Submitted:
27 April 2026
Posted:
28 April 2026
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Abstract
Keywords:
1. Introduction
2. Materials and Methods
Criteria
Definitions
Objectives
Literature Review
Analysis
3. Results
3.1. Study Selection
- A total of 96 primary, peer-reviewed articles were reviewed. Of those, 67 were excluded based on the following: non-human data, non-fungal data, secondary sources including literature reviews and C A reviews, articles written in languages other than English, and articles published before 1 January 2015. 28 studies were analyzed in this literature review.
3.2. Isolate Distribution
- Among the included studies, Candida auris isolates spanned four clades, with 13 articles reporting Clade I isolates, 4 Clade II, 5 Clade III, and 4 Clade IV. The geographic origins included Afghanistan, Bahrain, Bangladesh, China, Colombia, Egypt, India, Korea, Lebanon, Pakistan, Qatar, Saudi Arabia, South Africa, Spain, Turkey, United States, and Venezuela (Table 1).
3.3. Key Data Findings
3.4. Ibrexafungerp and Manogepix
- The novel antifungal Ibrexafungerp was found to have a MIC50 value of 0.50 mg/L and MIC90 value of 2.00 mg/L against C. auris after assessing its in vitro activity against a collection of 434 European blood isolates, with a MIC range of 0.5 mg/L to 8 mg/L[10] (Table 1). These values are comparable to those observed with second-generation azoles and echinocandins. Additionally, a separate study evaluating serial isolates from a single patient reported a comparable Ibrexafungerp MIC of 0.25 mg/L for multiple isolates, further supporting its retained activity against C. auris even in the context of evolving resistance [9] (Table 1). Another novel antifungal, Manogepix, or APX001A, displayed an average MIC50 of 0.014 mg/L and an average MIC90 of 0.026 mg/L [14,17,18] (Table 2). Manogepix was active against 16 strains of C. auris and was also shown to be active against 6 pan-resistant isolates [18]. Manogepix also exhibited the lowest average MIC50 and MIC90 values among all antifungals evaluated.
3.5. Comorbidities and Isolate Origins
4. Discussion
Author Contributions
Funding
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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| Study | Time Period of Isolate Collection | N total isolates; Region; Clade (n) a | MIC50 (mg/L) | MIC90 (mg/L) | Resistance (%) |
| Prayag[26] | N/A | 82; India | Caspo: 0.25 Mica: 0.12 Anidula: 0.25 |
Caspo: 8.0 Mica: 5.0 Anidula: 5.0 |
Caspo: 35.36% Mica: 0% Anidula: 0% |
| Ruiz-Gaitan[19] | N/A | 73; Spain | Flu: >64 Itra: 0.12 Isavu: 0.06 Vori: 2.0 Posa: 0.06 AmpB: 0.12 Mica: 0.06 Anidula: 0.03 |
Flu: >64 Itra: 0.25 Isavu: 0.12 Vori: 4.0 Posa: 0.12 AmpB: 0.25 Mica: 0.06 Anidula: 0.06 |
Flu: 100% AmpB: 0% Caspo: 0% Mica: 0% Anidula: 0% |
