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Clinical Microbiology and Infection :... Nov 2020EUCAST has revised the definition of the susceptibility category I from 'Intermediate' to 'Susceptible, Increased exposure'. This implies that I can be used where the... (Review)
Review
BACKGROUND
EUCAST has revised the definition of the susceptibility category I from 'Intermediate' to 'Susceptible, Increased exposure'. This implies that I can be used where the drug concentration at the site of infection is high, either because of dose escalation or through other means to ensure efficacy. Consequently, I is no longer used as a buffer zone to prevent technical factors from causing misclassifications and discrepancies in interpretations. Instead, an Area of Technical Uncertainty (ATU) has been introduced for MICs that cannot be categorized without additional information as a warning to the laboratory that decision on how to act has to be made. To implement these changes, the EUCAST-AFST (Subcommittee on Antifungal Susceptibility Testing) reviewed all, and revised some, clinical antifungal breakpoints.
OBJECTIVES
The aim was to present an overview of the current antifungal breakpoints and supporting evidence behind the changes.
SOURCES
This document is based on the ten recently updated EUCAST rationale documents, clinical breakpoint and breakpoint ECOFF documents.
CONTENT
The following breakpoints (in mg/L) have been revised or established for Candida species: micafungin against C. albicans (ATU = 0.03); amphotericin B (S ≤/> R = 1/1), fluconazole (S ≤/> R = 2/4), itraconazole (S ≤/> R = 0.06/0.06), posaconazole (S ≤/> R = 0.06/0.06) and voriconazole (S ≤/> R = 0.06/0.25) against C. dubliniensis; fluconazole against C. glabrata (S ≤/> R = 0.001/16); and anidulafungin (S ≤/> R = 4/4) and micafungin (S ≤/> R = 2/2) against C. parapsilosis. For Aspergillus, new or revised breakpoints include itraconazole (ATU = 2) and isavuconazole against A. flavus (S ≤/> R = 1/2, ATU = 2); amphotericin B (S ≤/> R = 1/1), isavuconazole (S ≤ /> R = 1/2, ATU = 2), itraconazole (S ≤/> R = 1/1, ATU = 2), posaconazole (ATU = 0.25) and voriconazole (S ≤/> R = 1/1, ATU = 2) against A. fumigatus; itraconazole (S ≤/> R = 1/1, ATU = 2) and voriconazole (S ≤/> R = 1/1, ATU = 2) against A. nidulans; amphotericin B against A. niger (S ≤/> R = 1/1); and itraconazole (S ≤/> R = 1/1, ATU = 2) and posaconazole (ATU = 0.25) against A. terreus.
IMPLICATIONS
EUCAST-AFST has released ten new documents summarizing existing and new breakpoints and MIC ranges for control strains. A failure to adopt the breakpoint changes may lead to misclassifications and suboptimal or inappropriate therapy of patients with fungal infections.
Topics: Amphotericin B; Antifungal Agents; Aspergillus; Candida; Fluconazole; Itraconazole; Microbial Sensitivity Tests; Practice Guidelines as Topic; Triazoles; Voriconazole
PubMed: 32562861
DOI: 10.1016/j.cmi.2020.06.007 -
Revista Da Sociedade Brasileira de... 2017Paracoccidioidomycosis is a systemic fungal disease occurring in Latin America that is associated with rural environments and agricultural activities. However, the...
Paracoccidioidomycosis is a systemic fungal disease occurring in Latin America that is associated with rural environments and agricultural activities. However, the incidence and prevalence of paracoccidiodomycosis is underestimated because of the lack of compulsory notification. If paracoccidiodomycosis is not diagnosed and treated early and adequately, the endemic fungal infection could result in serious sequelae. While the Paracoccidioides brasiliensis ( P. brasiliensis ) complex has been known to be the causal agent of paracoccidiodomycosis, a new species, Paracoccidioides lutzii ( P. lutzii ), has been reported in Rondônia, where the disease has reached epidemic levels, and in the Central West and Pará. Accurate diagnoses and availability of antigens that are reactive with the patients' sera remain significant challenges. Therefore, the present guidelines aims to update the first Brazilian consensus on paracoccidioidomycosis by providing evidence-based recommendations for bedside patient management. This consensus summarizes etiological, ecoepidemiological, molecular epidemiological, and immunopathological data, with emphasis on clinical, microbiological, and serological diagnosis and management of clinical forms and sequelae, as well as in patients with comorbidities and immunosuppression. The consensus also includes discussion of outpatient treatments, severe disease forms, disease prevalence among special populations and resource-poor settings, a brief review of prevention and control measures, current challenges and recommendations.
