Drugs To Treat Invasive Fungal Infections

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Invasive fungal infections (especially Aspergillus and Candida) are a major risk for people with immunocompromising conditions such as HIV+, cancer, immunosupressive drugs for organ/bone transplantation or cancer, severe malnutrition, or severe bacterial or viral infections.  Death rates from many types of invasive fungal infections such as Aspergillus often exceed 50%.   Invasive fungal infections also occasionally attack apparently healthy people. 

 

A number of drugs are used to treat and prevent invasive fungal infections.  A good review of the current drugs used to treat invasive fungal infections is provided by Ledoux et al (Ledoux, Toussaint et al. 2017). Some of the drugs currently used include the following:

Amphotericin B (AmBisome® ).  An intravenous drug with many adverse side effects.  Newer liposomonal formulations of amphotericin B have less toxicity to the kidney and liver.  Often used to treat invasive Aspergillosis and Mucor infections.  Some studies have shown that lower dose liposomal amphotericin (3 mg/kg/day) have comparable efficacy to higher doses (10 mg/kg/day) with less kidney damage and hypokalemia. 

Voriconazole (Vfend®).  An azole drug often considered the drug of choice for proven or probably invasive aspergillosis.  Some studies have reported that voriconazole has a significantly higher treatment efficacy as compared to amphotericin B.  

Itraconazole (Sporanox®).  Another azole drug often used for the prophylaxis of fungal infections in high risk patients and also for treatment of aspergillosis, blastomycosis, candidiasis, cryptococcosis, and histoplasmosis.  

Posaconazole (Noxafil®) Azole drug effective against many Aspergillus and Mucor strains.  Useful for preventing aspergillosis in bone marrow transplant patients. 

 

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Isavuconazole (Cresemba® ). A new triazole drug which is water soluble and can be given in either oral or intravenous form.  Two studies involving patients with invasive mold disease have reported that use of isavuconazole was associated with a somewhat higher survival rate than voriconazole. 

Echinocandins.  A new class of drugs which are useful for fungal infections (especially Candida and Aspergillus) resistant to other antifungal drugs.  Three Echinocandin drugs are currently available including caspofungin (Cancidas®), micafungin (Mycamine®), and anidulafungin (Eraxis® )  .

Fluconazole (Diflucan® )- A useful drug for Candida although many Candida strains have developed resistance to fluconazole.  Not useful for Aspergillus or Mucor infections 

Combination Therapy. A combination of 2 or more antifungal drugs may offer a broader treatment range than single drugs and may be especially useful in infections which involve more than 1 fungal species and/or involve a fungal strain with resistance to common anti fungal drugs.  A study of 30 patients with leukemia/lymphoma and probable or proven invasive aspergillosis reported that a combination treatment with caspofungin and low dose liposomal amphotericin B had significantly higher response rate and survival as compared to patients treated with high dose liposomal amphotericin B.


References / Sources

Ledoux, M. P., et al. (2017). “New pharmacological opportunities for the treatment of invasive mould diseases.” J Antimicrob Chemother 72(suppl_1): i48-i58. 

 

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