| Toth[28] | 2005-2018 | 19; Hungary | Flu: >32 AmpB: 0.5 Caspo: 0.5 Mica: 0.25 Anidula: 0.06 Reza: 0.12 |
Flu: >32 AmpB: 1 Caspo: 1 Mica: 0.5 Anidula: 0.25 Reza: 0.25 |
Flu: 68.40% AmpB: 0% Caspo: 0% Mica: 0% Anidula: 0% |
| Lee[20] | 2022 | 45; Korea | Flu: 16 Vori: 0.06 AmpB: 0.5 Caspo: 0.12 Mica: 0.12 5-FC: 0.12 |
Flu: 64 Vori: 0.5 AmpB: 2.0 Caspo: 0.5 Mica: 0.5 5-FC: 0.25 |
Flu: 37.80% AmpB: 24.40% Caspo: 0% Mica: 0% |
| Chowdhary [3] | 2009-2017 | 350; India | Flu: 64 Itra: 0.125 Isavu: 0.03 Vori: 0.25 Posa: 0.03 Serta: 0.5 AmpB: 1.0 Caspo: 1.0 Mica: 0.125 Anidula: 0.25 5-FC: 0.125 Terbin: 16.0 Nystatin: 4.0 |
Flu: 64 Itra: 0.5 Isavu: 0.5 Vori: 2.0 Posa: 0.125 Serta: 8.0 AmpB: 1.0 Caspo: 2.0 Mica: 0.25 Anidula: 1.0 5-FC: 64 Terbin: 32.0 Nystatin: 4.0 |
Fluc: 90% AmpB: 8% Caspo: 2% Mica: 2% Anidula: 2% |
| Maphanga[8] | 2016-2017 | 92; South Africa;III (77), I (13) and IV (2) | Flu: 128 Itra: 0.12 Vori: 0.5 Posa: 0.06 AmpB: 1.0 Caspo: 0.06 Mica: 0.06 Anidula: 0.12 5-FC: 0.12 |
Flu: 256 Itra: 0.25 Vori: 2.0 Posa: 0.12 AmpB: 2.0 Caspo: 0.25 Mica: 0.12 Anidula: 0.25 5-FC: 0.25 |
Flu: 90% AmpB: 27% Caspo: 1% Mica: 0.50% Anidula: 0% |
| Castanheira [11]b | 2013-2022 | 78; global; I (40), IV (30), III (7), II (1) | Flu: 64 AmpB: 1.0 Caspo: 0.12 Mica: 0.12 Anidula: 0.25 Reza: 0.25 |
Flu: >128 AmpB: 2.0 Caspo: 0.25 Mica: 0.25 Anidula: 0.5 Reza: 0.5 |
Flu: 82.10% AmpB: 17.90% Caspo: 1.30% Mica: 1.30% Anidula: 1.30% Reza: 3.8% |
| Jacobs[9]c | 2020 | 19; United States; Id | Flu: >256 Vori: 2.0 Itra: 1.0 Isavu: 2.0 Posa: 0.5 AmpB: 1.0 Caspo: 0.25 Mica: 0.12 Anidula: 0.25 5-FC: 0.094 Ibrexa: 0.25 |
None reported | Flu: 100% AmpB: 0% Caspo: 0% Mica: 0% Anidula: 0% |
| Valdez[32] | N/A | 8; United States; I (7) and II (1) | Flu: >256 AmpB: 1.0 Caspo: 0.25 |
Flu: >256 AmpB: 1.0 Caspo: 0.25 |
Flu: 87.50% AmpB: 0% Caspo: 0% |
| Ahmed[21]e | N/A | 4; Egypt; | Flu: 32 Itra: >16 Keto: 32 Vori: 0.25 Posa: 0.25 AmpB: 1.0 Caspo: >8.0 Mica: >8.0 5-FC: >64 |
Flu: 32 Itra: >16 Keto: 32 Vori: 1.0 Posa: 1.0 AmpB: 1.0 Caspo: >8.0 Mica: >8.0 5-FC: >64 |
Flu: 100% Itra: 100% Keto: 100% Vori: 0% Posa: 0% AmpB: 0% Caspo: 100% Mica: 100% 5-FC: 100% |
| Wang[22] | 2023-2024 | 7; China; I (3) and III (4) | Flu: 128 Itra: 0.12 Vori: 0.5 Posa: 0.03 AmpB: 1.0 Caspo: 0.12 Anidula: 0.12 5-FC: 0.06 |
Flu: 256 Itra: 0.25 Vori: 1.0 Posa: 0.12 AmpB: 2.0 Caspo: 0.5 Anidula: 1.0 5-FC: 0.12 |
Flu: 100% AmpB: 42.90% Caspo: 0% Anidula: 0% |
| Misas[30] | 2016-2021 | 182; Colombia: IV | Flu: 16 AmpB: 0.5 Caspo: 0.12 Mica: 0.125 Anidula: 0.25 |
Flu: 256 AmpB: 2.0 Caspo: 0.25 Mica: 0.5 Anidula: 1.0 |
Flu: 37% AmpB: 21% Caspo: 1% Mica: 0% Anidula: 0.60% |
| Bing[27] | 2018-2023 | 312; China; I, II, and III | None reported | None reported | Flu: 98.70% AmpB: 4.20% Caspo: 2.20% |
