ArticleAntimicrobial agents and chemotherapy2010
Efficacy of posaconazole against three clinical Aspergillus fumigatus isolates with mutations in the cyp51A gene.
Article in Antimicrobial agents and chemotherapy, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03121235 (PCR Based Detection of Azole Resistance in A. Fumigatus to Improve Patient Outcome. A Prospective Multicenter Observational Study.), which is not on this map. Cited by 55 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
PCR Based Detection of Azole Resistance in A. Fumigatus to Improve Patient Outcome. A Prospective Multicenter Observational Study.
Who cites it
55 citing papers in PubMed.
- Pharmacokinetics of Intravenous Posaconazole in Critically Ill Patients.Antimicrobial agents and chemotherapy · 2018Trial
- In Vitro-In Vivo Correlation of Posaconazole-Amphotericin B Combination againstJournal of fungi (Basel, Switzerland) · 2023Article
- Dose adjustment of venetoclax when co-administered with posaconazole: clinical drug-drug interaction predictions using a PBPK approach.Cancer chemotherapy and pharmacology · 2021Article
- Pharmacodynamics of Posaconazole in Experimental Invasive Pulmonary Aspergillosis: Utility of Serum Galactomannan as a Dynamic Endpoint of Antifungal Efficacy.Antimicrobial agents and chemotherapy · 2021Article
- Role and Interpretation of Antifungal Susceptibility Testing for the Management of Invasive Fungal Infections.Journal of fungi (Basel, Switzerland) · 2020Review
- Drug-Resistant Fungi: An Emerging Challenge Threatening Our Limited Antifungal Armamentarium.Antibiotics (Basel, Switzerland) · 2020Review
- Review
- High-dose posaconazole for azole-resistant aspergillosis and other difficult-to-treat mould infections.Mycoses · 2020Article
- Saliva for Precision Dosing of Antifungal Drugs: Saliva Population PK Model for Voriconazole Based on a Systematic Review.Frontiers in pharmacology · 2020Article
- ASP2397 Is a Novel Natural Compound That Exhibits Rapid and Potent Fungicidal Activity againstAntimicrobial agents and chemotherapy · 2019Article
- Itraconazole, Voriconazole, and Posaconazole CLSI MIC Distributions for Wild-Type and Azole-ResistantJournal of fungi (Basel, Switzerland) · 2018Article
- Triazole resistance surveillance in Aspergillus fumigatus.Medical mycology · 2018Review
- Pharmacokinetics of antifungal drugs: practical implications for optimized treatment of patients.Infection · 2017Review
- Molecular Tools for the Detection and Deduction of Azole Antifungal Drug Resistance Phenotypes in Aspergillus Species.Clinical microbiology reviews · 2017Review
- Morphological changes and induction of antifungal resistance inCurrent medical mycology · 2017Article
- Pharmacodynamics of the Orotomides againstmBio · 2017Article
- Article
- Prognostic value of galactomannan: current evidence for monitoring response to antifungal therapy in patients with invasive aspergillosis.Journal of pharmacokinetics and pharmacodynamics · 2017Review
- Rodent Models of Invasive Aspergillosis due toFrontiers in microbiology · 2017Review
- In Vivo Synergy of Amphotericin B plus Posaconazole in Murine Aspergillosis.Antimicrobial agents and chemotherapy · 2016Article
Corrections and comments
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Authors and funding
5 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The in vivo efficacy of posaconazole against 4 clinical Aspergillus fumigatus isolates with posaconazole MICs ranging from 0.03 to 16 mg/liter, as determined by CLSI method M38A, was assessed in a nonneutropenic murine model of disseminated aspergillosis. The underlying resistance mechanisms of the isolates included substitutions in the cyp51A gene at codon 220 (M220I), codon 54 (G54W), and codon 98 (L98H). The latter was combined with a 34-bp tandem repeat in the gene promoter region (TR L98H). The control isolate exhibited a wild-type phenotype without any known resistance mechanism. Oral posaconazole therapy was started 24 h after infection and was given once daily for 14 consecutive days. Mice were treated with four different doses (1 to 64 mg/kg of body weight), and survival was used as the end point. Survival was dependent both on the dose and on the MIC. The Hill equation with a variable slope fitted the relationship between the dose/MIC ratio and 14-day survival well (R2, 0.92), with a 50% effective dose (ED50) of 29.0 mg/kg (95% confidence interval [CI], 15.6 to 53.6 mg/kg). This also applied to the relationship between the area under the plasma concentration-time curve (AUC)/MIC ratio and 14-day survival (50% effective pharmacodynamic index [EI50], 321.3 [95% CI, 222.7 to 463.4]). Near-maximum survival was reached at an AUC/MIC ratio of nearly 1,000. These results indicate that treatment of infections with A. fumigatus strains for which MICs are 0.5 mg/liter requires doses exceeding the present licensed doses. Increasing the standard dosing regimen may have some effect and may be clinically useful if no alternatives are available.
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