Faculty Opinions recommendation of Defining fractional inhibitory concentration index cutoffs for additive interactions based on self-drug additive combinations, Monte Carlo simulation analysis, and in vitro-in vivo correlation data for antifungal drug combinations against Aspergillus fumigatus.

2009 ◽  
Author(s):  
Annette Fothergill
Keyword(s):  
Monte Carlo Simulation ◽  
Monte Carlo ◽  
Concentration Index ◽  
Inhibitory Concentration ◽  
Simulation Analysis ◽  
Fractional Inhibitory Concentration ◽  
Fractional Inhibitory Concentration Index ◽  
Correlation Data

scholarly journals Defining Fractional Inhibitory Concentration Index Cutoffs for Additive Interactions Based on Self-Drug Additive Combinations, Monte Carlo Simulation Analysis, and In Vitro-In Vivo Correlation Data for Antifungal Drug Combinations against Aspergillus fumigatus

2009 ◽  
Vol 54 (2) ◽  
pp. 602-609 ◽  
Author(s):  
Joseph Meletiadis ◽  
Spyros Pournaras ◽  
Emmanuel Roilides ◽  
Thomas J. Walsh
Keyword(s):  
Monte Carlo Simulation ◽  
Monte Carlo ◽  
Aspergillus Fumigatus ◽  
Inhibitory Concentration ◽  
Simulation Analysis ◽  
Invasive Pulmonary Aspergillosis ◽  
Drug Combinations ◽  
Fractional Inhibitory Concentration

ABSTRACT The fractional inhibitory concentration (FIC) index range of 0.5 to 4 that is commonly used to define additivity results in no interactions in most combination studies of antifungal agents. These results may differ from those of in vivo studies, where positive and negative interactions may be observed. We reassessed this in vitro FIC index range based on (i) the experimental variation of the checkerboard technique using multiple replicates, (ii) the ability to correctly determine purely additive self-drug and two-drug antagonistic combinations of amphotericin B (AMB) and voriconazole (VRC), (iii) Monte Carlo simulation analysis, and (iv) in vitro-in vivo correlation using experimental models of invasive pulmonary aspergillosis against the same Aspergillus fumigatus isolate based on visual, spectrophotometric, and colorimetric determinations of FICs after 24 and 48 h of incubation. FICs obtained after 24 h of incubation ranged from 0.5 to 1.25 for the self-drug additive combinations of AMB plus AMB and VRC plus VRC and from 2.25 to 4.25 for the antagonistic combination of AMB plus VRC. Monte Carlo simulation analysis showed that self-drug combinations were correctly classified as additive and that the combination of AMB plus VRC was correctly classified as antagonistic for >85% of the simulated FICs when deviation of the 95% confidence interval (CI) of replicate FICs from the additivity range of 1 to 1.25 was used to assess interactions after 24 h. In vitro-in vivo correlation analysis showed that the 95% CIs of the FICs of the in vivo synergistic combination anidulafungin plus VRC determined after 24 h were lower than 1 and the 95% CIs of the FICs of the in vivo antagonistic combination AMB plus ravuconazole were higher than 1.25. Adequate insight into weak pharmacodynamic interactions with in vivo relevance may be obtained by demonstrating that triplicate FICs at 24 h are outside an inclusive additivity range of 1 to 1.25.

scholarly journals In vitro synergy of isavuconazole in combination with colistin against Candida auris

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Patrick Schwarz ◽  
Anne-Laure Bidaud ◽  
Eric Dannaoui
Keyword(s):  
Response Surface ◽  
Surface Analysis ◽  
Concentration Index ◽  
Inhibitory Concentration ◽  
Response Surface Analysis ◽  
Fractional Inhibitory Concentration ◽  
Candida Auris ◽  
Fractional Inhibitory Concentration Index ◽  
Agar Diffusion

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.

scholarly journals In Vitro Interaction of Posaconazole and Caspofungin against Clinical Isolates of Candida glabrata

2005 ◽  
Vol 49 (8) ◽  
pp. 3544-3545 ◽  
Author(s):  
E. R. Oliveira ◽  
A. W. Fothergill ◽  
W. R. Kirkpatrick ◽  
B. J. Coco ◽  
T. F. Patterson ◽  
...  
Keyword(s):  
Candida Glabrata ◽  
Concentration Index ◽  
Inhibitory Concentration ◽  
Clinical Isolates ◽  
Fractional Inhibitory Concentration ◽  
Fractional Inhibitory Concentration Index ◽  
Fluconazole Resistant ◽  
In Vitro Interaction

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.

scholarly journals In Vitro Interactions of Echinocandins with Triazoles against Multidrug-Resistant Candida auris

2017 ◽  
Vol 61 (11) ◽  
Author(s):  
Hamed Fakhim ◽  
Anuradha Chowdhary ◽  
Anupam Prakash ◽  
Afsane Vaezi ◽  
Eric Dannaoui ◽  
...  
Keyword(s):  
Concentration Index ◽  
Inhibitory Concentration ◽  
Multidrug Resistant ◽  
Fractional Inhibitory Concentration ◽  
Candida Auris ◽  
Fractional Inhibitory Concentration Index ◽  
Synergistic Interactions ◽  
In Vitro Interactions

