Assessment of the Paradoxical Effect of Caspofungin in Therapy of Candidiasis

Clemons, Karl V.; Espiritu, Marife; Parmar, Rachana; Stevens, David A.

doi:10.1128/aac.00694-06

Cited by 33 publications

(38 citation statements)

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“…This can be due to the fact that CAS given as a single drug did not show a significant improvement in the clearance of fungal burden with dose escalation above 1 mg/ kg/day. These results are similar to those recently reported by others (1,5,9). Altogether, these data indicate that, to obtain a beneficial effect of this combination approach against C. parapsilosis, an adequate ratio of drug concentrations has to be achieved.…”

Section: Discussionsupporting

confidence: 83%

Caspofungin in Combination with Amphotericin B against Candida parapsilosis

Barchiesi¹,

Spreghini²,

Tomassetti³

et al. 2007

Antimicrob Agents Chemother

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Candida parapsilosis has emerged as an important nosocomial pathogen. In the present study, a checkerboard broth microdilution method was performed to investigate the in vitro activities of caspofungin (CAS) in combination with amphotericin B (AMB) against three clinical isolates of C. parapsilosis. Although there was a significant reduction of the MIC of one or both drugs used in combination, an indifferent interaction (fractional inhibitory concentration index greater than 0.50 and less than or equal to 4.0) was observed in 100% of cases. This finding was confirmed by killing curve studies. By a disk diffusion assay, the halo diameters produced by antifungal agents in combination were often significantly greater than those produced by each drug alone. Antagonism was never observed. In a murine model of systemic candidiasis, CAS at either 0.25 or 1 mg/kg/day combined with AMB at 1 mg/kg/day was significantly more effective than each single drug at reducing the colony counts in kidneys. Higher doses of the echinocandin (i.e., 5 and 10 mg/kg/day) combined with the polyene did not show any advantage over CAS alone. Overall, our study showed a positive interaction of CAS and AMB against C. parapsilosis.The frequency of invasive mycoses due to opportunistic fungal pathogens has increased dramatically over the past two decades, and now Candida spp. ranks as the fourth most common cause of nosocomial bloodstream infections (20). Although Candida albicans is the organism most often associated with serious fungal infections, other Candida spp. have emerged as clinically important pathogens associated with opportunistic infections (17,20).Candida parapsilosis is the second most frequent yeast species isolated from normally sterile body sites in North America, Europe, and Latin America (12,20). Moreover, studies conducted in the United States showed that C. parapsilosis is the most common non-C. albicans Candida spp. in pediatric patients (17,18,23).Caspofungin (CAS) is an echinocandin antifungal agent that has potent activity against many fungal species, including Candida spp. (13,20,22). Clinical studies have shown that CAS is at least as active as amphotericin B and fluconazole in the treatment of invasive candidiasis (13,20).Amphotericin B (AMB) targets fungal ergosterol, the main component of the fungal cell membrane, while CAS inhibits the synthesis of the fungal cell wall by blocking ␤-1,3-D-glucan (6, 7). Its innovative mechanism of action makes this drug a suitable candidate for antifungal combination therapy.Although CAS MICs for C. parapsilosis can be higher than those seen for C. albicans, the echinocandin is generally effective in infections caused by this yeast species (1, 4, 6-8, 13, 20, 22). Similarly, amphotericin B is active in vitro and in vivo against C. parapsilosis (20).In this study, we hypothesized that the combination of CAS and AMB could be advantageous over each monotherapy against C. parapsilosis. To investigate this interaction, we applied in vitro methods and an experimental mouse model of ...

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Section: Discussionsupporting

confidence: 83%

Caspofungin in Combination with Amphotericin B against Candida parapsilosis

Barchiesi¹,

Spreghini²,

Tomassetti³

et al. 2007

Antimicrob Agents Chemother

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“…They suggested that PG may contribute to this phenomenon. Similar in vivo effects were observed for infections by Aspergillus fumigatus and C. albicans (3,11).…”

supporting

confidence: 65%

In Vitro Study of Candida tropicalis Isolates Exhibiting Paradoxical Growth in the Presence of High Concentrations of Caspofungin

Sóczó

Kardos

Varga

et al. 2007

Antimicrob Agents Chemother

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“…Several researchers reported the fungicidal activity of caspofungin and amphotericin B (7,9,30). In this study, for 71% of C. albicans isolates the MFC of amphotericin B and caspofungin were equal to MIC (Table 2).…”

Section: Discussionmentioning

confidence: 76%

Susceptibility testing of Candida albicans isolated from oropharyngeal mucosa of HIV+ patients to fluconazole, amphotericin B and Caspofungin: killing kinetics of caspofungin and amphotericin B against fluconazole resistant and susceptible isolates

Lemos¹,

Costa²,

Araujo³

et al. 2009

Braz. J. Microbiol.

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A clear understanding of the pharmacodynamic properties of antifungal agents is important for the adequate treatment of fungal infections like candidiasis. For certain antifungal agents, the determination of Minimal Fungicidal Concentration (MFC) and time kill curve could be clinically more relevant than the determination of the Minimal Inhibitory Concentration (MIC). In this study, MIC and MFC to fluconazole, amphotericin B and caspofungin against C. albicans isolates and the killing patterns obtained with caspofungin and amphotericin B against susceptible and resistant strains to fluconazole were determined. The results of MICs showed that all C. albicans isolates were highly susceptible to amphotericin B, but two isolates were fluconazole resistant. The comparative analysis between MIC and MFC showed that MFC of fluconazole was fourfold higher than MIC in 41.9% of the C. albicans isolates. Same values of MFC and MIC of amphotericin B and caspofungin were found for 71% of the isolates. Correlation between time kill curves and MFC of amphotericin B and caspofungin against all 4 isolates tested was observed. The caspofungin killing effect was more evident at MFC in 6 hours of incubation than at MIC in this time, suggesting dependence of concentration. The similarity of results of time-kill curve and MFC values indicate that determination of MFC is an alternative for the detection of the fungicidal activity of these drugs.

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Assessment of the Paradoxical Effect of Caspofungin in Therapy of Candidiasis

Cited by 33 publications

References 0 publications

Caspofungin in Combination with Amphotericin B against Candida parapsilosis

Caspofungin in Combination with Amphotericin B against Candida parapsilosis

In Vitro Study of Candida tropicalis Isolates Exhibiting Paradoxical Growth in the Presence of High Concentrations of Caspofungin

Susceptibility testing of Candida albicans isolated from oropharyngeal mucosa of HIV+ patients to fluconazole, amphotericin B and Caspofungin: killing kinetics of caspofungin and amphotericin B against fluconazole resistant and susceptible isolates

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