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BioMed Research International 2022Mucormycosis is one among the life-threatening fungal infections with high morbidity and mortality. It is an uncommon and rare infection targeting people with altered... (Review)
Review
Mucormycosis is one among the life-threatening fungal infections with high morbidity and mortality. It is an uncommon and rare infection targeting people with altered immunity. This lethal infection induced by fungi belonging to the Mucorales family is very progressive in nature. The incidence has increased in recent decades owing to the rise in immunocompromised patients. Disease management involves a multimodal strategy including early administration of drugs and surgical removal of infected tissues. Among the antifungals, azoles and amphotericin B remain the gold standard drugs of choice for initial treatment. The order Mucorales are developing a high level of resistance to the available systemic antifungal drugs, and the efficacy still remains below par. Deciphering the molecular mechanisms behind the antifungal resistance in Mucormycosis would add vital information to our available antifungal armamentarium and design novel therapies. Therefore, in this review, we have discussed the mechanisms behind Mucormycosis antifungal resistance. Moreover, this review also highlights the basic mechanisms of action of antifungal drugs and the resistance landscape which is expected to augment future treatment strategies.
Topics: Humans; Mucormycosis; Antifungal Agents; Amphotericin B; Mucorales; Azoles
PubMed: 36277891
DOI: 10.1155/2022/6722245 -
PLoS Pathogens Oct 2022Mucormycosis (previously called zygomycosis) is a serious but rare fungal infection caused by a group of fungi belonging to the order Mucorales. These molds exist... (Review)
Review
Mucormycosis (previously called zygomycosis) is a serious but rare fungal infection caused by a group of fungi belonging to the order Mucorales. These molds exist throughout the environment and generally do not cause serious problems in humans. Mucormycosis mainly affects individuals who are immunocompromised. The clinical manifestations of mucormycosis are wide-ranging; they include sinusitis (pansinusitis, rhino-orbital, or rhino-cerebral) as well as cutaneous, gastrointestinal, pulmonary, and disseminate infections. Many uncertainties remain regarding how to control these infections despite the recent addition of triazoles to the antifungal arsenal for treating this infection. Currently, lipid formulations of amphotericin B have become the standard treatment for mucormycosis due to their efficiency. Moreover, a growing body of data supports the need for surgical excision of infected and/or necrosed tissue whenever practical. In this mini review, the current status of treatment options for mucormycosis and recent studies of novel therapeutic options will be presented.
Topics: Amphotericin B; Antifungal Agents; Debridement; Humans; Lipids; Mucormycosis; Triazoles
PubMed: 36227854
DOI: 10.1371/journal.ppat.1010858 -
Respiratory Medicine Apr 2020Aspergilloma, also known as mycetoma or fungus ball, is the most common manifestation of pulmonary involvement by Aspergillus species. The fungal ball typically forms... (Review)
Review
Aspergilloma, also known as mycetoma or fungus ball, is the most common manifestation of pulmonary involvement by Aspergillus species. The fungal ball typically forms within preexisting cavities of the lungs. Diagnosis requires both radiographic evidence along with serologic or microbiologic evidence of Aspergillus species involvement. While clinical features such as hemoptysis, chest pain, shortness of breath, cough, and fever are helpful in diagnosis, they are non-specific symptoms. Surgery is currently the mainstay of treatment for aspergilloma but is associated with considerable mortality and morbidity. Alternative options exist for patients who are poor surgical candidates and for those who prefer a less invasive treatment modality. Systemic treatment with amphotericin B is ineffective and is not recommended as a monotherapy, but systemic azoles is effective in approximately 50-80% of patients. Potential alternatives to surgery include intracavitary instillation or endobronchial administration of antifungal medication, as well as direct transbronchial aspergilloma removal. Bronchial artery embolization and radiotherapy are options to manage hemoptysis until definite eradication of the aspergilloma. More rigorous studies are needed to better establish non-surgical treatment paradigm for inoperable patients.
