The fractional inhibitory concentration (FIC) index as a measure of synergy

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.

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In VitroAntistaphylococcal Effects ofEmbelia schimperiExtracts and Their Component Embelin with Oxacillin and Tetracycline

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2015/175983 ◽

2015 ◽

Vol 2015 ◽

pp. 1-7 ◽

Cited By ~ 4

Author(s):

Johana Rondevaldova ◽

Olga Leuner ◽

Alemtshay Teka ◽

Ermias Lulekal ◽

Jaroslav Havlik ◽

...

Keyword(s):

Staphylococcus Aureus ◽

Medicinal Plants ◽

Bacterial Infections ◽

Inhibitory Concentration ◽

Developed Countries ◽

Positive Interactions ◽

Fractional Inhibitory Concentration ◽

Broth Microdilution ◽

Microdilution Method ◽

Broth Microdilution Method

Bacterial infections are in less-developed countries traditionally treated by remedies prepared from medicinal plants.Embelia schimperi(Vatke) is a plant used as a taenicide or disinfectant in Ethiopia, very often taken mixed with another plant species. In the present study, we examined two extracts prepared from seeds and twigs with leaves ofE. schimperiand its main present secondary metabolite embelin for their antibacterial combinatory effect with oxacillin and tetracycline against sensitive and resistantStaphylococcus aureusstrains. Minimum inhibitory concentrations were determined through the broth microdilution method, whereas the combinatory effect was evaluated through fractional inhibitory concentration sum (ΣFIC) indices. Results show many positive interactions and synergy occurring in embelin and oxacillin combinations against 4 out of 9 strains (ΣFIC 0.203–0.477) and for embelin and tetracycline combination against 3 out of 9 strains (ΣFIC 0.400–0.496). Moreover, the resistance to oxacillin has been overcome in 2 strains and to tetracycline in 3 strains. According to our knowledge, this is the first study showing antimicrobial combinatory effect ofE. schimperias well as of embelin. These findings can be used for the further research targeted on the development of new antistaphylococcal agents.

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Effect the combination of antibiotics on clinical isolates of Staphylococcus aureus

Baghdad Science Journal ◽

10.21123/bsj.6.4.683-692 ◽

2009 ◽

Vol 6 (4) ◽

pp. 683-692

Author(s):

Baghdad Science Journal

Keyword(s):

Staphylococcus Aureus ◽

Concentration Index ◽

Inhibitory Concentration ◽

Morphological Characterization ◽

Penicillin G ◽

Clinical Samples ◽

Fractional Inhibitory Concentration ◽

Fractional Inhibitory Concentration Index ◽

Lactam Antibiotic ◽

Susceptibility Tests

Atotal of 75 different clinical samples were collected from different hospitals in Baghdad Biochemical and morphological characterization tests showed that forty isolates were identified as Staphylococcus aureus Antibiotic susceptibility tests of all isolates towards ten antibiotics were carried out and results showed that many isolates (97.5 %) were resistant to ?-lactam antibiotic , 70 % were resistant to Tetracyclinee , 62.5% were resistant to co-trimoxazole , 60 % were resistant to ciprofloxacin , 55% were resistant both of chloramphenicol and erythromycin , 52.5% were resistant to gentamicin , 35% were resistant to rifampicin , 10% were resistant to vancomycin . According to the above results the S.aureus I1 which is isolated from patients with osteomyelitis showed resistant to all ten antibiotics therefore was used in the followed experiments. The minimum inhibitory concentration (MIC) of S.aureus I1 vancomycin, cefotaxim , penicillin G, amoxicillin , ciprofloxacin , co-trimoxazole ,gentamicin, rifampicin was checked.The results showed that isolates had MIC between (390-12500) ?g/ml. The combination of different antibiotics with vancomycin showed synergistic effect based on the Fractional inhibitory concentration index (FIC).

