Effect of Voriconazole Combined with Micafungin against
 Candida
 ,
 Aspergillus
 , and
 Scedosporium
 spp. and
 Fusarium solani

Heyn, Kathrin; Tredup, Antje; Salvenmoser, Stefanie; Müller, F.

doi:10.1128/aac.49.12.5157-5159.2005

Cited by 92 publications

(53 citation statements)

References 17 publications

(13 reference statements)

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“…were demonstrated for all echinocandins, with greater inhibition achieved for A. flavus. These results are in agreement with those published previously for caspofungin (1) but appear to be somewhat different from those of two other previous studies, which demonstrated a diminished inhibitory effect of micafungin against A. flavus compared to that against A. fumigatus or A. terreus by the XTT assay (15,17). However, in both of those studies, the final concentration of menadione added to the wells was 25 M, i.e., a concentration fourfold higher than the one (6.25 M) used in the present study.…”

Section: Discussionsupporting

confidence: 36%

Comparative In Vitro Pharmacodynamics of Caspofungin, Micafungin, and Anidulafungin against Germinated and Nongerminated Aspergillus Conidia

Antachopoulos

Meletiadis

Sein

et al. 2008

Antimicrob Agents Chemother

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The concentration-dependent effects of echinocandins on the metabolic activity of Aspergillus spp. were comparatively studied by using nongerminated and germinated conidia. The susceptibilities of 11 Aspergillus fumigatus, 8 A. terreus and 8 A. flavus isolates to caspofungin, micafungin, and anidulafungin were studied by a CLSI (formerly NCCLS) M38-A broth microdilution-based method. After 48 h of incubation the minimum effective concentration (MEC) was defined microscopically. Metabolic activity was assessed by the 2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide assay and modeled by using the sigmoid (E max ) or "bell-shaped" model. The median MEC values of caspofungin (0.5 to 1 g/ml), micafungin (0.06 to 0.12 g/ml), and anidulafungin (0.03 g/ml) against nongerminated conidia increased by 0 to 1, 1 to 2, and 2 to 3 twofold dilutions, respectively (depending on the species), over those against germinated conidia. A similar shift to the right was demonstrated for the corresponding curves of metabolic activity. There was a significant correlation between the degrees of maximal metabolic inhibition caused by different echinocandins at both the species level (greater inhibition for A. flavus) and the strain level (r ‫؍‬ 0.84 to 0.93; P < 0.0001). Paradoxical increases in metabolism in the presence of higher concentrations of caspofungin, micafungin, and anidulafungin were detected in 6, 2, and 5 of the A. fumigatus isolates, respectively; 5, 1, and 2 of the A. terreus isolates, respectively; and 1, 0, and 0 of the A. flavus isolates, respectively. Based on the model, 50% of the maximal paradoxical increase was detected with 4.2, 11.1, and 10.8 g/ml of caspofungin, micafungin, and anidulafungin, respectively. All echinocandins therefore exerted comparable levels of maximal metabolic inhibition against Aspergillus spp. at concentrations that were differentially increased for germinated versus nongerminated conidia. The paradoxical increase in metabolism occurred more frequently and at lower concentrations with caspofungin than with micafungin and anidulafungin.The echinocandins are a group of recently introduced cyclic lipopeptide agents that inhibit the (1,3)-␤-D-glucan synthase activity of Candida spp. and Aspergillus spp. (10). In vitro and at clinically relevant concentrations, these compounds do not usually cause the complete inhibition of Aspergillus growth but induce morphological hyphal changes. The minimum effective concentration (MEC), defined as the lowest drug concentration at which short, stubby, and highly branched hyphae are observed, has been introduced for the determination of echinocandin activity against Aspergillus spp. in vitro (3,13,16,24). The MEC, however, represents a subjective, qualitative assessment of hyphal morphology and does not provide a quantification of the antifungal activity at different concentrations.We recently developed a new, objective, and quantitative method for assessment of the in vitro activity of caspofungin against Aspergillus fumigatus, A. terr...

