Abstract
We have evaluated the in vitro activity of posaconazole (PSC) against 50 clinical strains of Rhizopus oryzae using a broth microdilution method, the Neo-Sensitabs tablet diffusion method, and minimal fungicidal concentration (MFC) determination. In general, PSC showed low MICs against this fungus, and the MICs correlated with the inhibition zone diameters. Most of the MFCs, however, were from 1 to 4 dilutions higher than their corresponding MICs. We then investigated the efficacies of several different doses of PSC in a murine model. All treatments began 24 h after challenge and lasted for 7 days. The drug was administered twice a day to mice infected with three strains that showed intermediate PSC susceptibility (MIC = 2 μg/ml) and three PSC-susceptible strains (MIC = 0.25 μg/ml). A dose of 10 mg/kg of body weight was ineffective, while doses of 20 and 30 mg/kg prolonged the survival of the mice. The 50 strains tested were segregated into two groups on the basis of the in vitro data. For the group with the most strains (85%), the strains had low PSC MICs, mice infected with the strains showed higher rates of survival (30 to 40%), and PSC was able to reduce the fungal load in the kidney and less regularly in the brain. For the second group (15% of the strains), the strains had intermediate PSC MICs, mice infected with the strains had lower survival rates (10 to 20%), and PSC treatment resulted in variable and no reductions in the fungal loads in the kidneys and brains, respectively.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1665-1669 |
| Number of pages | 5 |
| Journal | Antimicrobial Agents and Chemotherapy |
| Volume | 54 |
| Issue number | 5 |
| DOIs | |
| State | Published - May 2010 |
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ASJC Scopus subject areas
- Pharmacology (medical)
- Pharmacology
- Infectious Diseases
Cite this
Correlation between in vitro activity of posaconazole and in vivo efficacy against Rhizopus oryzae infection in mice. / Mar Rodríguez, M.; Javier Pastor, F.; Sutton, Deanna A.; Calvo, Enrique; Fothergill, Annette W.; Salas, Valentina; Rinaldi, Michael G.; Guarro, Josep.
In: Antimicrobial Agents and Chemotherapy, Vol. 54, No. 5, 05.2010, p. 1665-1669.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Correlation between in vitro activity of posaconazole and in vivo efficacy against Rhizopus oryzae infection in mice
AU - Mar Rodríguez, M.
AU - Javier Pastor, F.
AU - Sutton, Deanna A.
AU - Calvo, Enrique
AU - Fothergill, Annette W.
AU - Salas, Valentina
AU - Rinaldi, Michael G.
AU - Guarro, Josep
PY - 2010/5
Y1 - 2010/5
N2 - We have evaluated the in vitro activity of posaconazole (PSC) against 50 clinical strains of Rhizopus oryzae using a broth microdilution method, the Neo-Sensitabs tablet diffusion method, and minimal fungicidal concentration (MFC) determination. In general, PSC showed low MICs against this fungus, and the MICs correlated with the inhibition zone diameters. Most of the MFCs, however, were from 1 to 4 dilutions higher than their corresponding MICs. We then investigated the efficacies of several different doses of PSC in a murine model. All treatments began 24 h after challenge and lasted for 7 days. The drug was administered twice a day to mice infected with three strains that showed intermediate PSC susceptibility (MIC = 2 μg/ml) and three PSC-susceptible strains (MIC = 0.25 μg/ml). A dose of 10 mg/kg of body weight was ineffective, while doses of 20 and 30 mg/kg prolonged the survival of the mice. The 50 strains tested were segregated into two groups on the basis of the in vitro data. For the group with the most strains (85%), the strains had low PSC MICs, mice infected with the strains showed higher rates of survival (30 to 40%), and PSC was able to reduce the fungal load in the kidney and less regularly in the brain. For the second group (15% of the strains), the strains had intermediate PSC MICs, mice infected with the strains had lower survival rates (10 to 20%), and PSC treatment resulted in variable and no reductions in the fungal loads in the kidneys and brains, respectively.
AB - We have evaluated the in vitro activity of posaconazole (PSC) against 50 clinical strains of Rhizopus oryzae using a broth microdilution method, the Neo-Sensitabs tablet diffusion method, and minimal fungicidal concentration (MFC) determination. In general, PSC showed low MICs against this fungus, and the MICs correlated with the inhibition zone diameters. Most of the MFCs, however, were from 1 to 4 dilutions higher than their corresponding MICs. We then investigated the efficacies of several different doses of PSC in a murine model. All treatments began 24 h after challenge and lasted for 7 days. The drug was administered twice a day to mice infected with three strains that showed intermediate PSC susceptibility (MIC = 2 μg/ml) and three PSC-susceptible strains (MIC = 0.25 μg/ml). A dose of 10 mg/kg of body weight was ineffective, while doses of 20 and 30 mg/kg prolonged the survival of the mice. The 50 strains tested were segregated into two groups on the basis of the in vitro data. For the group with the most strains (85%), the strains had low PSC MICs, mice infected with the strains showed higher rates of survival (30 to 40%), and PSC was able to reduce the fungal load in the kidney and less regularly in the brain. For the second group (15% of the strains), the strains had intermediate PSC MICs, mice infected with the strains had lower survival rates (10 to 20%), and PSC treatment resulted in variable and no reductions in the fungal loads in the kidneys and brains, respectively.
UR - http://www.scopus.com/inward/record.url?scp=77951248570&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77951248570&partnerID=8YFLogxK
U2 - 10.1128/AAC.01463-09
DO - 10.1128/AAC.01463-09
M3 - Article
C2 - 20145077
AN - SCOPUS:77951248570
VL - 54
SP - 1665
EP - 1669
JO - Antimicrobial Agents and Chemotherapy
JF - Antimicrobial Agents and Chemotherapy
SN - 0066-4804
IS - 5
ER -