Azole-Resistant Aspergillus and Echinocandin-Resistant Candida: What Are the Treatment Options?

Novak, Alison; Bradley, Mary E.; Kiser, Tyree H.; Mueller, Scott W.

doi:10.1007/s12281-020-00379-2

Cited by 10 publications

(10 citation statements)

References 76 publications

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“…Despite a substantial number of studies, including at least 25 comparative studies performed for Aspergillus species, with more than 3000 isolates tested against antifungal agents [ 22 ], the endpoint reading of echinocandins MECs has been found to be subjective, time-consuming, and has been associated with VME [ 30 , 35 ]. We confirm these issues and stress the need for studies with CAS-MICs using Etest, as well as with AND, as previously recommended [ 36 ].…”

Section: Discussionmentioning

confidence: 99%

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Evaluation of the Sensititre YeastOne and Etest in Comparison with CLSI M38-A2 for Antifungal Susceptibility Testing of Three Azoles, Amphotericin B, Caspofungin, and Anidulafungin, against Aspergillusfumigatus and Other Species, Using New Clinical Breakpoints and Epidemiological Cutoff Values

Melhem

Coelho²,

Fonseca³

et al. 2022

Pharmaceutics

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Aspergillosis is an invasive fungal disease associated with high mortality. Antifungal susceptibility testing (AFST) is receiving increasing consideration for managing patients, as well as for surveilling emerging drug resistance, despite having time-consuming and technically complex reference methodologies. The Sensititre YeastOne (SYO) and Etest methods are widely utilized for yeasts but have not been extensively evaluated for Aspergillus isolates. We obtained Posaconazole (POS), Voriconazole (VCZ), Itraconazole (ITC), Amphotericin B (AMB), Caspofungin (CAS), and Anidulafungin (AND) minimum inhibitory concentrations (MICs) for both the Etest (n = 330) and SYO (n = 339) methods for 106 sequenced clinical strains. For 84 A. fumigatus, we analyzed the performance of both commercial methods in comparison with the CLSI-AFST, using available cutoff values. An excellent correlation could be demonstrated for Etest-AMB and Etest-VCZ (p < 0.01). SYO-MICs of AMB, VCZ, and POS resulted in excellent essential agreement (>93%), and >80% for AMB, VCZ, and ITC Etest-MICs. High categoric agreement was found for AMB, ITC, and CAS Etest-MICs (>85%) and AMB SYO-MICs (>90%). The considerable number of major/very major errors found using Etest and SYO, possibly related to the proposed cutoffs and associated with the less time-consuming processes, support the need for the improvement of commercial methods for Aspergillus strains.

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Section: Discussionmentioning

confidence: 99%

“…The combination of echinocandin with high-dose salvage posaconazole in cases of invasive Aspergillosis may be attempted and results from AFSTs could provide useful information for validating future CBPs or contribute to the improvement of data banks in establishing or implementing ECVs for these antifungal agents [ 35 ].…”

Section: Discussionmentioning

confidence: 99%

Evaluation of the Sensititre YeastOne and Etest in Comparison with CLSI M38-A2 for Antifungal Susceptibility Testing of Three Azoles, Amphotericin B, Caspofungin, and Anidulafungin, against Aspergillusfumigatus and Other Species, Using New Clinical Breakpoints and Epidemiological Cutoff Values

Melhem

Coelho²,

Fonseca³

et al. 2022

Pharmaceutics

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“…Watch list Invasive Pulmonary Aspergillosis (IPA) (Aigner and Lass-Flörl, 2015;Verweij et al, 2015;Novak et al, 2020) IV Liposomal Amphotericin B; 3-5 mg/kg/day IV Voriconazole a ; 6 mg/kg q12h for 1 day, followed by 4 mg/kg q12h IV/PO Posaconazole; 300 mg BD on day 1, then 300 mg OD IV Caspofungin a ; 70 mg/day on day 1, then 50 mg/day thereafter IV Micafungin a ; 100-150 mg/day (Continued on following page)…”

