Potential Implication of Azole Persistence in the Treatment Failure of Two Haematological Patients Infected with Aspergillus fumigatus
Abstract
:1. Introduction
2. Materials and Methods
2.1. Aspergillus fumigatus Strains
2.2. Clinical Antifungal Drugs Susceptibility Testing
2.3. Determination of Persistence
2.4. Cyp51A and Cyp51B Amplification, PCR Conditions and Sequencing
2.5. Strains Genotyping
2.6. Monitoring Antifungal Levels
3. Results
3.1. Patient 1
3.2. Patient 2
4. Discussion
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Isolate | Sample Type * | Day | MIC (mg/L) | Genotype | Persistence VRC | Persistence ISV | Resistance Mechanism | |||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
TRESPERG | ||||||||||||||||
AmB | ITC | VRC | POS | ISV | CSP | MP2 | CFEM | ERG4B | cyp51A | cyp51B | ||||||
H-2067 | BAL | 1 | 0.5 | 0.5 | 0.5 | 0.06 | 1 | t02 | m1.1 | c09 | e05 | TYPE I | - | - | WT | WT |
H-2099 | SP | 22 | 0.5 | 0.125 | 0.5 | 0.06 | 0.5 | t04A | m5.1 | c09 | e06 | TYPE II | - | - | WT | WT |
H-2100 | 22 | 1 | 0.5 | 1 | 0.125 | 1 | t04A | m5.1 | c09 | e06 | TYPE II | - | - | WT | WT | |
H-2101 | 22 | 1 | 0.5 | 0.5 | 0.06 | 1 | t03 | m1.1 | c07 | e07 | TYPE III | + | + | WT | WT | |
H-2116 | SP | 29 | 0.5 | 0.5 | 0.5 | 0.03 | 1 | t03 | m1.1 | c07 | e13 | TYPE III | + | + | WT | WT |
H-2117 | 29 | 0.5 | 0.25 | 0.5 | 0.03 | 1 | t11 | m1.8 | c07 | e13 | TYPE IV | + | + | WT | WT | |
H-2133 | SP | 37 | 1 | 0.5 | 0.5 | 0.06 | 2 | t11 | m1.8 | c07 | e07 | TYPE IV | + | + | WT | WT |
H-2134 | 37 | 0.5 | 0.125 | 0.5 | 0.03 | 0.5 | t03 | m1.1 | c07 | e07 | TYPE III | + | + | WT | WT | |
H-2154 | SP | 43 | 1 | 0.5 | 1 | 0.06 | 1 | t03 | m1.1 | c07 | e07 | TYPE III | + | + | WT | WT |
H-2155 | 43 | 1 | 0.125 | 0.5 | 0.03 | 0.5 | t03 | m1.1 | c07 | e07 | TYPE III | + | + | WT | WT | |
H-2165 | TA | 52 | 1 | 0.5 | 1 | 0.06 | 1 | t03 | m1.1 | c07 | e07 | TYPE III | + | + | WT | WT |
H-2173 | 52 | 1 | 0.125 | 0.5 | 0.03 | 0.5 | t03 | m1.1 | c07 | e07 | TYPE III | + | + | WT | WT | |
H-2226 | BAL | 64 | 1 | 0.5 | 0.5 | 0.125 | 1 | t11 | m1.8 | c07 | e13 | TYPE IV | + | - | WT | WT |
H-2285 | 64 | 1 | >8 | 8 | 0.5 | 8 | t10 | m1.1 | c07 | e05 | TYPE V | TR34/L98H | WT |
Isolate | Sample Type * | Day | MIC (mg/L) | Genotype | Persistence VRZ | Persistence ISV | Resistance Mechanism | |||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
TRESPERG | ||||||||||||||||
AmB | ITC | VRC | POS | ISV | CSP | MP2 | CFEM | ERG4B | cyp51A | cyp51B | ||||||
H-3161 | SP | 1 | 0.5 | 0.5 | 0.5 | 0.125 | 0.5 | t04A | m3.4 | c22b | e11 | TYPE I | - | - | WT | WT |
H-3168 | SP | 6 | 0.5 | 0.5 | 0.5 | 0.125 | 0.5 | t04A | m3.4 | c22b | e11 | TYPE I | + | + | WT | WT |
H-3178 | 6 | 0.5 | 0.5 | 0.5 | 0.25 | 1 | t04A | m3.4 | c22b | e11 | TYPE I | - | + | WT | WT | |
H-3180 | SP | 12 | 0.5 | 0.5 | 0.5 | 0.125 | 0.5 | t04A | m3.4 | c22b | e11 | TYPE I | + | + | WT | WT |
H-3181 | 12 | 0.5 | 0.5 | 0.25 | 0.125 | 0.25 | t02 | m5.1 | c08A | e11 | TYPE II | + | + | WT | WT | |
H-3183 | 12 | 0.5 | 0.5 | 0.25 | 0.125 | 0.5 | t04A | m3.4 | c22b | e11 | TYPE I | - | + | WT | WT | |
H-3184 | 12 | 0.5 | 0.5 | 0.5 | 0.125 | 0.5 | t04A | m3.4 | c22b | e11 | TYPE I | - | - | WT | WT | |
H-3185 | 12 | 0.5 | 0.5 | 0.5 | 0.125 | 0.5 | t04A | m3.4 | c22b | e11 | TYPE I | - | - | WT | WT | |
H-3192 | TA | 18 | 0.5 | 0.5 | 0.5 | 0.125 | 0.5 | t04A | m3.4 | c22b | e11 | TYPE I | - | + | WT | WT |
H-3200 | TA | 29 | 0.5 | 0.5 | 0.25 | 0.125 | 0.5 | t04A | m3.4 | c22b | e11 | TYPE I | - | + | WT | WT |
H-3201 | TA | 30 | 0.5 | 0.5 | 0.25 | 0.125 | 0.5 | t02 | m1.1 | c09 | e11 | TYPE III | + | + | WT | WT |
H-3202 | 30 | 1 | 0.5 | 0.25 | 0.125 | 0.5 | t04A | m3.4 | c22b | e11 | TYPE I | - | + | WT | WT |
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Peláez-García de la Rasilla, T.; Mato-López, Á.; Pablos-Puertas, C.E.; González-Huerta, A.J.; Gómez-López, A.; Mellado, E.; Amich, J. Potential Implication of Azole Persistence in the Treatment Failure of Two Haematological Patients Infected with Aspergillus fumigatus. J. Fungi 2023, 9, 805. https://doi.org/10.3390/jof9080805
Peláez-García de la Rasilla T, Mato-López Á, Pablos-Puertas CE, González-Huerta AJ, Gómez-López A, Mellado E, Amich J. Potential Implication of Azole Persistence in the Treatment Failure of Two Haematological Patients Infected with Aspergillus fumigatus. Journal of Fungi. 2023; 9(8):805. https://doi.org/10.3390/jof9080805
Chicago/Turabian StylePeláez-García de la Rasilla, Teresa, Álvaro Mato-López, Clara E. Pablos-Puertas, Ana Julia González-Huerta, Alicia Gómez-López, Emilia Mellado, and Jorge Amich. 2023. "Potential Implication of Azole Persistence in the Treatment Failure of Two Haematological Patients Infected with Aspergillus fumigatus" Journal of Fungi 9, no. 8: 805. https://doi.org/10.3390/jof9080805