| Koleri[23] | 2018-2021 | 33; Qatar; I | None reported (all Med MIC) | None reported (all Med MIC) | Flu: 91% AmpB: 84.80% Caspo: 9.10% Mica: 0% Anidula: 0% |
| Kathuria[16] | 2010-2014 | 90, India | Flu: 64 Itra: 0.125 Isavu: 0.25 Vori: 1 Posa: 0.06 AmpB: 1 Caspo: 0.5 Mica: 0.125 Anidula: 0.125 5-FC: 0.25 |
Flu: 64 Itra: 0.5 Isavu: 2 Vori: 8 Posa: 2 AmpB: 4 Caspo: 1 Mica: 0.25 Anidula: 0.5 5-FC: 8 |
AmpB: 15.50% Caspo: 8.90% |
| Calvo[2] | 2012-2013 | 18; Venezuela | Flu: 64 Vori: 4 AmpB: 1 Anidula: 0.125 5-FC: 0.5 |
Flu: 64 Vori: 4 AmpB: 2 Anidula: 0.125 5-FC: 0.5 |
Flu: 100% |
| Lockhart[1] | 2012-2015 | 54; Pakistan, India, South Africa, and Venezuela | Flu: 128 Itra: 0.5 Vori: 2 Posa: 0.5 AmpB: 1 Caspo: 0.25 Mica: 0.25 Anidula: 0.5 5-FC: 0.125 |
Flu: 256 Itra: 1 Vori: 8 Posa: 1 AmpB: 2 Caspo: 1 Mica: 2 Anidula: 1 5-FC: 0.5 |
Flu: 93% AmpB: 35% 5-FC: 6% |
| Zhu [5]f | 2016-2018 | 413; United States; I, II | Flu: >256 Itra: 0.5 Isavu: 0.5 Vori: 2 Posa: 0.25 AmpB: 2 Caspo: 0.12 Mica: 0.12 Anidula: 0.25 5-FC: 0.094 |
Flu: >256 Itra: 1 Isavu: 1 Vori: 2 Posa: 0.5 AmpB: 2 Caspo: 0.25 Mica: 0.25 Anidula: 0.5 5-FC: 0.125 |
Flu: 99% Vori: 81% AmpB: 61% Caspo: 0% Mica: 0% Anidula: 0% 5-FC: 0.70% |
| Erdem[13] | 2024 | 162; Turkey, India, Saudi Arabia, Egypt, Bahrain, Bangladesh, and Afghanistan | Flu: 32 Itra: 0.12 Vori: 1 Posa: 0.12 AmpB: 4 Caspo: 0.25 Mica: 0.12 Anidula: 0.12 5-FC: 0.5 |
Flu: 256 Itra: 16 Vori: 16 Posa: 4 AmpB: 32 Caspo: 2 Mica: 2 Anidula: 2 5-FC: 64 |
Flu: 90.3% AmpB: 70.1% Caspo: 14% Mica: 7.1% Anidula: 2.6% |
| Ninan[7] | 2016-2017 | 11; India | Flu: 32 Itra: 0.5 Vori: 0.5 Posa: 0.03 AmpB: 1.0 Caspo: 0.25 Anidula: 0.047 |
Flu: 64 Itra: 0.5 Vori: 1.0 Posa: 0.12 AmpB: 1.0 Caspo: 0.5 Anidula: 0.25 |
Flu: 91% |
| Akkaya[15] | 2023-2024 | 57; Turkey; I | Flu: 32 AmpB: 2 Caspo: 0.12 Mica: 0.06 Anidula: 0.12 |
Flu: 128 AmpB: 16 Caspo: 0.25 Mica: 0.12 Anidula: 0.5 |
Flu: 82% AmpB: 60% Caspo: 7% Mica: 5% |
| Kalkanci[24] | 2025 | 47; Turkey; I | Flu: 16 Itra: 1 Isavu: 0.12 Vori: 2 Posa: 0.12 AmpB: 0.5 Caspo: 0.12 |
Flu: 32 Itra: 2 Isavu: 0.5 Vori: 8 Posa: 0.5 AmpB: 1 Caspo: 0.25 |
Flu: 82% Amph B: 60% Caspo: 7% Mica: 5% |
| Quindos[10] | 2022 | 22; Europe | Flu: >=128 Caspo: 0.125 Mica: 0.125 Ibrexa: 0.5 |
Flu: >=128 Caspo: >8 Mica: 4 Ibrexa: 2 |
Flu: 31% Amph B: 4% |
| Quindos[24] | 2022 | N/A | Flu: >=128 Caspo: 0.125 Mica: 0.125 Ibrexa: 0.5 |
Flu: >=128 Caspo: >8 Mica: 4 Ibrexa: 2 |
Flu: 100% Caspo: 27.27% Mica: 18.18% |
| Reslan[25] | 2022 | Lebanon (I) | Flu: 32 Itra: 0.25 Vori: 0.25 Amph B: 8 Caspo: 0.25 Mica: 0.12 Flucyt: 1 |
Flu: >=32 Itra: 1 Vori: 0.25 Amph B: 8 Caspo: 0.25 Mica: 0.12 Flucyt: 1 |
Flu: 54% Itra: 25% Vori: 3% Amph B: 100% Caspo: 0% Mica: 0% |
| Arendrup[4]g | 2010-2015 | 123; India | CLSI: Flu: >=64 Itra: 0.125 Isavu: 0.125 Vori: 0.5 Posa: 0.016 AmpB: 0.5 Mica: 0.125 Anidula: 0.125 EUCAST: Flu: >=64 Itra: 0.125 Isavu: 0.125 Vori: 0.5 Posa: 0.032 AmpB: 1 Mica: 0.125 Anidula: 0.125 |
