In vitro interaction between azoles and cyclosporin A against clinical isolates of Candida albicans determined by the chequerboard method and time-kill curves

Li, Yan; Sun, Shujuan; Guo, Qiongjie; Ma, Lin; Chang-wen, Shi; Su, Le-Qun; Li, Hongjian

doi:10.1093/jac/dkm493

Cited by 46 publications

(38 citation statements)

References 28 publications

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“…The MIC of FLC against the quality control on May 9, 2018 by guest http://aac.asm.org/ strain C. albicans ATCC 10231 was 0.5 to 2 g/ml, within the reference range (11). According to the interpretive breakpoints for FLC (Յ8 and Ն64 g/ml, respectively), ITR (Յ0.1 and Ն1 g/ml, respectively) (24), and KCZ (Յ0.125 and Ն1 g/ml, respectively) (14), C. albicans isolates CA10, CA135, CA137, and CA138 are resistant to FLC, KCZ, and ITR; the others are sensitive.…”

Section: Susceptibility and Interaction Of Drugsmentioning

confidence: 64%

In Vitro Activities of Retigeric Acid B Alone and in Combination with Azole Antifungal Agents against Candida albicans

Sun

Cheng

et al. 2009

Antimicrob Agents Chemother

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The vitro antifungal activity of retigeric acid B (RAB), a pentacyclic triterpenoid from the lichen species Lobaria kurokawae, was evaluated alone and in combination with fluconazole, ketoconazole, and itraconazole against Candida albicans using checkerboard microdilution and time-killing tests. The MICs for RAB against 10 different C. albicans isolates ranged from 8 to 16 g/ml. A synergistic action of RAB and azole was observed in azole-resistant strains, whereas synergistic or indifferent effects were observed in azole-sensitive strains when interpreted by a separate approach of the fractional inhibitory concentration index and ⌬E model (the difference between the predicted and measured fungal growth percentages). In time-killing tests, we used both colony counts and a colorimetric assay to evaluate the combinational antifungal effects of RAB and azoles, which further confirmed their synergistic interactions. These findings suggest that the natural product RAB may play a certain role in increasing the susceptibilities of azole-resistant C. albicans strains.The incidence of candidiasis has increased during the last several decades due to the widespread use of antibacterials, corticosteroids, immunosuppressive agents, radiotherapy, and antitumoral chemotherapy (2,4,21,23). The azole antifungal agents have excellent efficacy-toxicity profiles and play an important role in the treatment of Candida infections (12). However, concomitant with their widespread use, reports of clinical failure and correlations with elevated MICs to azole have begun to appear (3, 21). Moreover, some of these clinical isolates exhibit cross-resistance to a variety of different azole drugs (15). At present, although three echinocandins (caspofungin, micafungin, and anidulafungin) and voriconazole are available for the treatment of infection caused by azole-resistant isolates, the cost is too high for the patients. New antifungal agent research and development is still needed. Moreover, identification of small molecules that synergize with current antifungals against azole-resistant Candida strains may be a better way to overcome antifungal drug resistance.Natural products with diverse bioactivities and structures are an important source of novel chemicals with pharmaceutical potentials (1, 26). Lichens, the symbiotic organisms of fungi and algae, are found commonly worldwide and can survive a variety of harsh environmental conditions. Lichens are inherently resistant to microbial infection due to the production of large numbers of unique secondary metabolites (6, 9). Therefore, we have focused our attention on lichens and their metabolites in an effort to find novel, naturally occurring antifungal potentiators. A thin-layer chromatography-bioautography screening guided phytochemical investigation for antifungal constituents from a lichen, Lobaria kurokawae Yoshim., led to the isolation of a pentacyclic triterpenoid, retigeric acid B (RAB) (Fig. 1), as the main active constituent (27). Interestingly, Lobaria kurokawae Yoshim. has been appl...

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Section: Susceptibility and Interaction Of Drugsmentioning

confidence: 64%

In Vitro Activities of Retigeric Acid B Alone and in Combination with Azole Antifungal Agents against Candida albicans

Sun

Cheng

et al. 2009

Antimicrob Agents Chemother

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“…This generally entails the use of recognized antifungal agents for which complementary mechanisms of action have been proven (8,12). In recent years, however, the concept of chemosensitization of fungal organisms to standard antifungal agents (e.g., azoles) by exposure to biological agents or nontraditional partner drugs, such as nitric oxide, cyclosporine, benzo analogues, or recombinant antibodies, has emerged (13,15,18,19,23). Each of these agents may alter the ability of fungal cells to respond or adapt to the insult of a specific antifungal exposure.…”

Section: Resultsmentioning

confidence: 99%

Activity of MGCD290, a Hos2 Histone Deacetylase Inhibitor, in Combination with Azole Antifungals against Opportunistic Fungal Pathogens

