In vitro synergy of eugenol and methyleugenol with fluconazole against clinical Candida isolates

2010 ◽  
Vol 59 (10) ◽  
pp. 1178-1184 ◽  
Author(s):  
Aijaz Ahmad ◽  
Amber Khan ◽  
Luqman Ahmad Khan ◽  
Nikhat Manzoor
Keyword(s):  
Inhibitory Concentration ◽  
High Sensitivity ◽  
Antagonistic Activity ◽  
Fractional Inhibitory Concentration ◽  
Antifungal Drug Resistance ◽  
Naturally Occurring ◽  
Opportunistic Pathogenic ◽  
Concentration Indices ◽  
Compromised Patients

The species Candida is a group of opportunistic pathogenic commensals in immune-compromised patients. Treatment of Candida infections is becoming increasingly difficult due to antifungal drug resistance, especially with fluconazole (FLC), which is a commonly used azole. In the present study the in vitro antifungal activity of eugenol (EUG) and methyleugenol (MEUG) alone and in combination against 64 FLC-sensitive and 34 FLC-resistant clinical Candida isolates is highlighted. All the strains were susceptible to both the naturally occurring phenyl propanoids. The nature of the interaction was studied from fractional inhibitory concentration indices (FICIs) for both EUG plus FLC, and MEUG plus FLC combinations calculated from chequerboard microdilution assays. FICI values depicted a high synergism of FLC with both compounds, which was greatest with MEUG. FLC-resistant Candida isolates showed high sensitivity to both compounds. No antagonistic activity was seen in the strains tested in the present study. From these results we suggest that EUG and MEUG have great potential as antifungals, and that FLC can be supplemented with EUG and MEUG to treat FLC-resistant Candida infections.

scholarly journals Synergy of Nitric Oxide and Azoles againstCandida Species In Vitro

1998 ◽  
Vol 42 (9) ◽  
pp. 2342-2346 ◽  
Author(s):  
Gail E. McElhaney-Feser ◽  
Robert E. Raulli ◽  
Ronald L. Cihlar
Keyword(s):  
Nitric Oxide ◽  
Candida Albicans ◽  
Half Life ◽  
Inhibitory Concentration ◽  
Therapeutic Strategies ◽  
Fractional Inhibitory Concentration ◽  
Concentration Indices

ABSTRACT The candidacidal activity of nitric oxide (NO) as delivered by a class of compounds termed diazeniumdiolates has been investigated. Diazeniumdiolates are stable agents capable of releasing NO in a biologically usable form at a predicted rate, and three such compounds were examined for activity. One compound, (Z)-1-[N-(2-aminoethyl)-N-(2-ammonioethyl)amino]diazen-1-ium-1,2-diolate (DETA-NO), proved to be most suitable for examining NO activity due to its relatively long half-life (20 h) and because of limited candidacidal activity of the uncomplexed DETA nucleophile. DETA-NO was active against six species of Candida for which the MICs necessary to inhibit 50% growth (MIC50s) ranged from 0.25 to 1.0 mg/ml. C. parapsilosis and C. kruseiwere the most susceptible to the compound. In addition to a determination of NO effects alone, the complex was utilized to investigate the synergistic potential of released NO in combination with ketoconazole, fluconazole, and miconazole. Activity was investigated in vitro against representative strains of Candida albicans, C. krusei, C. parapsilosis,C. tropicalis, C. glabrata, and C. dubliniensis. Determination of MIC50, MIC80 and MICs indicated that DETA-NO inhibits all strains tested, with strains of C. parapsilosis and C. krusei being consistently the most sensitive. The combination of DETA-NO with each azole was synergistic against all strains tested as measured by fractional inhibitory concentration indices that ranged from 0.1222 to 0.4583. The data suggest that DETA-NO or compounds with similar properties may be useful in the development of new therapeutic strategies for treatment of Candida infections.

Comparison of methodologies for synergism testing of drug combinations against resistant strains of Pseudomonas aeruginosa.

