In Vitro and In Vivo Evaluation of Voriconazole-Containing Antifungal Combinations against Mucorales Using a Galleria mellonella Model of Mucormycosis
Abstract
:1. Introduction
2. Materials and Methods
2.1. Fungal Isolates
2.2. Susceptibility Testing for Individual Drugs and Combination of Drugs
2.3. Galleria mellonella Mucormycosis Model for the Evaluation of the Effect of Antifungal Drugs Combinations
2.4. Data Analysis
3. Results
3.1. Individual Drug and Combined Susceptibility Testing
3.2. Galleria mellonella Infection and Antifungal Treatment Model
3.3. Evaluation of the Efficacy of the Drug Combinations in the Galleria mellonella Model
4. Discussion
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Isolate Nº | Organism | Isolation Site | MIC (mg/L) | ∑FIC Index (Interpretation) c | ||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
VRC + PSC | VRC + AMB | VRC + CSF | ||||||||||
VRC | PSC | AMB | CSF | MIC | HA | MIC | HA | MIC | HA | |||
LMDM-165 | R. microsporusa | Osteomyelitis | 8.00 | 1.00 | 2.00 | 16.00 | 0.75 (NI) | Yes | 0.75 (NI) | Yes | 0.75 (NI) | Yes |
LMDM-156 | R. microsporusa | Osteomyelitis | 4.00 | 1.00 | 2.00 | 16.00 | 1.00 (NI) | Yes | 2.04 (NI) | No | 1.00 (NI) | Yes |
LMDM-157 | R. microsporusa | Surgical wound | 4.00 | 0.50 | 1.00 | 16.00 | 0.50 (S) | Yes | 1.03 (NI) | No | 0.75 (NI) | Yes |
LMDM-158 | R. microsporusa | Surgical wound | 8.00 | 0.50 | 2.00 | 16.00 | 1.00 (NI) | Yes | 1.04 (NI) | No | 2.00 (NI) | Yes |
LMDM-159 | R. microsporusa | Surgical wound | 4.00 | 1.00 | 2.00 | 16.00 | 1.00 (NI) | No | 1.03 (NI) | No | 1.50 (NI) | No |
LMDM-164 | R. microsporusa | Osteomyelitis | 4.00 | 1.00 | 2.00 | 16.00 | 1.00 (NI) | No | 1.01 (NI) | Yes | 1.00 (NI) | No |
LMDM-167 | R. microsporusa | Hospital environment | 4.00 | 1.00 | 2.00 | 16.00 | 1.02 (NI) | Yes | 1.03 (NI) | No | 1.25 (NI) | No |
LMDM-168 | R. microsporusa | Hospital environment | 4.00 | 1.00 | 2.00 | 16.00 | 1.03 (NI) | No | 2.50 (NI) | No | 2.00 (NI) | No |
LMDM-176 | R. microsporusa | Osteomyelitis | 8.00 | 1.00 | 2.00 | 16.00 | 0.63 (NI) | Yes | 2.25 (NI) | Yes | 1.25 (NI) | No |
LMDM-184 | R. microsporusa | Osteomyelitis | 8.00 | 1.00 | 2.00 | 16.00 | 0.75 (NI) | Yes | 1.03 (NI) | Yes | 1.03 (NI) | No |
LMDM-379 | R. microsporusa | Rhinocerebral | 8.00 | 1.00 | 4.00 | 16.00 | 0.63 (NI) | Yes | 1.00 (NI) | No | 0.75 (NI) | Yes |
LMDM-596 | R. microsporusa | Rhinocerebral | 2.00 | 1.00 | 1.00 | 16.00 | 1.06 (NI) | No | 2.00 (NI) | No | 1.03 (NI) | No |
LMDM-1073 | R. microsporusb | Rhinocerebral | 2.00 | 1.00 | 0.50 | 16.00 | 1.06 (NI) | No | 1.06 (NI) | No | 2.00 (NI) | No |
LMDM-1074 | R. microsporusb | Rhinocerebral | 2.00 | 1.00 | 0.25 | 16.00 | 0.75 (NI) | No | 0.62 (NI) | No | 2.00 (NI) | No |
LMDM-1127 | R. microsporusb | Hospital environment | 8.00 | 2.00 | 1.00 | 16.00 | 0.50 (S) | No | 0.50 (S) | No | 0.75 (NI) | No |
