Literature DB >> 32201545

Extrapolating Antifungal Animal Data to Humans - Is it reliable?

Victoria M Stevens1, Scott W Mueller1, Paul M Reynolds1, Robert MacLaren1, Tyree H Kiser1.   

Abstract

PURPOSE OF REVIEW: This article aimed to review animal models of antifungals and identifies human literature to assess if the extrapolation of results is reliable. RECENT
FINDINGS: Animal studies have helped identify AUC/MIC targets for new drugs and formulations such as isavuconazole and delayed release posaconazole that have translated to successful outcomes in humans. Models have also been influential in the identification of possible combination therapies for the treatment of aspergillosis, such as voriconazole and echinocandins. However, challenges are endured with animal models when it comes to replicating the pharmacokinetics of humans which has been exemplified with the newest itraconazole formulation. Additionally, animal models have displayed a survival benefit with the use of iron chelators and amphotericin for mucormycosis which was not demonstrated in humans.
SUMMARY: Animal models have been a staple in the development and optimization of antifungal agents. They afford the ability to investigate uncommon diseases, such as invasive fungal infections, that would otherwise take years and many resources to complete. Although there are many benefits of animal models there are also shortcomings. This is why the reliability of extrapolating data from animal models to humans is often scrutinized.

Entities:  

Keywords:  Amphotericin B; Anidulafungin; Animal Model; Caspofungin; Echinocandin; Fluconazole; Invasive Fungal Infection; Isavuconazole; Itraconazole; Micafungin; Murine; Pharmacodynamics; Posaconazole; Rabbit; Rezafungin; Triazole; Voriconazole

Year:  2020        PMID: 32201545      PMCID: PMC7083583          DOI: 10.1007/s12281-020-00370-x

Source DB:  PubMed          Journal:  Curr Fungal Infect Rep        ISSN: 1936-3761


  85 in total

Review 1.  Echinocandins for the Treatment of Invasive Aspergillosis: from Laboratory to Bedside.

Authors:  Marion Aruanno; Emmanouil Glampedakis; Frédéric Lamoth
Journal:  Antimicrob Agents Chemother       Date:  2019-07-25       Impact factor: 5.191

2.  High-dose caspofungin as a component of combination antifungal therapy in 91 patients with neoplastic diseases and hematopoietic stem cell transplantation: a critical review of short-term and long-term adverse events.

Authors:  Amar Safdar; Gilhen Rodriguez; Jorge Zuniga; Fadi Al Akhrass; Anupam Pande
Journal:  J Pharm Pract       Date:  2013-12-23

Review 3.  Animal models in the pharmacokinetic/pharmacodynamic evaluation of antimicrobial agents.

Authors:  Miao Zhao; Alexander J Lepak; David R Andes
Journal:  Bioorg Med Chem       Date:  2016-11-09       Impact factor: 3.641

4.  In vivo comparison of the pharmacodynamic targets for echinocandin drugs against Candida species.

Authors:  D Andes; D J Diekema; M A Pfaller; J Bohrmuller; K Marchillo; A Lepak
Journal:  Antimicrob Agents Chemother       Date:  2010-04-12       Impact factor: 5.191

5.  Fluconazole MIC and the fluconazole dose/MIC ratio correlate with therapeutic response among patients with candidemia.

Authors:  Cornelius J Clancy; Victor L Yu; Arthur J Morris; David R Snydman; M Hong Nguyen
Journal:  Antimicrob Agents Chemother       Date:  2005-08       Impact factor: 5.191

6.  Posaconazole pharmacodynamic target determination against wild-type and Cyp51 mutant isolates of Aspergillus fumigatus in an in vivo model of invasive pulmonary aspergillosis.

Authors:  Alexander J Lepak; Karen Marchillo; Jaimie Vanhecker; David R Andes
Journal:  Antimicrob Agents Chemother       Date:  2012-11-12       Impact factor: 5.191

Review 7.  Antifungal pharmacokinetics and pharmacodynamics.

Authors:  Alexander J Lepak; David R Andes
Journal:  Cold Spring Harb Perspect Med       Date:  2014-11-10       Impact factor: 6.915

8.  Deferiprone iron chelation as a novel therapy for experimental mucormycosis.

Authors:  Ashraf S Ibrahim; John E Edwards; Yue Fu; Brad Spellberg
Journal:  J Antimicrob Chemother       Date:  2006-08-23       Impact factor: 5.790

9.  Evaluation of Sulfobutylether-β-Cyclodextrin Exposure in a Critically Ill Patient Receiving Intravenous Posaconazole While Undergoing Continuous Venovenous Hemofiltration.

Authors:  Amanda A Morris; Scott W Mueller; Joseph E Rower; Taylor Washburn; Tyree H Kiser
Journal:  Antimicrob Agents Chemother       Date:  2015-08-10       Impact factor: 5.191

10.  Pharmacodynamics of caspofungin in a murine model of invasive pulmonary aspergillosis: evidence of concentration-dependent activity.

Authors:  Nathan P Wiederhold; Dimitrios P Kontoyiannis; Jingduan Chi; Randall A Prince; Vincent H Tam; Russell E Lewis
Journal:  J Infect Dis       Date:  2004-09-10       Impact factor: 5.226

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  2 in total

Review 1.  The Antifungal Pipeline: Fosmanogepix, Ibrexafungerp, Olorofim, Opelconazole, and Rezafungin.

Authors:  Martin Hoenigl; Rosanne Sprute; Matthias Egger; Amir Arastehfar; Oliver A Cornely; Robert Krause; Cornelia Lass-Flörl; Juergen Prattes; Andrej Spec; George R Thompson; Nathan Wiederhold; Jeffrey D Jenks
Journal:  Drugs       Date:  2021-10-09       Impact factor: 9.546

2.  Azole-resistant Aspergillus and Echinocandin-resistant Candida - What are the treatment options?

Authors:  Alison R Novak; Mary E Bradley; Tyree H Kiser; Scott W Mueller
Journal:  Curr Fungal Infect Rep       Date:  2020-03-26
  2 in total

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