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Section: Discussionsupporting

confidence: 36%

Comparative In Vitro Pharmacodynamics of Caspofungin, Micafungin, and Anidulafungin against Germinated and Nongerminated Aspergillus Conidia

Antachopoulos

Meletiadis

Sein

et al. 2008

Antimicrob Agents Chemother

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“…The combination of voriconazole and amphotericin B with micafungin was synergistic against S. prolificans and S. apiospermum isolates, although at lower frequencies (31% to 75% of the tested isolates). For those isolates for which the interactions were not classified as synergistic, a significant reduction of the MICs were observed and no antagonism was found (188,489). This synergistic interaction could be explained by the different mechanisms of action of these drugs, where the action of one agent reduces the resistance to the second agent.…”

Section: In Vitro Susceptibilities To Combinations Of Antifungal Agentsmentioning

confidence: 95%

Infections Caused byScedosporiumspp

et al. 2008

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SUMMARY Scedosporium spp. are increasingly recognized as causes of resistant life-threatening infections in immunocompromised patients. Scedosporium spp. also cause a wide spectrum of conditions, including mycetoma, saprobic involvement and colonization of the airways, sinopulmonary infections, extrapulmonary localized infections, and disseminated infections. Invasive scedosporium infections are also associated with central nervous infection following near-drowning accidents. The most common sites of infection are the lungs, sinuses, bones, joints, eyes, and brain. Scedosporium apiospermum and Scedosporium prolificans are the two principal medically important species of this genus. Pseudallescheria boydii, the teleomorph of S. apiospermum, is recognized by the presence of cleistothecia. Recent advances in molecular taxonomy have advanced the understanding of the genus Scedosporium and have demonstrated a wider range of species than heretofore recognized. Studies of the pathogenesis of and immune response to Scedosporium spp. underscore the importance of innate host defenses in protection against these organisms. Microbiological diagnosis of Scedosporium spp. currently depends upon culture and morphological characterization. Molecular tools for clinical microbiological detection of Scedosporium spp. are currently investigational. Infections caused by S. apiospermum and P. boydii in patients and animals may respond to antifungal triazoles. By comparison, infections caused by S. prolificans seldom respond to medical therapy alone. Surgery and reversal of immunosuppression may be the only effective therapeutic options for infections caused by S. prolificans.

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“…For such cases, MCFG and voriconazole (VRCZ) combination therapy is expected to be effective. 17,18) However, VRCZ exhibits various interactive effects, and thus, combination with other drugs including antifungal agents should be carefully implemented. Since it is desirable to measure the blood concentration during administration of VRCZ, measurement of blood concentrations of both MCFG and VRCZ may be necessary for treatment of intractable deep mycosis with concomitant MCFG and VRCZ.…”

Section: Discussionmentioning

confidence: 99%

Effective Blood Concentration of Micafungin for Pulmonary Aspergillosis

Shimoeda

Ohta

Kobayashi

et al. 2006

Biological & Pharmaceutical Bulletin

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We previously reported that a 150 mg or higher daily dose is necessary for treatment of pulmonary aspergillosis with micafungin (MCFG) alone in patients with blood diseases. Since a delay in the treatment of pulmonary aspergillosis has a major influence on patient survival, clarification of the effective blood concentration of MCFG enables rapid treatment. Establishment of an appropriate dose is also useful for reducing the risk of adverse effects, such as MCFG-induced impairment of liver function. Aiming for the rapid and safe treatment of pulmonary aspergillosis, we established new clinical diagnostic criteria of mycosis and MCFG therapeutic effect judgment criteria, and investigated the effective blood concentration of MCFG for mycosis. The blood trough level of MCFG in patients with blood diseases at each clinical improvement rating of pulmonary aspergillosis was 5.23؎2.44 m mg/ml in markedly improved cases, 4.08؎2.63 m mg/ml in improved cases, and 3.45؎1.63 m mg/ml in successfully prevented cases, showing no significant difference among the 3 groups. Based on this finding, it is advisable to target a 5 m mg/ml or higher blood trough level of MCFG in establishing the dose for aspergillosis in patients with blood diseases.

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Effect of Voriconazole Combined with Micafungin against Candida , Aspergillus , and Scedosporium spp. and Fusarium solani

Cited by 92 publications

References 17 publications

Comparative In Vitro Pharmacodynamics of Caspofungin, Micafungin, and Anidulafungin against Germinated and Nongerminated Aspergillus Conidia

Comparative In Vitro Pharmacodynamics of Caspofungin, Micafungin, and Anidulafungin against Germinated and Nongerminated Aspergillus Conidia

Infections Caused byScedosporiumspp

Effective Blood Concentration of Micafungin for Pulmonary Aspergillosis

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