CLSI: Flu: >=64 Itra: 0.25 Isavu: 0.5 Vori: 4 Posa: 0.125 AmpB: 2 Mica: 0.25 Anidula: 0.5 EUCAST: Flu: >=64 Itra: 0.5 Isavu: 0.5 Vori: 2 Posa: 0.125 AmpB: 1 Mica: 0.25 Anidula: 1 |
Flu: 86% AmpB: 10% Mica: 6% Anidula: 5.69% |
| Hager[18] | 2018 | 16; Germany, Japan, South Korea, India, | Flu: 16*, >64** Itra: 0.5** Vori: 0.5*, 0.5** Posa: 0.25** AmpB: 2*, 4** Mica: 1* Mano: 0.004 |
Flu: >64*, >64** Itra: 1** Vori: 1*, 2** Posa: 1** AmpB: 4*, 8** Mica: 2* Mano: 0.031 |
None reported |
| Maphanga [14] | 2016-2017 | 394h; South Africa; III, I, IV | Flu: 128 Itra: 0.12 Vori: 0.5 Posa: 0.06 AmpB: 1 Caspo: 0.06 Mica: 0.06 Anidula: 0.12 5-FC: 0.12 Mano: 0.008 |
Flu: 256 Itra: 0.25 Vori: 2 Posa: 0.12 AmpB: 2 Caspo: 0.25 Mica: 0.12 Anidula: 0.25 5-FC: 0.25 Mano: 0.016 |
Flu: 90% AmpB: 27% Mica: 0.50% Anidula: 0% |
| Zhu [17] | 2017-2020 | 200; United States; I | Flu: 256 Itra: 0.5 Isavu: 1 Vori: 2 Posa: 0.25 AmpB: 1 Caspo: 0.12 Mica: 0.12 Anidula: 0.25 5-FC: 0.064 Mano: 0.03 |
Flu: 256 Itra: 1 Isavu: 1 Vori: 2 Posa: 0.5 AmpB: 2 Caspo: 0.25 Mica: 0.25 Anidula: 1 5-FC: 32 Mano: 0.03 |
Flu: 100% AmpB: 46.50% Caspo: 5.50% Mica: 5% Anidula: 5.50% |
| Antifungal | Average MIC50 (+/- SD) (Study n) | Average MIC90 (+/- SD) (Study n) | Average Resistance % (+/- SD) (Study n) |
| Fluconazole | 92.44 (+/- 79.79) (n=27) | 138.67 (+/- 96.54) (n=24) | 83.95 (+/- 21.29) (n=25) |
| Itraconazole | 1.33 (+/- 3.92) (n=16) | 2.72 (+/- 5.41) (n=15) | 62.50 (+/- 53.03) (n=2) |
| Isavuconazole | 0.51 (+/- 0.68) (n=8) | 0.80 (+/- 0.61) (n=7) | Not reported |
| Ketoconazole | 32.00 (n=1) | 32.00 (n=1) | 100.00 (n=1) |
| Voriconazole | 1.15 (+/- 1.03) (n=19) | 3.71 (+/- 4.01) (n=18) | 46.00 (+/- 51.98) (n=4) |
| Posaconazole | 0.16 (+/- 0.16) (n=18) | 0.74 (+/- 1.08) (n=19) | 0.00 (n=1) |
| Sertaconazole | 0.50 (n=1) | 8.00 (n=1) | Not reported |
| Amphotericin B | 1.40 (+/- 1.60) (n=24) | 4.01 (+/- 7.04) (n=23) | 28.67 (+/- 29.39) (n=23) |
| Caspofungin | 0.59 (+/- 1.67) (n=22) | 1.67 (+/- 2.70) (n=21) | 10.73 (+/- 23.10) (n=20) |
| Micafungin | 0.54 (+/- 1.72) (n=21) | 1.33 (+/- 2.09) (n=20) | 7.66 (+/- 22.80) (n=19) |
| Anidulafungin | 0.18 (+/- 0.11) (n=19) | 0.87 (+/- 1.13) (n=19) | 1.17 (+/- 1.97) (n=15) |
| Rezafungin | 0.19 (+/- 0.09) (n=2) | 0.38 (+/- 0.18) (n=2) | 3.80 (n=1) |
| Flucytosine | 4.80 (+/- 17.04) (n=14) | 18.08 (+/- 27.58) (n=13) | 35.57 (+/- 55.86) (n=2) |
| Terbinafine | 16.00 (n=1) | 32.00 (n=1) | Not reported |
| Nystatin | 4.00 (n=1) | 4.00 (n=1) | Not reported |
| Ibrexafungerp | 0.38 (+/- 0.18) (n=2) | 2.00 (n=1) | Not reported |
| Manogepix | 0.014 (+/- 0.014) (n=3) | 0.026 (+/- 0.008) (n=3) | Not reported |
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