scholarly journals In Vitro Activity of Micafungin (FK-463) against Candida spp.: Microdilution, Time-Kill, and Postantifungal-Effect Studies

2002 ◽  
Vol 46 (12) ◽  
pp. 3846-3853 ◽  
Author(s):  
Erika J. Ernst ◽  
Ellen E. Roling ◽  
C. Rosemarie Petzold ◽  
Douglas J. Keele ◽  
Michael E. Klepser

ABSTRACT We evaluated the in vitro activity of the new echinocandin antifungal micafungin against Candida spp. using microdilution and time-kill methods. Additionally, we examined the postantifungal effect (PAFE) of micafungin. Finally, we evaluated the effect of the addition of serum and plasma on the MIC of micafungin. Four Candida albicans isolates and two isolates of each Candida glabrata, Candida krusei, and Candida tropicalis were selected for testing. The MICs of micafungin were determined in RPMI 1640 medium buffered with morpholinepropanesulfonic acid alone and with the addition of 10, 20, and 50% human serum and plasma. MICs were determined by using two endpoints: a prominent reduction in growth (the MIC at which 80% of isolates are inhibited [MIC80]) and complete visual inhibition of growth (MIC100). The minimum fungicidal concentration (MFC) of micafungin for each isolate was also determined. Time-kill curves were determined for each isolate in RPMI 1640 medium with micafungin at concentrations ranging from 0.125 to 16 times the MIC80 to assess the correlation between MIC80 and fungicidal activity. PAFE studies were conducted with each isolate by using concentrations ranging between 0.25 and 4 times the MIC80. The MIC80s for the test isolates ranged from 0.0039 to 0.25 μg/ml. Overall, the addition of serum or plasma increased the MIC 6 to 7 doubling dilutions for C. albicans and 3 to 4 doubling dilutions for C. krusei and C. tropicalis. Micafungin time-kill studies demonstrated fungicidal activity at concentrations ranging from 4 to 16 times the MIC80. Micafungin is very potent agent against a variety of Candida spp., producing fungicidal activity against 7 of 10 isolates tested. A PAFE was observed against all isolates. The PAFE was influenced by the drug concentration, with the highest concentration resulting in the longest observed PAFE in each case. The highest concentration tested, four times the MIC, resulted in a PAFE of more than 9.8 h for 5 of 10 isolates tested (range, 0.9 to ≥20.1 h).

1998 ◽  
Vol 42 (11) ◽  
pp. 3012-3013 ◽  
Author(s):  
C. Rimaroli ◽  
T. Bruzzese

ABSTRACT The in vitro activity of a new water-soluble polyene, SPA-S-843, was evaluated against 116 strains of Candida,Cryptococcus, and Saccharomyces spp. and compared with that of amphotericin B. SPA-S-843 demonstrated better inhibitory activity against all of the yeasts examined and better fungicidal activity against Candida albicans, Candida glabrata, Candida krusei, and Candida tropicalis than did amphotericin B.


2009 ◽  
Vol 53 (7) ◽  
pp. 3108-3111 ◽  
Author(s):  
Emilia Cantón ◽  
Javier Pemán ◽  
Amparo Valentín ◽  
Ana Espinel-Ingroff ◽  
Miguel Gobernado

ABSTRACT We evaluated the in vitro activities of anidulafungin, micafungin, and caspofungin against Candida krusei by determining MIC and minimum fungicidal concentration (MFC) measurements and by the time-kill method. The geometric mean (GM)-MIC/GM-MFC values were 0.1/0.34, 0.25/0.44, and 1/2.29, respectively. The mean times to reach 99.9% growth reduction were 19.1 ± 18.2 h (mean ± standard deviation) for 2 mg/liter anidulafungin, 37.4 ± 8.8 h for 2 mg/liter caspofungin, and 30.7 ± 12.2 h for 1 mg/liter micafungin. Anidulafungin exhibited the highest time-kill rate, followed by micafungin. The three echinocandins showed fungicidal activity at concentrations reached in serum.


2008 ◽  
Vol 52 (4) ◽  
pp. 1529-1532 ◽  
Author(s):  
Carolina Serena ◽  
Marçal Mariné ◽  
Guillermo Quindós ◽  
Alfonso J. Carrillo ◽  
J. F. Cano ◽  
...  

ABSTRACT The in vitro activity of amphotericin B in combination with micafungin was evaluated against 115 isolates representing seven species of Candida. Overall, the percentages of synergistic interactions were 50% and 20% when the MIC-2 (lowest drug concentration to cause a prominent reduction in growth) and MIC-0 (lowest drug concentration to cause 100% growth inhibition) end point criteria, respectively, were used. Antagonism was not observed. Some of the interactions were confirmed by time-kill assays.


1999 ◽  
Vol 44 (5) ◽  
pp. 697-700 ◽  
Author(s):  
M. Chávez ◽  
S. Bernal ◽  
A. Valverde ◽  
M. J. Gutierrez ◽  
G. Quindós ◽  
...  

2017 ◽  
Vol 72 (5) ◽  
pp. 1355-1358 ◽  
Author(s):  
Dina A. Boikov ◽  
Jeffrey B. Locke ◽  
Kenneth D. James ◽  
Ken Bartizal ◽  
Jack D. Sobel

2017 ◽  
Vol 50 (1) ◽  
pp. 47-54
Author(s):  
George Tetz ◽  
Michael Cynamon ◽  
Gregory Hendricks ◽  
Daria Vikina ◽  
Victor Tetz

Author(s):  
Beverly Murray ◽  
Cindy Wolfe ◽  
Andrea Marra ◽  
Chris Pillar ◽  
Dean Shinabarger

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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