ArticleAntimicrobial agents and chemotherapy2012
Experimental central nervous system aspergillosis therapy: efficacy, drug levels and localization, immunohistopathology, and toxicity.
Article in Antimicrobial agents and chemotherapy, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 32 citations in OpenAlex.
- Successful Multimodal Therapy with Intracerebral Liposomal Amphotericin B and Systemic High-Dose Isavuconazole in Proven Disseminated Aspergillosis.Journal of fungi (Basel, Switzerland) · 2023Article
- Article
- Caspofungin Cerebral Penetration and Therapeutic Efficacy in Experimental Cerebral Aspergillosis.Microbiology spectrum · 2022Article
- Review
- Amphotericin B Penetrates into the Central Nervous System Through Focal Disruption of the Blood Brain Barrier in Experimental HematogenousAntimicrobial agents and chemotherapy · 2019Article
- Article
- Efficacy, Biodistribution, and Nephrotoxicity of Experimental Amphotericin B-Deoxycholate Formulations for Pulmonary Aspergillosis.Antimicrobial agents and chemotherapy · 2018Article
- Animal Models of Aspergillosis.Comparative medicine · 2018Review
- Relation between Skin Pharmacokinetics and Efficacy in AmBisome Treatment of Murine Cutaneous Leishmaniasis.Antimicrobial agents and chemotherapy · 2018Article
- Experimental Models of Short Courses of Liposomal Amphotericin B for Induction Therapy for Cryptococcal Meningitis.Antimicrobial agents and chemotherapy · 2017Article
- Review
- Chronic Invasive Aspergillus Sinusitis and Otitis with Meningeal Extension Successfully Treated with Voriconazole.Antimicrobial agents and chemotherapy · 2015Article
- Treatment options in Invasive Aspergillosis.Current treatment options in infectious diseases · 2014Article
- In vitro and in vivo evidence for amphotericin B as a P-glycoprotein substrate on the blood-brain barrier.Antimicrobial agents and chemotherapy · 2014Article
- Very-high-dose caspofungin combined with voriconazole to treat central nervous system aspergillosis: substantial penetration of caspofungin into cerebrospinal fluid.Antimicrobial agents and chemotherapy · 2014Article
- Tissue penetration of antifungal agents.Clinical microbiology reviews · 2014Review
- CNS Mold Infections.Current infectious disease reports · 2013Article
- What can we learn and what do we need to know amidst the iatrogenic outbreak of Exserohilum rostratum meningitis?Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2013Article
- Reflections on the approach to treatment of a mycologic disaster.Antimicrobial agents and chemotherapy · 2013Article
Corrections and comments
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Authors and funding
3 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
We have shown previously that high-dose lipid amphotericin preparations are not more efficacious than lower doses in aspergillosis. We studied toxicity, drug concentrations and localization, and quantitative infection concurrently, using a 4-day model of central nervous system (CNS) aspergillosis to assess early events. Mice given Aspergillus fumigatus conidia intracerebrally, under a cyclophosphamide immunosuppressive regimen, were treated for 3 days (AmBisome at 3 or 10 mg/kg of body weight, Abelcet at 10 mg/kg, amphotericin B deoxycholate at 1 mg/kg, caspofungin at 5 mg/kg, or voriconazole at 40 mg/kg). Sampling 24 h after the last treatment showed that AmBisome at 3 but not at 10 mg/kg, as well as Abelcet, caspofungin, and voriconazole, reduced brain CFU. All regimens reduced renal infection. Minor renal tubular changes occurred with AmBisome or Abelcet therapy, whereas heart, lung, and brain showed no drug toxicity. Amphotericin B tissue and serum concentrations did not correlate with efficacy. Endothelial cell activation (ICAM-1 and P-selectin in cerebral capillaries) occurred during infection. Amphotericin B derived from AmBisome and Abelcet localized in activated endothelium and from Abelcet in intravascular monocytes. In 10-day studies dosing uninfected mice, minor renal tubular changes occurred after AmBisome or Abelcet at 1, 5, or 10 mg/kg with or without cyclophosphamide treatment; nephrosis occurred only with Abelcet in cyclophosphamide-treated mice. Hepatotoxicity occurred with AmBisome and Abelcet but was reduced in cyclophosphamide-treated mice. Marked CFU reduction by AmBisome at 3 mg/kg occurred in association with relatively more intense inflammation. Abelcet renal localization appears to be a precursor to late nephrotoxicity. Hepatotoxicity may contribute to high-dose Abelcet and AmBisome failures. Our novel observation of endothelial amphotericin localization during infection may contribute to amphotericin mechanism of efficacy.
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