scholarly journals In Vitro and Intracellular Activity of Imipenem Combined with Tedizolid, Rifabutin, and Avibactam against Mycobacterium abscessus

2019 ◽  
Vol 63 (4) ◽  
Author(s):  
Eva Le Run ◽  
Michel Arthur ◽  
Jean-Luc Mainardi

ABSTRACT Mycobacterium abscessus infections are difficult to treat because of their resistance to many antibiotics. In vitro, tedizolid combined with imipenem displayed a moderate synergistic effect (fractional inhibitory concentration index, 0.41) but no bactericidal activity. Intracellularly, tedizolid 2 μg/ml (half of the MIC), corresponding to the peak serum concentration, increased the efficacy of imipenem at 8 and 32 μg/ml. Addition of avibactam and rifabutin, alone or in combination, improved the activity of the imipenem-tedizolid combination.

2017 ◽  
Vol 61 (12) ◽  
Author(s):  
Devika Mukherjee ◽  
Mu-Lu Wu ◽  
Jeanette W. P. Teo ◽  
Thomas Dick

ABSTRACT Lung disease caused by Mycobacterium abscessus is increasing, and current clarithromycin-based treatment regimens are only moderately effective. Here, we determined the effect of clarithromycin-vancomycin combination against M. abscessus complex isolates in vitro. Synergy was found with a fractional inhibitory concentration index (FICI) score of ≤0.5 and a 4- to 10-fold decrease in MIC.


OBJECTIVES: To compare the combined antimicrobial effect of Thuja orientalis and Ciprofloxacin against Pseudomonas aeruginosa in vitro samples. METHODS: In-vitro antibacterial activity of plant-extracts was evaluated alone and in combination with ciprofloxacin against Pseudomonas aeruginosa using disc-diffusion susceptibility assay (Kirby Bauer method) and minimum inhibitory concentration (96 well broth microdilution method) following CLSI guidelines. Pseudomonas aeruginosa clinical strains were collected from Rehman Medical Institute (RMI) and Northwest General Hospital Peshawar, Pakistan and ATCC strains (no.9721) of this bacterium were collected from Agriculture University Peshawar. The organism was tested six times with crude extract and fractionation with different solvents such as n-hexane, chloroform, ethyl acetate and butanol at concentrations of 1, 4, 8, 12, 16, 20, 24, 30 and 36 mg/ml. The mean MIC and FICI (fractional inhibitory concentration index) was obtained to report the synergism. The data were analysed using SPSS version-21. RESULTS: In combination, methanolic crude extract, chloroform and butanol fraction showed synergistic effect at all tested concentrations against Pseudomonas aeruginosa (ATCC 9721 and clinical) except with 1, 4, 16 mg/ml concentrations. Ethyl acetate and aqueous fractions shows indifference and synergistic effect against Pseudomonas aeruginosa (ATCC 9721 and clinical) at different concentrations. The fractional inhibitory concentration index (FICI) ranged from 1.24 to 3.24 against Pseudomonas aeruginosa alone and in combination with ciprofloxacin. CONCLUSION: By disc diffusion method, this study shows synergistic effect against Pseudomonas aeruginosa in combination with ciprofloxacin. However, through minimum inhibitory concentration method, it shows antagonism and indifference but no synergistic effect against different fractions of plant.


2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Patrick Schwarz ◽  
Anne-Laure Bidaud ◽  
Eric Dannaoui

AbstractThe in vitro interactions of isavuconazole with colistin were evaluated against 15 clinical Candida auris isolates by a microdilution checkerboard technique based on the EUCAST reference method for antifungal susceptibility testing and by agar diffusion using isavuconazole gradient concentration strips with or without colistin incorporated RPMI agar. Interpretation of the checkerboard results was done by the fractional inhibitory concentration index and by response surface analysis based on the Bliss model. By checkerboard, combination was synergistic for 93% of the isolates when interpretation of the data was done by fractional inhibitory concentration index, and for 80% of the isolates by response surface analysis interpretation. By agar diffusion test, although all MICs in combination decreased compared to isavuconazole alone, only 13% of the isolates met the definition of synergy. Essential agreement of EUCAST and gradient concentration strip MICs at +/− 2 log2 dilutions was 93.3%. Antagonistic interactions were never observed for any technique or interpretation model used.


2005 ◽  
Vol 49 (8) ◽  
pp. 3544-3545 ◽  
Author(s):  
E. R. Oliveira ◽  
A. W. Fothergill ◽  
W. R. Kirkpatrick ◽  
B. J. Coco ◽  
T. F. Patterson ◽  
...  

ABSTRACT Combinations of caspofungin and posaconazole were evaluated by fractional inhibitory concentration index against 119 Candida glabrata isolates. Synergy was seen in 18% of all isolates and in 4% of fluconazole-resistant isolates at 48 h without evidence of antagonism. This antifungal combination may have utility against this organism.