Pfaller¹,

Messer²,

et al. 2009

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We report on the in vitro activity of the Hos2 fungal histone deacetylase (HDAC) inhibitor MGCD290 (MethylGene, Inc.) in combination with azoles against azole-resistant yeasts and molds. Susceptibility testing was performed by the CLSI M27-A3 and M38-A2 broth microdilution methods. Testing of the combinations (MGCD290 in combination with fluconazole, posaconazole, or voriconazole) was performed by the checkerboard method. The fractional inhibitory concentrations were determined and were defined as <0.5 for synergy, >0.5 but <4 for indifference, and >4 for antagonism. Ninety-one isolates were tested, as follows: 30 Candida isolates, 10 Aspergillus isolates, 15 isolates of the Zygomycetes order, 10 Cryptococcus neoformans isolates, 8 Rhodotorula isolates, 8 Fusarium isolates, 5 Trichosporon isolates, and 5 Scedosporium isolates. MGCD290 showed modest activity when it was used alone (MICs, 1 to 8 g/ml) and was mostly active against azoleresistant yeasts, but the MICs against molds were high (16 to >32 g/ml).

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“…In the checkerboard assay, the FICI model has been frequently used to determine the interaction between antifungal drugs (7,9,12,17,21,23). The ⌬E model is a useful method for characterizing drug interactions.…”

mentioning

confidence: 99%

In Vitro Interaction between Fluconazole and Triclosan against Clinical Isolates of Fluconazole-Resistant Candida albicans Determined by Different Methods

Ling

Deng

et al. 2011

Antimicrob Agents Chemother

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The in vitro interaction between triclosan and fluconazole against 24 azole-resistant clinical isolates of Candida albicans was evaluated by the microdilution checkerboard technique. The synergisms were verified by time-killing curves and agar diffusion tests in selected strains. Antagonistic activity was not detected.Candida albicans is the primary cause of opportunistic fungal disease in humans. It is predominantly found at low levels among the normal oral flora but can thrive in immunocompromised individuals (16,25). Fluconazole has been used successfully as a prophylactic and a first-line therapeutic antifungal agent (5,6,19). However, the increase in azole use has precipitated a rise in drug resistance in clinical isolates. Triclosan, a chlorinated aromatic compound, has antimicrobial (4,8,20), antiparasitic (26), and anti-inflammatory (1, 24) activities. It has been used in personal care products (2). Combination therapy can improve the efficacy of antimicrobial therapy for infections recalcitrant to most treatments. Therefore, we aimed to assess the presence of combination effects with triclosan and fluconazole in C. albicans.A total of 24 clinical isolates of fluconazole-resistant C. albicans were used in this study, and C. albicans ATCC 10231, C. parapsilosis ATCC 90018, and C. krusei ATCC 6258 were used as quality controls. The drugs were purchased from Sigma (Sigma-Aldrich).The drug MICs were determined by broth microdilution according to CLSI method M27-A (3) with an inoculum of 2.5 ϫ 10 3 CFU/ml. The plates were incubated at 35°C, and the optical density (OD) value was determined at 492 nm after 48 h, a modification to the CLSI reference method. All experiments were conducted in triplicate, and the median MIC-1 endpoint value, which represents an 80% reduction in turbidity, and MIC-2 endpoint value, which represents a 50% reduction in turbidity, were calculated (3). The drug interactions were analyzed using the fractional inhibitory concentration index (FICI) and ⌬E models based on the Loewe additivity and Bliss independence theories, respectively (14, 21). The FICIs were defined as the sum of the MICs of each drug used in the combination divided by the MIC of the drug used alone. Synergy and antagonism were defined by FICIs of Յ0.5 and Ͼ4, respectively (15). The ⌬E model was calculated as the sums of the percentages of all statistically significant (SS) synergistic (ΑSYN) and antagonistic (ΑANT) interactions. Interactions that were Ͻ100% and Ͼ200% SS interactions were considered weak and strong, respectively. Interactions that were 100 to 200% SS interactions were considered moderate (14). The numbers of SS synergistic and antagonistic combinations were calculated for each strain.A 100-l sample of 10 6 CFU/ml C. albicans YL345, which exhibited the best synergistic effect, was spread onto a yeast extract-peptone-dextrose agar surface. Subsequently, 6-mmdiameter paper disks, impregnated with drugs or dimethyl sulfoxide (DMSO) alone, were placed onto the surface. The inhibition zones were measured usi...

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In vitro interaction between azoles and cyclosporin A against clinical isolates of Candida albicans determined by the chequerboard method and time-kill curves

Abstract: Cyclosporin A showed potent synergism when combined with the three azoles, especially against azole-R C. albicans strains, and there was good agreement between various methods used in this study.

Cited by 46 publications

References 28 publications

In Vitro Activities of Retigeric Acid B Alone and in Combination with Azole Antifungal Agents against Candida albicans

In Vitro Activities of Retigeric Acid B Alone and in Combination with Azole Antifungal Agents against Candida albicans

Activity of MGCD290, a Hos2 Histone Deacetylase Inhibitor, in Combination with Azole Antifungals against Opportunistic Fungal Pathogens

In Vitro Interaction between Fluconazole and Triclosan against Clinical Isolates of Fluconazole-Resistant Candida albicans Determined by Different Methods

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