Topics: Amphotericin B; Antifungal Agents; Azoles; Bronchial Arteries; Conservative Treatment; Embolization, Therapeutic; Female; Hemoptysis; Humans; Instillation, Drug; Male; Pulmonary Aspergillosis
PubMed: 32217289
DOI: 10.1016/j.rmed.2020.105903 -
The American Journal of Tropical... Oct 2019
Topics: Amphotericin B; Antiprotozoal Agents; Humans; Leishmaniasis
PubMed: 31482790
DOI: 10.4269/ajtmh.19-0568 -
Clinical Microbiology and Infection :... Oct 2020
Topics: Adult; Amphotericin B; Antiprotozoal Agents; Humans; Leishmania donovani; Leishmaniasis, Visceral; Male
PubMed: 32439594
DOI: 10.1016/j.cmi.2020.05.003 -
Revista Da Sociedade Brasileira de... 2023There is a consensus that the antifungal repertoire for the treatment of cryptococcal infections is limited. Standard treatment involves the administration of an... (Review)
Review
There is a consensus that the antifungal repertoire for the treatment of cryptococcal infections is limited. Standard treatment involves the administration of an antifungal drug derived from natural sources (i.e., amphotericin B) and two other drugs developed synthetically (i.e., flucytosine and fluconazole). Despite treatment, the mortality rates associated with fungal cryptococcosis are high. Amphotericin B and flucytosine are toxic, require intravenous administration, and are usually unavailable in low-income countries because of their high cost. However, fluconazole is cost-effective, widely available, and harmless with regard to its side effects. However, fluconazole is a fungistatic agent that has contributed considerably to the increase in fungal resistance and frequent relapses in patients with cryptococcal meningitis. Therefore, there is an unquestionable need to identify new alternatives or adjuvants to conventional drugs for the treatment of cryptococcosis. A potential antifungal agent should be able to kill cryptococci and "bypass" the virulence mechanism of the yeast. Furthermore, it should have fungicidal action, low toxicity, high selectivity, easily penetrate the central nervous system, and widely available. In this review, we describe cryptococcosis, its conventional therapy, and failures arising from the use of drugs traditionally considered to be the reference standard. Additionally, we present the approaches used for the discovery of new drugs to counteract cryptococcosis, ranging from the conventional screening of natural products to the inclusion of structural modifications to optimize anticryptococcal activity, as well as drug repositioning and combined therapies.
Topics: Humans; Antifungal Agents; Amphotericin B; Flucytosine; Fluconazole; Cryptococcosis; Cryptococcus neoformans
PubMed: 37493736
DOI: 10.1590/0037-8682-0121-2023 -
Current Opinion in Microbiology Dec 2022Fungal infections are responsible for significant morbidity and mortality. Resistance to the limited number of agents in the antifungal armamentarium among pathogenic... (Review)
Review
Fungal infections are responsible for significant morbidity and mortality. Resistance to the limited number of agents in the antifungal armamentarium among pathogenic fungi represents a growing public health threat. Particularly concerning is the emerging fungal pathogen Candida auris that frequently exhibits resistance to the triazole class of antifungals and amphotericin B, and for which isolates resistant to all of the major antifungal classes have been reported. In this brief review, we provide an overview of what is currently known about the molecular and genetic basis for antifungal resistance in this fungal pathogen.
Topics: Antifungal Agents; Candida; Candida auris; Drug Resistance, Fungal; Amphotericin B; Microbial Sensitivity Tests
PubMed: 36242897
DOI: 10.1016/j.mib.2022.102208 -
Antimicrobial Agents and Chemotherapy Jul 2022Candida albicans causes debilitating, often azole-resistant, infections in patients with chronic mucocutaneous candidiasis (CMC). Amphotericin B (AMB) resistance is...
Candida albicans causes debilitating, often azole-resistant, infections in patients with chronic mucocutaneous candidiasis (CMC). Amphotericin B (AMB) resistance is rare, but AMB use is limited by parenteral administration and nephrotoxicity. In this study, we evaluated cochleated AMB (CAMB), a new oral AMB formulation, in mouse models of oropharyngeal candidiasis (OPC) and vulvovaginal candidiasis (VVC) and in patients with azole-resistant CMC. OPC and VVC were modeled in mice, and mucosal tissue fungal burden was assessed after once-daily treatment with CAMB, vehicle, or AMB-deoxycholate (AMB-d). Four patients with azole-resistant CMC enrolled in a phase 2 CAMB dose-escalation study. The primary endpoint was clinical improvement at 2 weeks followed by optional extension for long-term CMC suppression to assess safety and efficacy. CAMB-treated mice had significantly reduced tongue and vaginal fungal burdens compared to vehicle-treated mice and exhibited comparable fungal burden reduction relative to AMB-d-treated mice. All CAMB-treated patients reached clinical efficacy by 2 weeks, three at 400 mg twice daily and one at 200 mg twice-daily dosing. All patients continued to the extension phase, with three having sustained clinical improvement of OPC and esophageal candidiasis (EC) for up to 60 months. One patient had a relapse of esophageal symptoms at week 24 and was withdrawn from further study. Clinical responses were not seen for onychomycosis or VVC. CAMB was safe and well-tolerated, without any evidence of nephrotoxicity. In summary, oral CAMB reduced tongue and vaginal fungal burdens during murine candidiasis. A proof-of-concept clinical trial in human CMC showed efficacy with good tolerability and safety. This study has been registered at ClinicalTrials.gov under identifier NCT02629419.