Topics: Antifungal Agents; Brazil; Consensus; Diagnosis, Differential; Disease Management; Humans; Itraconazole; Latin America; Paracoccidioides; Paracoccidioidomycosis
PubMed: 28746570
DOI: 10.1590/0037-8682-0230-2017 -
Molecules (Basel, Switzerland) Jun 2010This review provides a historical overview of the analog based drug discovery of miconazole and its congeners, and is focused on marketed azole antifungals bearing the... (Review)
Review
This review provides a historical overview of the analog based drug discovery of miconazole and its congeners, and is focused on marketed azole antifungals bearing the generic suffix "conazole". The antifungal activity of miconazole, one of the first broad-spectrum antimycotic agents has been mainly restricted to topical applications. The attractive in vitro antifungal spectrum was a starting point to design more potent and especially orally active antifungal agents such as ketoconazole, itraconazole, posaconazole, fluconazole and voriconazole. The chemistry, in vitro and in vivo antifungal activity, pharmacology, and clinical applications of these marketed conazoles has been described.
Topics: Antifungal Agents; Fluconazole; Itraconazole; Ketoconazole; Miconazole; Molecular Structure; Pyrimidines; Structure-Activity Relationship; Triazoles; Voriconazole
PubMed: 20657432
DOI: 10.3390/molecules15064129 -
BMJ Case Reports May 2016
Topics: Chromoblastomycosis; Female; Humans; Itraconazole; Middle Aged; Saccharomycetales; Treatment Outcome
PubMed: 27207987
DOI: 10.1136/bcr-2016-215391 -
Journal of the Chinese Medical... Jun 2014We describe a rare case of entomophthoromycosis of the pharynx in a previously healthy patient, unlike other fungal infections which are seen as opportunistic infections...
We describe a rare case of entomophthoromycosis of the pharynx in a previously healthy patient, unlike other fungal infections which are seen as opportunistic infections in immunocompromised hosts. This infection is commonly seen in subtropical and tropical areas of Africa, America, and Asia. Painless, erythematous, indurated plaques of subcutaneous tissue are characteristic of this infection. There are currently no standard antifungal regimens for this infection, making treatment difficult. An endoscopic surgical wide resection of the lesion was performed, itraconazole was administered, and the patient improved clinically.
Topics: Adult; Antifungal Agents; Entomophthorales; Humans; Itraconazole; Male; Pharyngeal Diseases; Zygomycosis
PubMed: 24746408
DOI: 10.1016/j.jcma.2014.02.013 -
Journal of Advanced Research Jun 2023Repurposing antifungal drugs in cancer therapy has attracted unprecedented attention in both preclinical and clinical research due to specific advantages, such as... (Review)
Review
BACKGROUND
Repurposing antifungal drugs in cancer therapy has attracted unprecedented attention in both preclinical and clinical research due to specific advantages, such as safety, high-cost effectiveness and time savings compared with cancer drug discovery. The surprising and encouraging efficacy of antifungal drugs in cancer therapy, mechanistically, is attributed to the overlapping targets or molecular pathways between fungal and cancer pathogenesis. Advancements in omics, informatics and analytical technology have led to the discovery of increasing "off-site" targets from antifungal drugs involved in cancerogenesis, such as smoothened (D477G) inhibition from itraconazole in basal cell carcinoma.
AIM OF REVIEW
This review illustrates several antifungal drugs repurposed for cancer therapy and reveals the underlying mechanism based on their original target and "off-site" target. Furthermore, the challenges and perspectives for the future development and clinical applications of antifungal drugs for cancer therapy are also discussed, providing a refresh understanding of drug repurposing.
KEY SCIENTIFIC CONCEPTS OF REVIEW
This review may provide a basic understanding of repurposed antifungal drugs for clinical cancer management, thereby helping antifungal drugs broaden new indications and promote clinical translation.
Topics: Humans; Antifungal Agents; Carcinoma, Basal Cell; Drug Repositioning; Itraconazole; Skin Neoplasms
PubMed: 36067975
DOI: 10.1016/j.jare.2022.08.018 -
Biomedicine & Pharmacotherapy =... Oct 2022Understanding cancer biology and the development of novel agents for cancer treatment has always been the goal of cancer researchers. However, the research and... (Review)
Review
Understanding cancer biology and the development of novel agents for cancer treatment has always been the goal of cancer researchers. However, the research and development of new drugs is hindered by its long development time, exorbitant cost, high regulatory hurdles, and staggering failure rates. Given the challenges involved drug development for cancer therapies, alternative strategies, in particular the repurposing of 'old' drugs that have been approved for other indications, are attractive. Itraconazole is an FDA-approved anti-fungal drug of the triazole class, and has been used clinically for more than 30 years. Recent drug repurposing screens revealed itraconazole exerts anti-cancer activity via inhibiting angiogenesis and multiple oncogenic signaling pathways. To explore the potential utilization of itraconazole in different types of malignancies, we retrieved the published literature relating to itraconazole in cancer and reviewed the mechanisms of itraconazole in preclinical and clinical cancer studies. Current research predicts the hedgehog signaling pathway as the main target by which itraconazole inhibits a variety of solid and hematological cancers. As clinical trial results become available, itraconazole could emerge as a new antitumor drug that can be used in combination with first-line antitumor drugs.
