Antifungal pharmacodynamic characteristics of fluconazole and amphotericin B against Cryptococcus neoformans

Klepser, Michael E.; Wolfe, Erika J.; Pfaller, Michael A.

doi:10.1093/jac/41.3.397

Cited by 92 publications

(89 citation statements)

References 9 publications

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“…When the drug concentration of both classes of agents was below the serum sub-mMIC and sub-MIC respectively, no antifungal activity against kidney fungal burden was detected. Our results are also consistent with those of Klepser et al (13), who identified three distinct effects (no effect, partial inhibition, or maximum plateau) in time-kill curves from in vitro analyses of fluconazole and amphotericin B.…”

Section: Discussionsupporting

confidence: 93%

Direct Comparison of the Pharmacodynamics of Four Antifungal Drugs in a Mouse Model of Disseminated Candidiasis Using Microbiological Assays of Serum Drug Concentrations

Maki

Holmes

Watabe

et al. 2007

Microbiology and Immunology

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The aim of this study was to compare the pharmacodynamics of the azole antifungal drugs fluconazole, itraconazole and ketoconazole, and the polyene antifungal amphotericin B, in a mouse model of disseminated Candida albicans infection. In order to directly compare effective serum concentrations of these antifungals, drug concentrations were assayed microbiologically by measuring inhibition of C. albicans mycelial growth (mMIC) in a mouse serum‐based assay (serum antifungal titer). Efficacy in the mouse infection model was determined using an organ‐based (kidney burden) endpoint. For all four drugs, the serum antifungal titers, 8 hr after administration of single doses of drugs at a range of drug concentrations, correlated closely with C. albicans kidney fungal burden in the mouse model. The results showed that determining serum antifungal titer may be used to accurately represent kidney fungal burden in a mouse model of disseminated candidiasis and allowed direct comparison of the pharmacodynamics of differing classes of antifungal drugs.

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Section: Discussionsupporting

confidence: 93%

Direct Comparison of the Pharmacodynamics of Four Antifungal Drugs in a Mouse Model of Disseminated Candidiasis Using Microbiological Assays of Serum Drug Concentrations

Maki

Holmes

Watabe

et al. 2007

Microbiology and Immunology

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“…Afterwards, 20 μL of 0.5% TTC (triphenyl tetrazolium chloride) were added to each of 96-well for MIC determination, and the plate was incubated for 24 h. MIC was defined as the lowest citral concentration that inhibited visible growth of the microorganism, as also indicated by TTC by reading 96-well plates. Three independent experiments were performed on different occasions (Klepser, et al, 1998;Ernst et al, 1999;Costa et al, 2008).…”

Section: Determination Of Minimum Inhibitory Concentration (Mic) and mentioning

confidence: 99%

Anti-Candida albicanseffectiveness of citral and investigation of mode of action

Lima

Nóbrega

Oliveira

et al. 2012

Pharmaceutical Biology

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“…C. glabrata tends to show intermediate to complete resistence with the minimum inhibitory concentration required to kill 90% of organisms (MIC 90 ) ≥ 16 µg/mL. An in vitro time-kill study showed that the rate of fluconazole fungistatic activity was not influenced by concentration once the maximal fungistatic concentration was surpassed (concentration-independent), which is in contrast to the concentration-dependent fungicidal activity of amphotericin B deoxycholate or caspofungin [56,57].…”

Section: Pharmacologymentioning

confidence: 99%

Triazole Use in the Nursery: Fluconazole, Voriconazole, Posaconazole, and Ravuconazole

Watt¹,

Manzoni²,

Cohen‐Wolkowiez³

et al. 2013

Current Drug Metabolism

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Invasive fungal infections in infants admitted to the neonatal intensive care unit are common and often fatal. The mainstay of therapy against invasive fungal infections is antifungal agents. Over the last two decades, the development and approval of these drugs evolved tremendously, and the azole class emerged as important agents in the treatment and prevention of invasive fungal infections. Among the azoles, fluconazole has been used extensively due to its favorable pharmacokinetics, excellent activity against Candida spp, and safety profile. This drug has been well studied in children but data for its use in infants are largely limited to Candida prophylaxis studies. Voriconazole, a second generation triazole, has excellent activity against Candida and Aspergillus spp. However, data on its use in neonates are extremely limited. Posaconazole and Ravuconazole are the newest agents of the triazole family. The antimicrobial spectrum of posaconazole is similar to voriconazole, but with additional activity against zygomycetes. Experience with posaconazole in children is very limited, and there are no reports of its use in infants. Ravuconazole is not approved for use by the FDA but studies in animals and humans show that it is often fungicidal and has favorable pharmacokinetics. In conclusion, the management of invasive fungal infections has progressed greatly over the last two decades with the azole antifungals playing a significant role. Related to this class, future research is needed in order to better assess dosing, safety, schedules and areas of use of these agents in infants admitted to the neonatal intensive care unit.

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Antifungal pharmacodynamic characteristics of fluconazole and amphotericin B against Cryptococcus neoformans

Cited by 92 publications

References 9 publications

Direct Comparison of the Pharmacodynamics of Four Antifungal Drugs in a Mouse Model of Disseminated Candidiasis Using Microbiological Assays of Serum Drug Concentrations

Direct Comparison of the Pharmacodynamics of Four Antifungal Drugs in a Mouse Model of Disseminated Candidiasis Using Microbiological Assays of Serum Drug Concentrations

Anti-Candida albicanseffectiveness of citral and investigation of mode of action

Triazole Use in the Nursery: Fluconazole, Voriconazole, Posaconazole, and Ravuconazole

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