Effect of Cumulative Intravenous Voriconazole Dose on Renal Function in Hematological Patients

Yasu, Takeo; Konuma, Takaaki; Kuroda, Seiichiro; Takahashi, Satoshi; Tojo, Arinobu

doi:10.1128/aac.00507-18

Cited by 18 publications

(10 citation statements)

References 14 publications

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“…Therefore, it is reassuring that the majority of studies evaluating IV voriconazole in patients with underlying renal disease have found no risk of nephrotoxicity (25,26). The only study which identified possible nephrotoxicity associated with IV voriconazole used a cumulative dose of > 400mg/kg (27). Achieving this cumulative dose would require at least 50 days of voriconazole therapy assuming a standard maintenance dose of 4mg/kg every 12 hours.…”

Section: Discussionmentioning

confidence: 99%

“…The only study which identified possible nephrotoxicity associated with i.v. voriconazole used a cumulative dose of ≥400 mg/kg ( 22 ). Achieving this cumulative dose would require at least 50 days of voriconazole therapy assuming a standard maintenance dose of 4 mg/kg every 12 h. Only two patients in our cohort received 10 days of remdesivir therapy, and we suspect the majority of patients would routinely receive a 5-day course in light of a randomized controlled trial which failed to show a significant benefit between a 5-day course versus a 10-day course of remdesivir in patients with severe SARS-CoV-2 ( 14 ).…”

Section: Discussionmentioning

confidence: 99%

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A Valid Warning or Clinical Lore: an Evaluation of Safety Outcomes of Remdesivir in Patients with Impaired Renal Function from a Multicenter Matched Cohort

Ackley

McManus

Topal

et al. 2021

Antimicrob Agents Chemother

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Objective: Per prescribing guidance, remdesivir is not recommended for SARS-CoV-2 in patients with renal disease given the absence of safety data in this patient population. Methods: This study was a multi-center, retrospective chart review of hospitalized patients with SARS-CoV-2 who received remdesivir. Safety outcomes were compared between patients with an estimated creatinine clearance (eCrCl) < 30 mL/min and an eCrCl ≥ 30 mL/min. The primary endpoint was acute kidney injury (AKI) at the end of treatment (EOT). Results: Of 359 patients who received remdesivir, 347 met inclusion criteria. Patients with an eCrCl < 30 mL/min were older [median, 80 years (IQR, 63.8-89) versus 62 (IQR, 54-74); P<0.001], were more likely to be on vasopressors on the day of remdesivir administration (30% versus 12.7%; P=0.003), and were more likely to be mechanically ventilated during remdesivir therapy (27.5% versus 12.4%; P=0.01) compared to those with an eCrCl ≥ 30 mL/min. Despite these confounders, there was no significant difference in the frequency of EOT AKI (5% versus 2.3%; P=0.283) or early discontinuation due to abnormal LFTs (0% versus 3.9%; P=0.374). Of the 5% of patients who developed EOT AKI on remdesivir with an eCrCl <30mL/min, no cases were attributable to remdesivir administration per the treating physician. Comparable safety outcomes were observed when 1:1 nearest neighbor matching was applied to account for baseline confounders. Conclusion: Remdesivir administration was not significantly associated with increased EOT AKI in patients with an eCrCl < 30mL/min compared to patients with an eCrCl ≥ 30mL/min.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

A Valid Warning or Clinical Lore: an Evaluation of Safety Outcomes of Remdesivir in Patients with Impaired Renal Function from a Multicenter Matched Cohort

Ackley

McManus

Topal

et al. 2021

Antimicrob Agents Chemother

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“…Previous work demonstrated various formulations of cyclodextrin ability to improve resveratrol biodistribution, utilizing the CD/resveratrol inclusion complex to overcome resveratrol's low aqueous solubility and bioavailability [53][54][55]. However, the majority of these formulations incorporated the monomer form of CD (either natural or modified), which unfortunately has limited translational use due to nephrotoxicity concerns and hastened delivery kinetics [56,57]. Therefore, in the study herein, we utilized a crosslinked CD vector, which operates through a different means than the soluble, monomer form of CD.…”