Topics: Amphotericin B; Animals; Antifungal Agents; Azoles; Candida albicans; Candidiasis; Candidiasis, Chronic Mucocutaneous; Candidiasis, Oral; Candidiasis, Vulvovaginal; Female; Humans; Mice
PubMed: 35699443
DOI: 10.1128/aac.00308-22 -
Antimicrobial Agents and Chemotherapy Oct 2023() is an encapsulated neurotropic fungal pathogen and the causative agent of cryptococcal meningoencephalitis (CME) in humans. Recommended treatment for CME is...
() is an encapsulated neurotropic fungal pathogen and the causative agent of cryptococcal meningoencephalitis (CME) in humans. Recommended treatment for CME is Amphotericin B (AmpB) and 5-fluorocytosine (5-FC). Though effective, AmpB has displayed numerous adverse side effects due to its potency and nephrotoxicity, prompting investigation into alternative treatments. Palmitoylethanolamide (PEA) is an immunomodulatory compound capable of promoting neuroprotection and reducing inflammation. To investigate the efficacy of PEA as a therapeutic alternative for CME, we intracerebrally infected mice with and treated them with PEA or AmpB alone or in combination. Our results demonstrate that PEA alone does not significantly prolong survival nor reduce fungal burden, but when combined with AmpB, PEA exerts an additive effect and promotes both survivability and fungal clearance. However, we compared this combination to traditional AmpB and 5-FC treatment in a survivability study and observed lower efficacy. Overall, our study revealed that PEA alone is not effective as an antifungal agent in the treatment of CME. Importantly, we describe the therapeutic capability of PEA in the context of infection and show that its immunomodulatory properties may confer limited protection when combined with an effective fungicidal agent.
Topics: Humans; Mice; Animals; Meningitis, Cryptococcal; Antifungal Agents; Cryptococcus neoformans; Cryptococcosis; Amphotericin B; Flucytosine; Meningoencephalitis
PubMed: 37750714
DOI: 10.1128/aac.00459-23 -
Zhejiang Da Xue Xue Bao. Yi Xue Ban =... Jun 2023Currently, the first-line drugs for invasive fungal infections (IFI), such as amphotericin B, fluconazole and itraconazole, have drawbacks including poor water... (Review)
Review
Currently, the first-line drugs for invasive fungal infections (IFI), such as amphotericin B, fluconazole and itraconazole, have drawbacks including poor water solubility, low bioavailability, and severe side effects. Using drug delivery systems is a promising strategy to improve the efficacy and safety of traditional antifungal therapy. Synthetic and biomimetic carriers have greatly facilitated the development of targeted delivery systems for antifungal drugs. Synthetic carrier drug delivery systems, such as liposomes, nanoparticles, polymer micelles, and microspheres, can improve the physicochemical properties of antifungal drugs, prolong their circulation time, enhance targeting capabilities, and reduce toxic side effects. Cell membrane biomimetic drug delivery systems, such as macrophage or red blood cell membrane-coated drug delivery systems, retain the membrane structure of somatic cells and confer various biological functions and specific targeting abilities to the loaded antifungal drugs, exhibiting better biocompatibility and lower toxicity. This article reviews the development of antifungal drug delivery systems and their application in the treatment of IFI, and also discusses the prospects of novel biomimetic carriers in antifungal drug delivery.
Topics: Antifungal Agents; Drug Delivery Systems; Amphotericin B; Liposomes; Nanoparticles; Drug Carriers
PubMed: 37476943
DOI: 10.3724/zdxbyxb-2023-0030