Potential lipid-based strategies of amphotericin B designed for oral administration in clinical application

Zhong, Xiaoming; Yang, Jiajun; Liu, Hongyan; Yang, Zhiwen; Luo, Ping

doi:10.1080/10717544.2022.2161671

Cited by 10 publications

(7 citation statements)

References 79 publications

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“…In recent years, two lipid-based formulations developed for oral administration, named amB lipid complex (ABLC) and liposomal amphotericin (L-AmB), have been authorized, characterized by greater selective toxicity towards sensitive fungi, and increased tolerability especially in terms of nephrotoxicity. Indeed, these lipidic formulations interact with ergosterol, leading to increased permeability to univalent and divalent cations and fungal cell death [ 17 ]. The most widely used triazoles in clinical practice are itraconazole, posaconazole, and voriconazole; other agents in the class are fluconazole and isavuconazole [ 18 ].…”

Section: Systemic Mycosis and Pharmacological Therapymentioning

confidence: 99%

Antifungal Drug Resistance: An Emergent Health Threat

Vitiello

Ferrara²,

Boccellino

et al. 2023

Biomedicines

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Fungal infections, named mycosis, can cause severe invasive and systemic diseases that can even lead to death. In recent years, epidemiological data have recorded an increase in cases of severe fungal infections, caused mainly by a growing number of immunocompromised patients and the emergence of fungal pathogenic forms that are increasingly resistant to antimycotic drug treatments. Consequently, an increase in the incidence of mortality due to fungal infections has also been observed. Among the most drug-resistant fungal forms are those belonging to the Candida and Aspergillus spp. Some pathogens are widespread globally, while others are endemic in some areas only. In addition, some others may represent a health threat for some specific subpopulations and not for the general public. In contrast to the extensive therapeutic armamentarium available for the antimicrobial chemotherapeutic treatment of bacteria, for fungal infections there are only a few classes of antimycotic drugs on the market, such as polyenes, azoles, echinocandins, and a few molecules are under trial. In this review, we focused on the systemic mycosis, highlighted the antifungal drug compounds available in the pipeline, and analyzed the main molecular mechanisms for the development of antifungal resistance to give a comprehensive overview and increase awareness on this growing health threat.

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Section: Systemic Mycosis and Pharmacological Therapymentioning

confidence: 99%

Antifungal Drug Resistance: An Emergent Health Threat

Vitiello

Ferrara²,

Boccellino

et al. 2023

Biomedicines

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“…The search for a new formulation led, in the late 1970s, to liposomal drug encapsulation which reduced but did not eliminate the nephrotoxicity [43,48,49]. AmB is usually administered intravenously since it is poorly absorbed from the gastrointestinal tract, is widely distributed to all tissues except to the central nervous system and elimination is mainly via slow hepatic metabolism with a small fraction of the drug excreted in the urine [39,45,50]. The drug exhibits concentration-dependent fungicidal activity with Cmax/MIC (minimum inhibitory concentration) and the PD index being the most predictive of efficacy; see Table 2 [44,45,48,51].…”

Section: Polyene Antifungalsmentioning

confidence: 99%

“…Moreover, AmB maintains fungicidal activity and fungal growth inhibition after the concentration has fallen below the MIC of the infecting organism [44,45,52]. Liposomal AmB is the main antifungal drug used in invasive fungal infection associated with Histoplasma capsulatum, Coccidioides immitis, Candida species, Blastomyces dermatitidis, Rhodotorula, Cryptococcus neoformans, Sporothrix schenckii, Mucor and Aspergillus fumigatus in critically ill patients [48,50,53]. In spite of the large spectrum of activity, Aspergillus terreus, Pseudallescheria boydii and Fusarium sp.…”