Section: Discussionmentioning

confidence: 99%

Resveratrol Delivery from Implanted Cyclodextrin Polymers Provides Sustained Antioxidant Effect on Implanted Neural Probes

Haley

Zuckerman²,

Dakhlallah

et al. 2020

IJMS

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Intracortical microelectrodes are valuable tools used to study and treat neurological diseases. Due in large part to the oxidative stress and inflammatory response occurring after electrode implantation, the signal quality of these electrodes decreases over time. To alleviate this response, resveratrol, a natural antioxidant which elicits neuroprotective effects through reduction of oxidative stress, was utilized. This work compares traditional systemic delivery of resveratrol to the novel cyclodextrin polymer (pCD) local delivery approach presented herein, both in vitro and in vivo. The pCD displayed an extended resveratrol release for 100 days, as well as 60 days of free radical scavenging activity in vitro. In vivo results indicated that our pCD delivery system successfully delivered resveratrol to the brain with a sustained release for the entire short-duration study (up to 7 days). Interestingly, significantly greater concentrations of resveratrol metabolites were found at the intracortical probe implantation site compared to the systemic administration of resveratrol. Together, our pilot results provide support for the possibility of improving the delivery of resveratrol in an attempt to stabilize long-term neural interfacing applications.

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“…Isavuconazole is a novel azole, as effective as voriconazole but less toxic than voriconazole. Toxicity is lower in isavuconazole, since it is highly water soluble and does not require beta-cyclodextrin in its intravenous (IV) formulation, which is required for voriconazole, causing reduced nephrotoxicity [8,9]. Isavuconazole can be administered both intravenously (IV) and orally and its toxicity profile is similar to that of fluconazole but is more active [10,11].…”

Section: Antifungals That Target Ergosterol and Its Biosynthesismentioning

confidence: 99%

Candidiasis and Mechanisms of Antifungal Resistance

2020

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Candidiasis can be present as a cutaneous, mucosal or deep-seated organ infection, which is caused by more than 20 types of Candida sp., with C. albicans being the most common. These are pathogenic yeast and are usually present in the normal microbiome. High-risk individuals are patients of human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS), organ transplant, and diabetes. During infection, pathogens can adhere to complement receptors and various extracellular matrix proteins in the oral and vaginal cavity. Oral and vaginal Candidiasis results from the overgrowth of Candida sp. in the hosts, causing penetration of the oral and vaginal tissues. Symptoms include white patches in the mouth, tongue, throat, and itchiness or burning of genitalia. Diagnosis involves visual examination, microscopic analysis, or culturing. These infections are treated with a variety of antifungals that target different biosynthetic pathways of the pathogen. For example, echinochandins target cell wall biosynthesis, while allylamines, azoles, and morpholines target ergosterol biosynthesis, and 5-Flucytosine (5FC) targets nucleic acid biosynthesis. Azoles are commonly used in therapeutics, however, because of its fungistatic nature, Candida sp. evolve azole resistance. Besides azoles, Candida sp. also acquire resistance to polyenes, echinochandins, and 5FC. This review discusses, in detail, the drug resistance mechanisms adapted by Candida sp.

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Effect of Cumulative Intravenous Voriconazole Dose on Renal Function in Hematological Patients

Cited by 18 publications

References 14 publications

A Valid Warning or Clinical Lore: an Evaluation of Safety Outcomes of Remdesivir in Patients with Impaired Renal Function from a Multicenter Matched Cohort

A Valid Warning or Clinical Lore: an Evaluation of Safety Outcomes of Remdesivir in Patients with Impaired Renal Function from a Multicenter Matched Cohort

Resveratrol Delivery from Implanted Cyclodextrin Polymers Provides Sustained Antioxidant Effect on Implanted Neural Probes

Candidiasis and Mechanisms of Antifungal Resistance

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