ArticleAntimicrobial agents and chemotherapy2013
Pharmacodynamics and dose-response relationships of liposomal amphotericin B against different azole-resistant Aspergillus fumigatus isolates in a murine model of disseminated 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 22 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
22 citing papers in PubMed, 1 synthesis or guideline pooled it, 45 citations in OpenAlex.
- Intensive care medicine research agenda on invasive fungal infection in critically ill patients.Intensive care medicine · 2017Pooled it
- Article
- Antibiotics, Analgesic Sedatives, and Antiseizure Medications Frequently Used in Critically Ill Neonates: A Narrative Review.Children (Basel, Switzerland) · 2024Review
- Article
- Genetic Analyses of Amphotericin B Susceptibility inJournal of fungi (Basel, Switzerland) · 2021Article
- Azole-resistant Aspergillus and Echinocandin-resistant Candida - What are the treatment options?Current fungal infection reports · 2020Article
- Therapies and Vaccines Based on Nanoparticles for the Treatment of Systemic Fungal Infections.Frontiers in cellular and infection microbiology · 2020Review
- Article
- Resistance mechanism and proteins inMycology · 2019Review
- Responding to the emergence of antifungal drug resistance: perspectives from the bench and the bedside.Future microbiology · 2018Review
- Animal Models of Aspergillosis.Comparative medicine · 2018Review
- Article
- Successful treatment of azole-resistant invasive aspergillosis in a bottlenose dolphin with high-dose posaconazole.Medical mycology case reports · 2017Article
- Rodent Models of Invasive Aspergillosis due toFrontiers in microbiology · 2017Review
- Pharmacodynamics of Voriconazole against Wild-Type and Azole-Resistant Aspergillus flavus Isolates in a Nonneutropenic Murine Model of Disseminated Aspergillosis.Antimicrobial agents and chemotherapy · 2017Article
- Triazole Resistance in Aspergillus spp.: A Worldwide Problem?Journal of fungi (Basel, Switzerland) · 2016Review
- High-Level Pan-Azole-Resistant Aspergillosis.Journal of clinical microbiology · 2015Article
- Pharmacodynamics of isavuconazole in an Aspergillus fumigatus mouse infection model.Antimicrobial agents and chemotherapy · 2015Article
- Posaconazole prophylaxis in experimental azole-resistant invasive pulmonary aspergillosis.Antimicrobial agents and chemotherapy · 2015Article
- Antifungal pharmacokinetics and pharmacodynamics.Cold Spring Harbor perspectives in medicine · 2014Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The management of invasive aspergillosis (IA) has become more complicated due to the emergence of acquired azole resistance in Aspergillus fumigatus, which is associated with treatment failure and a mortality rate of 88%. Treatment with liposomal amphotericin B (L-AmB) may be a useful alternative to improve therapeutic outcome in azole-resistant IA. Four clinical A. fumigatus isolates obtained from patients with proven IA were studied in a nonneutropenic murine model of infection: a wild-type isolate without mutations in the cyp51A gene and three azole-resistant isolates harboring a single mutation at codon 220 (M220I) and tandem repeat mutations (a 34-bp tandem repeat mutation in the promoter region of the cyp51A gene in combination with substitutions at codon L98 [TR(34)/L98H] and a 46-bp tandem repeat mutation in the promoter region of the cyp51A gene in combination with mutation at codons Y121 and T289 [TR(46)/Y121F/T289A]), respectively. Female CD-1 mice were infected intravenously 24 h prior to the start of therapy. Groups of 11 mice were treated at days 1, 2, and 5 postchallenge with increasing 4-fold doses of L-AmB ranging from 0.004 to 16 mg/kg/day and observed for 14 days. Survival for all 4 isolates at day 14 was significantly better than that of controls. A dose-response relationship was observed independent of the azole resistance mechanism. The Hill-type model with a variable slope fitted the relationship between the dose and 14-day survival well for all isolates, with R(2) values of 0.95 (wild-type), 0.97 (M220I), 0.85 (TR(34)/L98H), and 0.94 (TR(46)/Y121F/T289A), respectively. Multiple logistic regression analysis confirmed that there was no significant difference between groups. The results of these experiments indicate that L-AmB was able to prolong survival in vivo in disseminated IA independent of the presence of an azole resistance mechanism in a dose-dependent manner, and therefore, they support a role for L-AmB in the treatment of azole-resistant IA.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.