Fosfluconazole for Antifungal Prophylaxis in Very Low Birth Weight Infants

Takahashi, Daijiro; Nakamura, Tomohiko; Shigematsu, Reiko; Matsui, M; Araki, Shunsuke; Kubo, Kazuyasu; Sato, Hiroshi; Shirahata, Atsushi

doi:10.1155/2009/274768

Cited by 3 publications

(2 citation statements)

References 5 publications

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“…Therefore, it is conceivable that F-FLCZ is also rapidly converted to FLCZ for this population. F-FLCZ is increasingly applied as an antifungal prophylaxis among ELBWIs in routine clinical care at several institutions across Japan, including at our center ( 10 , 11 ). Given that the acceptable volume of infused fluid is smaller, this treatment option appears beneficial for infants on strict fluid management, particularly among low-birth-weight or preterm infants.…”

Section: Introductionmentioning

confidence: 99%

Fluconazole Population Pharmacokinetics after Fosfluconazole Administration and Dosing Optimization in Extremely Low-Birth-Weight Infants

et al. 2022

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Invasive fungal infection is an important cause of mortality and morbidity in very preterm or very-low-birth-weight infants. In order to limit the risk of invasive fungal infections in this population, the administration of fluconazole is generally recommended for extremely low-birth-weight infants admitted to a neonatal intensive care unit with a Candida species colonization prevalence rate of >10%, under the guidelines of the Infectious Diseases Society of America.

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Section: Introductionmentioning

confidence: 99%

Fluconazole Population Pharmacokinetics after Fosfluconazole Administration and Dosing Optimization in Extremely Low-Birth-Weight Infants

et al. 2022

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“…infection higher than 5% [6]. At our center, fosfluconazole, a water-soluble phosphate prodrug of fluconazole which is more highly soluble than fluconazole, is frequently used for antifungal prophylaxis in preterm neonates to minimize the infusion volume [7]. Although the pharmacokinetics of fluconazole after fosfluconazole treatment in adults is well documented, an appropriate, validated dosing regimen for neonates with VLBW and ELBW does not yet exist, and further clinical pharmacokinetic (PK) research is required.…”

Section: Introductionmentioning

confidence: 99%

A sensitive method for analyzing fluconazole in extremely small volumes of neonatal serum

Saito

Tanzawa

Kojo

et al. 2020

J Pharm Health Care Sci

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Background: The need for a large volume of serum sample significantly reduces the feasibility of neonatal pharmacokinetic studies in daily practice, which must often rely on scavenged or opportunistic sampling. This problem is most apparent in preterm newborns, where ethical and practical considerations prohibit the collection of large sample volumes. Most of the fluconazole analysis assays published thus far required a minimum serum sample of 50 to 100 μL for a single assay. The purpose of the present study was to develop and validate a sensitive method requiring a smaller sample volume (10 μL) to satisfy clinically relevant research requirements. Methods: Following simple protein precipitation and centrifugation, the filtrated supernatant was injected into a liquid chromatography system and separated with a C18 reverse-phase column. Fluconazole and the internal standard (IS, fluconazole-d4) were detected and quantified using tandem mass spectrometry. The method was validated with reference to the Food and Drug Administration's Guidance for Industry. Accuracy and precision were evaluated at six quality control concentration levels (ranging from 0.01 to 100 μg/mL). Results: Investigated calibration curves were linear in the 0.01-100 μg/mL range. Intra-and inter-day accuracy (− 7.7 to 7.4%) and precision (0.3 to 6.0%) were below 15%. The calculated limit of detection and the lower limit of quantification (LLOQ) was 0.0019 μg/mL and 0.0031 μg/mL, respectively. Fluconazole in the prepared samples was stable for at least 4 months at − 20°C and − 80°C. This method was applied to analyze 234 serum samples from ten neonates who received fosfluconazole, a water-soluble phosphate prodrug of fluconazole which converts to fluconazole in the body, as part of a pharmacokinetic study using daily scavenged laboratory samples. The median (range) concentration up to 72 h after fosfluconazole administration was 2.9 (0.02 to 26.8 μg/mL) μg/mL, which was within the range of the calibration curve. Conclusion: Fluconazole was able to be detected in an extremely small volume (10 μL) of serum from neonates receiving fosfluconazole. The method presented here can be used to quantify fluconazole concentrations for pharmacokinetic studies of the neonatal population by using scavenged samples.

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Augmenting Azoles with Drug Synergy to Expand the Antifungal Toolbox

Kane

Carter

2022

Pharmaceuticals

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Fungal infections impact the lives of at least 12 million people every year, killing over 1.5 million. Wide-spread use of fungicides and prophylactic antifungal therapy have driven resistance in many serious fungal pathogens, and there is an urgent need to expand the current antifungal arsenal. Recent research has focused on improving azoles, our most successful class of antifungals, by looking for synergistic interactions with secondary compounds. Synergists can co-operate with azoles by targeting steps in related pathways, or they may act on mechanisms related to resistance such as active efflux or on totally disparate pathways or processes. A variety of sources of potential synergists have been explored, including pre-existing antimicrobials, pharmaceuticals approved for other uses, bioactive natural compounds and phytochemicals, and novel synthetic compounds. Synergy can successfully widen the antifungal spectrum, decrease inhibitory dosages, reduce toxicity, and prevent the development of resistance. This review highlights the diversity of mechanisms that have been exploited for the purposes of azole synergy and demonstrates that synergy remains a promising approach for meeting the urgent need for novel antifungal strategies.

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Fosfluconazole for Antifungal Prophylaxis in Very Low Birth Weight Infants

Cited by 3 publications

References 5 publications

Fluconazole Population Pharmacokinetics after Fosfluconazole Administration and Dosing Optimization in Extremely Low-Birth-Weight Infants

Fluconazole Population Pharmacokinetics after Fosfluconazole Administration and Dosing Optimization in Extremely Low-Birth-Weight Infants

A sensitive method for analyzing fluconazole in extremely small volumes of neonatal serum

Augmenting Azoles with Drug Synergy to Expand the Antifungal Toolbox

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