Topics: Antineoplastic Agents; Drug Repositioning; Hedgehog Proteins; Hematologic Neoplasms; Humans; Itraconazole
PubMed: 36055112
DOI: 10.1016/j.biopha.2022.113616 -
Brazilian Journal of Microbiology :... Mar 2021Itraconazole is the first drug of choice for the treatment of sporotrichosis and it is available at different concentrations for veterinary patients. However,...
Itraconazole is the first drug of choice for the treatment of sporotrichosis and it is available at different concentrations for veterinary patients. However, therapeutic failure has been reported, limiting clinical treatment. This study evaluated the in vitro efficacy of brand-name and compounded itraconazole formulations against Sporothrix brasiliensis and estimated the itraconazole content in each tested formulation. Oral capsules were acquired from two brand-name products for human (H-IND) and veterinary (V-IND) uses, and three from compounding pharmacies in Pelotas, RS, for human (H-COMP1/H-COMP2) and veterinary (V-COMP) uses. Capsule purity was analyzed by liquid chromatography-electrospray ionization quadrupole time-of-flight mass spectrometry (LC-ESI-QTOF-MS). Antifungal activity was determined against 29 Sporothrix brasiliensis by the M38-A2 guideline of CLSI. H-IND/H-COMP1/H-COMP2 had high efficacy against S. brasiliensis (approximately 70% of total isolated susceptible), V-COMP showed moderate efficacy (51.7%), and V-IND was the least effective formulation (37.9%). Thirty-four percent of the total isolates were resistant to all formulations. Furthermore, itraconazole content did not match the concentration indicated by the manufacturers, ranging from 387.70 to 7.81 μg/mg (H-COMP2 > V-COMP > H-IND > H-COMP1 > V-IND). Therefore, it is possible that the formulations showed different in vitro efficacy due to the difference in their itraconazole contents. Given the emergence of antifungal resistance for all formulations, the choice product to be used must follow susceptibility testing. Stringent quality control measures are recommended for product manufactures to assure drug content uniformity.
Topics: Antifungal Agents; Drug Compounding; Drug Resistance, Fungal; Humans; Itraconazole; Mass Spectrometry; Microbial Sensitivity Tests; Sporothrix; Sporotrichosis
PubMed: 32333272
DOI: 10.1007/s42770-020-00280-7 -
Microbiology Spectrum Aug 2023The genus comprises lipid-dependent yeasts that have long been associated with common skin diseases, and have recently been linked with Crohn's disease and certain...
The genus comprises lipid-dependent yeasts that have long been associated with common skin diseases, and have recently been linked with Crohn's disease and certain cancers. Understanding susceptibility to diverse antimicrobial agents is crucial for identifying effective antifungal therapies. Here, we tested the efficacy of isavuconazole, itraconazole, terbinafine, and artemisinin against three species: , and . Using broth microdilution, we found antifungal properties for the two previously unstudied antimicrobials: isavuconazole and artemisinin. Overall, all species were particularly susceptible to itraconazole, with a MIC range from 0.007 to 0.110 μg/mL. The genus is known to be involved in a variety of skin conditions and has recently been associated with diseases such as Crohn's disease, pancreatic ductal carcinoma, and breast cancer. This work was completed to assess susceptibility to a variety of antimicrobial drugs on three species, in particular , which is an abundant species both on human skin and internal organs and has been implicated in Crohn's disease. We tested two previously unstudied drugs and developed a new testing method to overcome current limitations for measuring growth inhibition of slow-growing strains.
Topics: Humans; Antifungal Agents; Itraconazole; Malassezia; Crohn Disease; Dermatomycoses; Microbial Sensitivity Tests
PubMed: 37310217
DOI: 10.1128/spectrum.05076-22 -
BMJ Clinical Evidence Aug 2011Fungal infections are reported to cause 23% of foot diseases and 50% of nail conditions in people seen by dermatologists, but are less common in the general population,... (Review)
Review
INTRODUCTION
Fungal infections are reported to cause 23% of foot diseases and 50% of nail conditions in people seen by dermatologists, but are less common in the general population, affecting 3% to 5% of people.
METHODS AND OUTCOMES
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of oral treatments for fungal toenail infections? What are the effects of topical treatments for fungal toenail infections? We searched: Medline, Embase, The Cochrane Library, and other important databases up to March 2011 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
RESULTS
We found 12 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
CONCLUSIONS
In this systematic review we present information relating to the effectiveness and safety of the following interventions: amorolfine, butenafine, ciclopirox, fluconazole, griseofulvin, itraconazole, ketoconazole, mechanical debridement, terbinafine, and tioconazole.
Topics: Administration, Oral; Administration, Topical; Debridement; Humans; Itraconazole; Nails; Onychomycosis
PubMed: 21846413
DOI: No ID Found