ArticleAntimicrobial agents and chemotherapy2013
Posaconazole pharmacodynamic target determination against wild-type and Cyp51 mutant isolates of Aspergillus fumigatus in an in vivo model of invasive pulmonary aspergillosis.
Article in Antimicrobial agents and chemotherapy, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers, 1 of them a synthesis that pooled it.
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40 citing papers in PubMed, 1 synthesis or guideline pooled it, 71 citations in OpenAlex.
- Antifungal pharmacodynamics: Latin America's perspective.The Brazilian journal of infectious diseases : an official publication of the Brazilian Society of Infectious DiseasesPooled it
- Hypoalbuminemia and Posaconazole Therapeutic Drug Monitoring.Open forum infectious diseases · 2024Trial
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- Longitudinal multimodal imaging-compatible mouse model of triazole-sensitive and -resistant invasive pulmonary aspergillosis.Disease models & mechanisms · 2022Article
- Tafenoquine exhibits broad spectrum antifungal activity at clinically relevant concentrationsNew microbes and new infections · 2022Article
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- Model-Informed Drug Development for Anti-Infectives: State of the Art and Future.Clinical pharmacology and therapeutics · 2021Review
- Role and Interpretation of Antifungal Susceptibility Testing for the Management of Invasive Fungal Infections.Journal of fungi (Basel, Switzerland) · 2020Review
- A marine microbiome antifungal targets urgent-threat drug-resistant fungi.Science (New York, N.Y.) · 2020Article
- Modeling Invasive Aspergillosis: How Close Are Predicted Antifungal Targets?Journal of fungi (Basel, Switzerland) · 2020Review
- Azole-resistant Aspergillus and Echinocandin-resistant Candida - What are the treatment options?Current fungal infection reports · 2020Article
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- Extrapolating Antifungal Animal Data to Humans - Is it reliable?Current fungal infection reports · 2020Article
- High-dose posaconazole for azole-resistant aspergillosis and other difficult-to-treat mould infections.Mycoses · 2020Article
- Increased Efficacy of Oral Fixed-Dose Combination of Amphotericin B and AHCCPharmaceutics · 2019Article
- Emerging threat of triazole-resistant Aspergillus fumigatus.The Journal of antimicrobial chemotherapy · 2019Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Invasive pulmonary aspergillosis (IPA) is a devastating disease of immunocompromised patients. Pharmacodynamic (PD) examination of antifungal drug therapy in IPA is one strategy that may improve outcomes. The current study explored the PD target of posaconazole in an immunocompromised murine model of IPA against 10 A. fumigatus isolates, including 4 Cyp51 wild-type isolates and 6 isolates carrying Cyp51 mutations conferring azole resistance. The posaconazole MIC range was 0.25 to 8 mg/liter. Following infection, mice were given 0.156 to 160 mg/kg of body weight of oral posaconazole daily for 7 days. Efficacy was assessed by quantitative PCR (qPCR) of lung homogenate and survival. At the start of therapy, mice had 5.59 ± 0.19 log(10) Aspergillus conidial equivalents (CE)/ml of lung homogenate, which increased to 7.11 ± 0.29 log(10) CE/ml of lung homogenate in untreated animals. The infection was uniformly lethal prior to the study endpoint in control mice. A Hill-type dose response function was used to model the relationship between posaconazole free drug area under the concentration-time curve (AUC)/MIC and qPCR lung burden. The static dose range was 1.09 to 51.9 mg/kg/24 h. The free drug AUC/MIC PD target was 1.09 ± 0.63 for the group of strains. The 1-log kill free drug AUC/MIC was 2.07 ± 1.02. The PD target was not significantly different for the wild-type and mutant organism groups. Mortality mirrored qPCR results, with the greatest improvement in survival noted at the same dosing regimens that produced static or cidal activity. Consideration of human pharmacokinetic data and the current static dose PD target would predict a clinical MIC threshold of 0.25 to 0.5 mg/liter.
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