Caspofungin in Combination with Amphotericin B against
            <i>Candida parapsilosis</i>

Barchiesi, Francesco; Spreghini, Elisabetta; Tomassetti, Serena; Giannini, Daniele; Scalise, Giorgio

doi:10.1128/aac.00880-06

Cited by 32 publications

(23 citation statements)

References 23 publications

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“…With regard to echinocandins, most authors found no antagonism between micafungin and azoles or AMB (4,17,32). Barchiesi et al did not find advantages in associating caspofungin and the polyene, with the exception of C. parapsilosis, but the study in- cluded a much more limited number of strains (2). In some Candida strains, echinocandins are highly active, and so the fungicidal activity may be difficult to improve after combination (17).…”

Section: Discussionmentioning

confidence: 91%

Novel Method for Evaluating In Vitro Activity of Anidulafungin in Combination with Amphotericin B or Azoles

et al. 2012

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A combination of drugs possessing different targets has been used as salvage therapy, although without scientific support. In vitro studies validating such combinations are scarce, and the methodology is very laborious and time-consuming. This study proposes a flow cytometric (FC) protocol as an alternative to evaluate the effect of the combination of anidulafungin (AND) with amphotericin B (AMB) and azoles (fluconazole and voriconazole), tested upon 39 and 36 Candida strains, respectively. The concentration assayed in the combination was 0.5× MIC of each drug. The membrane potential marker DiBAC 4 (3) [Bis-(1,3-dibutylbarbituric acid) trimethine oxonol] was used for AND-AMB, and the metabolic marker FUN-1 was used for AND-azoles. Drug interaction was determined by calculating a staining index (SI): the sum of the percentage of depolarized cells (DC) after treatment with drug combinations divided by the DC of the drug alone, and the sum of the mean intensity of fluorescence (MIF) displayed by cells treated with drug combinations divided by the MIF of the drug alone for FUN-1. An SI of <1 means antagonism, an SI between 1 and 4 means no interaction, and an SI of >4 means synergism. The combination of AND and AMB by FC and checkerboard was synergistic for 46 and 43% of isolates and antagonistic for 5 and 8%, respectively. For the combination of AND and azoles, it was synergistic for 36% and antagonistic for 3% by FC and synergistic for 44% and antagonistic for 3% by checkerboard. When the FC method was compared to the gold standard checkerboard method, the agreement was 0.91 (95% confidence interval [95% CI] of 0.88 to 0.94), sensitivity was 0.88 (95% CI of 0.73 to 0.95), and specificity was 0.95 (95% CI of 0.84 to 1). Thus, FC is a rapid and reliable method (<2 h) to assess the effect of antifungal combinations.

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Section: Discussionmentioning

confidence: 91%

Novel Method for Evaluating In Vitro Activity of Anidulafungin in Combination with Amphotericin B or Azoles

et al. 2012

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“…Caspofungin has potent antifungal activities and has been shown to be as effective as, and less toxic than, amphotericin B in the treatment of invasive candidiasis caused by C. albicans, C. parapsilosis, C. tropicalis, C. glabrata, C. krusei, C. guilliermodii, C. lipolytica, and C. rugosa (180,262). However, caspofungin MICs for C. parapsilosis are higher than those for other Candida species, with average MIC 50 and MIC 90 values ranging between 0.85 to 2 g/ml and 2 to 2.33 g/ml, respectively (17,18,88,146,202). Although the basis for this resistance is not clearly understood, structural differences in the components of the cell wall, a reduced affinity for the glucan synthase protein complex, or a difference in its regulatory network may be responsible (17).…”

Section: Antimicrobial Susceptibilitymentioning

confidence: 88%

“…For C. parapsilosis, caspofungin in combination with amphotericin B can significantly improve potency in vitro and in a murine infection model (18). Clinical data detailing the effectiveness of combination therapy are rare, although a few case reports have been published.…”

Section: Antimicrobial Susceptibilitymentioning

confidence: 99%

Candida parapsilosis, an Emerging Fungal Pathogen

2008

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SUMMARY Candida parapsilosis is an emerging major human pathogen that has dramatically increased in significance and prevalence over the past 2 decades, such that C. parapsilosis is now one of the leading causes of invasive candidal disease. Individuals at the highest risk for severe infection include neonates and patients in intensive care units. C. parapsilosis infections are especially associated with hyperalimentation solutions, prosthetic devices, and indwelling catheters, as well as the nosocomial spread of disease through the hands of health care workers. Factors involved in disease pathogenesis include the secretion of hydrolytic enzymes, adhesion to prosthetics, and biofilm formation. New molecular genetic tools are providing additional and much-needed information regarding C. parapsilosis virulence. The emerging information will provide a deeper understanding of C. parapsilosis pathogenesis and facilitate the development of new therapeutic approaches for treating C. parapsilosis infections.