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.

scholarly journals Synergy between Trovafloxacin and Ceftriaxone against Penicillin-Resistant Pneumococci in the Rabbit Meningitis Model and In Vitro

2000 ◽  
Vol 44 (8) ◽  
pp. 2179-2181 ◽  
Author(s):  
Philippe Cottagnoud ◽  
Fernando Acosta ◽  
Marianne Cottagnoud ◽  
Klaus Neftel ◽  
Martin G. Täuber
Keyword(s):  
Clinical Practice ◽  
Concentration Index ◽  
Inhibitory Concentration ◽  
Fractional Inhibitory Concentration ◽  
Fractional Inhibitory Concentration Index ◽  
Killing Rate ◽  
Pneumococcal Strain ◽  
Bactericidal Activities

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.

scholarly journals In VitroEvaluation of the Type of Interaction Obtained by the Combination of Terbinafine and Itraconazole, Voriconazole, or Amphotericin B against Dematiaceous Molds

2011 ◽  
Vol 55 (9) ◽  
pp. 4485-4487 ◽  
Author(s):  
Fernanda Simas Corrêa Biancalana ◽  
Luzia Lyra ◽  
Angélica Zaninelli Schreiber
Keyword(s):  
Amphotericin B ◽  
Alternative Treatment ◽  
Concentration Index ◽  
Inhibitory Concentration ◽  
Drug Combinations ◽  
Fractional Inhibitory Concentration ◽  
Fractional Inhibitory Concentration Index ◽  
Single Drug ◽  
Microdilution Method

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.

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
Keyword(s):  
Serum Concentration ◽  
Synergistic Effect ◽  
Bactericidal Activity ◽  
Concentration Index ◽  
Inhibitory Concentration ◽  
Mycobacterium Abscessus ◽  
Fractional Inhibitory Concentration ◽  
Content Type ◽  
Fractional Inhibitory Concentration Index

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.

scholarly journals In Vitro Assessment of the Efficacy of Erythromycin in Combination with Oxytetracycline or Spectinomycin against Pasteurella Haemolytica

1989 ◽  
Vol 1 (4) ◽  
pp. 299-304 ◽  
Author(s):  
George E. Burrows ◽  
Patty Ewing
Keyword(s):  
Concentration Index ◽  
Inhibitory Concentration ◽  
Mechanisms Of Action ◽  
Pasteurella Haemolytica ◽  
Fractional Inhibitory Concentration ◽  
Disease Treatment ◽  
Tissue Concentrations ◽  
Fractional Inhibitory Concentration Index ◽  
In Vitro Assessment

The effects of combining erythromycin (Ery) with oxytetracycline (Oxy) or spectinomycin (Sp) on Pasteurella haemolytica were evaluated in vitro using the chessboard (checkerboard) technique. These combinations were selected because all are drugs widely used in bovine respiratory disease treatment, and they represent possible sequential or complementary mechanisms of action. Using the recommended breakpoints of >4 μg/ml for Ery, 16 μl for Oxy, and 32 μl for Sp, of the 33 P. haemolytica isolates, 32 were resistant to Oxy, 27 to Sp, and 14 to Ery. Based on the fractional inhibitory concentration index, Ery and Oxy in combination were synergistic or additive against 32 of 33 isolates. The combination of Ery and Sp was synergistic or additive against 27 of 33 isolates. No instances of antagonism were seen. When the effects were considered within the context of therapeutically achievable serum/tissue concentrations, the effects of Ery and Oxy in combination were only marginal. Thus, against P. haemolytica isolates, Ery and Sp appeared to represent an effective antimicrobial combination, whereas Ery and Oxy were only of marginal efficacy as a combination.

scholarly journals ANTIMICROBIAL ACTIVITY OF THUJA ORIENTALIS IN COMBINATION WITH CIPROFLOXACIN AGAINST PSEUDOMONAS AERUGINOSA

2019 ◽  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Minimum Inhibitory Concentration ◽  
Synergistic Effect ◽  
Concentration Index ◽  
Inhibitory Concentration ◽  
Disc Diffusion ◽  
Fractional Inhibitory Concentration ◽  
Fractional Inhibitory Concentration Index ◽  
Thuja Orientalis

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.

scholarly journals Vancomycin and Clarithromycin Show Synergy against Mycobacterium abscessus In Vitro

2017 ◽  
Vol 61 (12) ◽  
Author(s):  
Devika Mukherjee ◽  
Mu-Lu Wu ◽  
Jeanette W. P. Teo ◽  
Thomas Dick
Keyword(s):  
Lung Disease ◽  
Concentration Index ◽  
Inhibitory Concentration ◽  
Mycobacterium Abscessus ◽  
Fractional Inhibitory Concentration ◽  
Content Type ◽  
Fractional Inhibitory Concentration Index ◽  
Treatment Regimens

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.

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