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Quantifying synergy in the bioassay-guided fractionation of natural product extracts

10.1101/2020.06.23.166686 ◽

2020 ◽

Cited By ~ 1

Author(s):

Micah Dettweiler ◽

Lewis Marquez ◽

Max Bao ◽

Cassandra L. Quave

Keyword(s):

Inhibitory Concentration ◽

Viral Infections ◽

Fractional Inhibitory Concentration ◽

Drug Mixtures ◽

Natural Substances ◽

Complex Interactions ◽

Bioassay Guided Fractionation ◽

Using Data ◽

Living Organisms

AbstractMixtures of drugs often have greater therapeutic value than any of their constituent drugs alone, and such combination therapies are widely used to treat diseases such as cancer, malaria, and viral infections. However, developing useful drug mixtures is challenging due to complex interactions between drugs. Natural substances can be fruitful sources of useful drug mixtures because secondary metabolites produced by living organisms do not often act in isolation in vivo. In order to facilitate the study of interactions within natural substances, a new analytical method to quantify interactions using data generated in the process of bioassay-guided fractionation is presented here: the extract fractional inhibitory concentration index (EFICI). The EFICI method uses the framework of Loewe additivity to calculate fractional inhibitory concentration values by which interactions can be determined for any combination of fractions that make up a parent extract. The EFICI method was applied to data on the bioassay-guided fractionation of Lechea mucronata and Schinus terebinthifolia for growth inhibition of the pathogenic bacterium Acinetobacter baumannii. The L. mucronata extract contained synergistic interactions (EFICI = 0.4181) and the S. terebinthifolia extract was non-interactive overall (EFICI = 0.9129). Quantifying interactions in the bioassay-guided fractionation of natural substances does not require additional experiments and can be useful to guide the experimental process and to support the development of standardized extracts as botanical drugs.

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A Pilot Study of the Synergy between Two Antimicrobial Peptides and Two Common Antibiotics

Antibiotics ◽

10.3390/antibiotics8020060 ◽

2019 ◽

Vol 8 (2) ◽

pp. 60 ◽

Cited By ~ 11

Author(s):

Franziska Kampshoff ◽

Mark D. P. Willcox ◽

Debarun Dutta

Keyword(s):

Staphylococcus Aureus ◽

Antibacterial Agents ◽

Inhibitory Concentration ◽

Synergistic Activity ◽

Fractional Inhibitory Concentration ◽

First Line ◽

Checkerboard Assay ◽

Resistant Strains ◽

And Staphylococcus Aureus ◽

Broth Dilution

Background: Frequent and unrestricted use of antibiotics has been associated with the development of antibiotic resistance by microorganisms. Thus, there is a need to find novel antibacterial agents or a combination of agents as the first line of treatment for various infections. This study aimed to investigate the synergy between antimicrobial peptide (AMP) combinations or between AMP-antibiotics combinations using two common pathogens, Pseudomonas aeruginosa and Staphylococcus aureus. Methods: The AMPs melimine, Mel4 and protamine, and antibiotics cefepime and ciprofloxacin were used in this study. The minimum inhibitory concentration (MIC) of each were evaluated against P. aeruginosa and S. aureus strains by a microtiter broth dilution. Based on the MIC of each antimicrobial agent, a checkerboard assay was performed to investigate the synergy between them, which was expressed as the fractional inhibitory concentration (FIC). Results: The combination of melimine and ciprofloxacin showed synergistic activity against antibiotic sensitive or resistant strains of P. aeruginosa and with FIC values ≤0.5. Conclusion: Combinations of AMPs and the fluoroquinolone ciprofloxacin is a promising method for reducing resistance to the fluoroquinolone of P. aeruginosa.

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Activities of Three Quinolones, Alone and in Combination with Extended-Spectrum Cephalosporins or Gentamicin, against Stenotrophomonas maltophilia

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.42.8.2002 ◽

1998 ◽

Vol 42 (8) ◽

pp. 2002-2005 ◽

Cited By ~ 24

Author(s):

Melissa A. Visalli ◽

Michael R. Jacobs ◽

Peter C. Appelbaum

Keyword(s):