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“…are observed, whereas antagonism is rarely detected (2,3). However, the results of the Etest-1 study indicate that this method could be an acceptable alternative to time-kill studies with antifungal agents.…”

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confidence: 89%

“…The positive interaction between an echinocandin compound and a polyene can be explained by the fact that both drug families possess unique mechanisms of action. It can be postulated that the candins, which inhibit cell wall synthesis, may enhance the activity of AMB by increasing the rate or degree of their access to the cell membrane (3).…”

mentioning

confidence: 99%

Antifungal Activity of Caspofungin in Combination with Amphotericin B against Candida glabrata : Comparison of Disk Diffusion, Etest, and Time-Kill Methods

Kiraz¹,

Dag

Yamaç

et al. 2009

Antimicrob Agents Chemother

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The in vitro activities of caspofungin plus amphotericin B against 50 Candida glabrata isolates were evaluated by the time-kill, disk diffusion, and Etest methods. In vitro experiments showed a positive interaction. Even though each of these methods uses different conditions and endpoints, the results of the different methods frequently agreed.Candida glabrata is an opportunistic pathogen that mainly affects severely immunocompromised patients, causing disseminated and frequently fatal infections (9). Many isolates of C. glabrata have shown innate resistance to fluconazole, and treatment often fails. Combined therapy could be a therapeutic alternative, but it has been poorly explored (7).Caspofungin (CAS), an echinocandin, inhibits fungal cell wall synthesis. Amphotericin B (AMB) targets fungal ergosterol, the main component of the fungal cell membrane (5). With their different mechanisms of action, these two drugs could be effective in combination. In this study, we hypothesized that the combination of CAS with AMB could have an advantage against C. glabrata over monotherapy with either drug.Fifty strains of C. glabrata were isolated from clinical samples at our laboratory. Candida parapsilosis ATCC 22019 was included for quality control (4). Antifungal susceptibility testing was performed, following both the broth microdilution (4) and Etest (Etest technical guide 4; AB Biodisk, Solna, Sweden) methods. The final concentrations were 0.03 to 2.0 g/ml of AMB and 0.0625 to 64 g/ml of CAS. MICs were read after 48 h of incubation. The Etest was performed on RPMI 1640 agar plates as recommended (Etest technical guide 4) (1). For CAS, an 80% inhibition in growth was used as the MIC endpoint (microcolonies were ignored), and for AMB, the MIC endpoint was defined as the lowest concentration with complete (100%) growth inhibition (1).For the time-kill studies, the drugs alone and in combination were used at 1ϫ MIC (1.0 g/ml for both drugs). The numbers of CFU were determined at 0, 2, 6, and 24 h. The limit of detection was 50 CFU/ml. Fungicidal activity was considered to have been achieved when the number of CFU per milliliter was Ͻ99.9% compared with the initial inoculum size. Synergy and antagonism were defined, respectively, as a Ն100-fold increase or decrease in killing compared with that achieved with the most active single agent. If there was less than a 100-fold change, the interaction was considered indifferent (3). For the antifungal combination studies, two types of Etest methods were used. For the first method (Etest-1; described in reference 5), synergy was defined as a decrease of Ն3 dilutions, indifference as a decrease of Ͻ2 dilutions, and antagonism as an increase of Ն3 dilutions, respectively, in the resultant MIC. The second method (Etest-2) was carried out as described in a previous study (10). The fractional inhibitory concentration (FIC) index was calculated as follows: ⌺FIC ϭ FIC A ϩ FIC B, where FIC A is the MIC of the combination/the MIC of drug A alone, and FIC B is the MIC of the combination/the...

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Caspofungin in Combination with Amphotericin B against Candida parapsilosis

Cited by 32 publications

References 23 publications

Novel Method for Evaluating In Vitro Activity of Anidulafungin in Combination with Amphotericin B or Azoles

Novel Method for Evaluating In Vitro Activity of Anidulafungin in Combination with Amphotericin B or Azoles

Candida parapsilosis, an Emerging Fungal Pathogen

Antifungal Activity of Caspofungin in Combination with Amphotericin B against Candida glabrata : Comparison of Disk Diffusion, Etest, and Time-Kill Methods

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