Section: Azole-resistantmentioning

confidence: 99%

Review on Plant-Based Management in Combating Antimicrobial Resistance - Mechanistic Perspective

et al. 2022

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Antimicrobial resistance (AMR) occurs when microbes no longer respond to any pharmacological agents, rendering the conventional antimicrobial agents ineffective. AMR has been classified as one of the top 10 life-threatening global health problems needed multilevel attention and global cooperation to attain the Sustainable Development Goals (SDGs) according to the World Health Organization (WHO), making the discovery of a new and effective antimicrobial agent a priority. The recommended treatments for drug-resistant microbes are available but limited. Furthermore, the transformation of microbes over time increases the risk of developing drug resistance. Hence, plant metabolites such as terpenes, phenolic compounds and alkaloids are widely studied due to their antibacterial, antiviral, antifungal and antiparasitic effects. Plant-derived antimicrobials are preferred due to their desirable efficacy and safety profile. Plant metabolites work by targeting microbial cell membranes, interfering with the synthesis of microbial DNA/RNA/enzymes and disrupting quorum sensing and efflux pump expression. They also work synergistically with conventional antibiotics to enhance antimicrobial effects. Accordingly, this review aims to identify currently available pharmacological therapies against microbes and AMR, as well as to discuss the importance of plant and secondary metabolites as a possible solution for AMR together with their mechanisms of action. All the information was obtained from government databases, WHO websites, PubMed, Springer, Google Scholar and Science Direct. Based on the information obtained, AMR is regarded as a significant warning to global healthcare. Plant derivatives such as secondary metabolites may be considered as potential therapeutic targets to mitigate the non-ending AMR.

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“…Conventional antifungal therapy for the treatment of invasive fungal infections (IFIs) remains challenging due to a limited number of available drugs, considerable toxicities, drug-drug interactions, and the increasing global spread of resistant pathogens such as azole-resistant Aspergillus fumigatus and echinocandin-resistant Candida species ( 1 , 2 ). Investigational antifungal agents currently studied in phase 2 or 3 trials continue to have major gaps in their therapeutic spectrum, especially limited activity against Mucorales and Fusarium species ( 3 ).…”

Section: Introductionmentioning

confidence: 99%

Checkpoint inhibitors as immunotherapy for fungal infections: Promises, challenges, and unanswered questions

2022

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Opportunistic fungal infections have high mortality in patients with severe immune dysfunction. Growing evidence suggests that the immune environment of invasive fungal infections and cancers share common features of immune cell exhaustion through activation of immune checkpoint pathways. This observation gave rise to several preclinical studies and clinical case reports describing blockade of the Programmed Cell Death Protein 1 and Cytotoxic T-Lymphocyte Antigen 4 immune checkpoint pathways as an adjunct immune enhancement strategy to treat opportunistic fungal infections. The first part of this review summarizes the emerging evidence for contributions of checkpoint pathways to the immunopathology of fungal sepsis, opportunistic mold infections, and dimorphic fungal infections. We then review the potential merits of immune checkpoint inhibitors (ICIs) as an antifungal immunotherapy, including the incomplete knowledge of the mechanisms involved in both immuno-protective effects and toxicities. In the second part of this review, we discuss the limitations of the current evidence and the many unknowns about ICIs as an antifungal immune enhancement strategy. Based on these gaps of knowledge and lessons learned from cancer immunology studies, we outline a research agenda to determine a “sweet spot” for ICIs in medical mycology. We specifically discuss the importance of more nuanced animal models, the need to study ICI-based combination therapy, potential ICI resistance, the role of the immune microenvironment, and the impact of ICIs given as part of oncological therapies on the natural immunity to various pathogenic fungi.

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Azole-Resistant Aspergillus and Echinocandin-Resistant Candida: What Are the Treatment Options?

Cited by 10 publications

References 76 publications

Evaluation of the Sensititre YeastOne and Etest in Comparison with CLSI M38-A2 for Antifungal Susceptibility Testing of Three Azoles, Amphotericin B, Caspofungin, and Anidulafungin, against Aspergillusfumigatus and Other Species, Using New Clinical Breakpoints and Epidemiological Cutoff Values

Evaluation of the Sensititre YeastOne and Etest in Comparison with CLSI M38-A2 for Antifungal Susceptibility Testing of Three Azoles, Amphotericin B, Caspofungin, and Anidulafungin, against Aspergillusfumigatus and Other Species, Using New Clinical Breakpoints and Epidemiological Cutoff Values

Review on Plant-Based Management in Combating Antimicrobial Resistance - Mechanistic Perspective

Checkpoint inhibitors as immunotherapy for fungal infections: Promises, challenges, and unanswered questions

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