Active Compound ◽

Stenotrophomonas Maltophilia ◽

Inhibitory Concentration ◽

Fractional Inhibitory Concentration ◽

Determination Method ◽

Extended Spectrum ◽

Time Kill ◽

Synergy Testing ◽

Checkerboard Titration ◽

Concentration Indices

The present study examined the activities of trovafloxacin, levofloxacin, and ciprofloxacin, alone and in combination with cefoperazone, ceftazidime, cefpirome, and gentamicin, against 100 strains of Stenotrophomonas maltophilia by the MIC determination method and by synergy testing of the combinations by the time-kill and checkerboard titration methods for 20 strains. The respective MICs at which 50% and 90% of isolates were inhibited for the drugs used alone were as follows: trovafloxacin, 0.5 and 2.0 μg/ml; levofloxacin, 2.0 and 4.0 μg/ml; ciprofloxacin, 4.0 and 16.0 μg/ml; cefoperazone, >128.0 and >128.0 μg/ml; ceftazidime, 32.0 and >128.0 μg/ml; cefpirome, >128.0 and >128.0 μg/ml; and gentamicin, 128.0 and >128.0 μg/ml. Synergistic fractional inhibitory concentration indices (≤0.5) were found for ≥50% of strains for trovafloxacin-cefoperazone, trovafloxacin-ceftazidime, levofloxacin-cefoperazone, levofloxacin-ceftazidime, ciprofloxacin-cefoperazone, and ciprofloxacin-ceftazidime, with other combinations affecting fewer strains. For 20 strains tested by the checkerboard titration and time-kill methods, synergy (≥100-fold drop in count compared to the count achieved with the more active compound) was more pronounced after 12 h due to regrowth after 24 h. At 12 h, trovafloxacin at 0.004 to 0.5 μg/ml showed synergy with cefoperazone for 90% of strains, with ceftazidime for 95% of strains with cefpirome for 95% of strains, and with gentamicin for 65% of strains. Levofloxacin at 0.03 to 0.5 μg/ml and ciprofloxacin at 0.5 to 2.0 μg/ml showed synergy with cefoperazone for 80% of strains, with ceftazidime for 90 and 85% of strains, respectively, with cefpirome for 85 and 75% of strains, respectively, and with gentamicin for 65 and 75% of strains, respectively. Time-kill assays were more discriminatory than checkerboard titration assays in demonstrating synergy for all combinations.

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Antipneumococcal activities of cefpirome and cefotaxime, alone and in combination with vancomycin and teicoplanin, determined by checkerboard and time-kill methods.

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.40.9.1973 ◽

1996 ◽

Vol 40 (9) ◽

pp. 1973-1976 ◽

Cited By ~ 21

Author(s):

S Bajaksouzian ◽

M A Visalli ◽

M R Jacobs ◽

P C Appelbaum

Keyword(s):

Inhibitory Concentration ◽

Fractional Inhibitory Concentration ◽

Beta Lactams ◽

Pneumococcal Infections ◽

Titration Method ◽

Resistant Strains ◽

Time Kill ◽

Checkerboard Titration

The checkerboard titration method was used to test the synergy of cefpirome and cefotaxime with teicoplanin or vancomycin against 35 penicillin-susceptible, 34 penicillin-intermediate, and 31 penicillin-resistant pneumococci. The MICs at which 50 and 90% of isolates are inhibited (MIC50s and MIC90s, respectively) of both cefpirome and cefotaxime were 0.016 and 0.06 microgram/ml, respectively, for penicillin-susceptible strains and 0.125 and 0.5 microgram/ml, respectively, for penicillin-intermediate strains. The MIC50s and MIC90s of cefotaxime for penicillin-resistant strains were 1.0 and 2.0 micrograms/ml, respectively, and those of cefpirome were 0.5 and 1.0 microgram/ml, respectively. All pneumococci were inhibited by cefpirome at MICs of < or = 1.0 microgram/ml. The MIC50s and MIC90s of vancomycin and teicoplanin (0.25 and 0.25 microgram/ml and 0.03 and 0.03 microgram/ml, respectively) did not differ for the three groups. Checkerboard synergy studies showed that cefpirome and vancomycin showed synergy for 31 strains (fractional inhibitory concentration [FIC] indices, < or = 0.5) cefpirome and teicoplanin showed synergy for 18 strains, cefotaxime and vancomycin showed synergy for 51 strains, and cefotaxime and teicoplanin showed synergy for 27 strains. Cefpirome and vancomycin had FIC indices indicating indifference (2.0) for two strains, and cefotaxime and vancomycin had FIC indices indicating indifference for one strain. All other FIC indices indicating indifference or additivity were > 0.5 to 1.0. No FIC indices indicating antagonism (> 4.0) were found. Synergy between beta-lactams and glycopeptides for three susceptible, three intermediate, and three resistant strains were tested by the time-kill assay, and all combinations were synergistic by this method. Synergy between cephalosporins and glycopeptides can be demonstrated and may be useful for the treatment of pneumococcal infections, especially meningitis.

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

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.49.8.3544-3545.2005 ◽

2005 ◽

Vol 49 (8) ◽

pp. 3544-3545 ◽

Cited By ~ 19

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.

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