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A Better Amphotericin - About Time

I’ve written about amphotericin B (AmB) before around here, and my take on it has always been the same: if you’re having to take this drug, then you have some serious fungal infection problems. It’s an antifungal of last resort, a broad-spectrum agent that’s useful when you don’t even know what species is causing the problem (which is fairly often), and kills fungi that don’t respond to the more widely used azole compounds. So far, so good - but it also is very, very hard on the kidneys, and you can end up titrating renal toxicity against antifungal efficacy, which is obviously not a very good place to end up. I mean, if you have a systemic fungal infection you already need all the kidney…

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Featured

 Amphotericin B in the Era of New Antifungals: Where Will It Stand?

Amphotericin B (AmB) has long stood as a cornerstone in the treatment of invasive fungal infections (IFIs), especially among immunocompromised patients. However, the landscape of antifungal therapy is evolving. New antifungal agents, boasting novel mechanisms of action and better safety profiles, are entering the scene, presenting alternatives to AmB’s traditional dominance. This shift, prompted by an increase in the incidence of IFIs, the growing demographic of immunocompromised individuals, and changing patterns of fungal resistance, underscores the continuous need for effective treatments. Despite these challenges, AmB’s broad efficacy and low resistance rates maintain its essential status in antifungal therapy. Innovations in AmB formulations, such as lipid complexes and liposomal delivery systems, have significantly mitigated its notorious nephrotoxicity and infusion-related reactions, thereby enhancing its clinical utility. Moreover, AmB’s efficacy in treating severe and rare fungal infections and its pivotal role as prophylaxis in high-risk settings highlight its value and ongoing relevance.

Articles of Interest

Amphotericin B and Other Polyenes—Discovery, Clinical Use, Mode of Action and Drug Resistance

Although polyenes were the first broad spectrum antifungal drugs on the market, after 70 years they are still the gold standard to treat a variety of fungal infections. Polyenes such as amphotericin B have a controversial image. They are the antifungal drug class with the broadest spectrum, resistance development is still relatively rare and fungicidal properties are extensive. Yet, they come with a significant host toxicity that limits their use. Relatively recently, the mode of action of polyenes has been revised, new mechanisms of drug resistance were discovered and emergent polyene resistant species such as Candida auris entered the picture.

Amphotericin B, the Wonder of Today’s Pharmacology Science: Persisting Usage for More Than Seven Decades

Despite several available topical and systemic antifungal drugs for the treatment of fungal infections, Amphotericin B (AmB) is still one of the most common first-line choices in treating systemic fungal infection for more than seven decades after its discovery.

Amphotericin B: Time for a New “Gold Standard”

When introduced in 1959, amphotericin B deoxycholate (AmBD) was clearly a life-saving drug. Randomized studies demonstrating its efficacy were not thought to be necessary, and it was granted indications for many invasive fungal infections. Despite its formidable toxicities, AmBD is thus often used as the primary comparator in studies of invasive fungal infections. Safer lipid-based versions of amphotericin B (AmB) have been introduced, but difficulties with studying these agents generally led to licensure for salvage therapy, not primary therapy.

Deadly fungi are becoming drug-resistant. A new compound could beat them

Many of the drugs used to fight off bacterial or fungal infections come from the microbial world themselves: They’re based on compounds that microorganisms have developed to kill each other. Amphotericin B, for example, a so-called polyene, is used by the bacterium Streptomyces nodosus to ward off other fungi. It was discovered in the 1950s in soil samples collected near the Orinoco River in Venezuela.

Fungal Theory Debated in Amphotericin B Controversy

The use of the antifungal agent amphotericin B to treat noninvasive fungi in CRS has become one of otolaryngology’s hot-button issues. Even though the National Institutes of Health (NIH) announced in a 2004 press release that people with chronic sinus inflammation have an exaggerated immune response to common airborne fungi, many in the medical community are hesitant to embrace an antifungal, one-size-fits-all treatment for all CRS patients.

It only takes one to do many jobs: Amphotericin B as antifungal and immunomodulatory drug

“Amphotericin B acts through pore formation at the cell membrane after binding to ergosterol” is an accepted dogma about the action mechanism of this antifungal, and this sentence is widely found in the literature. But after 60 years of investigation, the action mechanism of Amphotericin B is not fully elucidated. Amphotericin B is a polyene substance that is one of the most effective drugs for the treatment of fungal and parasite infections.

Liposomal amphotericin B—the future

Liposomal amphotericin B will remain an essential therapeutic agent in the armamentarium needed to manage future challenges, given its broad antifungal spectrum, low level of acquired resistance and limited potential for drug–drug interactions.

Nasty Drug Molecules: Amphotericin B

You've probably seen the headlines about fungal meningitis showing up, caused (it appears) by contaminated injectable steroid supplies. As soon as I heard these stories, I wondered what you treat this condition with, and my first thought was "Amphotericin B, most likely". And so it appears. That compound still seems to be the usual answer for the nastiest fungal infections, a role it's occupied for decades. That's not by choice. It's an awful compound in many ways...

Sixty years of Amphotericin B: An Overview of the Main Antifungal Agent Used to Treat Invasive Fungal Infections

Introduced in the late 1950s, polyenes represent the oldest family of antifungal drugs. The discovery of amphotericin B and its therapeutic uses is considered one of the most important scientific milestones of the twentieth century . Despite its toxic potential, it remains useful in the treatment of invasive fungal diseases owing to its broad spectrum of activity, low resistance rate, and excellent clinical and pharmacological action. The well-reported and defined toxicity of the conventional drug has meant that much attention has been paid to the development of new products that could minimize this effect.

Resources

Amphotericin B

Video presentation...

Amphotericin B (conventional and liposomal)

INDICATIONS - Deep and/or systemic mycoses including: Candida esophagitis and systemic candidiasis, Invasive mucormycosis, Cryptococcal meningitis (with-5 flucyosine), Severe or rapidly progressive endemic mycoses (histoplasmosis, blastomycosis, coccidiomycosis, penicilliosis), invasive aspergillosis (salvage therapy), Neutropenic sepsis unresponsive to anti-bacterials.

StatPearls

This drug has witnessed significant advancements by introducing novel lipid formulations that exhibit a reduced nephrotoxic profile compared to the traditional formulation.