2017 ◽  
Vol 61 (11) ◽  
Author(s):  
Hamed Fakhim ◽  
Anuradha Chowdhary ◽  
Anupam Prakash ◽  
Afsane Vaezi ◽  
Eric Dannaoui ◽  
...  

ABSTRACT We determined the in vitro interactions between echinocandins and azoles against 10 multidrug-resistant Candida auris strains by use of a microdilution checkerboard technique. Our results suggest synergistic interactions between micafungin and voriconazole with fractional inhibitory concentration index (FICI) values of 0.15 to 0.5, and we observed indifferent interactions when micafungin was combined with fluconazole (FICI, 0.62 to 1.5). Combinations of caspofungin with fluconazole or voriconazole exhibited indifferent interactions. No antagonism was observed for any combination.


2000 ◽  
Vol 44 (8) ◽  
pp. 2179-2181 ◽  
Author(s):  
Philippe Cottagnoud ◽  
Fernando Acosta ◽  
Marianne Cottagnoud ◽  
Klaus Neftel ◽  
Martin G. Täuber

ABSTRACT The bactericidal activities of monotherapy with trovafloxacin (−0.37 ± 0.15 Δlog10 CFU/ml · h), vancomycin (−0.32 ± 0.12 Δlog10 CFU/ml · h), and ceftriaxone (−0.36 ± 0.19 Δlog10CFU/ml · h) for the treatment of experimental meningitis in rabbits due to a clinical penicillin-resistant pneumococcal strain (MIC, 4 mg/liter) were similar. The combination of ceftriaxone with trovafloxacin considerably improved the killing rates (−0.67 ± 0.16 Δlog10 CFU/ml · h) and was slightly superior to ceftriaxone with vancomycin (killing rate, −0.53 ± 0.22 Δlog10 CFU/ml · h), the regimen most commonly used in clinical practice. In vitro, synergy was demonstrated between ceftriaxone and trovafloxacin by the checkerboard method (fractional inhibitory concentration index, 0.5) and by time-killing assays over 8 h.


2012 ◽  
Vol 56 (7) ◽  
pp. 3785-3796 ◽  
Author(s):  
Alessandro Fiori ◽  
Patrick Van Dijck

ABSTRACTDoxycycline was found to act synergistically with the antifungal fluconazole againstCandida albicans. Combination with doxycycline converts fluconazole from fungistatic to fungicidal, prevents the onset of drug resistance, and is also effective against a clinical isolate characterized by elevated resistance to fluconazole. Investigation of the interactions between the two drugs by way of checkerboard assays indicated that doxycycline had an influence on the MIC for fluconazole, as defined by CLSI standards, only at high concentrations (200 μg/ml). However, lower concentrations were effective at eliminating residual cell growth at supra-MICs of fluconazole. Using MIC-0, defined as a drug combination resulting in optically clear wells, as an endpoint, doxycycline was found to be synergistic with fluconazole at a concentration as low as 25 μg/ml, with a fractional inhibitory concentration index of <0.5. Doxycycline-mediated growth inhibition can be reversed by externally added iron, indicating that iron depletion may account for the synergism. Consistently, we confirmed old literature data about iron-chelating activity of doxycycline. Synergism of fluconazole with doxycycline does not appear to be mediated by calcineurin, since doxycycline further aggravates the susceptibility to fluconazole of mutants lacking the catalytic or the regulatory subunits of calcineurin. Growth in the presence of fluconazole and doxycycline is restored by an elevated dosage ofERG11inSaccharomyces cerevisiaebut not inC. albicans, despite the full competence of the pathogen's protein to act as a suppressor in baker's yeast.


2019 ◽  
Vol 64 (2) ◽  
Author(s):  
Aubrey Watson ◽  
Karen Sauve ◽  
Cara Cassino ◽  
Raymond Schuch

ABSTRACT In vitro synergy between an antimicrobial protein lysin (cell wall hydrolase) called exebacase and each of 12 different antibiotics was examined against Staphylococcus aureus isolates using a nonstandard medium approved for exebacase susceptibility testing by the Clinical and Laboratory Standards Institute. In the checkerboard assay format, fractional inhibitory concentration index values of ≤0.5, consistent with synergy, were observed for the majority of interactions tested. Synergy was further confirmed in time-kill assays.


2011 ◽  
Vol 55 (9) ◽  
pp. 4485-4487 ◽  
Author(s):  
Fernanda Simas Corrêa Biancalana ◽  
Luzia Lyra ◽  
Angélica Zaninelli Schreiber

ABSTRACTIn vitroassociations using the checkerboard microdilution method indicated lower MIC ranges and MIC median values for each drug (terbinafine, itraconazole, voriconazole, and amphotericin B) in association than those obtained for each single drug. Fractional inhibitory concentration index (FIC) results showed 100% synergism in the association of terbinafine with voriconazole, 96.5% in the association of terbinafine with amphotericin B, and 75.9% in the association of terbinafine with itraconazole. Drug combinations may be useful for treatment of dematiaceous mold infections as an alternative treatment to enhance the effectiveness of each drug.


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