n = 15 | R. microsporus | 4.59 | 0.95 | 1.45 | 16.00 | 0.82 | 1.14 | 1.18 | ||||
LMDM-597 | R. oryzae | Rhinocerebral | 8.00 | 1.00 | 2.00 | 16.00 | 0.75 (NI) | No | 0.75 (NI) | No | 0.75 (NI) | No |
LMDM-1126 | R. oryzae | Rhinocerebral | 8.00 | 1.00 | 1.00 | 16.00 | 0.75 (NI) | No | 0.50 (S) | No | 1.00 (NI) | No |
LMDM-1075 | R. oryzae | Rhinocerebral | 4.00 | 1.00 | 0.25 | 16.00 | 1.00 (NI) | No | 0.62 (NI) | No | 2.00 (NI) | No |
n = 3 | R. oryzae | 6.35 | 1.00 | 0.79 | 16.00 | 0.83 | 0.61 | 1.14 | ||||
LMDM-1122 | S. racemosum | Rhinocerebral | 4.00 | 1.00 | 0.50 | 16.00 | 1.00 (NI) | Yes | 1.00 (NI) | Yes | 2.00 (NI) | Yes |
LMDM-1123 | S. racemosum | Hospital environment | 4.00 | 1.00 | 0.25 | 16.00 | 0.75 (NI) | No | 1.00 (NI) | No | 2.00 (NI) | Yes |
LMDM-1124 | S. racemosum | Hospital environment | 16.00 | 2.00 | 0.50 | 16.00 | 1.00 (NI) | No | 1.00 (NI) | No | 2.00 (NI) | No |
LMDM-576 | S. racemosum | Rhinocerebral | 16.00 | 2.00 | 2.00 | 16.00 | 0.50 (S) | Yes | 0.50 (S) | Yes | 1.00 (NI) | Yes |
n = 4 | S. racemosum | 8.00 | 1.40 | 0.59 | 16.00 | 0.78 | 0.88 | 1.75 | ||||
LMDM-1128 | L. blakesleeana | Cutaneous ulcera | 4.00 | 0.50 | 0.50 | 16.00 | 0.75 (NI) | Yes | 1.00 (NI) | Yes | 2.00 (NI) | No |
LMDM-1121 | L. corymbifera | Hospital environment | 8.00 | 1.00 | 0.25 | 16.00 | 0.50 (S) | Yes | 1.00 (NI) | No | 2.00 (NI) | Yes |
LMDM-1125 | L. ramosa | Clinical d | 16.00 | 1.00 | 1.00 | 16.00 | 0.31 (S) | No | 0.62 (NI) | No | 1.00 (NI) | No |
n = 3 | Lichtheimia spp. | 8.00 | 0.80 | 0.50 | 16.00 | 0.49 | 1.09 | 1.45 | ||||
n = 25 | Mucormycetes | 5.74 | 1.03 | 1.03 | 16.00 | 0.81 | 1.09 | 1.45 | ||||
n = 10 | non-R. microsporus | 8.00 | 1.15 | 0.62 | 16.00 | 0.73 | 0.80 | 1.70 |
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Macedo, D.; Leonardelli, F.; Dudiuk, C.; Vitale, R.G.; Del Valle, E.; Giusiano, G.; Gamarra, S.; Garcia-Effron, G. In Vitro and In Vivo Evaluation of Voriconazole-Containing Antifungal Combinations against Mucorales Using a Galleria mellonella Model of Mucormycosis. J. Fungi 2019, 5, 5. https://doi.org/10.3390/jof5010005
Macedo D, Leonardelli F, Dudiuk C, Vitale RG, Del Valle E, Giusiano G, Gamarra S, Garcia-Effron G. In Vitro and In Vivo Evaluation of Voriconazole-Containing Antifungal Combinations against Mucorales Using a Galleria mellonella Model of Mucormycosis. Journal of Fungi. 2019; 5(1):5. https://doi.org/10.3390/jof5010005
Chicago/Turabian StyleMacedo, Daiana, Florencia Leonardelli, Catiana Dudiuk, Roxana G. Vitale, Eleodoro Del Valle, Gustavo Giusiano, Soledad Gamarra, and Guillermo Garcia-Effron. 2019. "In Vitro and In Vivo Evaluation of Voriconazole-Containing Antifungal Combinations against Mucorales Using a Galleria mellonella Model of Mucormycosis" Journal of Fungi 5, no. 1: 5. https://doi.org/10.3390/jof5010005