro Activity ◽  
Mycobacterium Kansasii ◽  
Mycobacterium Xenopi ◽  
Mycobacterium Malmoense

ABSTRACT MICs of linezolid in broth microdilutions were tested against 341 slowly growing nontuberculous mycobacteria (NTM) belonging to 15 species. The proposed linezolid susceptibility MICs for all Mycobacterium marinum, Mycobacterium szulgai, Mycobacterium kansasii, Mycobacterium malmoense, and Mycobacterium xenopi isolates and for 90% of Mycobacterium gordonae and Mycobacterium triplex isolates were ≤8 μg/ml. Linezolid has excellent therapeutic potential against most species of NTM.

scholarly journals In Vitro Activity of Ibrexafungerp, a Novel Glucan Synthase Inhibitor against Candida glabrata Isolates with FKS Mutations

2019 ◽  
Vol 63 (11) ◽  
Author(s):  
Natalie S. Nunnally ◽  
Kizee A. Etienne ◽  
David Angulo ◽  
Shawn R. Lockhart ◽  
Elizabeth L. Berkow
Keyword(s):  
Candida Glabrata ◽  
Vitro Activity ◽  
Good Activity ◽  
In Vitro Activity ◽  
Broth Microdilution ◽  
Glucan Synthase ◽  
Content Type ◽  
Synthase Inhibitor

ABSTRACT Ibrexafungerp is a first-in-class glucan synthase inhibitor. In vitro activity was determined for 89 Candida glabrata isolates with molecularly identified FKS1 or FKS2 mutations conferring resistance to the echinocandins. All isolates were resistant to at least one echinocandin (i.e., anidulafungin, caspofungin, or micafungin) by broth microdilution. Results for ibrexafungerp were compared with those for each echinocandin. Ibrexafungerp had good activity against all echinocandin-resistant C. glabrata isolates.

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 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.

In vitro susceptibility of Mycobacterium abscessus complex and feasibility of standardizing treatment regimens

2020 ◽  
Author(s):  
Ka Lip Chew ◽  
Sophie Octavia ◽  
Joelle Go ◽  
Sally Ng ◽  
Yit Er Tang ◽  
...  
Keyword(s):  
Retrospective Review ◽  
Susceptibility Testing ◽  
Mycobacterium Abscessus ◽  
In Vitro Activity ◽  
Broth Microdilution ◽  
In Vitro Susceptibility ◽  
Treatment Regimens ◽  
Mycobacterium Abscessus Complex ◽  
Additional Testing

Abstract Objectives To determine the in vitro susceptibility of members of the Mycobacterium abscessus complex to routinely tested antibiotics and to an extended antibiotic panel. Methods Non-duplicate isolates for which susceptibility testing results were available were included in this study. Retrospective laboratory records were reviewed, including tigecycline susceptibility results, and testing was performed with additional drugs, including vancomycin, dalbavancin, telavancin, oritavancin, rifabutin, delafloxacin, eravacycline, clofazimine and bedaquiline using broth microdilution (Sensititre, Thermo Fisher). Results A total of 218 M. abscessus complex isolates were included for retrospective review, of which 151 were respiratory isolates. Of these 218 isolates, 211 were available for additional testing with the extended antibiotic panel. Of these, 146 were respiratory isolates. One isolate had a vancomycin MIC of 2 mg/L and MICs of all other isolates were >8 mg/L. All isolates had MICs of >8 mg/L for oritavancin, dalbavancin and telavancin. One isolate had a delafloxacin MIC of 4 mg/L and MICs of all other isolates were >8 mg/L. The MIC50/MIC90s of rifabutin, tigecycline, eravacycline, clofazimine and bedaquiline were 16/32, 0.5/1, 0.12/0.25, 0.12/0.25 and 0.06/0.12 mg/L, respectively. Conclusions In vitro activity was demonstrated for clofazimine, bedaquiline and eravacycline, indicating potential for inclusion as standardized therapy for M. abscessus complex infections.

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.

scholarly journals In vitro activity of a new echinocandin, LY303366, compared with those of amphotericin B and fluconazole against clinical yeast isolates.

1997 ◽  
Vol 41 (5) ◽  
pp. 1156-1157 ◽  
Author(s):  
O Uzun ◽  
S Kocagöz ◽  
Y Cetinkaya ◽  
S Arikan ◽  
S Unal
Keyword(s):  
Candida Albicans ◽  
Amphotericin B ◽  
Vitro Activity ◽  
In Vitro Activity ◽  
Broth Microdilution ◽  
Microdilution Method ◽  
Broth Microdilution Method

The in vitro activity of LY303366, a new echinocandin derivative, was evaluated with 191 yeast isolates by a broth microdilution method. The MICs at which 50% of the isolates were inhibited were 0.125 microg/ml for Candida albicans and C. tropicalis, 0.25 microg/ml for C. krusei, C. kefyr, and C. glabrata, and 2.0 microg/ml for C. parapsilosis.

scholarly journals In Vitro Activity of Terbinafine Combined with Caspofungin and Azoles against Pythium insidiosum

2009 ◽  
Vol 53 (5) ◽  
pp. 2136-2138 ◽  
Author(s):  
Ayrton S. Cavalheiro ◽  
Grazieli Maboni ◽  
Maria I. de Azevedo ◽  
Juliana S. Argenta ◽  
Daniela I. B. Pereira ◽  
...  
Keyword(s):  
Therapeutic Potential ◽  
Vitro Activity ◽  
In Vitro Activity ◽  
Pythium Insidiosum ◽  
Antagonistic Effects ◽  
Antifungal Activities ◽  
Synergistic Interactions

ABSTRACT In this text we evaluated the in vitro antifungal activities of terbinafine combined with caspofungin, miconazole, ketoconazole, and fluconazole against 17 Pythium insidiosum strains by using the microdilution checkerboard method. Synergistic interactions were observed with terbinafine combined with caspofungin (41.2% of the strains), fluconazole (41.2%), ketoconazole (29.4%), and miconazole (11.8%). No antagonistic effects were observed. The combination of terbinafine plus caspofungin or terbinafine plus fluconazole may have significant therapeutic potential for treatment of pythiosis.

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