Section: Polyene Antifungalsmentioning

confidence: 99%

Antifungals: From Pharmacokinetics to Clinical Practice

Carmo,

Rocha,

Pereirinha

et al. 2023

Antibiotics

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The use of antifungal drugs started in the 1950s with polyenes nystatin, natamycin and amphotericin B-deoxycholate (AmB). Until the present day, AmB has been considered to be a hallmark in the treatment of invasive systemic fungal infections. Nevertheless, the success and the use of AmB were associated with severe adverse effects which stimulated the development of new antifungal drugs such as azoles, pyrimidine antimetabolite, mitotic inhibitors, allylamines and echinochandins. However, all of these drugs presented one or more limitations associated with adverse reactions, administration route and more recently the development of resistance. To worsen this scenario, there has been an increase in fungal infections, especially in invasive systemic fungal infections that are particularly difficult to diagnose and treat. In 2022, the World Health Organization (WHO) published the first fungal priority pathogens list, alerting people to the increased incidence of invasive systemic fungal infections and to the associated risk of mortality/morbidity. The report also emphasized the need to rationally use existing drugs and develop new drugs. In this review, we performed an overview of the history of antifungals and their classification, mechanism of action, pharmacokinetic/pharmacodynamic (PK/PD) characteristics and clinical applications. In parallel, we also addressed the contribution of fungi biology and genetics to the development of resistance to antifungal drugs. Considering that drug effectiveness also depends on the mammalian host, we provide an overview on the roles of therapeutic drug monitoring and pharmacogenomics as means to improve the outcome, prevent/reduce antifungal toxicity and prevent the emergence of antifungal resistance. Finally, we present the new antifungals and their main characteristics.

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“…In up to 80% of cases, conventional AmB (AmB deoxycholate) may cause kidney impairment through various mechanisms (Figs. 2 and 3) [19,20 ▪ ,21 ▪▪ ,22].…”

Section: Antifungalsmentioning

confidence: 99%

“…Unfortunately, lipid-based formulations of AmB are expensive [21 ▪▪ ]. Alternative approaches like continuous infusion with therapeutic drug monitoring (TDM) [25] or mixing conventional AmB with intravenous lipid emulsions (e.g., Intralipid 20%) has shown cost-effectiveness and a similar nephrotoxicity profile to lipid-based formulations of AmB [24,26,27].…”

Section: Antifungalsmentioning

confidence: 99%

Prevention and management of antibiotic associated acute kidney injury in critically ill patients: new insights

Karimzadeh,

Strader,

Kane-Gill

et al. 2023

Current Opinion in Critical Care

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Purpose of review Drug associated kidney injury (D-AKI) occurs in 19–26% of hospitalized patients and ranks as the third to fifth leading cause of acute kidney injury (AKI) in the intensive care unit (ICU). Given the high use of antimicrobials in the ICU and the emergence of new resistant organisms, the implementation of preventive measures to reduce the incidence of D-AKI has become increasingly important. Recent findings Artificial intelligence is showcasing its capabilities in early recognition of at-risk patients for acquiring AKI. Furthermore, novel synthetic medications and formulations have demonstrated reduced nephrotoxicity compared to their traditional counterparts in animal models and/or limited clinical evaluations, offering promise in the prevention of D-AKI. Nephroprotective antioxidant agents have had limited translation from animal studies to clinical practice. The control of modifiable risk factors remains pivotal in avoiding D-AKI. Summary The use of both old and new antimicrobials is increasingly important in combating the rise of resistant organisms. Advances in technology, such as artificial intelligence, and alternative formulations of traditional antimicrobials offer promise in reducing the incidence of D-AKI, while antioxidant medications may aid in minimizing nephrotoxicity. However, maintaining haemodynamic stability using isotonic fluids, drug monitoring, and reducing nephrotoxic burden combined with vigilant antimicrobial stewardship remain the core preventive measures for mitigating D-AKI while optimizing effective antimicrobial therapy.

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Potential lipid-based strategies of amphotericin B designed for oral administration in clinical application

Cited by 10 publications

References 79 publications

Antifungal Drug Resistance: An Emergent Health Threat

Antifungal Drug Resistance: An Emergent Health Threat

Antifungals: From Pharmacokinetics to Clinical Practice

Prevention and management of antibiotic associated acute kidney injury in critically ill patients: new insights

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