1996 ◽  
Vol 40 (3) ◽  
pp. 677-683 ◽  
Author(s):  
D M Cappelletty ◽  
M J Rybak
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Clinical Isolate ◽  
Inhibitory Concentration ◽  
Laboratory Strain ◽  
Fractional Inhibitory Concentration ◽  
Beta Lactam ◽  
Beta Lactams ◽  
Drug Concentrations ◽  
Concentration Indices

The purpose of this study was to determine if synergism was maintained for various combinations of beta-lactams with an aminoglycoside against four clinical strains and one laboratory strain of Pseudomonas aeruginosa which were resistant, according to the MICs, to the beta-lactams and/or aminoglycoside. The results from both the checkerboard and killing curve methodologies were compared. The laboratory strain (ATCC 27853) was manipulated in vitro by serial passage onto agar containing increasing concentrations of each antibiotic to select for resistance. One clinical isolate (R61) was also serially passed to raise the MIC of piperacillin from 128 to 1,024 micrograms/ml. The fractional inhibitory concentration indices for all isolates indicated indifference for all combination therapies, with values ranging from 0.6 to 3. In contrast, killing curve results for all isolates demonstrated synergism with drug concentrations at either one-fourth or one-half the MIC for each organism. The MIC of piperacillin for the laboratory-manipulated clinical isolate R61 was 1,024 micrograms/ml, and synergism was still observed with concentrations of one-half the MIC of piperacillin and amikacin. For clinical isolate R166, which was beta-lactam and tobramycin resistant, synergism continued to be demonstrated with concentrations of tobramycin (1/16 MIC) in combination with piperacillin and cefepime at 1/2 the MIC. The results of this study indicate that against P. aeruginosa, synergism is observed in spite of resistance to beta-lactams and/or aminoglycosides. Synergism appears to be maintained even at very high MICs (piperacillin, 1,024 micrograms/ml; tobramycin, 128 micrograms/ml) with drug concentrations within achievable therapeutic ranges. With current definitions of synergism there was a complete lack of correlation between the results obtained by the checkerboard and killing curve methodologies, with the fractional inhibitory concentration indices showing indifference and killing curves resulting in synergism. The methodologies and definitions of synergism or antagonism are variable and not standardized and should be reevaluated.

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

1998 ◽  
Vol 42 (8) ◽  
pp. 2002-2005 ◽  
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.

scholarly journals Synergistic anticryptosporidial potential of the combination alpha-1-antitrypsin and paromomycin.

1997 ◽  
Vol 41 (9) ◽  
pp. 2006-2008 ◽  
Author(s):  
J R Forney ◽  
S Yang ◽  
M C Healey
Keyword(s):  
Inhibitory Concentration ◽  
Combined Treatment ◽  
Serine Protease Inhibitor ◽  
Synergistic Activity ◽  
Combined Treatments ◽  
Treatment Groups ◽  
The Mean ◽  
Alpha 1 Antitrypsin ◽  
Concentration Indices

The combined effect of the serine protease inhibitor alpha-1-antitrypsin (AAT) and the aminoglycoside paromomycin on Cryptosporidium parvum infection in vitro was investigated. AAT and paromomycin were mixed with C. parvum oocysts as either single or combined treatments and used to inoculate epithelial cell cultures. Single- and combined-treatment groups had significantly lower (P < 0.01) parasite numbers than untreated controls. The mean fractional inhibitory concentration indices suggested significant synergistic activity.

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 Interaction of Caspofungin Acetate with Voriconazole against Clinical Isolates of Aspergillus spp

2002 ◽  
Vol 46 (9) ◽  
pp. 3039-3041 ◽  
Author(s):  
Sofia Perea ◽  
Gloria Gonzalez ◽  
Annette W. Fothergill ◽  
William R. Kirkpatrick ◽  
Michael G. Rinaldi ◽  
...  
Keyword(s):  
Inhibitory Concentration ◽  
Fractional Inhibitory Concentration ◽  
Broth Microdilution ◽  
Microdilution Method ◽  
Broth Microdilution Method ◽  
In Vitro Interaction ◽  
Vitro Data ◽  
In Vitro Data

ABSTRACT The interaction between caspofungin acetate and voriconazole was studied in vitro by using 48 clinical Aspergillus spp. isolates obtained from patients with invasive aspergillosis. MICs were determined by the NCCLS broth microdilution method. Synergy, defined as a fractional inhibitory concentration (FIC) index of <1, was detected in 87.5% of the interactions; an additive effect, defined as an FIC index of 1.0, was observed in 4.2% of the interactions; and a subadditive effect, defined as an FIC index of 1.0 to 2.0, was found in 8.3% of the interactions. No antagonism was observed. Animal models are required to validate the in vivo significance of these in vitro data presented for the combination of caspofungin and voriconazole.

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.

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